Grifolin, a secondary metabolite isolated from the fresh fruiting bodies of the mushroom Albatrellus confluens, has been reported by us and others to display potent antitumor effects. However, the ...molecular target of grifolin has not been identified and the underlying mechanism of action is not fully understood. Here, we report that the ERK1/2 protein kinases are direct molecular targets of grifolin. Molecular modeling, affinity chromatography and fluorescence quenching analyses showed that grifolin directly binds to ERK1/2. And in vitro and ex vivo kinase assay data further demonstrated that grifolin inhibited the kinase activities of ERK1/2. We found that grifolin suppressed adhesion, migration and invasion of high-metastatic cancer cells. The inhibitory effect of grifolin against tumor metastasis was further confirmed in a metastatic mouse model. We found that grifolin decreased phosphorylation of Elk1 at Ser383, and the protein as well as the mRNA level of DNMT1 was also down-regulated. By luciferase reporter and ChIP assay analyses, we confirmed that grifolin inhibited the transcription activity of Elk1 as well as its binding to the dnmt1 promoter region. Moreover, we report that significant increases in the mRNA levels of Timp2 and pten were induced by grifolin. Thus, our data suggest that grifolin exerts its anti-tumor activity by epigenetic reactivation of metastasis inhibitory-related genes through ERK1/2-Elk1-DNMT1 signaling. Grifolin may represent a promising therapeutic lead compound for intervention of cancer metastasis, and it may also be useful as an ERK1/2 kinase inhibitor as well as an epigenetic agent to further our understanding of DNMT1 function.
Abstract Background The treatment of discoid meniscus is controversial. This study aimed to assess the clinical efficacy of combined outside-in and FasT-Fix suture for the treatment of serious ...discoid meniscal tear. Methods Thirty-two consecutive patients who underwent arthroscopic meniscal plasty for serious discoid meniscal tear (full thickness vertical, longitudinal tear > 10 mm) between October 2006 and June 2012. Combined outside-in and FasT-Fix suture for the treatment of serious discoid meniscal tear. Disappearance of clinical symptoms (locked knee, ache and clicking) and negativity of the McMurray and Apley grind test were assessed during follow-up (26-47 months). The Lysholm, International Knee Documentation Committee (IKDC) and Tegner scores were assessed for therapeutic efficacy. Some patients were followed up using magnetic resonance imaging (MRI). Results Symptoms (pain, snapping and interlocking) disappeared in all patients. The Lysholm score improved from 39.1±9.2 to 89.6±6.7 at 6 months and to 90.1±6.3 at the last follow-up. Same trends were observed in the IKDC score (38.0±9.5 to 90±6.3 and to 91.1±6.4) and in the Tegner score (2.8±0.6 to 5.2±0.6 and to 5.2±0.5). Among all patients, 13 patients were followed up with MRI. Among these patients, four had unhealing stitched edge, but they did not complain from any discomfort of the knees. Conclusions Combined outside-in and FasT-Fix suture for meniscal plasty resulted in good outcomes for serious discoid meniscal tear and could be regarded as a good surgical option.
For verification of spatial distribution of phosphorous retention capacity in constructed wetlands systems(CWs), two horizontal subsurface flow(HSSF) CWs and two vertical subsurface flow(VSSF) CWs, ...using sand as substrate and Typha latifolia as wetland plants, were constructed and put into use for synthetic wastewater treatment. Five months later, significant spatial variations of TP and inorganic phosphorus(Ca-P, Fe-P and Al-P) were observed, which were found to be greatly affected by CWs type and hydraulic loading. The results revealed that though spatial distribution of Fe-P and Al-P displayed a similar order of substrate content as "rhizosphere" > "near-rhizosphere" > "non-rhizosphere" and "inflow section" > "outflow section" regardless of types and loading, the distribution of Ca-P was positively correlated to that of Fe-P and Al-P in HSSF CWs, while negative correlation was shown in VSSF CWs. As a result, TP spatial distribution in HSSF CWs demonstrated a greater dissimilarity than that in VSSF CWs. For HSSF CWs with low hydraulic loading, the lowest TP content was found in non-rhizosphere substrate of outflow section, while the highest one was discovered in rhizonsphere substrate of inflow section. The values in 6 parts of areas ranged from 0.138 g.kg-1 to 2.710 g.kg-1, which also were from -33.5% to 1209% compared to the control value. On contrast, spatial difference of TP content in substrates of VSSF CWs was insignificant, with a variation ranging from 0.776 g.kg-1 to 1.080 g.kg-1, that was 275% to 421% higher than the control value. In addition, when hydraulic loading was increased, TP content in VSSF CWs sharply decreased, ranging from 0.210 g.kg-1 to 0.634 g.kg-1. Meanwhile, dissimilarity of TP spatial distribution in HSSF CWs was reduced, with TP content ranging from 0.258 g.kg-1 to 2.237 g.kg-1. The results suggested that P spatial distribution should be taken into account for CWs design and operation.
Purpose
The aim of this retrospective study was to compare the clinical outcomes of arthroscopic decompression of popliteal cysts and simultaneous management of intra-articular pathologies alone or ...in combination with posterior open cystectomy.
Material and methods
This study included 65 consecutive patients with the diagnosis of popliteal cysts. Of the patients 31 received arthroscopy alone (arthroscopic decompression of cysts and management of intra-articular pathologies, AA group) and 34 received arthroscopy combined with open cystectomy (AO group). At the last follow-up after a mean of 33.3 months, magnetic resonance imaging (MRI) scans were performed to assess the outcomes of cysts and functional scores. The Lysholm score and Rauschning and Lindgren grade were used for clinical evaluation.
Results
The procedure in the AA group took less time to perform and resulted in less postoperative complications in the perioperative period. At the last follow-up, no significant differences were observed between the groups in terms of the Lysholm score or Rauschning and Lindgren grade (
P
> 0.05). The results of MRI showed that the cysts disappeared in 17 (55%) patients, reduced in 9 (29%) patients and persisted in 5 (16%) patients in the AA group, and disappeared in 29 (85%) patients, reduced in 4 (12%) patients and persisted in 1 (3%) patients in the AO group, which was significantly different (
P
< 0.05). In the AA group 6 patients and 1 in the AO group were grade 2 or 3 and needed a second operation (arthroscopy combined with open cystectomy), which was significantly different (
P
< 0.05).
Conclusion
In comparison to arthroscopic decompression of cysts and management of intra-articular pathologies alone, the additional posterior open cystectomy reduced the recurrence of popliteal cysts, although it took longer to perform and brought more perioperative complications.
Surgical scar formation afflicts patients and current treatments are limited by inconsistent efficacy, long-term and painful treatment processes. In this report, a patient received 5-aminolevulinic ...acid-mediated photodynamic therapy (5-ALA PDT) on the first postoperative day, once a week for 5 sessions. At two-year follow-up, the intervention of 5-ALA PDT at early stage decreased the vascular density and improved extracellular matrix (ECM) deposition. The early intervention of surgical scar by 5-ALA PDT overcomes the penetration limits of photosensitizer and red light, making it a potential strategy for surgical scar prevention.
To explore the limit of dialogue generation pre-training, we present the models of PLATO-XL with up to 11 billion parameters, trained on both Chinese and English social media conversations. To train ...such large models, we adopt the architecture of unified transformer with high computation and parameter efficiency. In addition, we carry out multi-party aware pre-training to better distinguish the characteristic information in social media conversations. With such designs, PLATO-XL successfully achieves superior performances as compared to other approaches in both Chinese and English chitchat. We further explore the capacity of PLATO-XL on other conversational tasks, such as knowledge grounded dialogue and task-oriented conversation. The experimental results indicate that PLATO-XL obtains state-of-the-art results across multiple conversational tasks, verifying its potential as a foundation model of conversational AI.
The increase of storage and computing performance in embedded mobile platforms has provided better opportunities for the development of portable GPS software receiver. However, due to a large number ...of complex calculations in baseband operations, the real-time software receiver is still the biggest challenge, and in the baseband operations of the receiver, the largest time-consuming part is the satellite signal tracking period. In this paper, based on the practical application model and with the purpose of improving the initial positioning efficiency in the receiver, an initial section of the navigation data will be preprocessed to determine the ID of frames, then appropriate strategy will be formulated to handle the next navigation data. The frames that are not involved in the initial positioning will be dropped, therefore, the navigation data that will be processed has been reduced significantly. Finally, the initial positioning efficiency will be improved to reduce TTFF(Time To First Fix). Because our method is starting from the original data sources in the tracking loop to reduce the amount of data and computing, it could greatly reduce the TTFF. The empirical results demonstrate the expectation clearly, and this algorithm has improved initial positioning efficiency and reduced tracking operations significantly. Most importantly, it provides a solid foundation for real- time embedded platform.
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