Preparation of Lamivudinyl palmitate nanoemulsome for liver-targeting delivery.

The water solubility and side effects of lamivudine limit its application for the treatment of viral hepatitis type B and human immunodeficiency virus. In order to increase the solubility of LA and improve the in vivo membrane permeability of the drug, LA was modified with hexadecane acid to prepare the prodrug lamivudine palmitic acid (LAP) and loaded into nanoemulsome (NES). LAP-NES was prepared by the thin film dispersion method. The LAP-NES showed the sustained release performance up to 72h in pH 7.4 PBS. Moreover, the pharmacokinetics of LAP-NES after tail vein injection in rats and the biodistribution characteristics were evaluated. The tmax of LAP-NES was 2.5h. The t1/2, clearance rate and average retention time of LAP-NES obviously prolonged compared with free LAP. The tissue biodistribution behavior of NES in vivo showed the good targeting in the liver and spleen, with the maximum at 4h and then the fluorescence slowly decreased until 72h. LAP-NES could significantly delay the release of LA in vivo, effectively prolong the elimination time and had obvious liver-targeting ability. In summary, LAP-NES shows great potential for liver-targeting delivery to increase the therapeutic effect and decrease the side effects of LA.

Combination immunotherapy of PEG-modified preladenant thermosensitive liposomes and PD-1 inhibitor effectively enhances the anti-tumor immune response and therapeutic effects.

Immunotherapy is a promising cancer treatment strategy. In contrast, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors are associated with low response rates and are only useful in a small group of cancer patients. A combination of treatments may be effective for overcoming this clinical issue. Preladenant is an adenosine (ADO) receptor inhibitor that can block the ADO pathway and improve the tumor microenvironment (TME), thereby enhancing the immunotherapeutic effect of PD-1 inhibitors. However, its poor water solubility and low targeting limit its clinical applications. We designed a PEG-modified thermosensitive-liposome (pTSL) loaded with ADO small molecule inhibitor preladenant (P-pTSL) to overcome these problems and enhance the effect of PD-1 inhibitor on breast cancer immunotherapy. The prepared P-pTSL was round and uniformly distributed with a particle size of (138.9 ± 1.22) nm, PDI: 0.134 ± 0.031, and zeta potential (-10.1 ± 1.63) mV; preladenant was released slowly at 37 °C but released fast at 42 °C from P-pTSL, which was 76.52 ± 0.44%. P-pTSL has good long-term and serum stability and excellent tumor-targeting ability in mice. Moreover, the combination with PD-1 inhibitor significantly enhanced the anti-tumor effect, and the improvement of related factors in serum and lymph was more obvious under the condition of 42 °C thermotherapy in vitro.

Novel biomimetic nanostructured lipid carriers for cancer therapy: preparation, characterization, and in vitro/in vivo evaluation.

Nanostructured lipid carriers (NLC) have become a research hotspot, wherein cancer-targeting effects are enhanced and side effects of chemotherapy are overcome. Usually, accelerated blood clearance (ABC) occurs after repeated injections, without changing the immunologic profile, despite PEGylation which prolongs the circulation function. To overcome these problems, we designed a red blood cell-membrane-coated NLC (RBCm-NLC), which was round-like, with a particle size of 60.33 ± 3.04 nm and a core-shell structure. Its stability was good, the drug paclitaxel (PTX) release from RBCm-PTX-NLC was less than 30% at pH7.4 and pH6.5, and the integrity of RBC membrane surface protein was maintained before and after preparation. Additionally, in vitro assays showed that, with the RBCm coating, the cellular uptake of the NLC by cancer cells was significantly enhanced. RBCm-NLC can avoid recognition by macrophage cells and prolong circulation time in vivo. In S180 tumor-bearing mice, the DiR-labeled RBCm-NLC group showed a stronger fluorescence signal and longer retention in tumor tissues, indicating a prompt tumor-targeting effect and extended blood circulation. Importantly, RBCm-PTX-NLC enhanced the antitumor effect and extended the survival period significantly in vivo. In summary, biomimetic NLC offered a novel strategy for drug delivery in cancer therapy.

Chitosan-capped enzyme-responsive hollow mesoporous silica nanoplatforms for colon-specific drug delivery.

An enzyme-responsive colon-specific delivery system was developed based on hollow mesoporous silica spheres (HMSS) to which biodegradable chitosan (CS) was attached via cleavable azo bonds (HMSS-N=N-CS). Doxorubicin (DOX) was encapsulated in a noncrystalline state in the hollow cavity and mesopores of HMSS with the high loading amount of 35.2%. In vitro drug release proved that HMSS-N=N-CS/DOX performed enzyme-responsive drug release. The grafted CS could increase the biocompatibility and stability and reduce the protein adsorption on HMSS. Gastrointestinal mucosa irritation and cell cytotoxicity results indicated the good biocompatibility of HMSS and HMSS-N=N-CS. Cellular uptake results indicated that the uptake of DOX was obviously increased after HMSS-N=N-CS/DOX was preincubated with a colonic enzyme mixture. HMSS-N=N-CS/DOX incubated with colon enzymes showed increased cytotoxicity, and its IC50 value was three times lower than that of HMSS-N=N-CS/DOX group without colon enzymes. The present work lays the foundation for subsequent research on mesoporous carriers for oral colon-specific drug delivery.

Cancer cell membrane-coated mesoporous silica loaded with superparamagnetic ferroferric oxide and Paclitaxel for the combination of Chemo/Magnetocaloric therapy on MDA-MB-231 cells.

To effectively inhibit the growth of breast cancer cells (MDA-MB-231 cells) by the combination method of chemotherapy and magnetic hyperthermia, we fabricated a biomimetic drug delivery (CSiFePNs) system composed of mesoporous silica nanoparticles (MSNs) containing superparamagnetic ferroferric oxide and Paclitaxel (PTX) coated with MDA-MB-231 cell membranes (CMs). In the in vitro cytotoxicity tests, the MDA-MB-231 cells incubated with CSiFePNs obtained IC50 value of 0.8 µgL-1, 3.5-fold higher than that of SiFePNs. The combination method of chemotherapy and magnetic hyperthermia can effectively inhibit the growth of MDA-MB-231 cells.

Development and characteristics of novel sonosensitive liposomes for vincristine bitartrate.

The aim of drug delivery is to increase therapeutic efficacy. Externally triggered drug delivery systems enable site-specific and time-controlled drug release. To achieve this goal, our strategy was based on ultrasound-triggered release of an anticancer agent from sonosensitive liposomes (SL). To realize the ultrasound-triggered drug release, a lipophilic sonosensitizer, hematoporphyrin monomethyl ether (HMME) was incorporated into the lipid bilayer of liposomes. Once irradiated by the ultrasound in tumor tissues, the sonodynamic effect generated by HMME could lead to an efficient disruption of the lipid bilayer in the SL. After encapsulating vincristine bitartrate (VIN) as the model drug, the ultrasound-triggered lipid bilayer breakdown can trigger the instant release of VIN, enabling ultrasound-controlled chemotherapy with great specificity. In the in vitro and in vivo studies, by integrating tumor-specific targeting and stimuli-responsive controlled release into one system, VIN-loaded SL showed excellent antitumor efficacy. The SL could potentially produce viable clinical strategies for improved targeting efficiency of VIN for the treatment of related cancer. More importantly, this report provides an example of controlled release by means of a novel class of ultrasound triggering system.

Evaluation, characterization, expression profiling, and functional analysis of DXS and DXR genes of Populus trichocarpa.

1-Deoxy-D-xylulose-5-phosphate synthasse (DXS) and 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) are key enzymes in terpenoid biosynthesis. DXS catalyzes the formation of 1-deoxy-D-xylulose 5-phosphate (DXP) from pyruvate and D-glyceraldehyde-3-phosphate. DXR catalyzes the formation of 2-C-methyl-D-erythritol 4-phosphate (MEP) from DXP. Previous studies of the DXS and DXR genes have focused on herbs, such as Arabidopsis thaliana, Salvia miltiorrhiza, and Amomum villosum, but few studies have been conducted on woody plants. For that reason, we chose Populus trichocarpa as a model woody plant for investigating the DXS and DXR genes. PtDXS exhibited the highest expression level in leaves and the lowest expression in roots. PtDXR showed maximum expression in young leaves, and the lowest expression in mature leaves. The expression profiles revealed by RT-PCR following different elicitor treatments such as abscisic acid, NaCl, PEG6000, H2O2, and cold stress showed that PtDXS and PtDXR were elicitor-responsive genes. Our results showed that the PtDXS gene exhibited diurnal changes, but PtDXR did not. Moreover, overexpression of PtDXR in transgenic poplars improved tolerance to abiotic and biotic stresses. Those results showed that the PtDXR encoded a functional protein, and widely participates in plant growth and development, stress physiological process.

Effectiveness of electrical stimulation combined with pelvic floor muscle training on postpartum urinary incontinence.

BACKGROUND: Previous clinical trials have reported that electrical stimulation (ES) combined with pelvic floor muscle training (PFMT) can be used to treat postpartum urinary incontinence (PPUI) effectively. However, no systematic review has investigated the effectiveness and safety of ES plus PFMT for the treatment of patients with PPUI. In this systematic review, we will firstly assess the effectiveness and safety of ES and PFMT for treating PPUI. METHODS: In this study, we will search the following electronic databases: Cochrane Library, Web of Science, Springer, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inceptions to the present without language restrictions. All eligible randomized controlled trials (RCTs) on the effectiveness of ES plus PFMT for PPUI will be included. We will also search grey literature to avoid missing any other potential qualified studies. Two authors will independently conduct the study selection, data extraction, and risk of bias assessment. A third author will be consulted to solve any disagreements between 2 authors. RevMan 5.3 Software will be used to pool the data and to carry out the meta-analysis. RESULTS: This study will provide high quality evidence of ES and PFMT for PPUI. The primary outcome includes symptoms improvement. The secondary outcomes consist of incontinence-specific quality of life, clinician's observations, and adverse effects. CONCLUSION: The findings of this study will summary up-to-dated evidence for judging whether ES combined PFMT is an effective intervention for PPUI or not. ETHICS AND DISSEMINATION: This study does not needs ethical approval, because it will not involve individual patient data. Its findings will be disseminated through peer-reviewed journals. SYSTEMATIC REVIEW REGISTRATION: CRD42019122540.

Preparation of Glycyrrhetinic Acid Liposomes Using Lyophilization Monophase Solution Method: Preformulation, Optimization, and In Vitro Evaluation.

In this study, glycyrrhetinic acid (GA) liposomes were successfully prepared using lyophilization monophase solution method. Preformulation studies comprised evaluation of solubility of soybean phosphatidylcholine (SPC), cholesterol, and GA in tert-butyl alcohol (TBA)/water co-solvent. The influences of TBA volume percentage on sublimation rate were investigated. GA after lyophilization using TBA/water co-solvent with different volume percentage was physicochemically characterized by DSC, XRD, and FTIR. The XRD patterns of GA show apparent amorphous nature. FTIR spectroscopy results show that no chemical structural changes occurred. Solubility studies show aqueous solubility of GA is enhanced. The optimum formulation and processing variables of 508 mg SPC, 151 mg cholesterol, 55% volume percentage of TBA, 4:1 trehalose/SPC weight ratio were obtained after investigating by means of Box-Benhnken design and selection experiment of lyoprotectant. Under the optimum conditions, satisfactory encapsulation efficiency (74.87%) and mean diameter (191 nm) of reconstituted liposomes were obtained. In vitro drug release study showed that reconstituted liposomes have sustained-release properties in two kinds of release medium. Furthermore, in vitro cell uptake study revealed that uptake process of drug-loaded liposomes by Hep G2 cells is time-dependent.

MiR-136 contributes to pre-eclampsia through its effects on apoptosis and angiogenesis of mesenchymal stem cells.

INTRODUCTION: Mesenchymal stem cells (MSCs) play an important role in the pathology of preeclampsia (PE). The survival of MSCs and angiogenesis in the maternal-fetal interface are important for a successful pregnancy. MicroRNA-136 (miR-136) is highly expressed in decidua-derived MSCs (MSCs) from PE compared with healthy donors (NC). The role of the MSCs aberrant expressed miR-136 in PE development is still unclear. In the present study, we examined the impact of miR-136 on the survival of MSCs and angiogenesis in the maternal-fetal interface. METHODS: MSCs were extracted and transfected with miR-136 mimic and interfering RNAs using lipofectamine-2000. Then cell apoptosis were tested using flow cytometry. HUVEC tube formation ability was tested on Matrigel co-cultured with conditioned MSCs supernatants. RESULTS: High level of miR-136 could suppress cell proliferation and promote apoptosis of MSCs through targeting BCL2. It could also impairs HUVEC capillary formation by suppressing VEGF. DISCUSSION: MiR-136 significantly increase the apoptosis and suppress the proliferation of MSCs. It could also inhibit the capillary formation and trophoblast cell invasion. These data suggest that decidua-derived miR-136 that is increased in PE is a potential causal factor of PE.

Cerebrospinal fluid from patients with amyotrophic lateral sclerosis inhibits sonic hedgehog function.

Sonic hedgehog (Shh) is a morphogen essential to the developing nervous system that continues to play an important role in adult life by contributing to cell proliferation and differentiation, maintaining blood-brain barrier integrity, and being cytoprotective against oxidative and excitotoxic stress, all features of importance in amyotrophic lateral sclerosis (ALS). ALS is a fatal disease characterized by selective loss of motor neurons due to poorly understood mechanisms. Evidence indicates that Shh might play an important role in ALS, and that Shh signaling might be also adversely affected in ALS. Since little is known about the functional status of Shh pathway in patients with ALS, we therefore sought to determine whether Shh protein levels or biological activity in cerebrospinal fluid (CSF) was less in ALS patients than controls, and whether these measures could be correlated with ALS disease severity and disease progression, and with other CSF analytes of biological interest in ALS. Comparing Shh levels in the CSF of normal controls (n = 13), neurological controls (n = 12), and ALS patients (n = 9) measured by ELISA, we found that CSF Shh levels were not different between controls and ALS patients. However, when assessing Shh biological activity in CSF using in vitro cell-based assays, which measure Shh activity as inducible Gli-driven luminescence, we found that in the presence of exogenous recombinant Shh or the Shh agonist, purmorphamine, the inducible activity of CSF was significantly augmented in the control groups as expected, but not in the ALS group, suggesting the presence of an inhibitor of Shh signaling in ALS CSF samples. Since purmorphamine acts on Smoothened, downstream of Shh and its receptor Patched, the inhibitory action is downstream of Smoothened. Our results also demonstrated that while the inhibitory effect of ALS CSF on Shh signaling did not correlate significantly with ALS disease characteristics, the levels of IL-1ß and TNF-α did. In addition to being significantly elevated in ALS CSF, these cytokines negatively correlated with the disease duration, whereas GDF11 was a favorable predictor of ALS clinical score. We also found that TNF-α significantly inhibited Shh biological activity in vitro, potentially suggesting a novel role of TNF-α in ALS pathogenesis. Collectively, this is the first report demonstrating that Shh signaling in CSF of ALS patients is compromised.

Crosstalk between Notch and Sonic hedgehog signaling in a mouse model of amyotrophic lateral sclerosis.

The developmental morphogen Sonic hedgehog (Shh) may continue to play a sustaining role in adult motor neurons, of potential relevance to motor neuron diseases including amyotrophic lateral sclerosis. The Shh signaling pathway is incompletely understood and interactions with other signaling pathways are possible. We focus here on Notch, and first show that there is an almost linear reduction in light output from a Gli reporter in Shh Light II cells in the presence of increasing concentrations of the Notch inhibitor DAPT (r=0.982). Second, in the spinal cord of mutant superoxide dismutase mice, but not control mice, a key marker of Notch signaling changes with age. Before the onset of clinical signs, the Notch intracellular domain is expressed predominantly in motor neurons, but by 125 days of age, Notch intracellular domain expression is markedly reduced in motor neurons and increased in neighboring astroglia. Third, there is a parallel reduction in Gli protein expression in mutant superoxide dismutase mouse spinal motor neurons, consistent with the observed reduction in Notch signaling and also a redistribution of Gli away from the nucleus. Thus, there is a reduction in motor neuronal Notch signaling and associated changes in Shh signaling, occurring coincidentally with disease expression, that may contribute toward the dysfunction and death of motor neurons in amyotrophic lateral sclerosis.

Cytosolic localization of Fox proteins in motor neurons of G93A SOD1 mice.

NeuN is a nuclear protein expressed exclusively in mature neurons and has served for many years as a reliable neuronal marker in immunohistochemical labeling studies. In 2009, NeuN was identified as Fox3, one of three closely related RNA binding proteins important in pre-mRNA splicing. During the course of a previous study using G93A SOD1 mice, a model of amyotrophic lateral sclerosis (ALS), we observed that NeuN was significantly redistributed to the cytosol. Since altered splicing may be important in the pathogenesis of ALS, we compared the localization (predominantly nuclear or cytosolic) of all three Fox proteins in the lumbar spinal cord of wild-type and G93A SOD1 mice before and after the development of clinical signs of disease. The Fox proteins regulate their own splicing, and we also examined the major Fox protein isoforms in nuclear and cytosolic fractions of lumbar spinal cord by Western blotting. We report here that Fox3 and Fox2 undergo a major cytosolic relocalization in this ALS model that increases with age and that is associated with progressive alterations in the splicing profiles of all three Fox proteins.

Metabolomic analysis of exercise effects in the POLG mitochondrial DNA mutator mouse brain.

Mitochondrial DNA (mtDNA) mutator mice express a mutated form of mtDNA polymerase gamma that results an accelerated accumulation of somatic mtDNA mutations in association with a premature aging phenotype. An exploratory metabolomic analysis of cortical metabolites in sedentary and exercised mtDNA mutator mice and wild-type littermate controls at 9-10 months of age was performed. Pathway analysis revealed deficits in the neurotransmitters acetylcholine, glutamate, and aspartate that were ameliorated by exercise. Nicotinamide adenine dinucleotide (NAD) depletion and evidence of increased poly(adenosine diphosphate-ribose) polymerase 1 (PARP1)activity were apparent in sedentary mtDNA mutator mouse cortex, along with deficits in carnitine metabolites and an upregulated antioxidant response that largely normalized with exercise. These data highlight specific pathways that are altered in the brain in association with an accelerated age-related accumulation of somatic mtDNA mutations. These results may have relevance to age-related neurodegenerative diseases associated with mitochondrial dysfunction, such as Alzheimer's disease and Parkinson's disease and provide insights into potential mechanisms of beneficial effects of exercise on brain function.

The Accomplices of NF-κB Lead to Radioresistance.

Ionizing radiation (IR) plays an important role in the treatment of epithelial tumors, such as lung and prostate cancer, by wounding and killing cancer cells. However, IR also activates sophisticated anti-apoptotic transcriptional factors such that cancer cells fail to repair DNA damage and obtain resistance to apoptosis under conditions of radiotherapy. Among these transcription factors, the transcription factor nuclear factor kappa B (NF-κB) is recognized as a key feature for protecting cells from apoptosis in most cell types. Moreover, the induction of radioresistance is mediated by several genes that are regulated by NF- κB. The primary purpose of this review is to introduce the studies of the signaling mechanisms of IR in NF-κB activation, such as ROS/NF-κB, ATM or DNA-PK/MAPKK/ p90rsk, PI3K/AKT/IKK and k-ras/c-raf/ MEKK/ NF-κB pathways. Moreover, we describe how the expression of the target genes (e.g., XIAP, A20, FLIP, Bcl-xL) are induced by NF-κB to regulate the activation of survival signaling pathways and to inhibit apoptotic signaling pathways. In addition, IR activates NF-κB to express cell cycle-specific genes, for example cyclin D1, which is associated with reinforcing radioresistance. We exhibit the signaling pathways that are induced by IR stimulation of NF-κB and illustrate the molecular mechanisms of radioresistance.

Polymerase gamma mutator mice rely on increased glycolytic flux for energy production.

Several studies have illustrated that the polymerase gamma mutator (PolG) mice have reduced mitochondrial content secondary to systemic mitochondrial dysfunction, and subsequently a lower capacity to perform aerobic respiration and endurance exercise. We sought to delineate the extent of glycolysis as a means of energy production in the PolG mice in the absence of optimal mitochondrial function. PolG mice display an enhanced reliance on glycolysis as compared to their wild-type counterparts. This is evident by the resting hypoglycemia, higher PFK content, and elevated plasma lactate levels in the PolG mice. In vitro experiments provide further proof that PolG derived dermal fibroblasts have a higher rate of, and capacity for, glycolysis. PolG mice also have enhanced capacity to perform hepatic gluconeogenesis that is likely enhancing the Cori cycle capacity.

Extraction of carbamate pesticides in fruit samples by graphene reinforced hollow fibre liquid microextraction followed by high performance liquid chromatographic detection.

Graphene reinforced hollow fibre liquid phase microextraction combined with high performance liquid chromatography-diode array detection was developed for the determination of some carbamate pesticides (metolcarb, carbaryl, isoprocarb, and diethofencarb) in fruit samples. The main parameters that affect the extraction efficiency for the carbamates were investigated. Under the optimum conditions, a good linearity was observed in the range of 1.0-100.0 ng g(-1) for carbaryl and 3.0-100.0 ng g(-1) for the other three analytes, with the correlation coefficients (r) of 0.9965-0.9993. The limits of detection of the method ranged from 0.2 to 1.0 ng g(-1). The relative standard deviations were in the range from 6.2% to 7.8%. The results indicated that the developed method is sensitive and efficient for the determination of the carbamate pesticides in fruit samples.

Small peptide-modified nanostructured lipid carriers distribution and targeting to EGFR-overexpressing tumor in vivo.

Ala-Glu-Tyr-Leu-Arg (AEYLR) was identified as a small peptide ligand targeting epidermal growth factor receptors (EGFR) in vitro in our previous study. The in vivo targeting ability of AEYLR and AEYLR-conjugated nanostructured lipid carriers (NLC) was studied in this paper. Near-infrared fluorescent (NIFR) dye 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide (DiR)-loaded and AEYLR-modified NLC (A-D-NLC) were prepared. The average diameter, zeta potential, coupling efficiency between AEYLR and NLC and the amount of DiR released from A-D-NLC were used to evaluate their in vivo characteristics. AEYLR was labeled by Cy7 and A549 xenograft tumor-bearing mice model were establish. The in vivo distribution in tumor-bearing mice of A-D-NLC and Cy7-AEYLR was examined using NIRF imaging experiments at different times post-injection. AEYLR and AEYLR-conjugated NLC showed obvious targeting to A549 xenograft tumor compared with the control group. These results suggested that AEYLR-modified NLC could be considered as a promising targeted delivery system for combination cancer chemotherapy to improve therapeutic efficacy and to minimize adverse effects.

Trophic and proliferative effects of Shh on motor neurons in embryonic spinal cord culture from wildtype and G93A SOD1 mice.

BACKGROUND: The developmental morphogen sonic hedgehog (Shh) may continue to play a trophic role in the support of terminally-differentiated motor neurons, of potential relevance to motor neuron disease. In addition, it may support the proliferation and differentiation of endogenous stem cells along motor neuronal lineages. As such, we have examined the trophic and proliferative effects of Shh supplementation or Shh antagonism in embryonic spinal cord cell cultures derived from wildtype or G93A SOD1 mice, a mouse model of amyotrophic lateral sclerosis. RESULTS: Shh supported survival, and stimulated growth of motor neurons, neurite outgrowth, and neurosphere formation in primary culture derived from both G93A SOD1 and WT mice. Shh increased the percentage of ciliated motor neurons, especially in G93A SOD1 culture. Shh-treated cultures showed increased neuronal proliferation compared to controls and especially cyclopamine treated cultures, from G93A SOD1 and WT mice. Moreover, Shh enhanced cell survival and differentiation of motor neuron precursors in WT culture. CONCLUSIONS: Shh is neurotrophic to motor neurons and has mitogenic effects in WT and mSOD1 G93A culture in vitro.

Graphene grafted silica-coated Fe3O4 nanocomposite as absorbent for enrichment of carbamates from cucumbers and pears prior to HPLC.

In this paper, a novel graphene (G) grafted silica-coated Fe3O4 nanocomposite was fabricated by the chemical bonding of G onto the surface of silica-coated Fe3 O4 nanoparticles. Some carbamates (metolcarb, carbaryl, pirimicarb, and diethofencarb) in cucumber and pear samples were enriched by this nanocomposite prior to their determination by HPLC with UV detection. Experimental parameters that may affect the extraction efficiency were investigated. Under the optimum conditions, a linear response was achieved in the concentration range of 0.5-100.0 ng/g for metolcarb, carbaryl, and diethofencarb, and 1.0-100 ng/g for pirimicarb with the correlation coefficients (r) ranging from 0.9956 to 0.9984. The LOD (S/N = 3) of the method were found to be in the range from 0.08 to 0.2 ng/g. The RSDs were in the range from 2.4 to 5.8%. The results indicated that the G grafted silica-coated Fe3 O4 nanocomposite was stable and efficient for magnetic SPE and has a great application potential for the preconcentration of other organic pollutants from real samples.