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1.
J Pharm Biomed Anal ; 185: 113244, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32193041

RESUMO

Currently, controllable linker cleavage at the target site will facilitate the clinical treatment of cancer. Dual-functional prodrugs in combination of carbohydrate as targeting group and pH-sensitive cleavable linker are desired in clinical development. Here, a qualified structure of N-phenylcarbamate-d-gluconhydroximo-1,5-lactam was employed and proved to be a potential candidate prodrug in the drug design. To proof this concept, the possible mechanism of Beckmann rearrangement and the degraded products were confirmed by HPLC and LC-MS under the acid condition mimic lysosome. Hence, the strategy of d-gluconhydroximo-1,5-lactam as a prodrug carrier fabricated with interested drugs will provide a great potential approach for chemotherapy.

2.
Int J Mol Sci ; 21(6)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204457

RESUMO

Nitrogen deficiency usually occurs along with aluminum toxicity in acidic soil, which is one of the major constraints for wheat production worldwide. In order to compare adaptive processes to N deficiency with different Al-tolerant wheat cultivars, we chose Atlas 66 and Scout 66 to comprehensively analyze the physiological responses to N deficiency, coupled with label-free mass spectrometry-based proteomics analysis. Results showed that both cultivars were comparable in most physiological indexes under N deficient conditions. However, the chlorophyll content in Scout 66 was higher than that of Atlas 66 under N deficiency. Further proteomic analysis identified 5592 and 5496 proteins in the leaves of Atlas 66 and Scout 66, respectively, of which 658 and 734 proteins were shown to significantly change in abundance upon N deficiency, respectively. The majority of the differentially expressed proteins were involved in cellular N compound metabolic process, photosynthesis, etc. Moreover, tetrapyrrole synthesis and sulfate assimilation were particularly enriched in Scout 66. Our findings provide evidence towards a better understanding of genotype-dependent responses under N deficiency which could help us to develop N efficient cultivars to various soil types.

3.
Cancer Immunol Res ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32122992

RESUMO

Metabolic reprogramming is critical for the polarization and function of tumor associated macrophages (TAMs) and hepatocarcinogenesis, but how this reprogramming occurs is unknown. Here, we showed that receptor-interacting protein kinase 3 (RIPK3), a central factor in necroptosis, is downregulated in hepatocellular carcinoma (HCC)-associated macrophages, which correlated with tumorigenesis and enhanced the accumulation and polarization of M2 TAM. Mechanistically, RIPK3 deficiency in TAMs reduced reactive oxygen species (ROS) and significantly inhibited caspase1-mediated cleavage of peroxisome proliferator-activated receptors (PPARs). These effects enabled PPAR activation and facilitated fatty acid metabolism, including fatty acid oxidation (FAO), and induced M2 polarization in the tumor microenvironment (TME). RIPK3 upregulation or FAO blockade reversed the immunosuppressive activity of TAMs and dampened HCC tumorigenesis. Our findings provide molecular basis for the regulation of RIPK3-mediated, lipid metabolic reprogramming of TAMs, thus highlighting a potential strategy for targeting the immunometabolism of HCC.

4.
Inorg Chem ; 59(5): 2969-2977, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32049497

RESUMO

X-ray radio-luminescence materials have potential application in radiotherapy (RT) and biomedical imaging. Considering that lutecium ions (Lu3+) with high atomic number (Z) have high X-ray attenuation coefficients, Ce3+-doped A-type Lu2SiO5@SiO2 (A-LSO:Ce3+@SiO2) core-shell nanospheres with size in the range of 200-250 nm were prepared through coprecipitation method. The growth mechanism of A-LSO:Ce3+@SiO2 core-shell nanospheres was investigated through determining the phase transition and morphology evolution by XRD, FT-IR, and TEM. The emission spectra, decay profile, and X-ray excited luminescence spectra (XEL) of the obtained samples were collected. The results show that a new type of lutecium silicate core-shell nanospheres A-LSO:Ce3+@SiO2 can be fabricated and exhibit efficient radio-luminescence under X-ray radiation, which has potential application in the diagnosis and therapy of cancer.

5.
Food Chem ; 316: 126378, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32066074

RESUMO

Rhodamine B (RhB), which is vividly colored, although illegal and potentially carcinogenic, has been reported widely as present in various foods, including chili powder, preserved plums, sausage and sweets, presenting a significant health risk. In this work, solid-phase extraction (SPE), coupled with direct fluorescence detection on the same extraction medium, is proposed for rapid onsite screening for RhB in food without sample pretreatment. Parameters that affected extraction of RhB were explored. The lowest amount of RhB, detected on glass, was 2 ng and the lowest detectable concentration in food samples was 0.5 mg/kg, as verified by HPLC. The analysis time was less than 5 min, including sampling. In addition, the recovery rate of this method was found to be triple of that from the cotton gauze reported in literature. The proposed method has promise as a rapid, onsite screening protocol for food safety.

6.
Geroscience ; 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32088828

RESUMO

Aging is a crucial cause of cognitive decline and a major risk factor for Alzheimer's disease (AD); however, AD's underlying molecular mechanisms remain unclear. Recently, tetraspanins have emerged as important modulators of synaptic function and memory. We demonstrate that the level of tetraspanin CD82 is upregulated in the brains of AD patients and middle-aged mice. In young adult mice, injection of AAV-CD82 to the hippocampus induced AD-like cognitive deficits and impairments in neuronal spine density. CD82 overexpression increased TRPM7 α-kinase cleavage via caspase-3 activation and induced Numb phosphorylation at Thr346 and Ser348 residues. CD82 overexpression promoted beta-amyloid peptide (Aß) secretion which could be reversed by Numb T346S348 mutants. Importantly, hippocampus-related memory functions were improved in Cd82-/- mice. Taken together, our findings provide the evidence that links the elevated CD82-TRPM7-Numb signaling to age-related cognitive impairment.

7.
Clin Exp Rheumatol ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32105594

RESUMO

Rheumatoid arthritis (RA) is the most common autoimmune disease, resulting in synovitis, joint pain and stiffness, even deformity and disability. The interactions between leukotriene B4 (LTB4) and neutrophils in RA progression have not been elucidated in detail. Our review focuses on the correlation of LTB4 and neutrophils in the development of RA especially in terms of infiltration and delayed life span of neutrophils. In this article, the roles of LTB4 in the anti-apoptosis of neutrophils will be detailed, which is achieved by suppressed pro-apoptotic Bax and up-regulated anti-apoptotic Mcl-1, and several key molecules, as well as signalling pathways and factors relevant to the enhancement of LTB4 production and functions. The mechanisms of LTB4-induced anti-apoptosis and infiltration of neutrophils provide more potential targets in the treatment of RA and recent therapeutic strategies are also discussed.

9.
Inorg Chem ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32073840

RESUMO

Most of polyoxometallates (POMs) templated silver nanoclusters recorded so far are polyoxomolybdates and polyoxotungstates; however, as congeneric polyoxochromates, they are rarely observed in silver nanoclusters. Herein, a high-nuclearity polyoxochromate, (CrIII4CrVI8O36)12-, is uncovered in a novel silver nanocluster (SD/Ag56a) as an anion template. The mixed-valent (CrIII4CrVI8O36)12- consists of four edge-sharing CrIIIO6 octahedra and eight CrVIO4 tetrahedra, which are fused together by sharing one or two vertexes. The (CrIII4CrVI8O36)12- is the by far highest nuclearity polyoxochromate and is trapped by outer Ag56 bracelet-like shell coprotected by quaternary ligands including iPrS-, NapCOO- (2-naphthalenecarboxylate), CF3COO-, and CH3CN. The antiferromagnetic property and solution behavior of SD/Ag56a are discussed in detail.

10.
Int Immunopharmacol ; 81: 106200, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32044656

RESUMO

BACKGROUNDS: Asthma is characterized as an inflammatory disorder in the respiratory system with increasing tendency. Most of the asthma patients suffered from the disease since childhood. Thus, developing novel therapeutic targets of pediatric asthma is necessary. Here, we conducted the present study to investigate the effects of IL-36RN (Interleukin-36 receptor antagonist), a newly identified anti-inflammatory factor, on asthma. METHODS: Sixty asthmatic children (30 moderate and 30 mild) were recruited. The levels of IL-36RN in peripheral blood mononuclear cells (PBMCs), serum and induced sputum (IS) samples from asthma patients and healthy controls (HCs) were measured by qPCR and ELISA. The anti-inflammatory effects of IL-36RN were determined in vitro and potential therapeutic effect on asthma was evaluated in the mouse model of asthma. RESULTS: The mRNA and protein levels of IL-36RN were significant down-regulated in asthmatics than HCs. The IL-36RN significantly suppressed the expression of pro-inflammatory factors in PBMCs and sputum cells from asthma patients in vitro. And delivering IL-36RN into the mouse model of asthma showed disease alleviation. Pathway analysis showed that the IL-36RN may alleviate airway inflammation in asthma through suppressing the activation of IL-36 pathway. CONCLUSION: Our data here indicated that IL-36RN may alleviate airway inflammation in asthma through suppressing the activation of IL-36 pathway.

12.
Nat Commun ; 11(1): 193, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924759

RESUMO

Phonons are considered to be universal quantum transducers due to their ability to couple to a wide variety of quantum systems. Among these systems, solid-state point defect spins are known for being long-lived optically accessible quantum memories. Recently, it has been shown that inversion-symmetric defects in diamond, such as the negatively charged silicon vacancy center (SiV), feature spin qubits that are highly susceptible to strain. Here, we leverage this strain response to achieve coherent and low-power acoustic control of a single SiV spin, and perform acoustically driven Ramsey interferometry of a single spin. Our results demonstrate an efficient method of spin control for these systems, offering a path towards strong spin-phonon coupling and phonon-mediated hybrid quantum systems.

13.
Adv Mater ; : e1905132, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31967707

RESUMO

Nanoelectronic devices based on ferroelectric domain walls (DWs), such as memories, transistors, and rectifiers, have been demonstrated in recent years. Practical high-speed electronics, on the other hand, usually demand operation frequencies in the gigahertz (GHz) regime, where the effect of dipolar oscillation is important. Herein, an unexpected giant GHz conductivity on the order of 103 S m-1 is observed in certain BiFeO3 DWs, which is about 100 000 times greater than the carrier-induced direct current (dc) conductivity of the same walls. Surprisingly, the nominal configuration of the DWs precludes the alternating current (ac) conduction under an excitation electric field perpendicular to the surface. Theoretical analysis shows that the inclined DWs are stressed asymmetrically near the film surface, whereas the vertical walls in a control sample are not. The resultant imbalanced polarization profile can then couple to the out-of-plane microwave fields and induce power dissipation, which is confirmed by the phase-field modeling. Since the contributions from mobile-carrier conduction and bound-charge oscillation to the ac conductivity are equivalent in a microwave circuit, the research on local structural dynamics may open a new avenue to implement DW nano-devices for radio-frequency applications.

14.
Comput Inform Nurs ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31929354

RESUMO

Preoperative care is a critical, yet complex, time-sensitive process. Optimization of workflow is challenging for many reasons, including a lack of standard workflow analysis methods. We sought to comprehensively characterize electronic health record-mediated preoperative nursing workflow. We employed a structured methodological framework to investigate and explain variations in the workflow. Video recording software captured 10 preoperative cases at Arizona and Florida regional referral centers. We compared the distribution of work for electronic health record tasks and off-screen tasks through quantitative analysis. Suboptimal patterns and reasons for variation were explored through qualitative analysis. Although both settings used the same electronic health record system, electronic health record tasks and off-screen tasks time distribution and patterns were notably different across two sites. Arizona nurses spent a longer time completing preoperative assessment. Electronic health record tasks occupied a higher proportion of time in Arizona, while off-screen tasks occupied a higher proportion in Florida. The contextual analysis helped to identify the variation associated with the documentation workload, preparation of the patient, and regional differences. These findings should seed hypotheses for future optimization efforts and research supporting standardization and harmonization of workflow across settings, post-electronic health record conversion.

15.
Phytopathology ; 110(2): 483-493, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31638486

RESUMO

Ustilaginoidea virens is an economically important biotrophic fungal pathogen that causes rice false smut worldwide. However, the regulatory mechanisms of smut ball formation under U. virens infection remain unclear. Here, we identified an important transcription factor, UvCom1, from this pathogen, which regulates the formation of smut balls on rice spikelets. UvCom1 contains two conserved internal repeat 1 (RPT) domains and is found only in fungi, with specific conservation in species of Basidiomycetes and Ascomycetes. UvCom1 protein N- or C-terminal fusion vectors both showed transactivation activity in yeast. Deletion of UvCom1 significantly affected the vegetative growth and conidiation of U. virens. UvCom1 negatively regulated the responses to oxidative, osmotic, and cell wall stresses. Remarkably, UvCom1 was found to be essential for the formation of rice smut balls, and UvCom1 deletion mutants lost the ability to stably utilize nutrients from the rice host. UvCom1 was also highly expressed at the mycelial expansion stage. Transcriptomic analysis and quantitative real-time PCR revealed that UvCom1 could affect the expression of genes significantly enriched in transmembrane transport. This study demonstrates that UvCom1 is a key transcription factor governing smut ball formation of this biotrophic fungus.


Assuntos
Hypocreales , Oryza , Interações Hospedeiro-Patógeno , Humanos , Doenças das Plantas
16.
CJEM ; 22(1): 86-94, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31659952

RESUMO

BACKGROUND: Resource allocation planning for emergency medical services (EMS) systems determines appropriate resources including what paramedic qualification and how rapidly to respond to patients for optimal outcomes. The British Columbia Emergency Health Services implemented a revised response plan in 2013. METHODS: A pre- and post-methodology was used to evaluate the effect of the resource allocation plan revision on 24-hour mortality. All adult cases with evaluable outcome data (obtained through linked provincial health administrative data) were analyzed. Multivariable logistic regression was used to adjust for variations in other significant associated factors. Interrupted time series analysis was used to estimate immediate changes in level or trend of outcome after the start of the revised resource allocation plan implementation, while simultaneously controlling for pre-existing trends. RESULTS: The derived cohort comprised 562,546 cases (April 2012-March 2015). When adjusted for age, sex, urban/metro region, season, day, hour, and dispatch determinant, the probability of dying within 24 hours of an EMS call was 7% lower in the post-resource allocation plan-revision cohort (OR = 0.936; 95% CI: 0.886-0.989; p = 0.018). A subgroup analysis of immediately life-threatening cases demonstrated similar effect (OR = 0.890; 95% CI: 0.808-0.981; p = 0.019). Using time series analysis, the descending changes in overall 24-hour mortality trend and the 24-hour mortality trend in immediately life-threatening cases, were both statistically significant (p < 0.001). CONCLUSION: Comprehensive, evidence-informed reconstruction of a provincial EMS resource allocation plan is feasible. Despite change in crew level response and resource allocation, there was significant decrease in 24-hour mortality in this pan-provincial population-based cohort.

17.
Plant Dis ; 104(2): 474-482, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31790642

RESUMO

Tea-oil tree (Camellia oleifera Abel) is an important edible oil woody plant with a planting area over 3,800,000 hectares in southern China. Anthracnose is a serious disease of tea-oil tree in southern China, causing severe economic losses and posing a huge threat to the Ca. oleifera industry. Based on recent developments in the classification of Colletotrichum species, the objective of this study was to identify Colletotrichum species associated with tea-oil tree and examine their pathogenicity on leaves and fruits of Ca. oleifera. In total, 232 isolates were obtained from Ca. oleifera leaves and fruits with anthracnose symptoms. These isolates were further characterized based on morphology and multilocus phylogenetic analyses using partial DNA sequences at the ribosomal internal transcribed spacer regions and ß-tubulin, actin, calmodulin, glyceraldehyde-3-phosphate dehydrogenase, and chitin synthase-encoding genes. The fungal isolates belong to five species: C. camelliae, C. fructicola, C. siamense, C. aenigma, and C. gloeosporioides. C. camelliae was the most predominant and widely distributed species on fruits of Ca. oleifera (91.4%), followed by C. fructicola (6.3%). However, C. fructicola was common and widely distributed species on leaves (75.9%), followed by C. camelliae (17.2%). There was no evidence of geographical specialization of the different species. Pathogenicity assays showed that all tested isolates, including 20 of C. camelliae, 11 of C. fructicola, four of C. siamense, two of C. aenigma, and one of C. gloeosporioides, were pathogenic to leaves and fruits of Ca. oleifera. Among the five species, C. camelliae species showed strong pathogenicity on both leaves and fruits of Ca. oleifera, and C. fructicola, C. siamense, C. aenigma, and C. gloeosporioides all showed weak pathogenicity on both leaves and fruits. No relationship was found between origin of isolates and their virulence. This is the first description of C. camelliae, C. fructicola, C. siamense, and C. gloeosporioides from the fruits of Ca. oleifera in China.


Assuntos
Camellia , Colletotrichum , China , DNA Fúngico , Filogenia , Doenças das Plantas
18.
Bioresour Technol ; 297: 122471, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31787511

RESUMO

Hereon, tobacco stalk was deconstructed by lyophilization, ball-milling, ultrasound-assisted alkali extraction, hydrothermal pretreatment (HTP), and alkali presoaking, respectively, followed by dilute alkali cooking to both improve its enzymatic digestibility and isolate the hemicellulosic streams. It was found that a maximum cellulose saccharification rate of 93.5% was achieved from the integrated substrate by ball-milling and dilute alkali cooking, which was 4.4-fold higher than that from the raw material. Interestingly, in this case, 76.9% of hemicelluloses were simultaneously recovered during the integrated treatment. Structural determination indicated that the hemicelluloses released from tobacco stalk by dilute alkali cooking were mixed polysaccharides, and the (1 â†’ 4)-linked ß-D-Xylp backbone branched with L-Araf units at O-2/O-3 and 4-O-Me-α-D-GlcpA units at O-2 of the xylose residues was the main structure. In comparison, ultrasound-assisted alkali extraction, ball-milling, and HTP favored the extraction of hemicelluloses with less branched structure and lower molecular weights in the following alkali cooking.


Assuntos
Celulose , Tabaco , Hidrólise , Peso Molecular , Polissacarídeos
19.
Eur J Med Chem ; 187: 111913, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31837501

RESUMO

In order to produce an effective and multi-targeted clinical drug that could prevent progressive neurodegeneration, a series of diosgenin carbamate derivatives were designed, synthesized and tested for their anti-inflammatory, antioxidant and anti-Aß activities. The results demonstrated that compound M15 was the most promising derivative against inflammatory (NO inhibition 22.7 ± 2.2%,10 µM) and cellular damage induced by H2O2 (SH-SY5Y cell protection = 75.3 ± 3.4%, 10 µM) or Aß (astrocytes protection = 70.2 ± 6.5%, 10 µM). Molecular docking studies revealed the strong binding affinity of M15 to the active site of nNOS, Aß42 and pro-inflammatory proteins. Western blot demonstrated that M15 decreased IL-1ß, IL-6 and TNF-α level, which may contribute to its anti-inflammatory effects. In addition, M15 maintained mitochondrial function as well as cell viability through reducing H2O2-induced ROS production. The results indicated that oral administration of M15 attenuated memory deficits and played a neuroprotective effect on subcutaneous (s.c.) D-gal aging mice. In summary, M15 could be considered as a potential multifunctional neuroprotective agent due to the effects of anti-inflammatory, antioxidant and anti-Aß activities.

20.
Int Immunopharmacol ; 79: 106057, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31877496

RESUMO

Glucocorticoids play a key role in treatment of inflammatory lung diseases including both airway and parenchymal lung diseases. RNA viral infections are major causes of chronic lung disease exacerbations and can determine glucocorticoid resistance. The antibacterial peptide LL-37, the only member of human cathelicidin family, also functions as antiviral-activity enhancer. However, whether it can alleviate the glucocorticoid resistance caused by RNA viruses remains unclear. Here, we used type I (BEAS-2B) and type II (A549) lung epithelial cells to assess the effect of LL-37 on dsRNA-induced glucocorticoid resistance. We verified that LL-37 and polyinosinic-polycytidylic acid (poly I:C, a mimic of viral dsRNA) interact and enter both cell lines. Co-treatment with LL-37 and poly I:C increased glucocorticoid-induced expression of promyelocytic leukemia zinc finger (PLZF), an anti-inflammatory protein, compared to poly I:C alone. Pre-treatment with LL-37 also restored transactivation of the glucocorticoid response element (GRE). Moreover, LL-37 rescued poly I:C-induced glucocorticoid resistance by increasing phosphorylation and nuclear translocation of glucocorticoid receptor. Importantly, LL-37 downregulated poly I:C-induced Erk and Akt signaling pathways in lung epithelial cells. Finally, we verified our data in vivo, showing that mCRAMP, the mouse LL-37 ortholog, can alleviate poly I:C-induced glucocorticoid insensitivity in a murine asthma model. In summary, this study showed that LL-37 restored glucocorticoid sensitivity impaired by dsRNA possibly by inhibiting Akt pathway, in addition to Erk1/2 pathway. These findings suggest LL-37 as a therapeutic agent for treatment of viral infections in inflammatory pulmonary diseases.

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