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1.
Talanta ; 206: 120172, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514828

RESUMO

Derivatization is frequently used in liquid chromatography-mass spectrometry (LC-MS) to improve the ionization characteristics of analytes, and facilitate their structural elucidation and quantification. However, the off-line derivatization process usually requires more analysis time. Therefore, the present work develops a novel LC/post-column derivatization (PCD)/MS (LC-PCD-MS) method for rapid detection of aldehydes in complex samples. The PCD method is based on a bisulfite addition reaction with aldehydes that can be easily conducted by mixing the LC elute with an (NH4)2SO3 solution via a tee. The resulting derivatives readily produce diagnostic HSO3- ions under collision induced dissociation (CID) in the negative ion mode of MS, even at an extremely low CID energy such as 1 eV, which can significantly improve the detection selectivity of aldehydes and reduce the occurrence of false positives. The limits of detection (LODs) of hexanal and heptanal were 3 nM and 2 nM, respectively. Moreover, good linearity in the concentration range of 0.01-1 µM for hexanal and heptanal was obtained with the determination coefficient (R2) being greater than 0.996 and the intra- and inter-day relative standard deviations (RSDs) were lower than 13.5% and 17.9%, respectively, indicating the acceptable reproducibility of the method. The LC-PCD-MS method was successfully applied for the rapid quantification of aldehydes in human urine and solvent extracts of traditional Chinese medicines (TCMs). Furthermore, a precursor ion scan strategy based on the diagnostic HSO3- ion was also developed and applied for the preliminary screening of aldehydes in complex samples of cinnamon and lemongrass.

2.
J Nanosci Nanotechnol ; 20(4): 2205-2213, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492229

RESUMO

In this study, three-dimensional (3D) networked porous polyvinyl alcohol/sodium alginate/graphene oxide (PVA/SA/GO) spherical composites were fabricated by the sol-gel method and employed as adsorbents for the adsorption of methylene blue (MB) in aqueous solution. The obtained samples were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermal property analysis, and nitrogen adsorption/desorption isotherms. Moreover, the adsorption properties for MB were investigated by batch experiments. The pseudo-first-order and pseudo-second-order equations were used to fit the adsorption kinetics data, and the Langmuir and Freundlich isothermal models were used to analyze the adsorption isothermals. The results showed that the spherical composites had 3D porous structures, and GO, PVA and SA were fused and linked together by self-assembly, physical intertwining, hydrogen bonding, and Ca2+ and boric acid crosslinking. The maximum adsorption capacity of the 3D porous PVA/SA/GO spherical composites for MB was 759.3 mg/g. The adsorption kinetics had a better agreement with the pseudo-secondorder equation than the pseudo-first-order equation, and the equilibrium data followed the Freundlich model.

4.
J Neuroinflammation ; 16(1): 206, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699098

RESUMO

BACKGROUND: Oligodendrocytes (OLs) death after spinal cord injury (SCI) contributes to demyelination, even leading to a permanent neurological deficit. Besides apoptosis, our previous study demonstrated that OLs underwent receptor-interacting serine-threonine kinase 3(RIP3)/mixed lineage kinase domain-like protein (MLKL)-mediated necroptosis. Considering that necroptosis is always accompanied with pro-inflammatory response and quercetin has long been used as anti-inflammatory agent, in the present study we investigated whether quercetin could inhibit necroptosis of OLs and suppress the M1 macrophages/microglia-mediated immune response after SCI as well as the possible mechanism. METHODS: In this study, we applied quercetin, an important flavonoid component of various herbs, to treat rats with SCI and rats injected with saline were employed as the control group. Locomotor functional recovery was evaluated using Basso-Beattie-Bresnahan (BBB) scoring and rump-height Index (RHI) assay. In vivo, the necroptosis, apoptosis, and regeneration of OLs were detected by immunohistochemistry, 5'-bromo-2'-deoxyuridine (BrdU) incorporation. The loss of myelin and axons after SCI were evaluated by Luxol fast blue (LFB) staining, immunohistochemistry, and electron microscopic study. The polarization of macrophages/microglia after SCI and the underlying mechanisms were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. In vitro, the ATP and reactive oxygen species (ROS) level examination, propidium iodide (PI) labeling, and Western blotting were used to analyze the necroptosis of cultured OLs, while the signaling pathways-mediated polarization of cultured macrophages/microglia was detected by qRT-PCR and Western blotting. RESULTS: We demonstrated that quercetin treatment improved functional recovery in rats after SCI. We then found that quercetin significantly reduced necroptosis of OLs after SCI without influencing apoptosis and regeneration of OLs. Meanwhile, myelin loss and axon loss were also significantly reduced in quercetin-treated rats, as compared to SCI + saline control. Further, we revealed that quercetin could suppress macrophages/microglia polarized to M1 phenotype through inhibition of STAT1 and NF-κB pathway in vivo and in vitro, which contributes to the decreased necroptosis of OLs. CONCLUSIONS: Quercetin treatment alleviated necroptosis of OLs partially by inhibiting M1 macrophages/microglia polarization after SCI. Our findings suggest that necroptosis of OLs may be a potential therapeutic target for clinical SCI.

5.
Sci Rep ; 9(1): 16338, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704975

RESUMO

r-BN nanoflakes were synthesized using KBH4 and NH4Cl as the main raw material in a high-purity nitrogen atmosphere. The effects of salt and salt-free conditions and heating temperature on the synthesis of BN were studied. The molten-salt method was used to synthesize BN at 650 °C, which was 250 °C lower than the BN synthesis method without salt. Furthermore, at 1000 °C the prepared flake-like BN crystals showed good crystallinity, uniform morphology, a particle diameter of 200-300 nm, and a thickness of 40-70 nm. Moreover, the specific surface area of BN was 294.26 m2/g. In addition, the BN synthesized at 1100 °C had a large elastic modulus value and good oxidation resistance.

6.
Chem Commun (Camb) ; 55(90): 13562-13565, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31650997

RESUMO

We fabricated a robust porous copper oxide nanobelt coating on copper foam by a facile oxidation-dehydration reaction, which is firstly reported as a low-cost pure copper-based urea oxidization catalyst. This catalyst has enriched electrochemically active surface area, abudant nanopores and micropores for gas and electrolyte diffusion, and high conductivity from copper foam for electron transfer and herein shows superior UOR performance, outperforming noble metal catalysts or most of the as-reported nonprecious metal UOR catalysts especially at high current density.

7.
Nature ; 574(7779): 575-580, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31645732

RESUMO

The Warburg effect, which originally described increased production of lactate in cancer, is associated with diverse cellular processes such as angiogenesis, hypoxia, polarization of macrophages and activation of T cells. This phenomenon is intimately linked to several diseases including neoplasia, sepsis and autoimmune diseases1,2. Lactate, which is converted from pyruvate in tumour cells, is widely known as an energy source and metabolic by-product. However, its non-metabolic functions in physiology and disease remain unknown. Here we show that lactate-derived lactylation of histone lysine residues serves as an epigenetic modification that directly stimulates gene transcription from chromatin. We identify 28 lactylation sites on core histones in human and mouse cells. Hypoxia and bacterial challenges induce the production of lactate by glycolysis, and this acts as a precursor that stimulates histone lactylation. Using M1 macrophages that have been exposed to bacteria as a model system, we show that histone lactylation has different temporal dynamics from acetylation. In the late phase of M1 macrophage polarization, increased histone lactylation induces homeostatic genes that are involved in wound healing, including Arg1. Collectively, our results suggest that an endogenous 'lactate clock' in bacterially challenged M1 macrophages turns on gene expression to promote homeostasis. Histone lactylation thus represents an opportunity to improve our understanding of the functions of lactate and its role in diverse pathophysiological conditions, including infection and cancer.

8.
Sci Transl Med ; 11(513)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597755

RESUMO

One million patients with congenital heart disease (CHD) live in the United States. They have a lifelong risk of developing heart failure. Current concepts do not sufficiently address mechanisms of heart failure development specifically for these patients. Here, analysis of heart tissue from an infant with tetralogy of Fallot with pulmonary stenosis (ToF/PS) labeled with isotope-tagged thymidine demonstrated that cardiomyocyte cytokinesis failure is increased in this common form of CHD. We used single-cell transcriptional profiling to discover that the underlying mechanism of cytokinesis failure is repression of the cytokinesis gene ECT2, downstream of ß-adrenergic receptors (ß-ARs). Inactivation of the ß-AR genes and administration of the ß-blocker propranolol increased cardiomyocyte division in neonatal mice, which increased the number of cardiomyocytes (endowment) and conferred benefit after myocardial infarction in adults. Propranolol enabled the division of ToF/PS cardiomyocytes in vitro. These results suggest that ß-blockers could be evaluated for increasing cardiomyocyte division in patients with ToF/PS and other types of CHD.

9.
J Nanobiotechnology ; 17(1): 103, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581948

RESUMO

BACKGROUND: Immunocompromised individuals and those with lung dysfunction readily acquire pulmonary bacterial infections, which may cause serious diseases and carry a heavy economic burden. Maintaining adequate antibiotic concentrations in the infected tissues is necessary to eradicate resident bacteria. To specifically deliver therapeutics to the infected pulmonary tissues and enable controlled release of payloads at the infection site, a ROS-responsive material, i.e. 4-(hydroxymethyl) phenylboronic acid pinacol ester-modified α-cyclodextrin (Oxi-αCD), was employed to encapsulate moxifloxacin (MXF), generating ROS-responsive MXF-containing nanoparticles (MXF/Oxi-αCD NPs). RESULTS: MXF/Oxi-αCD NPs were coated with DSPE-PEG and DSPE-PEG-folic acid, facilitating penetration of the sputum secreted by the infected lung and enabling the active targeting of macrophages in the inflammatory tissues. In vitro drug release experiments indicated that MXF release from Oxi-αCD NPs was accelerated in the presence of 0.5 mM H2O2. In vitro assay with Pseudomonas aeruginosa demonstrated that MXF/Oxi-αCD NPs exhibited higher antibacterial activity than MXF. In vitro cellular study also indicated that folic acid-modified MXF/Oxi-αCD NPs could be effectively internalized by bacteria-infected macrophages, thereby significantly eradicating resident bacteria in macrophages compared to non-targeted MXF/Oxi-αCD NPs. In a mouse model of pulmonary P. aeruginosa infection, folic acid-modified MXF/Oxi-αCD NPs showed better antibacterial efficacy than MXF and non-targeted MXF/Oxi-αCD NPs. Meanwhile, the survival time of mice was prolonged by treatment with targeting MXF/Oxi-αCD NPs. CONCLUSIONS: Our work provides a strategy to overcome the mucus barrier, control drug release, and improve the targeting capability of NPs for the treatment of pulmonary bacterial infections.

10.
Curr Biol ; 29(20): 3359-3369.e4, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31588002

RESUMO

Mounting evidence in animal models indicates potential for rejuvenation of cellular and cognitive functions in the aging brain. However, the ability to utilize this potential is predicated on identifying molecular targets that reverse the effects of aging in vulnerable regions of the brain, such as the hippocampus. The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration. While speculation exists about the role of O-GlcNAc in neurodegenerative conditions, such as Alzheimer's disease, its role in physiological brain aging remains largely unexplored. Here, we report that countering age-related decreased O-GlcNAc transferase (OGT) expression and O-GlcNAcylation ameliorates cognitive impairments in aged mice. Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging. Conversely, overexpressing OGT in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice. Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory. Our data identify O-GlcNAcylaton as a key molecular mediator promoting cognitive rejuvenation.

11.
Theranostics ; 9(22): 6568-6586, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588236

RESUMO

Targeted therapy via the patient-friendly oral route remains the holy grail of chemotherapy for cancer. Herein we report a yeast-derived platform for targeted oral delivery of cisplatin (CDDP) that is one of the most effective drugs for chemotherapy of various types of cancers. Methods: The optimal conditions were first established to fabricate yeast microcapsules (YCs) with desirable loading capability. Then, CDDP-derived precursor nanoparticles (PreCDDP) were prepared and packaged into YC to produce orally deliverable PreCDDP/YC. The physiochemical properties, in vitro drug release profiles, in vitro antitumor activity, oral targeting capability, in vivo pharmacokinetics, and in vivo efficacy of the YC-based biomimetic delivery system were examined. Results: YCs obtained under the optimized condition showed desirable loading efficiency for quantum dots that were used as a model nanocargo. In vitro experiments demonstrated rapid endocytosis and prolonged retention of YC in macrophages. By electrostatic force-mediated self-deposition, PreCDDP was efficiently loaded into YC. PreCDDP/YC showed potent cytotoxicity in different tumor cells, indicating that PreCDDP loaded in YC maintained its antitumor activity after intracellular release. As compared to CDDP and PreCDDP, orally administered PreCDDP/YC displayed significantly higher bioavailability. Post oral delivery, YC could accumulate in A549 human lung carcinoma xenografts in mice, achieving by monocyte/macrophage-mediated translocation via the lymphatic system. Through this targeting effect, orally administered PreCDDP/YC showed desirable efficacy in A549 xenograft-bearing mice, which was comparable to that of free CDDP administered by intravenous injection. Orally administered free CDDP, however, did not afford antitumor effects. Furthermore, oral treatment with PreCDDP/YC displayed better safety than free CDDP administered via the oral or intravenous route. Conclusions: This biomimetic approach can serve as an effective strategy to develop targeted oral chemotherapies based on CDDP or its derivatives.

12.
JCI Insight ; 4(22)2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31600171

RESUMO

To develop a systems biology model of fibrosis progression within the human lung we performed RNA sequencing and microRNA analysis on 95 samples obtained from 10 idiopathic pulmonary fibrosis (IPF) and 6 control lungs. Extent of fibrosis in each sample was assessed by microCT-measured alveolar surface density (ASD) and confirmed by histology. Regulatory gene expression networks were identified using linear mixed-effect models and dynamic regulatory events miner (DREM). Differential gene expression analysis identified a core set of genes increased or decreased before fibrosis was histologically evident that continued to change with advanced fibrosis. DREM generated a systems biology model (www.sb.cs.cmu.edu/IPFReg) that identified progressively divergent gene expression tracks with microRNAs and transcription factors that specifically regulate mild or advanced fibrosis. We confirmed model predictions by demonstrating that expression of POU2AF1, previously unassociated with lung fibrosis but proposed by the model as regulator, is increased in B lymphocytes in IPF lungs and that POU2AF1-knockout mice were protected from bleomycin-induced lung fibrosis. Our results reveal distinct regulation of gene expression changes in IPF tissue that remained structurally normal compared with moderate or advanced fibrosis and suggest distinct regulatory mechanisms for each stage.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31660716

RESUMO

High magnetization materials are in great demand for the fabrication of advanced multifunctional magnetic devices. Notwithstanding this demand, the development of new materials with these attributes has been relatively slow. In this work, we propose a new strategy to achieve high magnetic moments above room temperature. Our material engineering approach invoked the embedding of magnetic nanoclusters in an oxide matrix. By precisely controlling pulsed laser deposition parameters, Co nanoclusters are formed in a 5 at % Co-TiO2 film. The presence of these nanoclusters was confirmed using transmission electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray absorption fine structure. The film exhibits a very high saturation magnetization of 99 emu/cm3. Detailed studies using X-ray magnetic circular dichroism confirm that Co has an enhanced magnetic moment of 3.5 µB/atom, while the Ti and O also contribute to the magnetic moments. First-principles calculations supported our hypothesis that the metallic Co nanoclusters surrounded by a TiO2 matrix can exhibit both large spin and orbital moments. Moreover, a quantum confinement effect results in a high Curie temperature for the embedded Co nanoclusters. These findings reveal that 1-2 nm nanoclusters that are quantum confined can exhibit very large magnetic moments above room temperature, representing a promising advance for the design of new high magnetization materials.

14.
World Neurosurg ; 133: 185-187, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31606509

RESUMO

We report a rare case of bony diastematomyelia associated with intraspinal teratoma. The patient was surgically treated with bony diastematomyelia and intradural teratoma resection, followed by lumbar duroplasty, and posterior fusion from L2-L4 in order to maintain the spinal stability of the approached segments. Despite the risks, it was necessary to perform early surgical treatment because of rapid neurologic deterioration. The patient had a good postoperative outcome.

15.
World Neurosurg ; 133: 275-277, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31629145

RESUMO

We report a rare case of cervicothoracic intramedullary and extramedullary lipoma. Complete resection of the extramedullary lipoma and almost complete resection of the intramedullary lipoma were performed using a microscope, followed by posterior fusion and internal fixation from C4-T2 to maintain the stability of the cervicothoracic junction. Despite the high risk, it was still necessary to perform the decompression surgery and the surgical results were favorable.

16.
J Mater Chem B ; 7(44): 6879-6889, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31657432

RESUMO

Fluorescence imaging is a non-invasive imaging technique, which facilitates the visualization of sub-cellular components in cells with high sensitivity and selectivity. Up to now, only indocyanine green (ICG) has been approved as a diagnostic reagent for intravenous application. But the intrinsic disadvantage of ICG has spurred more research attention to exploit new fluorescent materials in imaging fields. In the last decade, many materials, including inorganic and organic materials, have been developed for fluorescence imaging. There are some reviews about fluorescence bioimaging. In this review, we will summarize and highlight the reported organic nanoparticles for noninvasive long-term bioimaging. According to the emitting mechanism, fluorescent nanoparticles obtained from fluorophores with aggregation-caused quenching and aggregation-induced emission features are discussed respectively. Finally, we come up with some key issues and challenges in the future and clinical translation.

17.
World Neurosurg ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31629147

RESUMO

BACKGROUND: Selection of approach for subaxial cervical fracture-dislocation (SCFD) is controversial. The questions of whether a posterior ligamentous structure (PLS) can be functionally healed in patients with SCFD and how long this healing process takes are critical in these patients. METHODS: This study retrospectively enrolled 394 patients with SCFD who underwent anterior decompression, reduction, and fusion between January 2002 and December 2017. The definition of functional healing of PLS was based on evaluations of clinical function and radiographic stability of PLS. RESULTS: Follow-up was available for 354 patients (89.8%). The PLS of 339 cases was functionally healed at the first follow-up interval without any posterior surgical intervention. No hardware failure or progressive cervical kyphosis was observed at further follow-up. At 12 months postoperatively, interbody fusion was satisfactory. However, the other 15 patients experienced nonhealing PLS at 8 weeks postoperatively and developed cervical deformity at further follow-up. Five patients refused revision surgery; the other 10 patients obtained solid fusion after revision surgeries. CONCLUSIONS: Among 354 patients with SCFD and treated by single anterior reduction and fixation, simple PLS injury without any bony instability at the posterior column of the cervical spine can be functionally healed in 95.8% of patients by external fixation for 8 weeks. Whether this finding is applicable to various types of SCFD should be verified in further prospective studies with larger samples.

19.
Org Lett ; 21(18): 7342-7345, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31478381

RESUMO

An efficient and convenient cobalt-catalyzed ortho-C(sp2)-H amidation of benzaldehydes employing dioxazolones as the aminating reagent has been developed. The key feature of this protocol is the use of green and economic earth-abundant metals cobalt as the catalyst with the p-chloroaniline as the transient directing group. Further application of our approach was demonstrated by the synthesis of C1r serine protease inhibitor 45 and elastase inhibitor 49.

20.
Pain Physician ; 22(5): E495-E503, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31561662

RESUMO

BACKGROUND: Percutaneous vertebroplasty (PVP) is now well accepted in the treatment of painful osteopathic vertebral compression fractures (OVCF), providing early pain relief and strengthening of the bone of the vertebrae. However, some patients still experienced severe back pain after PVP. OBJECTIVES: To analyze the possible reason for unsatisfactory back pain relief (UBPR) after PVP at early stage. STUDY DESIGN: Retrospective analysis. SETTING: Hong-Hui Hospital in Xi'an. METHODS: Between March 2013 and January 2015, a total of 1,316 patients with OVCF were treated by PVP at our Hospital. Demographics, clinical data, and surgical data were collected to analyze the factors associated with UBPR after PVP. RESULTS: Sixty cases complained of UBPR, and the prevalence was 4.6%. Univariate analyses showed that preoperative bone mineral density (BMD), number of fractures, cement distribution and volume injected per level, lumbodorsal fascia contusion, and depression were associated with UBPR after PVP (P < 0.001). Multivariate analysis revealed that preoperative BMD (odds ratio [OR], 3.577; P = 0.029), lumbodorsal fascia contusion (OR, 3.805; P = 0.002), number of fractures (OR, 3.440; P < 0.001), cement volume injected per level (OR, 0.079; P < 0.001), cement distribution (OR, 3.009; P = 0.013), and depression (OR, 3.426; P = 0.028) were independently associated with UBPR after PVP at the early postoperative stage. LIMITATIONS: A further prospective controlled study is needed to explore the association between the different degrees of the aforementioned factors and UBPR after PVP. CONCLUSIONS: Preoperative low BMD, lumbodorsal fascial injury, multiple segment PVP, insufficient cement injected volume, unsatisfactory cement distribution, and depression were strong risk factors associated with UBPR after PVP in patients with OVCF. KEY WORDS: Unsatisfactory back pain relief, residual back pain, percutaneous vertebroplasty.

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