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miR-124 is a miRNA predominantly expressed in the nervous system and accounts for more than a quarter of the total miRNAs in the brain. It regulates neurogenesis, neuronal differentiation, neuronal maturation, and synapse formation and is the most important miRNA in the brain. Furthermore, emerging evidence has suggested miR-124 may be associated with the pathogenesis of various neurodevelopmental and neuropsychiatric disorders. Here, we provide an overview of the role of miR-124 in neurodevelopment and the underling mechanisms, and finally, we prospect the significance of miR-124 research to the field of neuroscience. [ABSTRACT FROM AUTHOR]

The establishment and maintenance of neuronal polarity are important for neural development and function. Abnormal neuronal polarity establishment commonly leads to a variety of neurodevelopmental disorders. Over the past three decades, with the continuous development and improvement of biological research methods and techniques, we have made tremendous progress in the understanding of the molecular mechanisms of neuronal polarity establishment. The activity of positive and negative feedback signals and actin waves are both essential in this process. They drive the directional transport and aggregation of key molecules of neuronal polarity, promote the spatiotemporal regulation of ordered and coordinated interactions of actin filaments and microtubules, stimulate the specialization and growth of axons, and inhibit the formation of multiple axons. In this review, we focus on recent advances in these areas, in particular the important findings about neuronal polarity in two classical models, in vitro primary hippocampal/cortical neurons and in vivo cortical pyramidal neurons, and discuss our current understanding of neuronal polarity.​ [ABSTRACT FROM AUTHOR]

The widespread use of neonicotinoids has led to their frequent detection in the environment and potential environmental risk in recent years. Clothianidin (CLO) and thiamethoxam (TMX), as the second generation of neonicotinoid insecticides, are usually used as seed agents with a high risk of residue in the soil. Efficient degradation of CLO and TMX in soil using peroxymonosulfate (PMS) process was investigated in the present study. The degradation efficiencies of CLO and TMX reached 91.4% and 98.6% in 60 min with the addition of 20 mM PMS at pH 5.5 and 25℃. High degradation efficiencies of CLO were achieved with a high PMS dosage and temperature or a low CLO concentration and initial pH. The degradation of CLO was reduced in the presence of high concentration of inorganic anions (Cl−, HCO3−). Soil organic matter might be one critical factor in the degradation of CLO and TMX. Radical scavenger experiments confirmed SO4•− and 1O2 were the dominant reactive species on the CLO and TMX degradation. Based on the detected degradation intermediates, the degradation pathways of CLO and TMX include dichlorination, hydroxylation, cleavage of C–N or C–C bond and further oxidation in the PMS-based soil. Overall, the PMS process is one effective and economical method for the remediation of the neonicotinoid contaminated soil. [ABSTRACT FROM AUTHOR]

Background: Many factors can affect the clinical outcome of extremely premature infants (EPIs), but the effect of sex is paradoxical. This study used propensity score matching to adjust baseline information to reassess the clinical outcome of EPIs based on sex. Methods: A retrospective analysis was performed on EPIs admitted in the Department of Neonatology of the Third Affiliated Hospital of Guangzhou Medical University from 2011 to 2020. A propensity score matching (PSM) analysis was used to adjust the confounding factors including gestational age, birth weight, 1-minute Apgar score ≤ 3, withholding or withdrawing life-sustaining treatment(WWLST), mechanical ventilation, duration of mechanical ventilation, the mother with advanced age (≥35 years old), complete-course antenatal steroid therapy and hypertensive disorders of pregnancy. The survival rate at discharge and the incidence of major complications were evaluated between the male and female groups. Results: A total of 439 EPIs were included, and 240 (54.7%) infants were males. After matching the nine confounding factors, 148 pairs of infants were finally enrolled. There was no significant difference in the survival rate at discharge, as well as the mortality of activating treatment or WWLST between the two groups (all P >0.05). However, the incidence of respiratory distress syndrome, bronchopulmonary dysplasia (BPD), and moderate to severe BPD in the male group was significantly increased (all P <0.01), especially at birth weight between 750 and 999 grams. Conclusions: The male EPIs have a higher risk of respiratory complications than females, particularly at 750 to 999 grams of birth weight. [ABSTRACT FROM AUTHOR]

Objectives: Necrotizing enterocolitis (NEC) is a catastrophic gastrointestinal emergency in preterm infants, whose exact aetiology remains unknown. The role of lithocholic acid (LCA), a key component of secondary bile acids (BAs), in NEC is unclear. Methods: Clinical data were collected to analyse the changes of BAs in NEC patients. In vitro studies, the cell proliferation and cell death were assessed. In vivo experiments, the newborn rats were administered with low or high dose of LCA and further induced NEC. Results: Clinically, compared with control group, total BAs in the NEC patients were significantly higher when NEC occurred. In vitro, LCA treatment significantly inhibited the cell proliferation through arresting cell cycle at G1/S phase without inducing apoptosis or necroptosis. Mechanistically, the Wnt/β‐catenin pathway was involved. In vivo, LCA inhibited intestinal cell proliferation leading to disruption of intestinal barrier, and thereby increased the severity of NEC. Specifically, LCA supplementation caused higher levels of FITC‐labelled dextran in serum, reduced PCNA expression and inhibited the activity of Wnt/β‐catenin pathway in enterocytes. The LC–MS/MS test found that LCA was significantly higher in intestinal tissue of NEC group, and more obviously in the NEC‐L and NEC‐H group compared with the DM group. Conclusion: LCA exacerbates NEC by inhibiting intestinal cell proliferation through downregulating the Wnt/β‐catenin pathway. [ABSTRACT FROM AUTHOR]

The dissipation and residue levels of thiamethoxam and its metabolite clothianidin in cowpea were investigated under field conditions. Samples of cowpea were analyzed using a QuEChERS technique with ultra-performance liquid chromatography tandem mass spectrometry. The recoveries were 86.5–118.9% for thiamethoxam and 75.6–104.1% for clothianidin, with the coefficient of variation of < 13%. The water dispersible granule formulation of thiamethoxam was applied on cowpea at 30 and 45 g active ingredient ha−1 in accordance with good agricultural practice. The half-life of thiamethoxam in cowpea was 0.8–1.6 days. The cowpea samples were gathered at 3, 7, and 10 days after the last application, and the residues of thiamethoxam in cowpea were < 0.005–0.054 mg kg−1, while those of clothianidin were < 0.005–0.008 mg kg−1. The final residues of thiamethoxam and clothianidin were below the European Union (EU) maximum residue level (0.3 mg kg−1 for thiamethoxam; 0.2 mg kg−1 for clothianidin) in cowpea after a preharvest interval (PHI) of 7 days. This study provided basic data on the use and safety of thiamethoxam and clothianidin in cowpea to help the Chinese government formulate a maximum residue level for thiamethoxam in cowpea. [ABSTRACT FROM AUTHOR]

In this study, a simple and accurate sample preparation method based on dispersive solid‐phase extraction and dispersive liquid‐liquid microextraction has been developed for the determination of seven novel succinate dehydrogenase inhibitor fungicides (isopyrazam, fluopyram, pydiflumetofen, boscalid, penthiopyrad, fluxapyroxad, and thifluzamide) in watermelon. The watermelon samples were extracted with acetonitrile, cleaned up by dispersive solid‐phase extraction procedure using primary secondary amine, extracted and concentrated by the dispersive liquid‐liquid microextraction procedure with 1,1,2,2‐tetrachloroethane, and then analyzed by ultra high performance liquid chromatography with tandem mass spectrometry. The main experimental factors affecting the performance of dispersive solid‐phase extraction and dispersive liquid‐liquid microextraction procedure on extraction efficiency were investigated. The proposed method had a good linearity in the range of 0.1–100 µg/kg with correlation coefficients (r) of 0.9979–0.9999. The limit of quantification of seven fungicides was 0.1 µg/kg in the method. The fortified recoveries of seven succinate dehydrogenase inhibitor fungicides at three levels ranged from 72.0 to 111.6% with relative standard deviations of 3.4–14.1% (n = 5). The proposed method was successfully used for the rapid determination of seven succinate dehydrogenase inhibitor fungicides in watermelon. [ABSTRACT FROM AUTHOR]

In multicellular organisms, receptor tyrosine kinases (RTKs) control a variety of cellular processes, including cell proliferation, differentiation, migration, and survival. Sprouty (SPRY) proteins represent an important class of ligand‐inducible inhibitors of RTK‐dependent signaling pathways. Here, we investigated the role of SPRY1 in cells of the central nervous system (CNS). Expression of SPRY1 was substantially higher in neural stem cells than in cortical neurons and was increased during neuronal differentiation of cortical neurons. We found that SPRY1 was a direct target gene of the CNS‐specific microRNA, miR‐124 and miR‐132. In primary cultures of cortical neurons, the neurotrophic factors brain‐derived neurotrophic factor (BDNF) and Basic fibroblast growth factor (FGF2) downregulated SPRY1 expression to positively regulate their own functions. In immature cortical neurons and mouse N2A cells, we found that overexpression of SPRY1 inhibited neurite development, whereas knockdown of SPRY1 expression promoted neurite development. In mature neurons, overexpression of SPRY1 inhibited the prosurvival effects of both BDNF and FGF2 on glutamate‐mediated neuronal cell death. SPRY1 was also upregulated upon glutamate treatment in mature neurons and partially contributed to the cytotoxic effect of glutamate. Together, our results indicate that SPRY1 contributes to the regulation of CNS functions by influencing both neuronal differentiation under normal physiological processes and neuronal survival under pathological conditions. [ABSTRACT FROM AUTHOR]

Fluazinam and dimethomorph 35% suspension concentrate (SC) is a new combined fungicide formulation introduced in China to improve fungicidal efficacy and decrease the risk of resistance in potatoes. Fluazinam and dimethomorph dissipation and residues in potatoes, potato plants, and soil under field conditions were determined by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Fluazinam and dimethomorph 35% SC was applied at two doses to potatoes and soil in Ningxia Autonomous Region and Anhui Province, China. Fluazinam and dimethomorph dissipation fitted first-order kinetics, and the fluazinam half-lives in potato plants and soil were 3.3-5.4 and 9.4-9.5 days, respectively. The dimethomorph half-lives in potato plants and soil were 2.1-2.6 and 5.9-8.6 days, respectively. Fluazinam and dimethomorph 35% SC was sprayed onto potato plants three or four times at application rates of 420 and 630 g a.i. ha−1 with 7 days between applications. Potato and soil samples were collected at 3, 7, and 14 days after the last application. Potatoes and soil had fluazinam concentrations of < 0.01 and < 0.05-0.183 mg kg−1, respectively, and dimethomorph concentrations of < 0.01 and 0.129-0.677 mg kg−1, respectively. The final fluazinam and dimethomorph concentrations in potatoes were below the EU maximum residue limits (0.02 and 0.05 mg kg−1, respectively) 3 days after application. Fluazinam and dimethomorph can therefore be applied to potatoes at the recommended doses. [ABSTRACT FROM AUTHOR]

Background/Aims: The mechanistic target of rapamycin (mTOR) signaling pathway is essential for angiogenesis and embryonic development. DEP domain-containing mTOR-interacting protein (DEPTOR) is an mTOR binding protein that functions to inhibit the mTOR pathway In vitro experiments suggest that DEPTOR is crucial for vascular endothelial cell (EC) activation and angiogenic responses. However, knowledge of the effects of DEPTOR on angiogenesis in vivo is limited. This study aimed to determine the role of DEPTOR in tissue angiogenesis and to elucidate the molecular mechanisms. Methods:Cre/loxP conditional gene knockout strategy was used to delete the Deptor gene in mouse vascular ECs. The expression or distribution of cluster of differentiation 31 (CD31), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 alpha (HIF-1α) were detected by immunohistochemical staining or western blot. Tube formation assay was used to measure angiogenesis in vitro. Results:Deptor knockdown led to increased expression of CD31, VEGF and HIF-1α in heart, liver, kidney and aorta. After treatment with rapamycin, their expression was significantly down regulated. In vitro, human umbilical vein endothelial cells (HUVECs) were transfected with DEPTOR-specific small interfering RNA (siRNA), which resulted in a significant increase in endothelial tube formation and migration rates. In contrast, DEPTOR overexpression markedly reduced the expression of CD31, VEGF and HIF-1α. Conclusions: Our findings demonstrated that deletion of the Deptor gene in vascular ECs resulted in upregulated expression of CD31 and HIF-1α, and further stimulated the expression of VEGF which promoted angiogenesis, indicating that disruption of normal angiogenic pathways may occur through hyperactivation of the mTORC1/HIF-1α/VEGF signaling pathway. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a group of chronic remittent or progressive inflammatory gastrointestinal tract diseases, accompanying impaired barrier function. Effective real-time monitoring of the IBD progression in time is critical to the success of bowel therapy and the improvement of patient outcomes. However, there is relatively little information regarding the detection of the intestinal barrier. In this study, we have judiciously designed and synthesized a novel D–π–A based far-red-emissive AIE active fluorescent Probe (PTZB-FR). PTZB-FR exhibits properties suitable for in vivo imaging, such as FR emission, good photostability, large Stokes shift (∼184 nm), and low cytotoxicity. Moreover, confocal fluorescence microscopy and flow cytometry assay reveal the effective internalization of PTZB-FR. Most importantly, imaging living mice after oral administration of PTZB-FR confirms that fluorescence in the intestinal lumen diminishes in Dextran sulfate sodium (DSS)-induced colitis, which is attributed to disruption of intestinal barrier integrity caused by a DSS-induced colitis model, highlighting PTZB-FR as a promising reagent in the detection of intestinal barrier function during clinical examination. [ABSTRACT FROM AUTHOR]

BACKGROUND The residue concentrations and dissipation rate of a new oxathiapiprolin fungicide in grapes and soil were investigated to provide an evaluation for the safe use of oxathiapiprolin in grapes. Pesticide residue was extracted by acetonitrile, then purified by solid-phase extraction with an Envi-Carb cartridge and determined by ultrahigh-performance liquid chromatography-tandem mass spectrometry. RESULTS The fortified recoveries ranged from 85.2% to 99.0%, with relative standard deviations of 1.7-4.5%. The limit of quantitation for oxathiapiprolin in grapes and soil was 0.002 mg kg−1. The mean initial deposits of oxathiapiprolin in grapes were 0.345-0.565 mg kg−1, with half-lives of 8.6-9.2 days. The mean initial deposits of oxathiapiprolin in soil were 0.078-0.273 mg kg−1, with half-lives of 7.6-12.0 days. The oxathiapiprolin residue in grapes and soil was 0.002-0.022 mg kg−1 and 0.002-0.123 mg kg−1 when sampling 14 days after application, respectively. CONCLUSION The residue in the grapes was less than 0.01 mg kg−1 when sampling 28 days after application, which suggested that the application rate of 20 mg a.i. kg−1 for this fungicide should be used to ensure that treated grapes can be considered safe for humans to consume when sampling 28 days after the final application. © 2016 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

A rapid, selective and sensitive sample preparation method based on solid-phase extraction combined with the dispersive liquid-liquid microextration was developed for the determination of pyrethroid pesticides in wheat and maize samples. Initially, the samples were extracted with acetonitrile and water solution followed phase separation with the salt addition. The following sample preparation involves a solid-phase extraction and dispersive liquid-liquid microextraction step, which effectively provide cleanup and enrichment effects. The main experimental factors affecting the performance both of solid-phase extraction and dispersive liquid-liquid microextration were investigated. The validation results indicated the suitability of the proposed method for routine analyze of pyrethroid pesticides in wheat and maize samples. The fortified recoveries at three levels ranged between 76.4 and 109.8% with relative standard deviations of less than 10.7%. The limit of quantification of the proposed method was below 0.0125 mg/kg for the pyrethoroid pesticides. The proposed method was successfully used for the rapid determination of pyrethroid residues in real wheat and maize samples from crop field in Beijing, China. [ABSTRACT FROM AUTHOR]

This study demonstrates a new, rapid, and sensitive analytical method for the simultaneous determination of tebufenozide and phoxim in cabbage and soil using a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) sample preparation procedure followed by ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry. Tebufenozide and phoxim were extracted with acetonitrile and subsequently cleaned up with a primary and secondary amine sorbent prior to sample analysis. Recoveries ranged from 77.2 to 107.3 % for all analytes, with relative standard deviation values lower than 8.8 % in matrices at three levels (0.005, 0.01, 0.1 mg/kg). The limit of quantification for tebufenozide and phoxim in cabbages and soil was 0.005 mg/kg, respectively. The developed method was used to study the dissipation of the pesticides in cabbage and soil in a field trial. The tebufenozide and phoxim dissipated with half-life of 4.5-4.8 and 0.7-0.7 days (in cabbage) and 10.8-12.7 and 1.1-1.5 days (in soil), respectively. The final residue concentrations of tebufenozide and phoxim were 0.022-0.482 and 0.029-0.042 mg/kg (in cabbage) and 0.029-0.487 and 0.025-0.043 mg/kg (in soil), respectively. The results further confirmed the reliability and efficacy of the proposed method for routine pesticide residue monitoring in soil and cabbage samples. [ABSTRACT FROM AUTHOR]

ABSTRACT The cytokine receptor activator of nuclear factor-κB ligand (RANKL) induces osteoclast formation from monocyte/macrophage lineage cells. However, the mechanisms by which RANKL expression is controlled in cells that support osteoclast differentiation are still unclear. We show that deletion of TSC1 (tuberous sclerosis complex 1) in murine B cells causes constitutive activation of mechanistic target of rapamycin complex 1 (mTORC1) and stimulates RANKL but represses osteoprotegerin (OPG) expression and subsequently promotes osteoclast formation and causes osteoporosis in mice. Furthermore, the regulation of RANKL/OPG and stimulation of osteoclastogenesis by mTORC1 was confirmed in a variety of RANKL-expressing cells and in vivo. Mechanistically, mTORC1 controls RANKL/OPG expression through negative feedback inactivation of Akt, destabilization of β-catenin mRNA, and downregulation of β-catenin. Our findings demonstrate that mTORC1 activation-stimulated RANKL expression in B cells is sufficient to induce bone loss and osteoporosis. The study also established a link between mTORC1 and the RANKL/OPG axis via negative regulation of β-catenin. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

A new combined difenoconazole and fluxapyroxad fungicide formulation, as an 11.7 % suspension concentrate (SC), has been introduced as part of a resistance management strategy. The dissipation of difenoconazole and fluxapyroxad applied to apples and the residues remaining in the apples were determined. The 11.7 % SC was sprayed onto apple trees and soil in Beijing, Shandong, and Anhui provinces, China, at an application rate of 118 g a.i. ha, then the dissipation of difenoconazole and fluxapyroxad was monitored. The residual difenoconazole and fluxapyroxad concentrations were determined by ultrahigh-performance liquid chromatography tandem mass spectrometry. The difenoconazole half-lives in apples and soil were 6.2-9.5 and 21.0-27.7 days, respectively. The fluxapyroxad half-lives in apples and soil were 9.4-12.6 and 10.3-36.5 days, respectively. Difenoconazole and fluxapyroxad residues in apples and soil after the 11.7 % SC had been sprayed twice and three times, with 10 days between applications, at 78 and 118 g a.i. ha were measured. Representative apple and soil samples were collected after the last treatment, at preharvest intervals of 14, 21, and 28 days. The difenoconazole residue concentrations in apples and soil were 0.002-0.052 and 0.002-0.298 mg kg, respectively. The fluxapyroxad residue concentrations in apples and soil were 0.002-0.093 and 0.008-1.219 mg kg, respectively. The difenoconazole and fluxapyroxad residue concentrations in apples were lower than the maximum residue limits (0.5 and 0.8 mg kg, respectively). An application rate of 78 g a.i. ha is therefore recommended to ensure that treated apples can be considered safe for humans to consume. [ABSTRACT FROM AUTHOR]

ABSTRACT The roles of different immune cell populations and cytokines in bone metabolism have been extensively investigated. However, the influence of whole immune organ removal on osteopathology remains unknown. In the current study, we investigated the effects of splenectomy on bone metabolism and microarchitecture in rats with or without concurrent ovariectomy. Ovariectomized (OVX) rats were used as osteoporosis model. Sixty 12-week-old female rats were randomized into 4 groups ( n = 15): sham, splenectomized (SP), ovariectomized, as well as ovariectomized and splenectomized (OVX + SP). Bone microarchitecture was assessed by micro CT analysis at 4 week and 12 week post-operation, respectively. Bone pathology and metabolism were evaluated via immunohistochemical staining. The serum levels of alkaline phosphatase (ALP), tumor necrosis factor-alpha (TNF-α), tartrate-resistant acid phosphatase 5b (Tracp5b), and C-terminal telopeptide (CTx) were analyzed at 4 and 12 weeks post-operation. Removal of the spleen led to alterations in the homeostasis of bone metabolism and increased bone formation in rats. In this study, our findings indicate that the spleen is involved in skeletal metabolism. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1356-1363, 2015. [ABSTRACT FROM AUTHOR]

Background: Targeting protein for Xklp2 (TPX2) is a microtubule-associated protein involved in targeting the motor protein Xklp2 to microtubules. TPX2 overexpression plays a key role in the progression of human cancers. But the underlying mechanism remains unclear. Aims: This study aimed to investigate the effects and mechanisms of TPX2 on the cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC). Methods: The tissue TPX2 mRNA and protein were assessed by quantitative reverse transcriptase PCR and immunoblot. Cell proliferation, cell cycle, apoptosis, and invasion were determined by CCK-8, FACS, TdT-UTP nick end-labeling, and transwell assays. Immunoblotting was performed to detect the expression of target proteins. Results: TPX2 was highly expressed in tumor tissues compared with non-tumoral tissues, and TPX2 overexpression was positively correlated with poor prognosis. Knockdown TPX2 effectively reduced cell growth, G2/M arrest, induced apoptosis and cell death, and inhibited EMT. Mechanistically, in the TPX2-siRNA-treated groups, cell-cycle-related proteins cyclin A1, cyclin B1, cyclin E1, and cdk4 were up-regulated, while cyclin D1, cdk2, and p21 proteins were down-regulated. Cell-apoptosis-related proteins Bax, p53, caspase-3, and caspase-8 levels were increased. EMT-related proteins E-cadherin was up-regulated, while N-cadherin, β-catenin, MMP-9, MMP-2, and Slug were down-regulated. We also found that knockdown TPX2 in HCC cell lines caused a significant decrease in the level of p-Akt and p-ERK which are important signaling pathways in tumor formation. Conclusions: TPX2 expression is associated with proliferation, apoptosis, and EMT in hepatocellular carcinoma cell and patients. [ABSTRACT FROM AUTHOR]

A new analytical method for the determination of organophosphorus pesticides in cereal samples was developed by combining dispersive SPE (d-SPE) and salting-out homogeneous liquid-liquid extraction (SHLLE). The pesticides were first extracted from cereal grains with acetonitrile, followed by d-SPE cleanup. A 2 mL aliquot of the extract was then added to a centrifuge tube containing 9.2 mL water and 3.3 g NaCl for SHLLE. Analysis of the extract was carried out by gas chromatography coupled with flame photometric detection. The d-SPE procedure effectively provides the necessary cleanup of the extract while SHLLE is used as an efficient concentration technique. Experimental parameters influencing the extraction efficiency including amounts of added water and salt were investigated. Recovery studies were carried out at three fortification levels, yielding recoveries in the range of 57.7-98.1% with the RSD from 3.7 to 10.9%. The reported limits of determination obtained from this study were 1 μg/kg, which is better than the conventional methods. In the analysis of 40 wheat and corn samples taken from Beijing suburbs, only two wheat samples have chlorpyrifos residue over the limits of determination. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated an important role for miR-124, the most abundant and well-conserved brain-specific microRNA(miRNA), in promoting neurite outgrowth and elongation during neuronal differentiation. This miRNA's target genes and the mechanisms that execute this role remain unclear. In this study, we identified ROCK1, a small GTPase Rho kinase, as a direct target of miR-124 for regulating neurite elongation. miR-124 significantly inhibited ROCK1 expression in M17 cells. Inhibiting ROCK1 promoted neurite elongation, and the overexpression of ROCK1 strongly repressed the neurite elongation-enhancing effect of miR-124 in M17 cells. We determined that Akt functions as a novel ROCK1 downstream effector in regulating neurite outgrowth and elongation. [ABSTRACT FROM AUTHOR]

In order to study the dissipation rates and final residues of kresoxim-methyl in strawberry and soil, two independent filed trials were performed in Beijing China. The application rates are set at 195 g of active gradient per hectare. A simple analytical method has been developed for the determination of kresoxim-methyl in strawberry and soil. Kresoxim-methyl residues were extracted with acetonitrile from strawberry and soil samples which is determined by gas chromatography coupled with mass spectrometry detection (GC-MSD). The recoveries of kresoxim-methyl in strawberry and soil were observed from 78.9 % to 104.5 % at fortification levels of 0.01-0.5 mg/kg with relative standard deviations of 4.3 %-7.3 %. The reported limits of detection were 0.05 and 0.01 mg/kg for strawberry and soil, respectively. The results showed that kresoxim-methyl dissipation in strawberry could be described as first-order equation with the half-life time of 6.24 and 6.91 days. 14 days later, the dissipation rate is 84.9 % and 83.3 %, respectively. The final residues of kresoxim-methly in the strawberry were in the range of 2.7-4.8 mg/kg at pre-harvest intervals of 1, 3, 5, 7 days which is below the Japan maximum residue limits (MRLs) standards (5 mg/kg in strawberry). [ABSTRACT FROM AUTHOR]

The dissipation and residues of flutriafol in wheat and soil under field conditions in Beijing, Anhui and Shandong in China were determined based on high performance liquid chromatography. Flutriafol were extracted with acetonitrile and cleaned up by solid-phase extraction with florisil cartridges before UV detection. The limits of detection and quantification of flutriafol were 0.04 ng and 0.01 mg/kg for both wheat and soil samples, respectively. The mean recoveries ranged from 93.4% to 96.4%, with relative standard deviation between 3.8% and 6.8% at three spiked levels (0.01, 0.1, 1.0 mg/kg). Half-lives were 13.3, 9.9 and 13.6 days in soil, while 15.2, 10.8 and 9.2 days in wheat plant in Beijing, Anhui and Shandong, respectively. The terminal residues of flutriafol were below the maximum residue limit 0.02 mg/kg set by Japan in wheat when pre-harvest interval were 35 days. [ABSTRACT FROM AUTHOR]

Most of breast cancers are resistant to mammalian target of rapamycin complex 1 (mTORC1) inhibitors rapamycin and rapalogs. Recent studies indicate mTORC2 is emerging as a promising cancer therapeutic target. In this study, we compared the inhibitory effects of targeting mTORC1 with mTORC2 on a variety of breast cancer cell lines and xenograft. We demonstrated that inhibition of mTORC1/2 by mTOR kinase inhibitors PP242 and OSI-027 effectively suppress phosphorylation of Akt (S473) and breast cancer cell proliferation. Targeting of mTORC2 either by kinase inhibitors or rictor knockdown, but not inhibition of mTORC1 either by rapamycin or raptor knockdown promotes serum starvation- or cisplatin-induced apoptosis. Furthermore, targeting of mTORC2 but not mTORC1 efficiently prevent breast cancer cell migration. Most importantly, in vivo administration of PP242 but not rapamycin as single agent effectively prevents breast tumor growth and induces apoptosis in xenograft. Our data suggest that agents that inhibit mTORC2 may have advantages over selective mTORC1 inhibitors in the treatment of breast cancers. Given that mTOR kinase inhibitors are in clinical trials, this study provides a strong rationale for testing the use of mTOR kinase inhibitors or combination of mTOR kinase inhibitors and cisplatin in the clinic. [ABSTRACT FROM AUTHOR]

In this study, a solid-phase microextraction (SPME) method based on a bare stainless steel wire as the fiber has been developed for extraction and determination of five pyrethroid insecticides (fenpropathrin, cyhalothrin, cypermethrin, fenvalerate and deltamethrin) in water and soil samples. The influences of extraction parameters (extraction time, stirring rate and salt addition) on the SPME extraction efficiency were investigated, and the optimum conditions were applied for the extraction of the target analytes from water samples. The method showed linear behavior ranging from 0.05 to 2 µg L with detection limits of 0.6-1.9 ng L for water analysis. Recoveries were from 71 to 112% for all the target insecticides in water and soil sample, with RSDs from 6.8 to 19.4% ( n = 3). The study demonstrated the feasibility of the proposed SPME fiber based on stainless steel wire for the extraction of pyrethroid insecticides in water and soil. [ABSTRACT FROM AUTHOR]

Hepatic stellate cells are of mesenchymal cell type located in the space of Disse. Upon liver injury, HSCs transactivate into myofibroblasts with increase in expression of fibrillar collagen, especially collagen I and III, leading to liver fibrosis. Previous studies have shown mTOR signaling is activated during liver fibrosis. However, there is no direct evidence in vivo. The aim of this study is to examine the effects of conditional deletion of TSC1 in mesenchymal on pathogenesis of liver fibrosis. Crossing mice bearing the floxed TSC1 gene with mice harboring Col1α2-Cre-ER(T) successfully generated progeny with a conditional knockout of TSC1 (TSC1 CKO) in collagen I expressing mesenchymal cells. TSC1 CKO and WT mice were subjected to CCl4, oil or CCl4+ rapamycin treatment for 8 weeks. TSC1 CKO mice developed pronounced liver fibrosis relative to WT mice, as examined by ALT, hydroxyproline, histopathology, and profibrogenic gene. Absence of TSC1 in mesenchymal cells induced proliferation and prevented apoptosis in activated HSCs. However, there were no significant differences in oil-treated TSC1 CKO and WT mice. Rapamycin, restored these phenotypic changes by preventing myofibroblasts proliferation and enhancing their apoptosis. These findings revealed mTOR overactivation in mesenchymal cells aggravates CCl4− induced liver fibrosis and the rapamycin prevent its occurance. [ABSTRACT FROM AUTHOR]