An electrochemiluminescent aptasensor for amplified detection of exosomes from breast tumor cells (MCF-7 cells) based on G-quadruplex/hemin DNAzymes.

Exosomes are non-invasive biomarkers for cancer diagnosis. Herein, we describe an electrochemiluminescent (ECL) aptasensor for the detection of exosomes from breast tumor cells. Mercaptopropionic acid (MPA)-modified Eu3+-doped CdS nanocrystals (MPA-CdS:Eu NCs) and H2O2 were used as ECL emitters and coreactant, respectively. The exosomes are recognized and captured by the CD63 aptamer, and then form a G-quadruplex/hemin DNAzyme, which efficiently catalyzes the decomposition of H2O2, resulting in the decreased ECL signal of MPA-CdS:Eu NCs. The exosomes from breast tumor cells (MCF-7 cells) can be detected in the range of 3.4 × 105 to 1.7 × 108 particles per mL. The limit of detection (LOD) was estimated to be 7.41 × 104 particles per mL at a signal-to-noise ratio of 3. The aptasensor has been successfully used to detect exosomes in the serum.

Genetic variations in interleukin-6 polymorphism and the association with susceptibility and overall survival of osteosarcoma.

Interleukin-6 (IL-6), a central proinflammatory cytokine, may be involved in both development and progression of many human malignancies. Therefore, we aimed to evaluate any associations of IL-6 gene polymorphisms with susceptibility and overall survival of osteosarcoma in a Chinese population. A total of 412 subjects, including 206 patients with osteosarcoma and 206 healthy controls, were recruited and were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in this study. Significant differences of genotype distribution were observed between osteosarcoma cases and controls at the IL-6 -174 G/C genotypes. Compared with the homozygote GG, the heterozygous GC genotype was associated with significantly increased risk for osteosarcoma (odds ratio [OR] = 1.58, 95 % confidence interval [CI] = 1.13-3.05, p = 0.028); the CC genotype was associated with increased risk for osteosarcoma (OR = 1.57, 95 % CI = 1.21-3.26, p = 0.022). Moreover, the genotype CC of IL-6 -174 G/C carried a higher risk of osteosarcoma metastasis and later Enneking stages, compared with the GG genotype. The IL-6 -174 G/C genotype was associated with risk for development and metastasis of osteosarcoma in Chinese Han population.

Arbuscular mycorrhizal fungi associated with vegetation and soil parameters under rest grazing management in a desert steppe ecosystem.

The impact of rest grazing on arbuscular mycorrhizal fungi (AMF) and the interactions of AMF with vegetation and soil parameters under rest grazing condition were investigated between spring and late summer in a desert steppe ecosystem with different grazing managements (rest grazing with different lengths of resting period, banned or continuous grazing) in Inner Mongolia, China. AMF diversity and colonization, vegetation biomass, soil properties and soil phosphatase activity were examined. In rest grazing areas of 60 days, AMF spore number and diversity index at a 0-10 cm soil depth as well as vesicular and hyphal colonization rates were higher compared with other grazing treatments. In addition, soil organic matter and total N contents were highest and soil alkaline phosphatase was most active under 60-day rest grazing. In August and September, these areas also had the highest amount of aboveground vegetation. The results indicated that resting grazing for an appropriate period of time in spring has a positive effect on AMF sporulation, colonization and diversity, and that under rest grazing conditions, AMF parameters are positively correlated with some soil characteristics.

Ultrafast self-assembly of supramolecular hydrogels toward novel flame-retardant separator for safe lithium ion battery.

Traditional polyolefin separators for lithium-ion batteries (LIBs) often experience limited thermal stability and intrinsic flammability, resulting in great safety risks during their usage. Therefore, it is highly important to develop novel flame-retardant separators for safe LIBs with high performance. In this work, we report a flame-retardant separator derived from boron nitride (BN) aerogel with a high BET surface area of 1127.3 m2 g-1. The aerogel was pyrolyzed from a melamine-boric acid (MBA) supramolecular hydrogel, which was self-assembled at an ultrafast speed. The in-situ evolution details of the nucleation-growth process of the supramolecules could be observed in real-time using a polarizing microscope under ambient conditions. The BN aerogel was further composited with bacterial cellulose (BC) to form a BN/BC composite aerogel with excellent flame-retardant performance, electrolyte-wetting ability and high mechanical property. By using the BN/BC composite aerogel as the separator, the developed LIBs exhibited high specific discharge capacity of 146.5 mAh g-1 and excellent cyclic performance, maintaining 500 cycles with a capacity degradation of only 0.012% per cycle. The high-performance flame-retardant BN/BC composite aerogel represents a promising candidate for separators not only in LIBs but also in other flexible electronics.

A novel catalyst derived from Co-ZIFs to grow N-doped carbon nanotubes for all-solid-state supercapacitors with high performance.

Carbon nanotubes (CNTs) have been widely used as electrode materials for electrochemical energy storage devices (e.g., supercapacitors) due to their excellent chemical and physical properties. However, conventional approaches (e.g., electron-beam vapor deposition and atomic layer deposition) to fabricate catalysts for the growth of CNTs are complex and demand high energy consumption. Herein, we report a facile method to synthesize catalysts derived from cobalt-containing zeolitic imidazolate frameworks (Co-ZIFs), which is exploited to in situ construct the three-dimensional (3D) CNT hybrid materials for all-solid-state supercapacitors. In brief, Co-ZIFs with a controllable structure is first grown on the inner porous surface of carbon foams pyrolyzed from commercial melamine foams, followed by thermal annealing and chemical vapor deposition to grow CNTs, achieving 3D free-standing CNT-based hybrids. The well-distributed Co-ZIFs in the carbon foam enable the grown CNTs with uniform structures and morphologies. Using the fabricated CNT-based hybrid as electrodes, the assembled all-solid-state supercapacitors show a high specific capacitance of 19.4 mF cm-2 at a current density of 0.5 mA cm-2, which could be further optimized to as high as 871.8 mF cm-2 by incorporating the pseudocapacitive material of manganese dioxide in CNT-based hybrids. This study provides a facile solution approach to fabricate the catalyst for the growth of a CNT inner porous substrate; the resultant 3D free-standing hybrids could be used as efficient electrodes for high-performance energy storage devices beyond supercapacitors.

Fabrication of an antifouling PES ultrafiltration membrane via blending SPSF.

Sulfonated polysulfone (SPSF) with different sulfonation degrees (10%, 30%, and 50%) was added to polyethersulfone (PES) to improve the separation and antifouling performance of polyethersulfone ultrafiltration membranes. The PES/SPSF blend ultrafiltration membrane was prepared by the non-solvent induced phase inversion method (NIPS), and the effect of sulfonation degree on the ultrafiltration performance was studied. The compatibility of SPSF and PES was calculated by the group contribution method, and confirmed by differential scanning calorimetry (DSC). The morphology and surface roughness of the membrane were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM), the chemical composition of the membrane was analyzed by X-ray photoelectron spectroscopy (XPS) and infrared spectroscopy (FTIR), and the permeability and anti-fouling performance of the blend membrane were studied through filtration experiments. The research shows that the flux and anti-fouling performance of the blend membrane have been improved after adding SPSF. When the sulfonation degree of the SPSF is 30%, the pure water flux of the blend membrane can reach 530 L m-2 h-1, the rejection rate of humic acid (HA) is 93%, the flux recovery rate of HA increases from 69.23% to 79.17%, and the flux recovery rate of BSA increases from 72.56% to 83%.

Fabrication of a hybrid ultrafiltration membrane based on MoS2 modified with dopamine and polyethyleneimine.

The hydrophobicity of ultrafiltration membranes is the main cause of membrane fouling and reduced permeability, so it is necessary to improve the hydrophilicity and anti-fouling performance of ultrafiltration membrane materials. MoS2 nanoparticles that were modified with polydopamine (PDA) and polyethyleneimine (PEI), named MoS2-PDA-PEI, were added to fabricate a polyethersulfone ultrafiltration membrane (PES/MoS2-PDA-PEI) for the first time. The effects of modified MoS2 nanoparticles on membrane performance were clarified. The results indicated that the permeability, rejection, and anti-fouling capability of the hybrid PES/MoS2-PDA-PEI membrane have been improved compared with the pristine PES membrane. When the content of MoS2-PDA-PEI nanoparticles in the membrane is 0.5%, the pure water flux of the hybrid membrane reaches 364.03 L m-2 h-1, and the rejection rate of bovine serum albumin (BSA) and humic acid (HA) is 96.5% and 93.2% respectively. The flux recovery rate of HA reached 97.06%. As expected, the addition of MoS2-PDA-PEI nanoparticles promotes the formation of the porous structure and improves the hydrophilicity of the membrane, thereby improving its antifouling performance.

TNF-α increases the expression of inflammatory factors in synovial fibroblasts by inhibiting the PI3K/AKT pathway in a rat model of monosodium iodoacetate-induced osteoarthritis.

Osteoarthritis is a degenerative disease that often causes patients to experience joint pain and deformity. It has been demonstrated that tumor necrosis factor (TNF)-α is associated with the progression of osteoarthritis; however, to the best of our knowledge, the mechanisms by which TNF-α simulates the progression of osteoarthritis and the signaling pathway(s) it influences remain unknown. Therefore, the aim of the present study was to investigate the therapeutic effects of TNF-α inhibitor in an iodoacetate-induced rat model of osteoarthritis and identify its potential mechanisms of action. Western blotting, ELISA and histological analyses were performed to assess the effects of the TNF-α inhibitor on osteoarthritis. The effects of TNF-α and phosphoinositide 3-kinase (PI3K) inhibition on synovial fibroblasts isolated from rats with osteoarthritis were tested in vitro. Furthermore, the expression of various inflammatory cytokines and the PI3K/protein kinase B (AKT) signaling pathway were assessed in vitro. The results indicated that the inflammatory factors TNF-α, interleukin (IL)-1ß, IL-17a and IL-8 were upregulated in synovial fibroblasts taken from rats with osteoarthritis compared with normal rats. By contrast, TNF-α inhibition downregulated IL-1ß, IL-17a and IL-8 expression in synovial fibroblasts in vitro. The PI3K/AKT pathway was also upregulated in synovial fibroblasts harvested from rats with osteoarthritis compared with that in normal rats. It was demonstrated that treatment with the TNF-α inhibitor downregulated the serum and protein levels of IL-1ß, IL-17a and IL-8 in rats with osteoarthritis. Furthermore, treatment with the TNF-α inhibitor also decreased matrix metalloproteinase (MMP)-3, MMP-9, vascular endothelial growth factor and ADAMTS4 expression in synovial fibroblasts isolated from rats with osteoarthritis. Treatment with the TNF-α inhibitor also inhibited the PI3K/AKT pathway in synovial fibroblasts isolated from rats with osteoarthritis. Treatment with the PI3K inhibitor ameliorated TNF-α-induced increases in IL-1ß, IL-17a and IL-8 expression in synovial fibroblasts isolated from rats with osteoarthritis. Furthermore, treatment with the TNF-α inhibitor decreased inflammation, as well as joint and cartilage destruction in vivo. Taken together, the results of the present study indicate that TNF-α inhibition may downregulate the expression of inflammatory factors in synovial fibroblasts, suggesting that TNF-α inhibition may be a novel method for treating osteoarthritis by downregulating the PI3K/AKT signaling pathway.

Hydrophilic and antimicrobial core-shell nanoparticles containing guanidine groups for ultrafiltration membrane modification.

Physical blending is a common technique to improve the water flux and antifouling performance of ultrafiltration (UF) membranes. In the present work, a novel hydrophilic and antimicrobial core-shell nanoparticle was synthesized through the chemical grafting of poly(guanidine-hexamethylenediamine-PEI) (poly(GHPEI)) on the surface of silica nanoparticles (SNP). The synthesized core-shell nanoparticles, poly(GHPEI) functionalized silica nanoparticles (SNP@PG), were incorporated into polyethersulfone (PES) to fabricate hybrid UF membranes by a phase inversion process. The chemical composition, surface and cross section morphologies, hydrophilicity, water flux and protein rejection of the membranes were evaluated by a series of characterizations. Results show that the prepared PES/SNP@PG hybrid membrane exhibits not only improved water flux, which is around 2.6 times that of the pristine PES membrane, but also excellent resistance to organic fouling and biofouling.

Effects of apoptosis-inducing nucleosides released from CD57+HLA-DRbright natural suppressor cell line on human breast cancer cell death and growth.

The CD57+HLA-DRbright-natural suppressor (57.DR-NS) cell line induced apoptosis in estrogen-non-responsive human breast carcinoma MDA-MB-435 cells by apoptosis-inducing nucleosides (AINs) released into the cultures. We obtained six active AINs isolated by high performance liquid chromatography (HPLC) from 57.DR-NS cell cultures. Each AIN isolated from 57.DR-NS cell cultures induced apoptosis in MDA-MB-435 cells. We found the occurrence of DNA strand breaks followed by the activation of caspase-3 during AIN-induced apoptosis in MDA-MB-435 cells. The data obtained here indicated that 57.DR-NS cells could induce apoptosis in MDA-MB-435 cells mediated by AINs through DNA strand breaks and activation of caspase-3. Furthermore, the administration of AINs into MDA-MB-435 tumor-bearing SCID mice culminated in strong suppression of tumor growth with no change of body weight of experimental mice suggesting no side effects of AINs.

Therapeutic effects of novel anti-tumor reagent, apoptosis inducing nucleosides from CD57+HLA-DRbright natural suppressor cell line on human gastric carcinoma-bearing SCID mice.

To further provide scientific evidence before clinical application, the anti-tumor effects of apoptosis inducing nucleosides (AINs) released from CD57+HLA-DRbright natural suppressor (CD57.DR-NS) cell line on human gastric carcinoma (GCIY)-bearing severe combined immunodeficiency (SCID) mice were examined by monitoring tumor cell growth and change of body weight of mice. The results obtained evidenced that AINs strongly induced apoptosis in the tumor tissues in SCID mice with decrease of tumor size and without loss of body weight. We found that peak 5 and peak 6 (P5 and P6) components among six components (AINs) isolated from CD57.DR-NS cell cultures by high performance liquid chromatography (HPLC) are the most effective. The anti-tumor effective dosage of P5, P6 and their mixture, P5+P6, were obtained in dose-dependent manner. Thus, the most effective method of administration of AINs for tumor regression without exhaustion was established in the present study. Corresponding to the previous study that AINs could generate apoptosis in malignant cells while lacking the toxicity in normal cells, the results obtained in the present preclinical experiments suggested anti-tumor efficacy of AINs with possible refrainment from side-effects in clinical trials.

In vitro and in vivo induction of human LoVo cells into apoptotic process by non-invasive microwave treatment: a potentially novel approach for physical therapy of human colorectal cancer.

The human LoVo and WI-38 cells were exposed to high power non-invasive microwaves. The apoptotic effect of the microwaves on the cells was examined with TUNEL, DNA fragmentation and flow cytometry. The human colon cancer LoVo cells showed pathological change of apoptosis but the normal human WI-38 cells showed no detectable apoptotic response. Exposure of the mice bearing tumor tissue to microwave resulted in a significant regression of the tumor tissue in the animal models. We demonstrate that the LoVo cells can be induced into apoptosis by microwave treatment both in in vitro and in vivo. The data described in this communication implies the possibility that microwave therapy may become a novel approach in human colorectal cancer treatment.

Sox2 transcriptionally regulates PQBP1, an intellectual disability-microcephaly causative gene, in neural stem progenitor cells.

PQBP1 is a nuclear-cytoplasmic shuttling protein that is engaged in RNA metabolism and transcription. In mouse embryonic brain, our previous in situ hybridization study revealed that PQBP1 mRNA was dominantly expressed in the periventricular zone region where neural stem progenitor cells (NSPCs) are located. Because the expression patterns in NSPCs are related to the symptoms of intellectual disability and microcephaly in PQBP1 gene-mutated patients, we investigated the transcriptional regulation of PQBP1 by NSPC-specific transcription factors. We selected 132 genome sequences that matched the consensus sequence for the binding of Sox2 and POU transcription factors upstream and downstream of the mouse PQBP1 gene. We then screened the binding affinity of these sequences to Sox2-Pax6 or Sox2-Brn2 with gel mobility shift assays and found 18 genome sequences that interacted with the NSPC-specific transcription factors. Some of these sequences had cis-regulatory activities in Luciferase assays and in utero electroporation into NSPCs. Furthermore we found decreased levels of expression of PQBP1 protein in NSPCs of heterozygous Sox2-knockout mice in vivo by immunohistochemistry and western blot analysis. Collectively, these results indicated that Sox2 regulated the transcription of PQBP1 in NSPCs.