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Spontaneous heating in the active goaf area during normal mining processes poses increased threats to mine productivity and safety, as evidenced in events induced by spontaneous combustion of coal. To control and mitigate this engineering problem, there is a need to gain critical knowledge of spontaneous combustion in the longwall goaf area, which can be achieved through a combination of field tests and numerical modeling. This paper introduces the spontaneous combustion management system widely used in Australia and presents Computational Fluid Dynamics (CFD) models for the simulation of gas flow dynamics in the goaf area, based on the site conditions of an underground coal mine where coal seam gas is predominantly comprised of carbon dioxide. The models were validated with gas monitoring data and used to conduct parametric studies for proactive goaf inertisation optimization. Qualitative and quantitative analysis of simulation results indicated that better goaf inertisation could be achieved when nitrogen was injected via cut-through at 250 m on the maingate (MG) side and surface boreholes at 100 m and 700 m on the tailgate (TG) side, with a total injection rate greater than 1750 1/s. The oxygen concentration on the MG and TG side dropped below 5% at distances of 120 m and 75 m behind the longwall face, with an oxidation zone area of 35375 m2, which was approximately one-third of the oxidation zone area of the scenario without inert gas injection. Simulation results help shed light on improving current goaf inertisation practices to effectively reduce the risk of heating in goaf areas and improve mining process safety based on Australian conditions and practices. [ABSTRACT FROM AUTHOR]

Generalized anxiety disorder (GAD) is a significant and common mental illness with a lifetime prevalence of 3.7%. Regardless of the complexity of treatment decisions for GAD, few studies have conducted systematic comparisons of the efficacies of varying interventions. Thus, this study performed a valid network meta-analysis (NMA) of randomized controlled trials (RCTs) to synthesize direct and indirect evidence for alternative interventions for GAD. We searched four major bibliographic databases, the Cochrane Central Register of Controlled Trials, Embase, PsycINFO, and PubMed, for published RCTs of adult patients with a diagnosis of GAD and allowed for all comorbidities. A total of 91 articles (14,812 participants) were identified in the final NMA. The results showed that all pharmacological treatments except for serotonin modulators and second-generation antipsychotics had greater effects than placebo: norepinephrine–dopamine reuptake inhibitors (standardized mean difference (SMD) −1.84, 95% credible interval −3.05 to −0.62), noradrenergic and specific serotonergic antidepressants (−0.91, −1.62 to −0.20), melatonergic receptor agonists (−0.68, −1.15 to −0.21), selective serotonin reuptake inhibitors (SSRIs; −0.67, −0.90 to −0.43), azapirones (−0.58, −1.00 to −0.17), anticonvulsants (−0.56, −0.85 to −0.28), serotonin–norepinephrine reuptake inhibitors (SNRIs; −0.54, −0.79 to −0.30), and benzodiazepines (BZDs; −0.40, −0.65 to −0.15). Most psychological and self-help interventions exerted greater effects than the waitlist group. However, no psychological interventions had greater effects compared with the psychological placebo. Overall, most pharmacological interventions had larger effect sizes than psychological interventions, and most psychological interventions showed larger effect sizes than self-help interventions. [ABSTRACT FROM AUTHOR]

Compared to traditional DNA markers, genome-scale datasets can provide mass information to effectively address historically difficult phylogenies. Primula is the largest genus in the family Primulaceae, with members distributed mainly throughout temperate and arctic areas of the Northern Hemisphere. The phylogenetic relationships among Primula taxa still maintain unresolved, mainly due to intra- and interspecific morphological variation, which was caused by frequent hybridization and introgression. In this study, we sequenced and assembled four complete plastid genomes (Primula handeliana, Primula woodwardii, Primula knuthiana, and Androsace laxa) by Illumina paired-end sequencing. A total of 10 Primula species (including 7 published plastid genomes) were analyzed to investigate the plastid genome sequence divergence and their inferences for the phylogeny of Primula. The 10 Primula plastid genomes were similar in terms of their gene content and order, GC content, and codon usage, but slightly different in the number of the repeat. Moderate sequence divergence was observed among Primula plastid genomes. Phylogenetic analysis strongly supported that Primula was monophyletic and more closely related to Androsace in the Primulaceae family. The phylogenetic relationships among the 10 Primula species showed that the placement of P. knuthiana-P. veris clade was uncertain in the phylogenetic tree. This study indicated that plastid genome data were highly effective to investigate the phylogeny. [ABSTRACT FROM AUTHOR]

The contents of lead, cadmium, chromium, copper, and nickel were determined in 25 tea samples from China, including green, yellow, white, oolong, black, Pu'er, and jasmine tea products, using high-resolution continuum source graphite furnace atomic absorption spectrometry. The methods used for sample preparation, digestion, and quantificational analysis were established, generating satisfactory analytical precisions (represented by relative standard deviations ranging from0.6% to 2.5%) and recoveries (98.91e101.32%). The lead contents in tea leaveswere 0.48e10.57 mg/kg, and 80% of these valueswere below themaximumvalues stated by the guidelines in China. The contents of cadmiumand chromiumranged from0.01mg/kg to 0.39mg/kg and from0.27mg/kg to 2.45mg/kg, respectively, remaining in compliancewith the limits stipulated by China'sMinistry ofAgriculture. Thecopper contentswere 7.73e63.71mg/kg; only 64% of these values compliedwith the standards stipulated by theMinistry of Agriculture. The nickel contents ranged from2.70mg/kg to 13.41mg/kg.Consequently,more attentionmust be paid to the risks of heavymetal contaminationintea.The quantitativemethod established in this work lays a foundation for preventing heavymetal toxicity in human from drinking tea and will help establish regulations to control the contents of heavy metals in tea. [ABSTRACT FROM AUTHOR]

In this study, P- and S-wave velocity models were built based on two pre-stack depth migration (PSDM) profiles of long-offset reflection data and 25 four-component ocean-bottom seismometers (OBS) data at Jiulong Methane Reef off SW Taiwan in the passive margin of the northern South China Sea (SCS). According to the velocity models, the average P-wave velocity and Vp/Vs ratio of the free gas beneath the bottom-simulating reflector (BSR) are 1.52–1.58 km/s and 4.5–5.10, respectively. The depth of the BSR is found at 80–300 m below the sea floor and the sedimentary thickness of the hydrate and the free gas are about 50–100 m and 70–100 m, respectively. P-wave velocity of about 1.75 km/s in the hydrate-bearing sediment is southeastward increased to about 1.85 km/s above the BSR. Similarly, Vp/Vs ratio of about 3.06 in the hydrate-bearing sediment is increased southeastward to about 3.48 above the BSR. Based on the pseudo-3D map of gas-hydrate saturation estimated from the PSDM and OBS models, the average saturations of hydrate and free gas at Jiulong Methane Reef are about 7% and 0.9–2.4%, respectively. The highest hydrate saturation (11%) is located at 5–20 m above the BSR in the SE portion of the Jiulong Methane Reef. On the other hand, the highest gas saturation of about 2% is observed at 10–70 m below the BSR in the NW portion of the Jiulong Methane Reef. We suggested that several normal faults dipping southeastward beneath the continental slope provided conduits for gas migrating northwestward at Jiulong Methane Reef. Therefore, the highest gas saturation is observed below the anticline in the NW portion of the Jiulong Methane Reef and the highest hydrate saturation (high P-wave velocity and high Vp/Vs ratio) is identified above the BSR in the SE portion of the Jiulong Methane Reef. [ABSTRACT FROM AUTHOR]

One-third of all cancer categories in clinics have a high incidence of neoplasm metastasis. Neoplasm metastasis is one of the leading causes of cancer deaths. However, the prevailing therapeutic approach to this pathogenic process is presently unsatisfactory. Paradoxically to our efforts and expectations, except for some antibodies, no obvious improvements and therapeutic benefits in currently used drugs have been achieved until now. Therapeutic benefits in late-stage or elderly cancer patients are especially poor and useless. One of the reasons for this, we would guess, is the lack of therapeutic targets specifically related to neoplasm metastasis. In order to enhance the therapeutic efficacy, the development of antimetastatic drugs transcending from current drug-screening pathways is urgently needed. Antimetastatic drugs targeting aberrantly sialylated in tumors have evolved for about a quarter of a century and might be a future therapeutic option other than the currently utilized antimetastatic drugs, such as antivascular and MMP inhibitors. Since neoplasm tissues often manifest high levels of sialic acids and sialyl antigens or glycoligands, some types of sialic acid analogue, such as N-glycolylneuraminic acid (Nau5Gc), occurred in most tumor tissues which is normally absent in most humans. Consequently, more attention is needed to work with new therapeutic approaches to target these changes. This review addresses and discusses the latest six types of therapeutic approaches targeting sialic acids in metastatic tissues. [ABSTRACT FROM AUTHOR]

The present study explored the feasibility of using hexagonal-phase NaYF4:Ce,Tb,Gd nanocrystals as bimodal probes for fluorescence and magnetic resonance (MR) imaging. Using a facile and user-friendly strategy, the NaYF4:Ce,Tb,Gd nanocrystals were synthesized with good water dispensability, high quantum yield (26%), and decent MR T1 relaxivity (r1 = 2.87mM-1 s-1). The NaYF4:Ce, Tb, Gd NCs conjugated by folic acid presented great efficiency in fluorescence imaging of C6 glioma cells in vitro. Meanwhile, in in vivo MR experiments on rats, the NaYF4:Ce,Tb,Gd NCs also significantly increased T1 signal in the liver, spleen, and kidney even with a low probe dose. The proposed NaYF4:Ce,Tb,Gd nanoprobes hold promise for simultaneous bimodal fluorescence and MR bioimaging. [ABSTRACT FROM AUTHOR]

We prepared silica−dye−nanocrystal hybrid particles and studied the energy transfer from semiconductor nanocrystals (= donor) to organic dye molecules (= acceptor). Multishell CdSe/CdS/ZnS semiconductor nanocrystals were adsorbed onto monodisperse Stöber silica particles with an outer silica shell of thickness 2−23 nm containing organic dye molecules (Texas Red). The thickness of this dye layer has a strong effect on the energy transfer efficiency, which is explained by the increase in the number of dye molecules homogeneously distributed within the silica shell, in combination with an enhanced surface adsorption of nanocrystals with increasing dye amount. Our conclusions were underlined by comparison of the experimental results with numerically calculated FRET efficiencies and by control experiments confirming attractive interaction between the nanocrystals and Texas Red freely dissolved in solution. [ABSTRACT FROM AUTHOR]

Quorum sensing (QS) through signal chemical molecules is known to be essential to bacterial adhesion and biofilm formation. In this study, the QS ability of aerobic granules—a special form of biofilms used for biological wastewater treatment—was investigated and compared with that of conventional activated sludge flocs. A novel sectional membrane bioreactor was used together with a flow-cell to evaluate the possible influence of signal chemicals produced by the source sludge on the growth mode of bacterial cells. The results demonstrate the apparent production of QS chemicals from granules and its impact on initial cell attachment and granule formation. When granules were used as the signal-producing biomass, the attached-growth mode was dominant for the free cells, and the biofilm formation rate in the flow-cell was about ten times faster than in cases which used activated sludge as the signal source biomass. In addition, the intracellular extract from mature granules significantly accelerated the sludge granulation process. It is argued that the production and expression of QS signal chemicals from granules and granule precursors might have induced the gene expression of bacteria in suspension for attached growth rather than suspended growth, leading to granule formation and its stable structure. [ABSTRACT FROM AUTHOR]

Introduction: Hepatocyte growth factor (HGF) is a target of gene therapy for renal fibrosis. The aim of this study was to establish a human HGF gene expression system that is regulated by tetracycline (Tet) in normal rat kidney tubular epithelial cells (NRK52E cells). Materials and Methods: The plasmids pTet-on, pBI-L-HGF and pTK-Hyg were transfected sequentially into NRK52E cells using Lipofectamine 2000. The expression of HGF gene was measured, and the activity of expressed HGF was detected. Results: A clone of pBI-L-HGF/NRK52E cells showing strong reaction to doxycycline (Dox) was selected using a luciferase reporter assay system. The expression of both HGF mRNA and protein was significantly higher (both p < 0.01) in the Dox group than that in the control group. Furthermore, the bioactivity of expressed HGF was confirmed in the assay. Conclusions: A Tet-regulated human HGF gene expression system in NRK52E cells has been established. This cell line may prove useful for gene therapy against renal fibrosis. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

DNA computation (DNAC) has been proposed to solve the satisfiability (SAT) problem due to operations in parallel on extremely large numbers of strands. This paper attempts to treat the DNA-based bio-molecular solution for the SAT problem from the quantum mechanical perspective with a purpose to explore the relationship between DNAC and quantum computation (QC). To achieve this goal, it first builds up the correspondence of operations between QC and DNAC. Then it gives an example for the case of two variables and three clauses for details of this theory. It also demonstrates a three-qubit experiment for solving the simplest SAT problem with a single variable on a liquid-state nuclear magnetic resonance ensemble to verify this theory. Some discussions are made for the potential application and for further exploration of the present work. [ABSTRACT FROM AUTHOR]

Settling velocity of microbial aggregates, such as anaerobic and aerobic granules, in biological wastewater treatment systems is highly related to their drag coefficient. In this work a new approach, taking the porosity and the permeability into account, was established to evaluate the drag coefficient of porous and permeable microbial granules. The effectiveness of this approach was demonstrated by the experimental results with both the anaerobic and the aerobic granules. The drag coefficient of the microbial granules was found to be less than that of smooth rigid spheres and Biofilm-covered particles. In addition, this study demonstrates that the drag coefficient of microbial granules depended heavily on their permeability and porosity. A fractal-cluster model was found to be able to predict the distribution of the primary particles in the microbial granules. [ABSTRACT FROM AUTHOR]

Bismuth nanowires with width of 10~20 nm, and length of ~200 nm were rapidly prepared from the reduction of Bi(NO3)3•5H2O by ethylene glycol (EG) in alkaline solution under microwave irradiation for 5 minutes. The product was characterized by XRD, TEM and SAED. The effects of the microwave irradiation, the alkaline solution, and the solvent on the formation of bismuth nanowires were also investigated. [ABSTRACT FROM AUTHOR]

Highlights • We pointed out the erratum of recent paper by Yu et al., (2018) in Journal of Affective Disorders. • The unit of prevalence was mistakenly written as ‰ in Table 2 of Guo et al. (2016) and also the article of Yu et al. (2018). • The current and lifetime prevalence of GAD and prevalence by location should be 5.17‰, 4.66‰ and 4.56‰, respectively. [ABSTRACT FROM AUTHOR]

The magnitude and frequency of induced seismicity increase as mining excavation reaches greater depth, leading to the increasingly severe damage to roadways caused by highenergy seismic waves. To comprehensively simulate the damage caused by dynamic loads, a synchrosqueezing transform and empirical mode decomposition method was developed, which effectively decomposed raw seismic wave signals into transverse and longitudinal components. This novel method produced more accurate results in terms of velocity, displacement, rock yielding patterns, and reflecting theoretically orthogonal oscillating directions of transverse and longitudinal waves compared to using raw mixed waves at the seismic source. Under the disturbance of transverse and longitudinal waves, the vertical displacement was much higher than horizontal displacement at the top position of the roadway, while the horizontal displacement was greater at the sidewalls. The particle vibration velocity, displacement and yielding zone of the surrounding rock of roadway were proportional to the energy level of seismic, while inversely proportional to the sourceroadway distance. The proportion of damage attributed to transverse waves increased with the energy level, ranging from 75.8% to 85.8%. Eventually, a roadway dynamic support design was optimized based on the proposed seismic wave processing and modeling methodology. The methodology offers guidance for roadway dynamic support design, with the goal of averting excessive or insufficient support strength. [ABSTRACT FROM AUTHOR]

Broodiness is the primary factor influencing egg production in geese, in which several genes and miRNAs participate. Detailed spatiotemporal profiles of miRNAs encompassing follicle development levels, however, are lacking. In this study, we collected preovulatory follicles (classified as small white follicles, large white follicles, and small yellow follicles) from brooding and laying geese and aimed to analyze microRNA (miRNA or miR) during folliculogenesis. High-throughput sequencing and bioinformatics analysis were used to identify the miRNAs involved in follicle development. The let7 family, miR-10 family, and miR-143 family were abundant in these libraries, and they have been suggested to play a housekeeping role during folliculogenesis. Joint comparisons revealed 23 upregulated and 21 downregulated miRNAs (in at least two comparisons of follicles during brooding and laying, P < 0.1) in the laying stage. Unlike reproduction pathways reported for ovaries, GO and KEGG analysis suggested pathways for cell apoptosis and proliferation, such as the regulation of actin cytoskeleton, endocytosis, axon guidance, pathways in cancer, tight junctions, focal adhesion, the MAPK signaling pathway, cytokine-cytokine receptor interactions, and the Wnt signaling pathway in folliculogenesis. This study revealed the miRNAs that were directly involved in follicular atresia, and our results added to the understanding of the functional involvement of miRNAs during specific stages of follicle development. [ABSTRACT FROM AUTHOR]

Damage-associated molecular patterns secreted from activated kidney cells initiate the inflammatory response, a critical step in the development of sepsis-induced acute kidney injury (AKI). However, the underlying mechanism remains to be clarified. Here, we established a mouse model of sepsis-induced AKI through intraperitoneal injection of lipopolysaccharide (LPS) and demonstrated that LPS induced dramatical upregulation of C-C motif chemokine ligand 2 (CCL2) at both the mRNA and protein levels in the kidney, which was mainly expressed by tubular epithelial cells (TECs), especially by proximal TECs. Proximal tubule-specific ablation of CCL2 reduced LPS-induced macrophage infiltration, proinflammatory cytokine expression, and attenuated AKI. In vitro, using a Transwell migration assay, we found that deficiency of CCL2 in TECs decreased macrophage migration ability. However, myeloid-specific depletion of CCL2 could not protect the kidneys from the aforementioned effects. Mechanistically, LPS activated Toll-like receptor (TLR)2 signaling in TECs, which induced activation of its downstream effector NF-κB. Blockade of TLR2 signaling or inhibition of NF-κB activation in TECs significantly suppressed LPS-induced CCL2 expression. Furthermore, chromatin immunoprecipitation analyses confirmed a direct binding of NF-κB p65 in the CCL2 promoter region, and LPS increased the binding of NF-κB p65 to the CCL2 promoter, suggesting that TLR2/NF-κB p65 regulates CCL2 expression in TECs. Together, these results demonstrate that endogenous CCL2 released from proximal TECs, not from myeloid cells, was responsible for sepsis-induced kidney inflammation and AKI. Specifically targeting tubular TLR2/NF-κB/CCL2 signaling may be a potential therapeutic strategy for the prevention or attenuation of septic AKI. [ABSTRACT FROM AUTHOR]

Crustal structures near a linear oceanic ridge, the Gagua Ridge, between the West Philippine Basin and the Huatung Basin in the western Philippine Sea were imaged based on head-wave, refracted and reflected P-wave arrivals recorded from 24 oceanbottom seismometers (OBS). Velocity anomaly zones, one below the Gagua Ridge summit and the others beneath two toes of the Gagua Ridge, imaged by large lateral variations in P-wave velocity of 5.5 - 6.4 km s-1 and low velocity of 4 - 5 km s-1 in the upper crust may have been generated when the Gagua Ridge was formed. East of the ridge, velocity anomaly zones, constrained by large lateral variations in P-wave velocity (4.8 - 6.4 km s-1), relatively low velocity (4-5 km s-1) and laterally high anomaly of Poisson's ratio (0.02 - 0.04) in the upper crust and abrupt crustal thickening (6 - 8.5 km) northward were obtained. West of the ridge, the velocity anomaly zones indicated by large lateral variations in P-wave velocity (5.2 - 6.2 km s-1) and laterally high anomaly of Poisson's ratio (0.02 - 0.04) in the upper crust and thick crust (thickening southward from 9- 12 km) were found below the Huatung Basin and the Western Trough of the Gagua Ridge. Abrupt crustal thickening northward east of the ridge may be related to northwestward convergence of the Philippine Sea Plate. These velocity anomaly zones in the upper crust at both sides of the ridge might result from deformed, fractured or faulted zones. These zones support E - W compression, N - S shearing (or transpression) and uplifting that may have also created the Gagua Ridge and crustal thickening west of the ridge. [ABSTRACT FROM AUTHOR]

As coal resources become exhausted in shallow mines, mining operations will inevitably progress from shallow depth to deep and gassy seams due to increased demands for more coal products. However, during the extraction process of deeper and gassier coal seams, new challenges to current gas control methods have emerged, these include the conflict between the coal mine safety and the economic benefits, the difficulties in reservoirs improvement, as well as the imbalance between pre-gas drainage, roadway development and coal mining. To solve these problems, a sequential approach is introduced in this paper. Three fundamental principles are proposed: the mining-induced stress relief effect of the first-mined coalbed should be sufficient to improve the permeability of the others; the coal resource of the first-mined seams must be abundant to guarantee the economic benefits; the arrangement of the vertical wells must fit the underground mining panel. Tunlan coal mine is taken as a typical example to demonstrate the effectiveness of this approach. The approach of integrating surface coalbed methane (CBM) exploitation with underground gas control technologies brings three major benefits: the improvement of underground coal mining safety, the implementation of CBM extraction, and the reduction of greenhouse gas emissions. This practice could be used as a valuable example for other coal mines having similar geological conditions. [ABSTRACT FROM AUTHOR]

Six murine tumors, including ascetic tumors HepA, EC, P388 leukemia, S180 and solid tumor S180, and Lewis lung carcinoma, were employed in this work. The free sialic acid concentrations in both blood and ascites were measured in tumor-bearing mice. The results showed that the content of sialic acids in blood was increased in tumor growth and certain tumor types. Higher sialic acid content was observed in ascites than that present in blood. The influence of antineoplastic agents (vincristine, thiotepa, adriamycin, probimane, cisplatin, oxalysine, cortisone, nitrogen mustard, lycobetaine, Ara-C, harringtonine, and cyclophosphamide) on the content of sialic acids in mice blood bearing solid tumors of either S180 or Lewis lung carcinoma was observed. Different inhibitions of antineoplastic drugs on both tumor growth and serum sialic acid levels in mice bearing tumors were found. Among these antineoplastic drugs, probimane, cisplatin, nitrogen mustard, and lycobetaine were able to decrease the serum sialic acid levels in mice bearing tumors. Since these four antineoplastic drugs are all DNA chelating agents, it was proposed that the inhibition of tumor sialic acids by these drugs might be through the DNA template via two ways. Since we have found no effect of antineoplastic drugs on serum sialic acid levels in normal mice, this suggests that the inhibition of antineoplastic drugs on sialic acids is by tumor involvement. [ABSTRACT FROM AUTHOR]

The wall-associated kinase (WAK) gene family is a unique subfamily of receptor-like kinases (RLKs) in plants. WAK-RLKs play roles in cell expansion, pathogen resistance, and metal tolerance in Arabidopsis (Arabidopsis thaliana). Rice (Oryza sativa) has far more WAK-RLK genes than Arabidopsis, but the functions of rice WAK-RLKs are poorly understood. In this study, we found that one rice WAK-RLK gene, DEFECT IN EARLY EMBRYO SAC1 (OsDEES1), is involved in the regulation of early embryo sac development. OsDEES1 silencing by RNA interference caused a high rate of female sterility. Crossing experiments showed that female reproductive organs lacking OsDEES1 carried a functional defect. A detailed investigation of the ovaries from OsDEES1 RNA interference plants indicated that the knockdown of OsDEES1 expression did not affect megasporogenesis but that it disturbed female gametophyte formation, resulting in a degenerated embryo sac and defective seed formation. OsDEES1 exhibited a tissue-specific expression pattern in flowers and seedlings. In the ovary, OsDEES1 was expressed in the megagametophyte region and surrounding nucellus cells in the ovule near the micropylar region. OsDEES1 was found to be a membrane-localized protein with a unique sequence compared with other WAK-RLKs. These data indicate that OsDEES1 plays a role in rice sexual reproduction by regulating female gametophyte development. This study offers new insight into the functions of the WAK-RLK family. [ABSTRACT FROM AUTHOR]

Spontaneous neoplasm metastasis, a fatalist pathological feature of cancer, is a long-evolving, multi-steps process that can now only be treated or controlled by drugs or immuno-modulators. Probimane (Pro), as a representative of the well-known class of antimetastatic agents 'Bisdioxopiperazine compounds (Biz)', is systematically studied for its absorption, distribution and excretion in mice bearing Lewis lung carcinoma by a radioactivity-detective method in this investigation. It is found that the 14C-Pro concentrations in different normal organs of mice at 2 hrs are very high and dramatically declined at 24 and 48 hrs. However, Pro concentrations in metastatic foci are slightly changed at the same time. Almost no change of Pro concentrations is observed in pulmonary metastatic nodules within 48 hrs. This evidence can be used to explain the characteristics of good metastatic inhibition by Biz compounds. The radioactivity in brain is relatively low because Pro can hardly penetrate into the blood-brain-barrier to eliminate brain tumors. The excretion of 14C-Pro is observed at the same ratios from both urine and feces and also at constant rates. These data are much useful for better understanding of the general pharmacological characters and possible antimetastatic mechanisms of actions of probimane and other Biz compounds from a new perspective and research angles. [ABSTRACT FROM AUTHOR]

Abstract: Power harmonic estimation is essential for evolving suitable protection and control strategies of power networks. Parametric approaches exhibit super-resolution and have been gradually applied in practice. However, they are susceptible to the presence of noise in the signals. The analysis accuracy will be abruptly reduced and even ineffective under non-Gaussian or impulsive noise environment. In this paper, a novel approach based on M-Estimators for harmonic estimation is proposed to overcome the above shortcomings. The derivation of Gauss–Newton iteration equations of harmonic frequency, amplitude and phase is presented. Further, the ESPRIT algorithm is also employed to acquire the initial values of harmonic frequencies, which avoids the objective function of M-Estimator to be stuck in local minima and improves the convergence rate of optimization. The numerical simulations and experimental results verify the feasibility and effectiveness of the proposed method. [Copyright &y& Elsevier]

A new species Tongoloa arguta (Apiaceae) is described and illustrated in this article. The new species grows in alpine bushes and meadows in south-western China. It resembles T. silaifolia, but differs from the latter by the length of the stem, ultimate segments of leaf and rays of the umbel. Phylogenetic analysis, based on nuclear ribosomal DNA internal transcribed spacer (ITS) sequences, is provided, as well as comparative morphology between related species. [ABSTRACT FROM AUTHOR]

DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), which plays an important role in inducing drug resistance against alkylating agents that modify the O6 position of guanine in DNA, is an attractive target for anti-tumor chemotherapy. A series of MGMT inhibitors have been synthesized over the past decades to improve the chemotherapeutic effects of O6-alkylating agents. In the present study, we performed a three-dimensional quantitative structure activity relationship (3D-QSAR) study on 97 guanine derivatives as MGMT inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. Three different alignment methods (ligand-based, DFT optimization-based and docking-based alignment) were employed to develop reliable 3D-QSAR models. Statistical parameters derived from the models using the above three alignment methods showed that the ligand-based CoMFA (Qcv 2 = 0.672 and Rncv 2 = 0.997) and CoMSIA (Qcv 2 = 0.703 and Rncv 2 = 0.946) models were better than the other two alignment methods-based CoMFA and CoMSIA models. The two ligand-based models were further confirmed by an external test-set validation and a Y-randomization examination. The ligand-based CoMFA model (Qext 2 = 0.691, Rpred 2 = 0.738 and slope k = 0.91) was observed with acceptable external test-set validation values rather than the CoMSIA model (Qext 2 = 0.307, Rpred 2 = 0.4 and slope k = 0.719). Docking studies were carried out to predict the binding modes of the inhibitors with MGMT. The results indicated that the obtained binding interactions were consistent with the 3D contour maps. Overall, the combined results of the 3D-QSAR and the docking obtained in this study provide an insight into the understanding of the interactions between guanine derivatives and MGMT protein, which will assist in designing novel MGMT inhibitors with desired activity. [ABSTRACT FROM AUTHOR]

Onabotulinumtoxin A (BoNTA) has been reported to be effective in the therapy for migraines. Acupuncture has been used worldwide for the treatment of migraine attacks. Injection of a small amount of drug at acupuncture points is an innovation as compared to traditional acupuncture. The purpose of this study was to evaluate and compare the effectiveness of fixed (muscle)-site and acupoint-site injections of BoNTA for migraine therapy in a randomized, double-blinded, placebo-controlled clinical trial extending over four months. Subjects with both episodic and chronic migraines respectively received a placebo (n = 19) or BoNTA (2.5 U each site, 25 U per subject) injection at fixed-sites (n = 41) including occipitofrontalis, corrugator supercilii, temporalis and trapeziue, or at acupoint-sites (n = 42) including Yintang (EX-HN3), Taiyang (EX-HN5), Baihui (GV20), Shuaigu (GB8), Fengchi (GB20) and Tianzhu (BL10). The variations between baseline and BoNTA post-injection for four months were calculated monthly as outcome measures. BoNTA injections at fixed-sites and acupoint-sites significantly reduced the migraine attack frequency, intensity, duration and associated symptoms for four months compared with placebo (p < 0.01). The efficacy of BoNTA for migraines in the acupoint-site group (93% improvement) was more significant than that in the fixed-site group (85% improvement) (p < 0.01). BoNTA administration for migraines is effective, and at acupoint-sites shows more efficacy than at fixed-sites. Further blinded studies are necessary to establish the efficacy of a low dose toxin (25 U) introduced with this methodology in chronic and episodic migraines. [ABSTRACT FROM AUTHOR]

Chondrosarcoma is a soft tissue sarcoma with a poor prognosis that is unresponsive to conventional chemotherapy. The regulatory mechanisms for the rapid proliferation of chondrosarcoma cells and the particular aggressiveness of this sarcoma remain poorly understood. In this study, we investigate the effect of epigallocatechin-3-gallate (EGCG) on growth and apoptosis of chondrosarcoma cells. The chondrosarcoma cell lines, SW1353 and CRL-7891, were cultured with and without EGCG. The MTT assay was used to test the cytotoxicity of EGCG. Flow cytometry and DAPI staining were used to observe cell apoptosis caused by EGCG. To explore the effect of EGCG on the Indian Hedgehog signaling pathway and apoptosis-related proteins, RT-PCR and Western blotting were used to detect the expression of PTCH and Gli-1 in the Indian Hedgehog signaling pathway. Meanwhile, expression of Bcl-2, Bax, and caspase-3 were also evaluated by Western blot analysis. EGCG effectively inhibited cellular proliferation and induced apoptosis of SW1353 and CRL-7891. EGCG inhibited the human Indian Hedgehog pathway, down-regulated PTCH and Gli-1 levels, and induced apoptosis as confirmed by DAPI staining followed by flow cytometry. Protein expression levels of caspase-3 were unchanged in response to EGCG treatment in chondrosarcoma cells; however, the expression levels of Bcl-2 were significantly decreased and the levels of Bax were significantly increased. Our findings demonstrate that EGCG is effective for growth inhibition of a chondrosarcoma cell lines in vitro, and suggest that EGCG may be a new therapeutic option for patients with chondrosarcoma. [ABSTRACT FROM AUTHOR]

Spontaneous neoplasm metastasis, a fatalist pathological feature of cancer, is a long-evolving, multi-steps process that can now only be treated or controlled by drugs or immuno-modulators. As we have previously hypothesized, each drug or immuno-modulator might act differently within various stages of a metastasis. Therefore any researches helping to determine these differences will be beneficial for updating therapeutics for metastasis. In this work, we have testified this hypothesis by using a series of well-known anti-metastatic agents - Bisdioxopiperazine compounds. [ABSTRACT FROM AUTHOR]

Abstract: Inspired by polyhydroxylated pyrrolidine alkaloid natural products, a 18-membered library of 2-aryl polyhydroxylated pyrrolidines has been efficiently prepared in two or three synthetic steps from the known chiral cyclic nitrones with high yield and purity and excellent stereoselectivity. The inhibitory activity of all these compounds against various glycosidase enzymes was evaluated. Interestingly, 15 and 19 show better inhibitory activities than radicamine A (20) and B (18) against α-glucosidases. The IC50 values of 15 and 19 are 1.1 and 0.5μM, respectively. In this study, we also discovered the substituent(s) on the aryl ring could affect the inhibition potency and selectivity against glycosidases. [Copyright &y& Elsevier]

p37 protein is a membrane lipoprotein of Mycoplasma hyorhinis, and our previous work showed that there was high ratio of M. hyorhinis infection in human gastric carcinoma. To investigate the possible functions of p37 in cancer development, the nucleotide sequence of p37 gene was modified and expressed well in transfected cells. We found that p37 localized at the Golgi apparatus and could be secreted out of the cell. Human gastric cancer cells AGS, after being transfected with the p37 gene, were smaller, more spherical and easy to detach from each other. Their adhesion to matrix was also diminished and cytoskeleton in these stable p37 AGS cell was rearranged and transcription co-factor β-actin was transferred to nucleolus with down-regulation of ICAM-1 and integrin β1. These findings will be helpful for us to elucidate the effects of p37 on eukaryotic cells as well as to better understand the potential relationship between cancer and mycoplasma infection. [ABSTRACT FROM AUTHOR]

[Display omitted] • The Jigongcun Mo deposit formed during the early Miocene. • High Re concentrations are due to isovalent Re substitution for Mo in molybdenite. • Relatively oxidized fluids caused Re enrichment in the Jigongcun deposit. The Jigongcun Re-rich quartz vein-type Mo deposit is located in the Gangdese porphyry Cu belt, southern Tibet, China. The stratiform and lenticular orebodies are hosted within the quartz veins and are controlled by the NW-/EW-trending faults. In this study, we have identified four hydrothermal stages, namely the (1) pre-ore stage (stage Ⅰ) characterized by the development of thick Mo-free quartz veins; (2) stage Ⅱ, mainly forming thick quartz veins with Re-rich massive molybdenite (Mo1-type; mean = 1811 ppm) and bladed molybdenite (Mo2-type; mean = 1312 ppm); (3) stage III, mainly forming quartz veins with Re-barren bladed molybdenite (Mo3-type) and abundant galena and pyrite; (4) the post-ore stage (stage Ⅳ) characterized by formation of thick ore-barren quartz–calcite veins. Both electron probe micro-analysis and in situ laser ablation–inductively coupled plasma–mass spectrometry analysis of different types of molybdenite show that high Re concentrations are due to isovalent Re substitution for Mo in molybdenite. Fluid evolution during the four stages of mineralization was constrained by a detailed fluid inclusion study. Fluid inclusions during the formation of the early pre-ore stage indicate relatively high-temperature (311–337 °C), high-pressure (1300–1600 bars), low-salinity (0.2–2.6 wt% NaCl-equiv.), and CO 2 -rich hydrothermal fluids. Fluid immiscibility assemblages in CO 2 -rich inclusions coexisting with aqueous inclusions occur in quartz–K-feldspar veins of stage Ⅱ, and likely record phase separation at a temperature of 262–300 °C and pressure of 900–1100 bars, with the precipitation of Re-rich molybdenite. The subsequent fluid mixing occurs at a temperature of 220–271 °C, with the precipitation of Re-barren molybdenite at stage III. H–O–S isotope compositions show that sulfur and ore-forming fluids are derived from a deep-seated igneous source. Re-Os dating of molybdenite samples yielded an isochron age of 22.0 ± 0.4 Ma, indicating that the Jigongcun deposit formed in the Early Miocene, which is earlier than most of the porphyry Cu deposits in the Gangdese porphyry Cu belt. Combined our new geochemical and isotopic results with previous regional investigations, we suggest that the Re-rich Mo mineralization of Jigongcun deposit may be related to the Early Miocene northward subduction of the Indian continental plate. [ABSTRACT FROM AUTHOR]

• Two IMPDH inhibitors and a DHODH inhibitor showed antiviral activity against FMDV in vitro. • The antiviral effect of AVN-944, mycophenolate mofetil and teriflunomide occurred in the early phases of FMDV replication. • The antiviral effect of teriflunomide could be attenuated by uridine supplementation. • Exogenous guanosine could abolish the antiviral activity of AVN-944 and mycophenolate mofetil. • In vivo activity of AVN-944 and teriflunomide were confirmed in a mouse model of infection. Foot-and-mouth disease virus (FMDV) is an important pathogen that affects livestock breeding and causes huge economic losses worldwide. Currently, the development of antiviral agents to combat FMDV infection at the early stages is being explored. As viral replication critically depends on the host for nucleoside supply, host enzymes involved in nucleotides biosynthesis may represent potential targets for the development of antiviral agents. In the present study, the effects of IMP dehydrogenase (AV N-9 44 and mycophenolate mofetil) and dihydroorotate dehydrogenase (teriflunomide) inhibitors were evaluated both in vitro and in vivo. The results revealed that these compounds were effective in suppressing FMDV (O/MY98/BY/2010 and A/GD/MM/2013) infection. With regard to the antiviral mechanism, time-of-addition experiments revealed that these compounds were effective when added at the early stages of viral lifecycle (0–8 h post infection). However, exogenous guanosine/uridine eliminated the antiviral activity of these compounds. Importantly, treatment AV N-9 44 and teriflunomide significantly improved the survival of mice that were subcutaneously treated with FMDV. Together, the results of the present study indicate the broad-spectrum activities of anti-FMDV agents targeting IMP dehydrogenase or dihydroorotate dehydrogenase, which could be useful in developing strategies to prevent FMD. [ABSTRACT FROM AUTHOR]