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1.
Biomaterials ; 226: 119541, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31634652

RESUMO

Arthritis, an inflammatory condition that causes pain and cartilage destruction in joints, affects over 54.4 million people in the US alone. Here, for the first time, we demonstrated the emerging role of neural EGFL like 1 (NELL-1) in arthritis pathogenesis by showing that Nell-1-haploinsufficient (Nell-1+/6R) mice had accelerated and aggravated osteoarthritis (OA) progression with elevated inflammatory markers in both spontaneous primary OA and chemical-induced secondary OA models. In the chemical-induced OA model, intra-articular injection of interleukin (IL)1ß induced more severe inflammation and cartilage degradation in the knee joints of Nell-1+/6R mice than in wildtype animals. Mechanistically, in addition to its pro-chondrogenic potency, NELL-1 also effectively suppressed the expression of inflammatory cytokines and their downstream cartilage catabolic enzymes by upregulating runt-related transcription factor (RUNX)1 in mouse and human articular cartilage chondrocytes. Notably, NELL-1 significantly reduced IL1ß-stimulated inflammation and damage to articular cartilage in vivo. In particular, NELL-1 administration markedly reduced the symptoms of antalgic gait observed in IL1ß-challenged Nell-1+/6R mice. Therefore, NELL-1 is a promising pro-chondrogenic, anti-inflammatory dual-functional disease-modifying osteoarthritis drug (DMOAD) candidate for preventing and suppressing arthritis-related cartilage damage.

2.
Chemosphere ; 239: 124737, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31493755

RESUMO

Antibiotics are of concern due to their prevalent detection in aquatic environment. Sulfate radical based advanced oxidation processes show a great capacity to degrade antibiotics, but the mechanisms are still unclear. In this work, the degradation mechanism of fluoroquinolones (FQs), a major group of antibiotics, in UV/Fe2+/PMS was deeply investigated. The degradation process was in-situ and real-time monitoring by illumination-assisted droplet spray ionization mass spectrometry. A series of reactive intermediates were captured, and further characterized by high-resolution mass spectrometry (HRMS) and tandem MS. About 50 different transformation products have been identified for ciprofloxacin and norfloxacin. More than 15 products were the first time reported. Taking into consideration of the sequential formation and intensity change of intermediates, the feasible and complete transformation pathways of FQs were proposed. Compared with the photolysis process, the defluorination of FQs was not observed in this system. This work provided abundant information of FQs degradation by persulfate advanced oxidation processes (AOPs) and meanwhile demonstrated the importance of HRMS and on-line MS in mechanism research of AOPs.

3.
Nano Lett ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769995

RESUMO

The reconfigurability of the electrical heterostructure featured with external variables, such as temperature, voltage and strain, enabled electronic/optical phase transition in functional layers has great potential for future photonics, computing and adaptive circuits. VO2 has been regarded as an archetypal phase transition building block with superior metal-insulator transition characteristics. However, reconfigurable VO2-based heterostructure and the associated devices are rare due to the fundamental challenge in integrating high quality VO2 in technologically important substrates. In this report, for the first time, we show the remote epitaxy of VO2 and the demonstration of a vertical diode device in graphene/epitaxial VO2/single crystalline BN/graphite structure with VO2 as a reconfigurable phase change material and hexagonal boron nitride (h-BN) as an insulating layer. By diffraction and electrical transport studies, we show that the remote epitaxial VO2 films exhibits higher structural and electrical quality than direct epitaxial one. By high resolution transmission electron microscopy and Cs-corrected scanning transmission electron microscopy we show that graphene buffered substrate leads to less strained VO2 film than bare substrate. In the reconfigurable diode, we find that the Fermi level change and spectral weight shift along with metal-insulator transition of VO2 could modify the transport characteristics. The work suggests the feasibility of developing single crystalline VO2-based reconfigurable heterostructure with arbitrary substrates and sheds light on designing novel adaptive photonics and electrical devices and circuits.

4.
Neurotherapeutics ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667754

RESUMO

In 2011, a hexanucleotide repeat expansion in the first intron of the C9orf72 gene was identified as the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The proposed disease mechanisms include loss of C9orf72 function and gain of toxicity from the bidirectionally transcribed repeat-containing RNAs. Over the last few years, substantial progress has been made to determine the contribution of loss and gain of function in disease pathogenesis. The extensive body of molecular, cellular, animal, and human neuropathological studies is conflicted, but the predominance of evidence favors gain of toxicity as the main pathogenic mechanism for C9orf72 repeat expansions. Alterations in several downstream cellular functions, such as nucleocytoplasmic transport and autophagy, are implicated. Exciting progress has also been made in therapy development targeting this mutation, such as by antisense oligonucleotide therapies targeting sense transcripts and small molecules targeting nucleocytoplasmic transport, and these are now in phase 1 clinical trials.

5.
Nanotechnology ; 31(8): 085202, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675743

RESUMO

Nanoparticle materials have many potential applications in the area of electronics and optoelectronics due to their unique and versatile properties. In particular, lead sulfide nanoparticles (PbS NPs) have shown excellent ultrafast photonics and can be applied to communication systems because of their low bandgap, high thermal damage threshold and stability. The wavelength division multiplexor (WDM) technique is vital to fiber optical communication, which allows the transmission of many different-wavelength signals in one fiber cable. However, PbS NPs for multi-wavelength pulse generation has not been reported until now. In this work, PbS NPs have been investigated and successfully applied in an Er-doped fiber laser as a saturable absorber (SA) to generate a dual-wavelength short pulse for the first time. A picosecond-level ultrashort pulse at center wavelengths of 1545 and 1585 nm can be achieved simultaneously or respectively. It is worth mentioning that the two wavelengths are separated up to 40 nm, which can significantly expand the optical communication capacity. The result suggests that PbS NPs as smart nonlinear optical components have wide applications in optical communications, short-pulse lasers, and even high-performance photodectors.

6.
Autoimmun Rev ; : 102422, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31733369

RESUMO

Paraneoplastic autoimmune disorders (PAD) represent a group of autoimmune diseases associated with neoplasms. As a consequence of a remote autoimmunity-mediated effect, PAD are found in multiple organs or tissues, including the skin, blood and nervous system. Compared with non-paraneoplastic autoimmune diseases, PAD have different aetiologies, pathologies, disease symptoms and treatment responses. There are two main origins of autoimmunity in PAD: neoplasm-mediated dysregulated homeostasis in immune cells/organs and in autoantigens. Pathologically, PAD are mediated predominantly by either autoantibodies or autoreactive T-cells. In the past decade, significant progress has been achieved in increasing our understanding of the aetiology and pathology of PAD. In this review article, we aim to provide a comprehensive overview of the recent advances in this field.

7.
Food Chem ; : 125824, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31732245

RESUMO

In this work, a home-made portable dielectric barrier discharge-atomic emission spectrometer (DBD-AES) was explored to the determination of heavy metal in foodstuffs. A rapid and simple method was developed for Cd determination in rice based on this instrument. Rice was pretreated with diluted acid dissolution without complex operations and apparatus. The detection time by DBD-AES is about 3 min and the total analysis time for rice sample is within 11 min. The effects of some key experiment parameters were investigated. The limit of detection was 11.9 µg kg-1 for Cd in rice, much lower than the maximum allowable level established by EC (200 µg kg-1). The practical performance of this method was demonstrated by analyzing real and CRM rice samples. With the portability of DBD-AES, the method is suitable for rapid and in-field analysis of Cd in rice. It will be a useful tool for the routine analysis of rice.

8.
Nanoscale ; 11(42): 20199-20205, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31617546

RESUMO

Various in-plane anisotropic properties are observed for the layered semiconducting transition metal dichalcogenide (TMD), rhenium disulfide (ReS2) due to its reduced symmetry. The understanding of these unique anisotropic behaviors in ReS2 will promote its applications in optoelectronics. In this work, angle-resolved polarized optical contrast spectroscopy has proved to be an efficient, quantitative, and non-destructive method to probe the optical anisotropy in ReS2 flakes with different thicknesses. The contrast value of ReS2 displays the maximum intensity when the polarization of incident light is along the Re-Re chain direction, while the contrast shows the minimum value when the polarization is perpendicular. An empirical equation for in-plane anisotropic refractive index calculation has been proposed and the angle-resolved polarized optical contrasts of 1-3-layer ReS2 are calculated. The calculation results show good agreements with the experimental observations. This indicates that the proposed equation is indeed appropriate for the quantitative understanding of birefringence and dichroism in ReS2 flakes. Our results not only shed light on the identification of crystal axes in anisotropic materials by using angle-resolved polarized contrast spectroscopy, but also provide quantitative information about anisotropy in anisotropic materials such as ReS2.

9.
J Hazard Mater ; : 121319, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31607581

RESUMO

Cadmium (Cd), a naturally occurring heavy metal, is toxic to animals and plants. Minimization of Cd in rice grain is important to human health since rice is the main source of Cd intake for human populations feeding on it as staple food. Glutamate (Glu) is reportedly involved in plant abiotic stress responses, whereas the underlying molecular mechanism remains poorly understood. In this study, we showed that supplement of Glu, but not glutamine, significantly alleviated Cd toxicity in hydroponically grown rice plants. Cd accumulation was reduced by 44.1% and 65.6% in root and shoot of rice plants respectively, after Glu supplementation (3 mM). Glu supplement restored chlorophyll biosynthesis and significantly ameliorated Cd-induced oxidative stress with reduced levels of H2O2, 1O2, MDA, and increased activities of major anti-oxidant enzymes, catalase, peroxidase and glutathione S-transferase. Levels of stress-associated free amino acids proline, arginine and γ-aminobutyric acid were also reduced after Glu supplement. We further demonstrated that Glu supplement suppressed the Cd-induced expression of metal transporter genes OsNramp1, OsNramp5, OsIRT1, OsIRT2, OsHMA2 and OsHMA3 in roots of Cd-treated plants. Taken together, our results suggest that Glu supplement could alleviate Cd toxicity in rice by suppressing Cd uptake and translocation.

10.
Nat Prod Res ; : 1-6, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31617784

RESUMO

A new diketopiperazine cyclo-(L-Phe-N-ethyl-L-Glu) (1), along with two known diketopiperazines cyclo-(L-Pro-L-Leu) (2) and cyclo-(L-Pro-L-Phe) (3) were isolated from the cultures of an endophytic fungus Aspergillus aculeatus F027. The structures of these compounds were elucidated based on spectroscopic data. The configurations of these compounds were determined by advanced Marfey's analysis. Antibacterial activity of the diketopiperazines against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were also evaluated.

12.
Ecotoxicol Environ Saf ; 185: 109722, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31577991

RESUMO

Methylmercury (MeHg) is a toxicant that mainly originates from in situ microbial methylation of inorganic mercury (Hg) in the environment and poses a severe health risk to the public. However, the characteristics of the Hg-methylating microbial community and its relationship with MeHg production in various environments remain to be understood. In the present study, Hg-methylating microbial communities and genes (hgcAB cluster) in the sediments of the Pearl River (PR), Pearl River Estuary (PRE) and South China Sea (SCS) were investigated at a large spatial scale using high-throughput sequencing-based approaches. The results showed that sulfur-reducing bacteria (SRB) and iron-reducing bacteria (IRB) were consistently the dominant microbial strains responsible for the methylation of inorganic Hg in all three regions investigated. The abundance and diversity of Hg-methylating communities and genes were both found to be higher in the PR sediments compared to that in the PRE and SCS sediments, and in good agreement with the spatial distribution of MeHg. Furthermore, a significant correlation was observed between the MeHg concentration and the abundance of both hgcA and hgcB genes in the sediments of the PR, PRE and SCS regions. Overall, the present study suggested that there was the presence of a close link between MeHg and Hg-methylating communities or genes in the ambient aquatic environment, which could be used to reflect the potential of in situ MeHg production.

13.
Analyst ; 144(23): 6898-6904, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31638109

RESUMO

The accurate determination of disulfide bonds for protein identification is in high demand. In this study, a simple electrochemical-mass spectrometry (EC-MS) method that possesses advantages of real-time information, simultaneous disulfide bond electroreduction and tagging was developed. In this EC-MS, an ITO glass corner functions as a counter electrode and spray system, and allows the direct sampling of the droplet-scale reacting solution in real-time. The application of this method was successfully demonstrated by electrochemical reduction of oxidized glutathione (GSSG) with one disulfide bond as well as insulin with multiple disulfide bonds. The preferred electroreduction of intermolecular-bonded disulfides for insulin has been observed and the intramolecular bond was not favored. Moreover, simultaneously tagging the formed thiol residues from electroreduction of GSSG using electrogenerated intermediates such as dopamine orthoquinone (DQ) and benzoquinone (Q) was performed. A proof-of-concept was also demonstrated with a large molecule, ß-lactoglobulin A. The relationship between signal strength and operating parameters was also studied. This method successfully detected the reduction reaction of the disulfide bond in the polypeptide and protein. The detection limit (S/N ≥ 3) is 0.398 µg mL-1. These results suggest that this EC-MS platform can count cysteine moieties in proteins using a single drop of sample and in real-time and is promising for protein identification experiments.

14.
J Biol Chem ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659118

RESUMO

Tumor cells adapt to nutrient-limiting environments by inducing gene expression that ensures adequate nutrients to sustain metabolic demands. For example, during amino acid limitations, ATF4 in the amino acid response induces expression of asparagine synthetase (ASNS), which provides for asparagine biosynthesis. Acute lymphoblastic leukemia (ALL) cells are sensitive to asparagine depletion, and administration of the asparagine-depletion enzyme L-asparaginase is an important therapy option. ASNS expression can counterbalance L-asparaginase treatment by mitigating nutrient stress. Therefore understanding the mechanisms regulating ASNS expression is important to define the adaptive processes underlying tumor progression and treatment. Here, we show that DNA hypermethylation at the ASNS promoter prevents its transcriptional expression following asparagine depletion. Insufficient expression of ASNS leads to asparagine deficiency, which facilitates an ATF4-independent induction of C/EBP homologous protein (CHOP) that triggers apoptosis. We conclude that chromatin accessibility is critical for ATF4 activity at the ASNS promoter, which can switch ALL cells from an ATF4-dependent adaptive response to ATF4-independent apoptosis during asparagine depletion.  This work may also help explain why ALL cells are most sensitive to L-asparaginase treatment when compared to other cancers.

15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(9): 957-967, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31645483

RESUMO

OBJECTIVE: To investigate association between the single nucleotide polymorphisms of endothelial protein C receptor (EPCR) gene and the risk of Kawasaki disease (KD) in a Chinese children.
 Methods: A total of 103 KD patients including 23 patients with coronary artery lesions (CAL) and 158 controls were recruited. Seven tagging SNPs (rs6088738, rs2069940, rs2069945, rs2069952, rs867186, rs9574, and rs1415774) of EPCR gene were selected for TaqMan allelic discrimination assay. The plasma soluble EPCR (sEPCR) levels of 53 KD and 52 healthy children were detected by ELISA.
 Results: We found a significant association between rs2069952, rs9574 or rs1415774 and higher probability for the occurrence of KD but not CAL formation. Interestingly, males with these 3 SNPs and rs2069945 SNPs bore a much greater risk of KD than females. The level of plasma sEPCR in children with KD didnot predict the formation of CAL. However, the allele G of rs867186 in EPCR was associated with the increased level of plasma sEPCR in KD patients.
 Conclusion: The SNPs of EPCR are associated with KD susceptibility in a Chinese Han children.


Assuntos
Receptor de Proteína C Endotelial/genética , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Grupo com Ancestrais do Continente Asiático , Criança , China/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo de Nucleotídeo Único
16.
Cell Death Dis ; 10(10): 748, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582729

RESUMO

Mucosal epithelial apoptosis with non-specific inflammation is an essential pathological characteristic in portal hypertensive gastropathy (PHG). However, whether a coordinated crosstalk between myeloid cells and epithelial cells involved in PHG remains unclear. IL-6, which is induced in the mucosa of PHG patients and mice, promotes FasL production via enhancing NF-κBp65 activation in myeloid cells, while blockage of IL-6 signaling by Tocilizumab or deletion of NF-κBp65 in myeloid cells attenuates the inflammatory response and Fas/FasL-mediated epithelial apoptosis in PHG. IL-6-driven FasL from myeloid cells combines with epithelial Fas receptor to encourage NF-κBp65/PUMA-mediated epithelial apoptosis in PHG, and inhibition of NF-κBp65 or knockout of PUMA alleviates Fas/FasL-mediated epithelial apoptosis in PHG. These results indicate that IL-6 drives FasL generation via NF-κBp65 in myeloid cells to promote Fas/NF-κBp65/PUMA-mediated epithelial apoptosis in PHG, and this coordinated crosstalk between myeloid cells and epithelial cells may provide a potential therapeutic target for PHG.

17.
Cardiovasc Diabetol ; 18(1): 131, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594547

RESUMO

BACKGROUND: Accumulating evidence has shown that type 2 diabetes (T2D) and coronary artery disease (CAD) may stem from a 'common soil'. The aim of our study was to examine the association between genetic predisposition to T2D and the risk of severe CAD among patients with acute coronary syndromes (ACS) undergoing angiography. METHODS: The current case-control study included 1414 ACS patients with at least one major epicardial vessel stenosis > 50% enrolled in the ACS Genetic Study. The severity of CAD was quantified by the number of coronary arteries involved. Genetic risk score (GRS) was calculated using 41 common variants that robustly associated with increased risk of T2D in East Asians. Logistic regression models were used to estimate the association between GRS and the severity of CAD. RESULTS: In the age-, sex- and BMI-adjusted model, each additional risk allele was associated with a 6% increased risk of multi-vessel disease (OR = 1.06, 95% CI 1.02-1.09). The OR was 1.43 (95% CI 1.08-1.89) for the risk of severe CAD when comparing the extreme tertiles of T2D-GRS. The association was not reduced after further adjustment for conventional cardiovascular risk factors. Additional adjustment for T2D status in our regression model attenuated the association by approximately one quarter. In subgroup analysis, the strengths of the associations between GRS and the severity of CAD were broadly similar in terms of baseline demographic information and disease characteristics. CONCLUSIONS: Our data indicated that genetic predisposition to T2D is associated with elevated risk of severe CAD. This association revealed a possible causal relationship and is partially mediated through diabetic status.

18.
BMC Cancer ; 19(1): 937, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601173

RESUMO

BACKGROUND: We aimed to investigate the correlation of Circ-SMARCA5 with disease severity and prognosis in multiple myeloma (MM), and its underlying mechanisms in regulating cell proliferation and apoptosis. METHODS: Bone marrow samples from 105 MM patients and 36 healthy controls were collected for Circ-SMARCA5 expression measurement. And the correlation of Circ-SMARCA5 expression with patients' characteristics and survival was determined. In vitro, the effect of Circ-SMARCA5 on MM cell proliferation and apoptosis was evaluated by altering Circ-SMARCA5 expression through transfection. Rescue experiments and luciferase assay were further performed to explore the mechanism of Circ-SMARCA5 as well as its potential target miR-767-5p in regulating MM cell activity. RESULTS: Circ-AMARCA5 was downregulated in MM and presented a good value in distinguishing MM patients from controls and it was also negatively correlated with Beta-2-microglobulin (ß2-MG) level and International Staging System (ISS) stage. Additionally, Circ-SMARCA5 high expression was associated with higher CR as well as better PFS and OS. As for in vitro experiments, Circ-SMARCA5 expression was lower in MM cell lines compared with normal cells, and Circ-SMARCA5 overexpression inhibited cell proliferation but promoted cell apoptosis in RPMI8226 cells. Rescue experiments disclosed that the effect of Circ-SMARCA5 on cell activity was attenuated by miR-767-5p, and luciferase reporter assay revealed direct binding between Circ-SMARCA5 and miR-767-5p. CONCLUSIONS: Circ-SMARCA5 is downregulated and correlated with lower ß2-MG level and ISS stage as well as better prognosis in MM patients, and it inhibits proliferation but promotes apoptosis of MM cells via directly sponging miR-767-5p.

19.
Pest Manag Sci ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489764

RESUMO

BACKGROUND: Interactions between herbivorous insects and entomoviruses may depend on host plant, perhaps mediated through changes in herbivore innate immunity. RESULTS: Caterpillars (Spodoptera exigua) fed Glycine max had high viral loads and low melanization rates together with low melanization enzyme [PO, DDC, TH] activities and gene expressions. Caterpillars fed Ipomoea aquatica had low viral loads and high melanization, gene activities and gene expressions while those fed Brassica oleracea or artificial diet had intermediate levels of each. Melanization rates were negatively correlated with viral loads and positively correlated with activity and expression of each of the three enzymes. Some diet effects on enzymes were constitutive because the same diets led to low (G. max) or high (I. aquatica) melanization related gene activities and expressions without infection. CONCLUSION: Diet influences the interactions between insect herbivores and viruses by shaping the innate immune response both at the onset of infection and afterwards as viral loads accumulate over a period of days. In addition, diets that lead to low viral loads are associated with high activities and gene expressions of a variety of melanization related enzymes suggesting a common causative mechanism. © 2019 Society of Chemical Industry.

20.
Int Urol Nephrol ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31552576

RESUMO

BACKGROUND: Laparoscopic partial nephrectomy (LPN) with segmental renal artery clamping has become an important method to minimize the warm ischemia of the kidney during the surgery. In the present study, we adopted a new model of calculating surgery-related kidney volume loss (SKVL), which was derived from the imaging technology to predict the outcomes of LPN with segmental renal artery clamping. METHODS: A total of 111 consecutive patients underwent LPN with available pre- and post-operation computed tomography (CT) scanning data were retrospectively analyzed. The SKVL was calculated using the parameter derived from the CT scan. The correlation between the SKVL and the perioperative outcomes as well as the renal function loss was estimated by the logistic regression analyses. RESULTS: The mean SKVL was 8.99 cm3; kidney volume and tumor volume was 147.48 cm3 and 25.87 cm3, respectively. The SKVL was associated with maximum diameter of tumor (P = 0.001), tumor volume (P < 0.001), intraoperative blood loss (P < 0.001), and the warm ischemia time (P = 0.004), but not associated with the surgery time (P = 0.322) and complications (P = 0.638). Besides, the SKVL was associated with the renal function loss after LPN (P < 0.001). The multivariable logistic regression showed that SKVL was an independent parameter to predict the renal function loss. CONCLUSIONS: SKVL is a pre-operation parameter derived from the imaging data, which may be used to predict the perioperative outcomes and renal function loss of patients undergoing LPN.

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