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Chlorogenic acid (CGA) and luteolin (Lut) are the predominant constituents of Caulis Lonicerae, which is usually used in the treatment for rheumatoid arthritis (RA).In this study, we investigated whether CGA and Lut could synergistically inhibit the proliferation of fibroblast-like synoviocytes (FLSs) in RA synovial tissues.Rat FLS cells (RSC-364) induced by interleukin (IL)-1β were treated by CGA, Lut or both of them. The apoptosis rates were detected by flow cytometer. Protein expression of key molecules of NF-κB and JAK/STAT signaling pathways were detected by Western blot.Treatment with CGA and Lut inhibited the proliferation of RSC-364 cells stimulated by IL-1β significantly and induced cell apoptosis notably. The ratio of apoptosis in RSC-364 cells induced with IL-1β accompanied by both CGA and Lut increased approximately 7-fold compared with those incubated with IL-1β alone. The results of immunoblot analysis revealed that the key molecules involved in the NF-κB and JAK/STAT-signaling pathways, including NF-κB p50, p100, IKKα/β, gp103, JAK1 and STAT3, were decreased significantly in RSC-364 cells treated by IL-1β plus CAG and Lut compared with those incubated with IL-1β alone. Additionally, the amounts of phospho-IKKα/β and phospho-STAT3 were also decreased significantly in cells treated with CGA and Lut. Furthermore, the synergistic effect of CGA and Lut was superior to the effect of one of these two ingredients.Our finding suggested that the combination of CGA and Lut may be a potential therapeutic treatment for the inflammatory proliferation of synoviocytes in patients with RA.

The role of the Mas receptor in the activity of valsartan against intimal hyperplasia is unclear. Herein, we investigated the role of the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis on the activity of valsartan against intimal hyperplasiain balloon-injured rat aortic arteries. Wistar rats were randomized equally into the sham control group, injured group, and injured plus valsartan (20 mg/kg/d)-treated group. Valsartan significantly attenuated the vascular smooth muscle cell proliferation and intimal and medial thickening on days 14 and 28 after injury. The angiotensin-(1-7) levels as well as ACE2 and Mas receptor mRNA/protein expression were significantly decreased in the injured rats, compared to the uninjured rats; meanwhile, the angiotensin II level as well as the ACE and AT1 receptor mRNA/protein expression were increased (all P

Chlorogenic acid (CGA) is the primary constituent of Caulis Lonicerae, a Chinese herb used for the treatment of rheumatoid arthritis (RA). The present study aimed to investigate whether CGA was able to inhibit the proliferation of the fibroblast-like synoviocyte cell line (RSC-364), stimulated by interleukin (IL)-6, through inducing apoptosis. Following incubation with IL-6 or IL-6 and CGA, the cellular proliferation of RSC-364 cells was detected by MTT assay. The ratio of apoptosed cells were detected by flow cytometry. Western blot analysis was performed to observe protein expression levels of key molecules involved in the Janus-activated kinase/signal transducer and activator of transcription 3 (JAK/STAT) signaling pathway [phosphorylated (p)-STAT3, JAK1 and gp130] and the nuclear factor κB (NF-κB) signaling pathway [phosphorylated (p)-inhibitor of κB kinase subunit α/β and NF-κB p50). It was revealed that CGA was able to inhibit the inflammatory proliferation of RSC-364 cells mediated by IL-6 through inducing apoptosis. CGA was also able to suppress the expression levels of key molecules in the JAK/STAT and NF-κB signaling pathways, and inhibit the activation of these signaling pathways in the inflammatory response through IL-6-mediated signaling, thereby resulting in the inhibition of the inflammatory proliferation of synoviocytes. The present results indicated that CGA may have potential as a novel therapeutic agent for inhibiting inflammatory hyperplasia of the synovium through inducing synoviocyte apoptosis in patients with RA.

Background To validate a gradient-based segmentation method for gross tumor volume(GTV) delineation on 8F-fluorothymidine (FLT)positron emission tomography (PET)/ computer tomography (CT) in esophageal squamous cell cancer through pathologic specimen, in comparison with standardized uptake values (SUV) threshold-based methods and CT. The corresponding impact of this GTV delineation method on treatment planning was evaluated. Methods and materials Ten patients with esophageal squamous cell cancer were enrolled. Before radical surgery, all patients underwent FLT-PET/CT. GTVs were delineated by using four methods. GTVGRAD, GTV1.4 and GTV30%max were segmented on FLT PET using a gradient-based method, a fixed threshold of 1.4 SUV and 30% of SUVmax, respectively. GTVCT was based on CT data alone. The maximum longitudinal tumor length of each segmented GTV was compared with the measured tumor length of the pathologic gross tumor length (LPath). GTVGRAD, GTV1.4 and GTV30%max were compared with GTVCT by overlap index. Two radiotherapy plannings (planGRAD) and (planCT) were designed for each patient based on GTVGRAD and GTVCT. The dose-volume parameters for target volume and normal tissues, CI and HI of planGRAD and planCT were compared. Results The mean ± standard deviation of LPath was 6.47 ± 2.70 cm. The mean ± standard deviation of LGRAD,L1.4, L30%max and LCT were 6.22 ± 2.61, 6.23 ± 2.80, 5.95 ± 2.50,7.17 ± 2.28 cm, respectively. The Pearson correlation coefficients between LPath and each segmentation method were 0.989, 0.920, 0.920 and 0.862, respectively. The overlap indices of GTVGRAD, GTV1.4, GTV30%max when compared with GTVCT were 0.75 ± 0.12, 0.71 ± 0.12, 0.57 ± 0.10, respectively. The V5, V10, V20, V30 and mean dose of total-lung,V30 and mean dose of heart of planGRAD were significantly lower than planCT. Conclusions The gradient-based method provided the closest estimation of target length. The radiotherapy plannings based on the gradient-based segmentation method reduced the irradiated volume of lung, heart in comparison to CT.

To discuss the clinical significance of Federation International of Gynecology and Obstetrics (FIGO) 2009 staging I and its prognostic related factors in endometrial carcinoma.A retrospective analysis was carried out on 233 cases with FIGO 2009 staging I endometrial carcinoma who were admitted to Department of Obstetrics and Gynecology, Peking University People's Hospital from Dec. 1998 to Dec. 2009 and were carried with complete staging operation then compared with FIGO 1988 staging. All follow-up data were complete.Of the 233 cases, including FIGO 1988 staging I a 41 cases, I b 146 cases, I c 29 cases and II a 17 cases. The univariate analysis revealed that there were no significant difference between staging I a and I b group in histological grade, pathological type, intravascular vessel cancer embolus, the expression of ER, PR, postoperative chemotherapy or postoperative chemoradiotherapy (all P0.05). The univariate analysis revealed that there were no significant difference between staging I and II a group in histological grade, pathological type, intravascular vessel cancer embolus, the depth of myometrial invasion, the expression of ER and PR postoperative chemotherapy or postoperative chemoradiotherapy (all P0.05).FIGO 2009 staging I in endometrial carcinoma is more consistent with the patient's clinical status than that in FIGO 1988 stage I and II a.

Multiway spatial join plays an important role in GIS (Geographic Information Systems) and their applications. With the increase in spatial data volumes, the performance of multiway spatial join has encountered a computation bottleneck in the context of big data. Parallel or distributed computing platforms, such as MapReduce and Spark, are promising for resolving the intensive computing issue. Previous approaches have focused on developing single-threaded join algorithms as an optimizing and partition strategy for parallel computing. In this paper, we present an effective high-performance multiway spatial join algorithm with Spark (MSJS) to overcome the multiway spatial join bottleneck. MSJS handles the problem through cascaded pairwise join. Using the power of Spark, the formerly inefficient cascaded pairwise spatial join is transformed into a high-performance approach. Experiments using massive real-world data sets prove that MSJS outperforms existing parallel approaches of multiway spatial join that have been described in the literature.

Discovery of the isoform-selective histone deacetylases (HDACs) inhibitors is of great medical importance and still a challenge. The comparison studies on the structure-function relationship of the conserved residues, which are located in the linker binding channel among class I HDACs (including 4 isoforms: HDAC1/2/3/8), have been carried out by using ab initio QM/MM MD simulations, a state-of-the-art approach to simulate metallo-enzymes. We found that the conserved tyrosine (Y303/308/286/306 in HDAC1/2/3/8, respectively) could modulate the zinc-inhibitor chelation among all class I HDACs with different regulatory mechanisms. For HDAC1/2/3 selective-inhibitor benzamide, the conserved tyrosine could modulate the coordinative ability of the central atom (Zn(2+)), while for pan-inhibitor SAHA, the conserved tyrosine could increase the chelating ability of the ligand (SAHA). Moreover, it is first found that the conserved tyrosine is correlated with the intertransformation of π-π stacking styles (parallel shift vs T-shaped) by the aromatic ring in benzamide and the two conserved phenylalanine residues of HDACs. In addition, the catalytic roles of the conserved tyrosine in stabilizing the transition state and intermediate are further revealed. These findings provide useful molecular basis knowledge for further isoform-selective inhibitor design among class I HDACs.

Universal sensing the motion of mechanical resonators with high precision and low back-action is of paramount importance in ultra-weak signal detection which plays a fundamental role in modern physics. Here we present a universal scheme that transfer mechanically the motion of the resonator not directly measurable to the one can be precisely measured using mechanical frequency conversion. Demonstration of the scheme at room temperature shows that both the motion imprecision and the back-action force are below the intrinsic level of the objective resonator, which agree well with our theoretical prediction. The scheme developed here provides an effective interface between an arbitrary mechanical resonator and a high quantum efficient displacement sensor, and is expected to find extensive applications in high-demanding mechanical-based force measurements., 4 pages, 4 figures

Under resonant conditions, a long sequence of landau-zener transitions can lead to Rabi oscillations. Using a nitrogen-vacancy (NV) center spin in diamond, we investigated the interference between more than 100 Landau-Zener processes. We observed the new type of Rabi oscillations of the electron spin resulting from the interference between successive Landau-Zener processes in various regimes, including both slow and fast passages. The combination of the control techniques and the favorable coherent properties of NV centers provides an excellent experimental platform to study a variety of quantum dynamical phenomena.

A one-dimensional linear inverse heat conduction problem is studied in this paper. This ill-posed problem is replaced by the perturbed problem with a non-localized boundary condition. After the derivation of its closed-form analytical solution, the calculation error can be determined by the comparison between the numerical and exact solutions.

A salt-sensitive mutant designated rice salt sensitive 2 (rss2) was isolated from the M2 generation of the rice cultivar Nipponbare mutagenized with ethyl methanesulfonate (EMS). This mutant exhibited a greater decrease in salt tolerance with a significant increase in Na(+) content in its shoots. Genetic analysis indicated that the increase in Na(+) in rss2 was controlled by a single recessive gene. Further genome-wide analysis of the linkage map constructed from the F2 population of rss2/Zhaiyeqing 8 (ZYQ8) showed that two quantitative trait loci (QTLs) on chromosomes 1 and 6 were responsible for the Na(+) concentration in shoots, which explained 14.5% and 53.3%, respectively, of the phenotypic variance. The locus on chromosome 1, but not that on chromosome 6, was also detected in the F2 population of Nipponbare/ZYQ8, suggesting that the QTL on chromosome 6 was responsible for the salt sensitivity in rss2. By analyzing the recombination events in 220 mutant individuals of an enlarged mapping population of rss2/ZYQ8, the rss2 locus was precisely mapped to an interval of 605.3 kb between insertion/deletion (InDel) markers IM21962 and IM22567. This finding will facilitate the cloning of the rss2 locus and provide insight into the physiological mechanisms of salt sensitivity in rice.

We demonstrate quantum coherent control of single electronic spins in a nitron-vacancy center in diamond by exploiting and implementing the general concept of Landau-Zener-Stückelberg interferometry at room temperature. The interferometry manipulates an effective two-level system of electronic spins which are coupled to the nearby ^{14}N nuclear spin in the nitron-vacancy center as well as the nuclear spin bath in the diamond. With a microwave field to control the energy gap between the two levels and an AC field as the time-dependent driving field in Landau-Zener-Stückelberg interferometry, the interference pattern can be generated and controlled by controlling a number of parameters in the fields, corresponding to coherent control of the state of the electronic spins. In particular, the interference pattern is observed oscillating as a function of the frequency of the microwave field. Decays in the visibility of the interference pattern are also observed and well explained by numerical simulation which takes into account the thermal fluctuations arising from the nuclear bath. Therefore, our work also demonstrates that Landau-Zener-Stückelberg interferometry can be used for probing decoherence processes of electronic spins.

Three soil bacterial strains were identified as Chryseobacterium sp. TFB on the basis of their 16S rRNA gene sequences. Conidia of Arthrobotrys oligospora produced a few mycelial traps (MT) and conidial traps (CT) when cultured with bacterial cells that they did not produce when cultured with a bacterial cell-free culture filtrate. However, co-culture of A. oligospora with bacterial cells and bacteria-free filtrate simultaneously induced MT and CT in large amounts. With the increased concentration of bacteria-free filtrate, the number of typical CT increased, but conidial germination was progressively inhibited. Scanning electron microscopy of A. oligospora co-cultured with bacteria revealed that bacterial attachment to hyphae was a prerequisite to trap formation and that bacteria-free filtrate facilitated bacterial attachments to hyphae. The results that the addition of nutrients in co-culture medium decreased the number of traps suggest that this type of trap formation may be favoured at a low nutrient status. Eight fungi tested were able to form MT and CT when co-cultured with bacterial cells and bacteria-free culture filtrate, but the abilities varied among species. This study provides novel evidence that under laboratory conditions, soil bacteria attaching to hyphae could induce traps in nematode-trapping fungi.

Chrysanolide A, a novel guaianolide-type sesquiterpenoid trimer (3), along with its biogenetically related monomer (Chrysanolide B, 1) and dimer (Chrysanolide C, 2), were simultaneously isolated from Chrysanthemum indicum L flowers. Their structures and absolute configurations were elucidated via spectroscopic and computational methods. All isolated compounds were evaluated for their anti-HBV activities.