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The VEGF receptor is mock-coupled with a known active compound and the active groups of the inhibitor which can bind to VEGF were analyzed. Using asiatic acid as a lead compound, 10 novel skeleton candidate compounds were designed through introduction of the active groups onto the special location and synthesized simultaneously. Furthermore, the structure of these compounds was determined by

Oleanolic acid has previously been shown to possess PI3K inhibitory activity, thus, the purpose of this work was to generate a series of derivatives that improve the potency. Twenty rationally designed oleanolic acid derivatives were synthesized and tested the cytotoxicity and PI3K inhibitory activity. The results suggested that attachment of additional structural elements such as association of thiazole group to A ring and insertion of phenylurea group was important for increasing activities. The most active derivative was compound

Cleidocranial dysplasia (CCD) represents a rare autosomal dominant skeletal dysplasia caused by mutations that induce haploinsufficiency in RUNX2, the important transcription factor of osteoblasts related to bone/cartilage development and maintenance. Clavicular hypoplasia, which involves aberrant tooth/craniofacial bone/skeletal formation, is a feature of classic CCD. RUNX2 mutations can be found in approximately 60-70% of patients with CCD, and around ∼10% of these mutations are microdeletions. The present paper describes the radiological and clinical characteristics of a 5-year-old girl who showed representative CCD features, including extra teeth, aplasia of clavicles, sloping shoulders, marked calvarial hypomineralization, and osteoporosis.We obtained genomic DNA of her family members and performed whole-genome sequencing (WGS) for samples collected from the proband. Quantitative fluorescent PCR (QF-PCR) and specific PCR plus electrophoresis were then performed as validation assays for all participants. In vitro analysis was performed. Luciferase assay for Runx2 transcription activity and evaluation of mRNA levels of Runx2 downstream osteogenic markers were conducted.WGS identified a 11.38-kb microdeletion in RUNX2 comprising 8-9 exons, which was validated by QF-PCR and specific PCR plus electrophoresis. In vitro experiments confirmed the pathogenicity of this variation.The present study identified a 11.38-kb microdeletion in RUNX2 that causes CCD. The deletion in the PST domain of RUNX2 reduces its transcription activity and reduces osteogenic marker levels, eventually decreasing the differentiation of osteoblasts. These findings clarify the role of the CCD-related mechanism in the development of CCD and suggest that it is important to consider copy number variation for the suspected familial patients early.

This study aimed to characterize the genetic, pathological, and clinical alterations of 17 patients in China presenting with nondystrophic myotonia (NDM) and to analyze the relationship between genotype and clinical phenotype.CLCN1 and SCN4A genes in patients with clinical features and muscle pathology indicative of NDM were sequenced. Furthermore, KCNE3 and CACNA1S genes were assessed in patients with wild-type CLCN1 and SCN4A.Patients may have accompanying atypical myopathy as well as muscle hypertrophy, secondary dystonia, and joint contracture as determined by needle electromyography. All the study participants were administered mexiletine in combination with carbamazepine and showed significant improvements in myotonia symptoms in response to this therapy. CLCN1 gene mutation was detected in 8 cases diagnosed with myotonia congenital using gene screening. The detected mutations included 5 missense, 2 nonsense, 1 deletion, and 2 insertions. Further gene analysis showed 4 mutations in the SCN4A gene in patients diagnosed with paramyotonia congenita.Myotonia congenita and paramyotonia congenita are the predominant forms of NDM in China. NDM may be best diagnosed using genetic analysis in associated with clinical features.

In this study, twenty-four oleanolic acid (OA) derivatives were rationally designed based on molecule docking studies and their VEGFR-2 inhibitory activities were tested by Homogeneous time-resolved fluorescence (HTRF) method

Based on the simulation of the docking of survivin protein with known small molecule inhibitors, the active groups which can bind to target proteins were analyzed by the techniques of computer-aided drug design (CADD). These active groups were introduced into the A-ring of asiatic acid and their C-28 sites were reconstructed simultaneously. Ten asiatic acid derivatives were designed and synthesized, and their structures were confirmed by MS and NMR. The inhibitory activities of the asiatic acid derivatives against HepG2 and SGC7901 cell lines were evaluated and confirmed by the tetrazolium bromidesalt (MTT) assay. The results showed that compounds I6 and II4 exhibited more potent cytotoxicity than the positive control drug gefitinib, which was comparable to that of adriamycin.[Formula: see text].

To assess the efficacy and safety of rituximab (RTX) in the treatment of neuromyelitis optica spectrum diseases (NMOSDs), and give a guideline on clinical medication.The databases of Pubmed, Embase, Cochrane Library, CNKI, and Wan fang were systematically searched by computer, and the search period was from the establishment of the databases until January 2022. To collect the trials of RTX in the treatment of NMOSDs, two researchers completed literature screening, quality assessment, and data extraction independently. Statistical analysis was performed using Review Manager 5.3 and Stata 15.1 software.There were 37 studies in the meta-analysis, including 5 randomized controlled trials (RCTs) and 32 observational studies. Meta-analysis results revealed that NMOSDs patients treated with RTX significantly reduced the annualized relapse rate (ARR) (weighted mean difference [WMD] = 1.45, 95% confidence interval [CI]: 1.24-1.66, P .01) and the Expanded disability status scale (EDSS) scores (WMD = 1.34, 95%CI: 1.25-1.44, P .01). RTX is more effective than azathioprine (AZA) in the treatment of NMOSDs (ARR: WMD = -0.54, 95% CI: -0.75 to -0.33; EDSS: WMD = -0.65, 95% CI: -0.83 to -0.48; P .0001).There was no difference in ARR and EDSS scores between anti-aquapor in-4-antibody seropositive NMOSD and seronegative NMOSD patients treated with RTX (ARR: WMD = -0.01, 95% CI: -0.25 to 0.24, P = .96 0.05; EDSS: WMD = 0, 95% CI: -0.30 to 0.31, P = .99 0.05). In this study, 681 patients were recorded safety data of RTX therapy, 23% (156 patients) had adverse events, and 0.7% (5 patients) of NMOSDs discontinued due to severe adverse reactions.NMOSDs patients treated with RTX can significantly reduce the relapse frequency and EDSS scores, and also improve neurological dysfunction, besides the efficacy is better than azathioprine. RTX has a high incidence of adverse reactions, which are mild and with certain self limited, it should be cautious in clinical medication.

Recently, several randomized controlled trials on the use of cholinesterase inhibitors or memantine as treatments for cognitive impairment in Parkinson's disease (CIND-PD), Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) were completed. The present study provided a meta-analysis of these studies to evaluate the efficacy of cholinesterase inhibitors and memantine on CIND-PD, PDD and DLB. The Cochrane Library, Pubmed, Embase and Web of Science databases were searched to retrieve eligible studies. As primary efficacy outcomes, cognitive function, global impression, behavioral symptoms and motor function were selected, while falling and adverse events were regarded as safety outcomes. Of note, domain-specific cognitive function was assessed as a primary efficacy outcome and falling as a safety outcome, which, to the best of our knowledge, has not been studied previously in CIND-PD, PDD and DLB. A total of 15 trials were included in the present meta-analysis. The results revealed that treatment with cholinesterase inhibitors resulted in improvements in cognitive function, the clinician's global impression, behavioral symptoms and motor function, in accordance with the results of previous studies. Furthermore, it was revealed that cholinesterase inhibitors had a significant effect on attention, processing speed, executive functions, memory and language; however, they did not improve visuospatial cognition compared with placebos. Memantine had a significant effect on attention, processing speed and executive functions. In addition, cholinesterase inhibitors and memantine did not significantly reduce falling. It was demonstrated that an increased number of adverse events occurred in the pooled cholinesterase inhibitors and memantine group, compared with that in the placebo group (risk ratio (RR)=1.09; 95% confidence interval (CI): 1.04-1.16; P=0.001); however, in the subgroup analysis, only the rivastigmine group experienced significantly more adverse events than the placebo group (85 vs. 73%; RR=1.18; 95% CI: 1.08-1.29; P=0.0001), but donepezil and memantine did not produce any significant adverse events. In conclusion, cholinesterase inhibitors and memantine have an effect not only on global cognitive function and motor function, but also on attention, processing speed, executive functions, memory and language. However, careful monitoring of the side effects of rivastigmine may be required. Further clinical trials are required to verify these conclusions.

A series of asiatic acid derivatives were synthesized and their cytotoxicities in vitro against two cancer cell lines (HepG2 and SGC7901) were evaluated by MTT assay. The results showed that compounds I2, I6, and II6 have more potent anticancer activity than that of the positive control drug paclitaxel. The interactions between the compounds I2, I6, and II6 and survivin were also studied by docking simulations.

The PDGF receptor is mock-coupled with a known active compound, and 14 novel skeleton candidate compounds were designed and synthesized. The structure was confirmed by 1H NMR, 13C NMR and MS. The i...

Eighteen uronic acid derivatives were designed and synthesized, and the cytotoxicities in vitro of two cancer cell lines (BEL7402 and SGC7901) were evaluated by MTT assay. The results showed that the inhibitory rate of the compounds on both cell lines was significantly higher than the parent compound. The IC50 of compounds II4, II6, III4, and III6 are comparable or stronger than the positive control drug, the interactions between compounds II4, II6, III4, III6, and NF-κB were also studied by docking simulations.

Myricetin (Myr) is a common plant-derived polyphenol and is well recognized for its multiple activities including antioxidant, anti-inflammation, anticancer, and antidiabetes. Our previous studies indicated that Myr protected mouse heart from lipopolysaccharide and streptozocin-induced injuries. However, it remained to be unclear whether Myr could prevent mouse heart from pressure overload-induced pathological hypertrophy. Wild type (WT) and cardiac Nrf2 knockdown (Nrf2-KD) mice were subjected to aortic banding (AB) surgery and then administered with Myr (200 mg/kg/d) for 6 weeks. Myr significantly alleviated AB-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction in both WT and Nrf2-KD mice. Myr also inhibited phenylephrine- (PE-) induced neonatal rat cardiomyocyte (NRCM) hypertrophy and hypertrophic markers’ expression in vitro. Mechanically, Myr markedly increased Nrf2 activity, decreased NF-κB activity, and inhibited TAK1/p38/JNK1/2 MAPK signaling in WT mouse hearts. We further demonstrated that Myr could inhibit TAK1/p38/JNK1/2 signaling via inhibiting Traf6 ubiquitination and its interaction with TAK1 after Nrf2 knockdown in NRCM. These results strongly suggested that Myr could attenuate pressure overload-induced pathological hypertrophy in vivo and PE-induced NRCM hypertrophy via enhancing Nrf2 activity and inhibiting TAK1/P38/JNK1/2 phosphorylation by regulating Traf6 ubiquitination. Thus, Myr might be a potential strategy for therapy or adjuvant therapy for malignant cardiac hypertrophy.

Background The effect of statin treatment on circulating coenzyme Q10 (CoQ10) has been studied in numerous randomized controlled trails (RCTs). However, whether statin treatment decreases circulating CoQ10 is still controversial. Methods PubMed, EMBASE, and the Cochrane Library were searched to identify RCTs to investigate the effect of statin treatment on circulating CoQ10. We calculated the pooled standard mean difference (SMD) using a fixed effect model or random effect model to assess the effect of statin treatment on circulating CoQ10. The methodological quality of the studies was determined according to the Cochrane Handbook. Publication bias was evaluated by a funnel plot, the Egger regression test, and the Begg–Mazumdar correlation test. Results Twelve RCTs with a total of 1776 participants were evaluated. Compared with placebo, statin treatment resulted in a reduction of circulating CoQ10 (SMD, − 2.12; 95% CI, − 3.40 to − 0.84; p = 0.001), which was not associated with the duration of statin treatment (Exp, 1.00; 95% CI, 0.97 to 1.03; p = 0.994). Subgroup analysis demonstrated that both lipophilic statins (SMD, − 1.91; 95% CI, − 3.62 to 0.2; p = 0.017) and hydrophilic statins (SMD, − 2.36; 95% CI, − 4.30 to − 0.42; p = 0.028) decreased circulating CoQ10, and no obvious difference was observed between the two groups (SMD, − 0.20; 95% CI, − 0.208 to 0.618; p = 0.320). In addition, both low-middle intensity statins (SMD, − 2.403; 95% CI, − 3.992 to − 0.813; p

Whether aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of aucubin on cardiac remodeling. Taken together, aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.

Using the techniques of computer-aided drug design, the docking of survivin and known active small molecules was simulated and then the key amino acid residue fragments of the target protein were analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through the use of the natural product, oleanolic acid, as a lead compound, the introduction of the active groups onto the A-ring, and the modification of the carboxyl group at the C-28 position using esterification or amidation, 20 new oleanolic acid derivatives had been designed and synthesized. HepG2 and SGC-7901 cells were used to screen the antitumor activity through the standard MTT method. The compounds, II3, III5 and IV4, exhibited more potent cytotoxicity than positive drugs. Western blot experiment demonstrated that compound II3 can effectively inhibit the proliferation of HepG2 cells.

The concrete covercorrosion-induced cracking is the key to service life predicting of reinforcedconcrete structures. The existing research results make engineering andtechnical personnel in specific applications bewilderment. In this paper, therepresentative theoretical analysis methods of existing have been classifiedand the characteristics of various methods have been analyzed, the accuracy ofvarious methods has been comparatively analyzed by a concrete case.

Two conversion methods were used to correct regional errors of geochemical data. The results showed that both normalization method and conversion method of standard normal distribution could correct regional errors of geochemical data well. Normalization method had simple correction course but lower accuracy. Conversion method of standard normal distribution was more complex than normalization method, but correction effect was better. There was no obvious regional error in geochemical isograds with data which had been converted.

Distribution characteristics of content of total PAHs, single PAH and PAHs of various rings in meager coal, coking coal, gas-fat coal, gas coal and lignite were comprehensively analyzed in this paper. The study showed that PAHs were detected in all coal samples. The content gas-fat coal was the highest, while that in lignite was the lowest. Content of total PAHs increased in turn from meager to coking coal and to gas coal. Content of Pyr was higher in lignite, content of BghiP, BbFA and Phe was higher in gas coal and content of Phe was higher in gas-fat coal, coking coal and meager coal. Except for gas coal, PAHs content of 3 rings and 4 rings was higher than that of 5 rings and 6 rings in the rest coal samples.

In cane sugar production field, there are a few indexes should be highlighted, which are the product quality, refining efficiency, sugar boiling time and heat transfer performance. And those indexes are all related to the massecuite circulation flow. With the goal of better sugar production, this paper developed a model for optimal global coordination of all the sugar boiling facilities based on the multiple coupling synergies of the sugar boiling system. With a synergy solver developed by knowledge base and data base, the model solution was yielded. Emulation and experimental results showed that the higher synergy of all multiple fields, the better was the massecuite circulation flow. In other words, the optimal solution this paper yielded could result the higher production of sugar and more identical size of the sugar crystals.

The performance of grid-connected Photovoltaic (PV) power generation system operating in the field is inevitably affected by environmental parameters (solar irradiance, temperature, humidity, wind speed, spectrum, cloud cover, dust, etc.), of which the main factors are solar irradiance and temperature. Based on the data of 100kW PV system of ShangYi PV Plant captured form June 1, 2012 to May 31, 2013 (1 min resolution) and the data of Qinghai Delingha 20MW PV Plant in China captured in 2012., the influence of solar irradiance and temperature on PV system is analyzed. The results show hourly PV array DC power has highly significant positive correlation with hourly total solar radiation, also PV system AC power output and solar irradiance have good consistency. Both of them show irradiance is the main environment factor to the PV system. Then using the captured data, the relationship between maximum load and PV panels surface temperature is also analyzed, the surface temperature is higher, the maximum load is lower.

In order to select favorable coal bed methane (CBM) areas in western Guizhou and Eastern Yunnan, 5 typical mining areas were used to estimate. Based on physical properties, reservoir capacity and coal geological features, coal reservoirs evaluation model was constructed through hierarchical fuzzy comprehensive evaluation method. The results showed that: coal reservoirs were divided into 4 types, and among them, type I was the best reservoir which was mainly distributed in the western part of Zhina and Gemudi, the southeast of Panguan, and the northern part of Enhong and Laochang.

Ultrasonic standing wave (USW) manipulation of suspension microparticles separation has attracted wide attention due to its non-direct contact, being harmless to the particles, easy to manufacture, low energy consumption and high separation efficiency. USW is widely used in industrial processes, environmental assessment, biochemical analysis, clinical diagnosis and other fields. In this article, particles stress and movement process is analyzed, meanwhile, aggregation and separation of the particles is discussed respectively and the future direction of development is pointed out.

Distribution characteristics of coalbed methane in Huanghebei mining area were studied and influence of geological factors such as faults, lithology of coal seam roof and floor, magmatic activities, burial depth and upper bedrock thickness of coal seam and hydrogeological conditions on occurrence of coalbed methane were deeply discussed in this paper. Coalbed methane content of mining area increased gradually from southeast to northwest. Coalbed methane in deep well points of mining area is dominated by methane and that in shallow parts contained higher content of nitrogen.

Built-up steel H-shaped beam with variable cross-section design can save steel and realize the economy requirements of structure.The existing design method of variable width of flange of steel beam is only applicable to beam under uniformly distributed load.This paper presents optimization design procedures of the Variable cross-section.The related formulas used to optimization design of section for bisymmetric built-up steel H-shaped beams under concentrated load were derived,and the position of varying cross section of beams under concentrated load was calculated ,it is convenient to be used in engineering design,and provides theoretical foundation for variable cross-section design .

Eu2+, Dy3+co-doped strontium aluminate (SrAl2O4) phosphor with high brightness and long afterglow were prepared by nano pseudo-boehmite particulate sol method. The precursor was prepared by peptizing AlOOH powders with HNO3 as peptize agent. The influence of preparation parameters on crystal structure and luminescent properties of the phosphor have been studied systematically. Monoclinic SrAl2O4host with single-phase can be obtained by controlling sintering temperature at 1200°C, 4Wt%B2O3 and RSr/Al=0.34. The sample exhibits an intensive emission peak at 515 nm and the luminescent intensity decay with I=277.78t-1.079 .

Ten novel oleanolic acid (OA) derivatives were synthesized through modifications at positions of A ring and C-28. Inhibitory activities of the oleanolic acid derivatives against SGC7901 and A549 cell lines were evaluated and confirmed by the tetrazolium bromidesalt (MTT) assay. The lab results revealed that all these compounds displayed some antitumor activity against SGC-7901 and A-549 cell lines. Among them, II4 and II5 exhibited excellent antitumor activities against SGC7901 cells and A549 cells, compared with gefitinib. Molecular docking studies have shown that compounds II4 and II5 produce potent antitumor activities by interacting with C-kit receptor through hydrogen bonds and hydrophobic bonds.

Aiming at operation problems of DFIG under grid fault condition, the improved control strategy of coordinating control rotor converter and Crowbar circuit switching logic for enhancing LVRT ability is proposed. The over-current cause on the stator and rotor of DFIG under grid fault is analyzed and complete improved control strategy flow chart is given during entire voltage dip. Experimental verification results show that adopting this improved control strategy can effectively suppress the generator stator and rotor over-current and over-voltage, enhance wind turbine operation ability, and provide important theoretical basis and reference for large-scale wind turbine to respond to grid transient fault.

© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10-14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10-4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10-8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10-9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10-7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS-SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved.

The identification of disease-specific genetic and electrophysiological patterns for myotonia congenital (MC) could help clinicians apply in the findings of genetic studies to improve diagnosis. We examined the molecular, clinical, and histopathological characteristics of eight patients with MC.Optimization PCR was used to exclude myotonic dystrophies and the CLCN1 gene was sequenced in patients having clinical and electrophysiological features indicative of MC.Genetic screening identified nine CLCN1 mutations among the eight patients, including two missense, three nonsense, two insertion, and two deletion mutations. The patients showed typical myotonia and muscle hypertrophy. In contrast to the previous studies, secondary dystonia, joint contracture, and abnormal cardiac activity were also observed. Patients with novel mutations did not show any new muscle pathology compared with established mutations. Disscussion: Molecular genetics analysis offers an accurate method for diagnosing MC. The results of this analysis should be considered alongside clinical and electrophysiological characteristics. In this study, novel mutations in CLCN1 were detected, and the spectrum of CLCN1 mutations known to be associated with MC was expanded.

The paper analyzes the method of direct tension control, provides repaired method of closed loop speed for tension control of underfeed winder, and designs the systematic hardware figuration and software to effectively meet the demands of different volume control. Furthermore, the problems including pressure control of pressing roller, load distribution control of two-drum winder, tension control of paper, and dynamic compensation control were analyzed and solved through the design of hardware and software of S7-300 PLC.

The test on was rammed soil-cement pile composite foundation was done,On the basis of the test. Numerical simulation was analyzed to rammed soil-cement piles.The conclusions were draw from the main frequency,level acceleration, vertical acceleration and influence factors.Theory basis was provided for the study on rammed soil-cement pile composite foundation in the future

The piezoelectric ceramic (PZT) smart aggregates as sensor and actuator were embedded into large eccentric compression column to generate sin-sweep signals on-line and detect real-time signals before and after damage. The PZT active health monitoring and wavelet packets energy method were focused experimentally on the effectiveness validation of damage detection. The index of root mean square deviation is used to evaluate the damage information by compare of the energy change of damage signals. A statistical pattern identification algorithm is proposed by wavelet packets decomposition and statistical characteristics analysis of damage signal amplitude. The results show that the amplitude of active monitoring signals produces a larger attenuation. The sweep wave signal as active health monitoring is an effective method to identify damage degree and general location of concrete structure. The developed method can primarily be used in the damage evaluation.

The mechanical properties and aging of 65Mn were investigated with the controlled rolling and cooling process of spring steel. The parameter of rolling technology was determined.

This paper describes the research and implementation of ground source heat pump unit remote real-time monitoring system, researches in remote real-time monitoring system's overall design, hardware design, software design and implementation of OPC communication. The host computer takes advantage of the human-computer interaction interface of configuration software to achieve the remote real-time monitoring for ground source heat pump unit's running state; the lower computer uses data collector to intensively collect the data which is measured by field measuring instruments, and to achieve remote data transmission based on Ethernet, and then to carry out the communication between the host computer and the lower computer via OPC technology. The results show that the system achieves remote real-time monitoring of ground source heat pump unit, and is stable, easy to operate and provides a reliable basis for the actual energy saving effect's evaluation of ground source heat pump system.

An improved control strategy for harmonics restraint of doubly fed wind power system is studied in this paper. Considered low order current harmonics (5th, 7th and so on) caused by the distortion or unbalanced grid voltage conditions and the variations of generator itself parameters, an improved control strategy is proposed. In this control strategy, a proportional integral (PI) regulator paralleled with a harmonic resonant (R) controller in the synchronous reference frame is proposed for restraining the stator current harmonics. The control strategy presented in this paper has not effect on the control of fundamental current, and need not the harmonic separation filter and the sequence decomposition in multi reference frames. To verify the effectiveness of this control strategy, simulation model of DFIG system is developed in Matlab/Simulink, and experiments are implemented on the doubly fed experiment platform. The results of both simulations and experiments show that the control strategy proposed in this paper could restrain harmonic currents effectively and it is easy to implement digital control.

The DTC for PMSM possesses many advantages: simple control configuration, lesser parameters dependence and fast dynamic response and is a good choice for the drive of EV. But the DTC suffers from high torque ripples. The switching table is used as the hysteresis control rule that determines the control performance. An improved switching table is proposed based on effects of voltage vectors on the drive. Simulation results show this switching table can suppress torque ripple compared to the conventional switching table.

The \(L_{r}\) convergence and a class of weak laws of large numbers are obtained for sequences of \(\widetilde{\rho}\)-mixing random variables under the uniform CesA ro-type condition. This is weaker than the \(p\)th-order CesA ro uniform integrability. doi:10.1017/S1446181117000037

Alpha-Momorcharin (α-MMC) is a ribosome inactivating protein from Momordica charantia with anti-tumor activity. Previously, we had observed that modification of α-MMC with polyethylene glycol (PEG) could reduce toxicity, but it also reduces its anti-tumor activity in vitro. This study aims to investigate whether the metabolism-extended properties of α-MMC resulting from PEGylation could preserve its anti-tumor efficacy in vivo through pharmacokinetics and antitumor experiments. The pharmacokinetics experiments were conducted in rats using the TCA (Trichloroacetic Acid) method. Antitumor activity in vivo was investigated in murine mammary carcinoma (EMT-6) and human mammary carcinoma (MDA-MB-231) transplanted tumor mouse models. The results showed that PEGylation increased the plasma half-life of α-MMC in rats from 6.2-7.5 h to 52-87 h. When administered at 1 mg/kg, α-MMC-PEG and α-MMC showed similar anti-tumor activities in vivo, with a T/C% of 38.56% for α-MMC versus 35.43% for α-MMC-PEG in the EMT-6 tumor model and 36.30% for α-MMC versus 39.88% for α-MMC-PEG in the MDA-MB-231 tumor model (p0.05). Importantly, at the dose of 3 mg/kg, all the animals treated with α-MMC died while the animals treated with α-MMC-PEG exhibited only moderate toxic reactions, and α-MMC-PEG exhibited improved anti-tumor efficacy with a T/C% (relative tumor growth rate) of 25.18% and 21.07% in the EMT-6 and MDA-MB-231 tumor models, respectively. The present study demonstrates that PEGylation extends the half-life of α-MMC and alleviates non-specific toxicity, thereby preserving its antitumor efficacy in vivo, and a higher lever of dosage can be used to achieve better therapeutic efficacy.

CD4+ T cells play critical roles in orchestrating adaptive immune responses. Their activation and proliferation are critical steps that occur before they execute their biological functions. Despite the important role of this process, the underlying molecular events are not fully understood. MicroRNAs (miRNAs) have been shown to play important roles in lymphocyte development and function. However, the miRNAs that regulate T-cell differentiation, activation and proliferation are still largely unknown. In our previous study, using a miRNA array, we found that several miRNAs (including miR-202, 33b, 181c, 568 and 576) are differentially expressed between resting and activated CD4+ T cells. In this study, we focused on the function of miR-568 during CD4+ T-cell activation. We showed that the expression level of miR-568 decreased during the activation of T cells, including Jurkat cells and human peripheral blood CD4+ T cells. When Jurkat or human peripheral blood CD4+ T cells were transfected with miR-568 mimics, cell activation was significantly inhibited, as shown by the inhibited expression of activation markers such as CD25, CD69 and CD154; decreased IL-2 production; and inhibited cell proliferation. Using software predictions and confirmatory experiments, we demonstrated that nuclear factor of activated T cells 5 (NFAT5) is a target of miR-568. Treg cells are an important CD4+ T-cell subpopulation, so we also evaluated the function of miR-568 in Treg-cell activation and differentiation. We showed that the miR-568 level decreased, while the NFAT5 protein level increased during CD4+CD25+ Treg-cell activation, and the transfection of miR-568 mimics inhibited the NFAT5 expression, inhibited the production of both TGF-β and IL-10 and also inhibited the proliferation of Treg cells. Our further study showed that over-expression of miR-568 can inhibit Treg-cell differentiation and can inhibit the suppressive effect of these cells on effector cells. In addition, inhibition of NFAT5 by siRNA-mediated knockdown can inhibit the activation and differentiation of Treg cells. These findings reveal that miR-568 can inhibit the activation and function of both CD4+ T cells and Treg cells by targeting NFAT5. Since miR-568 plays an important role in both CD4+ T cells and Treg cells, these findings may provide leads for the development of novel treatments for human inflammatory and autoimmune diseases.

Little is known about the molecular mechanisms of ascending thoracic aortic aneurysms (ATAAs). Abnormal extracellular matrix changes and variations of vascular smooth muscle cells (VSMCs) have been implicated in abdominal aortic aneurysm formation. Our objective was to investigate the alterations of collagen, stimulators of collagen synthesis and synthetic VSMCs in patients with ATAA. Surgical samples from ATAA were taken from 20 patients, and 18 control aortas were obtained during coronary artery bypass surgery. All aortic wall specimens were fixed for histology and immunohistochemistry for collagen, connective tissue growth factor (CTGF) and osteopontin. Realtime polymerase chain reaction was used to determine their mRNA expression. Histology and semi-quantitative analysis demonstrated that protein levels of collagen, CTGF and osteopontin significantly increased by 1.9-, 1.4- and 2.2-fold, respectively ( P < 0.01 for all) in the ATAA group than in the control group. Similar results were shown in mRNA levels of type Iα1and IIIα1 collagen, CTGF and osteopontin. The protein levels of CTGF and osteopontin were positively correlated with aortic diameter ( r = 0.67, r = 0.73; P < 0.01 for both). In conclusion, overexpression of aortic CTGF and synthetic VSMCs marker (osteopontin), which is likely to be responsible for elevated aortic collagen content, may provide a potential mechanism for aneurysmal enlargement.

A Gram-negative, aerobic, rod-shaped, motile, non-spore-forming bacterial strain, designated 13-Q(T), was isolated from seaside soil under the stacks of the red algae in Hainan province in China. Identification was carried out on the basis of polyphasic taxonomy. Phylogenetic analysis of 16S rRNA gene sequences showed that strain 13-Q(T) belonged to the genus Pedobacter, and the highest similarity was 94.4 % with Pedobacter terricola KCTC 12876(T). Strain 13-Q(T) was able to grow at 10-40 °C, in pH 5.0-10.0, in the presence of 0-2.0 % NaCl. The major fatty acids were iso-C(15:0) (40.4 %), summed feature 3 (comprising iso-C(15:0) 2-OH and/or C(16:1) ω7c) (18.9 %) and iso-C(17:0) 3-OH (18.4 %). The predominant menaquinone was MK-7. The G+C content of the genomic DNA was 42.7 mol%. Strain 13-Q(T) could be distinguished from the nearest phylogenetic neighbors by various chemotaxonomic and phenotypic properties. The results of the polyphasic analyses suggested that strain 13-Q(T) should be considered to represent a novel species of the genus Pedobacter, for which the name Pedobacter hainanensis sp. nov. is proposed. The type strain is 13-Q(T) (=CCTCC AB 2012076(T) = NRRL B-59850(T)).

α-momorcharin (α-MMC), a type I ribosome-inactivating protein (RIP) from Momordica charantia, is well known for its antitumor and antivirus activities. However, the immunotoxicity and hepatotoxicity hampers its potential therapeutic usage. In order to reduce its toxicity, we had modified the α-MMC with polyethylene glycol (PEG), and detected the toxicity of the PEGylated α-MMC conjugates (α-MMC-PEG) in vivo.After α-MMC purified from bitter melon seeds, α-MMC-PEG was constructed with a branched 20 kDa (mPEG) 2-Lys-NHS, the tests of immunogenicity, immunotoxicity, and general toxicity of α-MMC-PEG were conducted in guinea pig and rat.The titer of specific IgG in rats, immunized by α-MMC-PEG, were approximately one-third of those that by α-MMC, all the guinea pigs treated with α-MMC died of anaphylaxis shock within 5 min, while no animals treated with α-MMC-PEG died in the active systemic anaphylaxis (ASA) test. The passive cutaneous anaphylaxis (PCA) reaction of α-MMC-PEG challenge in rats was significantly smaller than that of the α-MMC. The liver damage was greatly released, such as the change of globulin (GLB), aspartate aminotransferase (AST), total bilirubin (TBIL) cholesterol (CHOL), albumin (ALB), and the degree of hepatocyte necrosis in repeated toxicity study.PEGylation is effective in reducing the immunogenicity, immunotoxicity, and hepatotoxicity of α-MMC in vivo.

ObjectiveTo observe the effect on the inhibition of coronary atherosclerosis hardening of the paraoxonase gene (PON-1) which transfected to the rabbit epicardial adipose tissue.MethodsRabbit coronary atherosclerosis model was established by high-fat feeding, liposome-encapsulated recombinant plasmid pEGFP-PON-1 50 μ L was injected to the rabbit pericardial cavity, and was harvested 4 weeks after transfection.ResultsThe epicardial fat transfected PON-1 gene had effect on the high lipid level. It significantly increased expression of PON-1 in peripheral arterial vascular tissue (P

N-t-Butyloxycarbonyl-amino acid(aspartic acid:Asp, glutamic acid:Glu, β-aminoglutaric acid: β-Agl)anhydrides were deprotected upon heating at temperatures slightly higher than the melting points of these compounds and polypeptides were synthesized easily in high yield.

Background Formaldehyde can induce misfolding and aggregation of Tau protein and β amyloid protein, which are characteristic pathological features of Alzheimer’s disease (AD). An increase in endogenous formaldehyde concentration in the brain is closely related to dementia in aging people. Therefore, the discovery of effective drugs to counteract the adverse impact of formaldehyde on neuronal cells is beneficial for the development of appropriate treatments for age-associated cognitive decline. Methods In this study, we assessed the neuroprotective properties of TongLuoJiuNao (TLJN), a traditional Chinese medicine preparation, against formaldehyde stress in human neuroblastoma cells (SH-SY5Y cell line). The effect of TLJN and its main ingredients (geniposide and ginsenoside Rg1) on cell viability, apoptosis, intracellular antioxidant activity and the expression of apoptotic-related genes in the presence of formaldehyde were monitored. Results Cell counting studies showed that in the presence of TLJN, the viability of formaldehyde-treated SH-SY5Y cells significantly recovered. Laser scanning confocal microscopy revealed that the morphology of formaldehyde-injured cells was rescued by TLJN and geniposide, an effective ingredient of TLJN. Moreover, the inhibitory effect of geniposide on formaldehyde-induced apoptosis was dose-dependent. The activity of intracellular antioxidants (superoxide dismutase and glutathione peroxidase) increased, as did mRNA and protein levels of the antiapoptotic gene Bcl-2 after the addition of geniposide. In contrast, the expression of the apoptotic-related gene - P53, apoptotic executer - caspase 3 and apoptotic initiator - caspase 9 were downregulated after geniposide treatment. Conclusions Our results indicate that geniposide can protect SH-SY5Y cells against formaldehyde stress through modulating the expression of Bcl-2, P53, caspase 3 and caspase 9, and by increasing the activity of intracellular superoxide dismutase and glutathione peroxidase.