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1.
Nat Commun ; 11(1): 2193, 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366851

RESUMO

Innate immunity to nucleic acids forms the backbone for anti-viral immunity and several inflammatory diseases. Upon sensing cytosolic viral RNA, retinoic acid-inducible gene-I-like receptors (RLRs) interact with the mitochondrial antiviral signaling protein (MAVS) and activate TANK-binding kinase 1 (TBK1) to induce type I interferon (IFN-I). TRAF3-interacting protein 3 (TRAF3IP3, T3JAM) is essential for T and B cell development. It is also well-expressed by myeloid cells, where its role is unknown. Here we report that TRAF3IP3 suppresses cytosolic poly(I:C), 5'ppp-dsRNA, and vesicular stomatitis virus (VSV) triggers IFN-I expression in overexpression systems and Traf3ip3-/- primary myeloid cells. The mechanism of action is through the interaction of TRAF3IP3 with endogenous TRAF3 and TBK1. This leads to the degradative K48 ubiquitination of TBK1 via its K372 residue in a DTX4-dependent fashion. Mice with myeloid-specific gene deletion of Traf3ip3 have increased RNA virus-triggered IFN-I production and reduced susceptibility to virus. These results identify a function of TRAF3IP3 in the regulation of the host response to cytosolic viral RNA in myeloid cells.

2.
J Environ Sci (China) ; 93: 129-136, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32446448

RESUMO

Chlorine dioxide (ClO2), an alternative disinfectant to chlorine, has a superior ability to inactivate microorganisms, in which protein damage has been considered as the main inactivation mechanism. However, the reactivity of ClO2 with amino acid residues in oligopeptides and proteins remains poorly investigated. In this research, we studied the reaction rate constants of ClO2 with tryptophan residues in five heptapeptides and four proteins using stopped-flow or competition kinetic method. Each heptapeptide and protein contain only one tryptophan residue and the reactivity of tryptophan residue with ClO2 was lower than that of free tryptophan (3.88 × 104 (mol/L)-1sec-1 at pH 7.0). The neighboring amino acid residues affected the reaction rates through promoting inter-peptide aggregation, changing electron density, shifting pKa values or inducing electron transfer via redox reactions. A single amino acid residue difference in oligopeptides can make the reaction rate constants differ by over 60% (e.g. 3.01 × 104 (mol/L)-1sec-1 for DDDWNDD and 1.85 × 104 (mol/L)-1sec-1 for DDDWDDD at pH 7.0 (D: aspartic acid, W: tryptophan, N: asparagine)). The reaction rates of tryptophan-containing oligopeptides were also highly pH-dependent with higher reactivity for deprotonated tryptophan than the neutral specie. Tryptophan residues in proteins spanned a 4-fold range reactivity toward ClO2 (i.e. 0.84 × 104 (mol/L)-1sec-1 for ribonuclease T1 and 3.21 × 104 (mol/L)-1sec-1 for melittin at pH 7.0) with accessibility to the oxidant as the determinating factor. The local environment surrounding the tryptophan residue in proteins can also accelerate the reaction rates by increasing the electron density of the indole ring of tryptophan or inhibit the reaction rates by inducing electron transfer reactions. The results are of significance in advancing understanding of ClO2 oxidative reactions with proteins and microbial inactivation mechanisms.

3.
Environ Int ; 141: 105776, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32402983

RESUMO

To improve air quality, China has been implementing strict clean air policies since 2013. These policies not only substantially improved air quality but may also modify the spatial distribution of air pollution, since urban emission sources were under stricter control and some were moved to rural regions with lower air quality improvement targets and lacking of monitoring. Here, we predicted satellite-based monthly PM2.5 concentrations during 2000-2018 at a 1-km resolution with complete spatial-temporal coverage to analyze changes in the spatial pattern of PM2.5 pollution in China. We found that the PM2.5 concentration in urban regions was higher than that in rural regions of the same city by an average of 3.3 µg/m3 during 2000-2018. This urban-rural disparity in PM2.5 concentration significantly increased from 2.5 µg/m3 in 2000 and peaked in 2007 of 3.8 µg/m3, then it sharply declined by 49% during 2013-2018 with the implementation of clean air policies. This shrinkage in the urban-rural PM2.5 gap was partly due to the 1.3 µg/m3 greater average decrease in the PM2.5 level in the urban region than in the rural region of the same town during 2013-2018 on average. We also observed that cities that started monitoring earlier experienced greater decreases in the urban-rural PM2.5 difference, and regions surrounding monitor showed significantly greater PM2.5 decrease than regions far away from monitor during 2013-2018. Additionally, clean air policies modified the relationship between PM2.5 concentrations and per capita gross domestic product (GDP), leading to a lower PM2.5 level with the same per capita GDP after 2013. Emissions in rural and suburban regions should be considered to further improve air quality in China.

5.
Radiother Oncol ; 148: 203-210, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32342870

RESUMO

The epidemic of Coronavirus Disease 2019 (COVID-19) first broke out in Wuhan in December 2019, and reached its peak in Wuhan in February 2020. It became a major public health challenge for China, and evolved into a global pandemic in March 2020. For radiation oncology departments, the COVID-19 pandemic presents a unique challenge for disease protection and prevention for both patients and staff, owing to the weakened immune systems of cancer patients and the need to deliver timely and uninterrupted radiotherapy. At the Hubei Cancer Hospital, the only hospital in Wuhan that specializes in oncology, we organized an emergency infection control team to lead special efforts to combat COVID-19 during this challenging time. Under its lead, the following measures were implemented in the radiation oncology department: the radiotherapy clinic was divided into different infection control zones with varying levels of protection; special staff and patient infection control training sessions were conducted and appropriate measures deployed; daily symptom testing criteria were implemented for patients undergoing treatment; special rotating schedules and infection control methods were implemented for various staff members such as medical physicists/dosimetrists and radiation therapists; modified radiotherapy workflow and specialized treatment area cleaning and disinfection policies and procedures were designed and executed; and special medical waste disposal methods were implemented. We began treating patients using this new COVID-19 radiotherapy treatment workflow and infection control measures on January 30, 2020. During more than one and a half months of uninterrupted radiation oncology clinical operation through the worst of the Wuhan outbreak, no known COVID-19 infection occurred at our radiotherapy center to our patients or employees. This report may provide valuable information for other radiation oncology departments during this unprecedented public health crisis.

6.
Med Phys ; 2020 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-32279337

RESUMO

PURPOSE/OBJECTIVES: To provide an order of magnitude estimate of the minimum dose rate ( R min ) required by pulsed ultra-high dose rate radiotherapy (FLASH RT) using dimensional analysis. MATERIALS/METHODS: In this study, we postulate that radiation-induced transient hypoxia inside normal tissue cells during FLASH RT results in better normal tissue sparing over conventional dose rate radiotherapy. We divide the process of cell irradiation by an ultra-short radiation pulse into three sequential phases: (a) The radiation pulse interacts with the normal tissue cells and produces radiation-induced species. (b) The radiation-induced species react with oxygen molecules and reduce the cell environmental oxygen concentration ( O 2 ). (c) Oxygen molecules, from nearest capillaries, diffuse slowly back into the resulted low O 2 regions. By balancing the radiation-induced oxygen depletion in phase II and diffusion-resulted O 2 replenishment in phase III, we can estimate the maximum allowed pulse repetition interval to produce a pulse-to-pulse superimposed O 2 reduction against the baseline O 2 . If we impose a threshold in radiosensitivity reduction to achieve clinically observable radiotherapy oxygen effect and combine the processes mentioned above, we could estimate the R min required for pulsed FLASH RT through dimensional analysis. RESULTS: The estimated R min required for pulsed FLASH RT is proportional to the product of the oxygen diffusion coefficient and O 2 inside the cell, and inversely proportional to the product of the square of the oxygen diffusion distance and the drop of intracellular O 2 per unit radiation dose. Under typical conditions, our estimation matches the order of magnitude with the dose rates observed in the recent FLASH RT experiments. CONCLUSIONS: The R min introduced in this paper can be useful when designing a FLASH RT system. Additionally, our analysis of the chemical and physical processes may provide some insights into the FLASH RT mechanism.

7.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(2): 215-220, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32275009

RESUMO

OBJECTIVE: To explore the effect of treatment opportunity and course of hyperbaric oxygen (HBO) on the curative effect of cerebral resuscitation patients after successful cardiopulmonary resuscitation (CPR). METHODS: Eighty-nine patients who underwent cerebral resuscitation after CPR admitted to the second department of the First Hospital of Jilin University from June 2015 to June 2019 were enrolled. All patients underwent conventional drug therapy after admission, and HBO therapy was added on the basis of conventional drug therapy at different intervention times, and all patients received at least 3 courses of HBO treatment. Glasgow coma scale (GCS) score and amplitude-integrated electroencephalography (aEEG) score on different treatment opportunity (i.e. intervention of HBO within 12 hours, 12-72 hours, 4-7 days, 8-21 days after successful CPR) and different course of HBO (i.e. 1, 2 and 3 courses of treatment) were recorded. Repeated measurement analysis of variance was used to assess whether the treatment opportunity or course of treatment affects the GCS score and aEEG score. Then, paired sample t test was used to further analyze the results of repeated measurement analysis of variance and evaluate the specific effect of treatment course or intervention time on the efficacy. RESULTS: A total of 89 patients were enrolled. 8, 20, 33 and 28 patients started HBO treatment at < 12 hours, 12-72 hours, 4-7 days and 8-21 days after successful CPR. (1) GCS score: repeated measurement analysis of variance (the Greenhouse-Geisser correction method was used) showed that the effect of course of HBO treatment on GCS score was statistically significant (F = 71.735, P = 0.000). The interaction between the duration of HBO treatment and the timing of intervention was not statistically significant (F = 0.455, P = 0.817). Paired sample t test showed that the means of GCS scores before HBO treatment and treatment 1, 2, 3 courses were 3.56, 4.80, 5.55 and 6.49 respectively, and the difference of pairwise pairing between different groups were statistically significant (all P < 0.01). (2) aEEG score: repeated measurement analysis of variance (the Greenhouse-Geisser correction method was used) showed that the effect of course of HBO treatment on aEEG score was statistically significant (F = 96.965, P = 0.000).The interaction between the duration of HBO treatment and the timing of intervention was not statistically significant (F = 1.735, P = 0.112). Paired sample t test showed that the means of aEEG scores before HBO treatment and treatment 1, 2, 3 courses were 1.71, 2.21, 2.52 and 3.03 respectively (all P < 0.01). CONCLUSIONS: The effect of HBO on cerebral resuscitation after CPR is obvious. The longer the course of HBO is, the more significant the effect of cerebral resuscitation is. Within 21 days after successful CPR, the treatment opportunity of HBO had no significant effect on the effect of cerebral resuscitation.

8.
Biomed Res Int ; 2020: 7131590, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32258140

RESUMO

Results: The VMAT plans showed superior to PTV dose conformity index (CI), homogeneity index (HI), protection of the ipsilateral lung, monitor units (MUs), and maximum dose (Dmax) to the contralateral breast compared with TSP and 9FIMRT plans. The TSP provided better protection for Dmean of the heart and left ventricle (p < 0.05). A dose for left anterior descending artery from the three techniques had no significant difference. Compared with the 9FIMRT plans, the V5Gy (%) and V10Gy (%) for the ipsilateral lung were significantly reduced with TSP and VMAT (p < 0.05). The V5Gy (%) and V10Gy (%) for the ipsilateral lung turned out to be similar between VMAT and TSP techniques. Conclusions: Our study indicates that VMAT should be a better choice of radiotherapy for left-sided breast cancer patients after radical mastectomy. If VMAT is unavailable, 9FIMRT can achieve better CI and HI values and be more MU-efficient compared with TSP; however, TSP can effectively reduce the low dose volume of the ipsilateral lungs and heart.

9.
Sci Rep ; 10(1): 4233, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144313

RESUMO

Cancers are characterized by reprogrammed glucose metabolisms to fuel cell growth and proliferation. Carbohydrate response element binding protein (ChREBP) is a glucose-mediated transcription factor that strongly regulates glycolytic and lipogenic pathways. It has been shown to associate with metabolic diseases, such as obesity, diabetes and non-alcoholic fatty liver diseases. However, how it associates with cancers has not been well understood. In this study, ChREBP expression was assessed by immunohistochemistry in colon tissue arrays containing normal colon tissue and cancer tissue at different clinical stages. Tissue mRNA levels of ChREBP were also measured in a cohort of colon cancer patients. We found that ChREBP mRNA and protein expression were significantly increased in colon cancer tissue compared to healthy colon (p < 0.001), and their expression was positively correlated to colon malignancy (for mRNA, p = 0.002; for protein p < 0.001). Expression of lipogenic genes (ELOVL6 and SCD1) in colon cancer was also positively associated with colon malignancy (for both genes, p < 0.001). In vitro, ChREBP knockdown with siRNA transfection inhibited cell proliferation and induced cell cycle arrest without changes in apoptosis in colon cancer cell lines (HT29, DLD1 and SW480). Glycolytic and lipogenic pathways were inhibited but the p53 pathway was activated after ChREBP knockdown. Taken together, ChREBP expression is associated with colon malignancy and it might contribute to cell proliferation via promoting anabolic pathways and inhibiting p53. In addition, ChREBP might represent a novel clinical useful biomarker to evaluate the malignancy of colon cancer.

10.
ACS Nano ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32208674

RESUMO

Doping lies at the heart of modern semiconductor technologies. Therefore, for two-dimensional (2D) semiconducting transition metal dichalcogenides (TMDs), the significance of controlled doping is no exception. Recent studies have indicated that, by substitutionally doping 2D TMDs with a judicious selection of dopants, their electrical, optical, magnetic, and catalytic properties can be effectively tuned, endowing them with great potential for various practical applications. Herein, and inspired by the sol-gel process, we report a liquid-phase precursor-assisted approach for in situ substitutional doping of monolayered TMDs and their in-plane heterostructures with tunable doping concentration. This highly reproducible route is based on the high-temperature chalcogenation of spin-coated aqueous solutions containing host and dopant precursors. The precursors are mixed homogeneously at the atomic level in the liquid phase prior to the synthesis process, thus allowing for an improved doping uniformity and controllability. We further demonstrate the incorporation of various transition metal atoms, such as iron (Fe), rhenium (Re), and vanadium (V), into the lattice of TMD monolayers to form Fe-doped WS2, Re-doped MoS2, and more complex material systems such as V-doped in-plane WxMo1-xS2-MoxW1-xS2 heterostructures, among others. We envisage that our developed approach is universal and could be extended to incorporate a variety of other elements into 2D TMDs and create in-plane heterointerfaces in a single step, which may enable applications such as electronics and spintronics at the 2D limit.

11.
J Immunol ; 204(8): 2177-2191, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32169848

RESUMO

Emerging evidence suggests comprehensive immune profiling represents a highly promising, yet insufficiently tapped approach to identify potentially prognostic signatures for periodontitis. In this report, we agnostically identified a periodontitis-associated inflammatory expression network with multiple biomarkers identified within gingival crevicular fluid samples from study participants by applying principal component analysis. We identified an IL-17-dominated trait that is associated with periodontal disease and is inversely modified by the level of IL-10. IL-10 mitigated chemokine CXCL5 and CXCL1 expressions in IL-17-stimulated peripheral blood monocytic cells and peripheral blood monocytic cell-derived macrophages. Il10-deficient mice presented more bone loss, which was associated with more Il17 and IL-17-mediated chemokine and cytokine expression at the transcriptional levels in comparison with control wild-type mice in both the Porphyromonas gingivalis-induced experimental murine periodontitis and ligature-induced alveolar bone-loss models. The dampening effect of IL-10 on the excessive signaling of IL-17 appeared to be mediated by innate immune cells populations rather than by gingival epithelial cells, which are the major cell target for IL-17 signaling. Additionally, elevated IL-17 response in Il10-deficient mice specifically elicited an M1-skewing macrophage phenotype in the gingiva that was associated with the advanced bone loss in the ligature model. In summary, IL-17 dominated an inflammatory network characteristic of periodontitis, and IL-10 dampens this excessive IL-17-mediated periodontitis trait.

12.
Angew Chem Int Ed Engl ; 59(16): 6428-6434, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32017320

RESUMO

Hierarchically porous metal-organic frameworks (HP-MOFs) are promising in various applications. Most reported HP-MOFs are prepared based on the generation of mesopores in microporous frameworks, and the formed mesopores are connected by microporous channels, limiting the accessibility of mesopores for bulky molecules. A hierarchical structure is formed by constructing microporous MOFs in uninterrupted mesoporous tunnels. Using the confined space in as-prepared mesoporous silica, highly dispersed metal precursors for MOFs are coated on the internal surface of mesoporous tunnels. Ligand vapor-induced crystallization is employed to enable quantitative formation of MOFs in situ, in which sublimated ligands diffuse into mesoporous tunnels and react with metal precursors. The obtained hierarchically porous composites exhibit record-high adsorption capacity for the bulky molecule trypsin. The thermal and storage stability of trypsin is improved upon immobilization on the composites.

13.
Microbiologyopen ; 9(4): e997, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32022464

RESUMO

Parsing the relative importance of environmental (recent disturbances) and spatial factors (historical processes) in determining community structure is a core issue in ecology. The Bohai Bay is a typical semi-enclosed bay located in the north of China, surrounding by the metropolitan area with anthropogenic disturbances made it a complex marine coastal system with pollution gradients, where the distributions and determinants of bacterioplankton communities remain unclear. In this study, we collected surface water samples from 19 sites across Bohai Bay at about 100 km scale to investigate the relative roles of local environments and regional spatial factors in shaping bacterioplankton community composition (BCC). The environmental parameters in the sampling region showed gradient change according to the geographic variation. Several abundant OTUs were significantly correlated with the pollution parameters in the studied area, and 16 OTUs of them showed distinct distribution pattern in different polluted regions with obvious geographic segmentation, which indicated the effects of pollution gradient and dispersal limitation on specific taxon. The BCCs did not show obviously clustering effect between different polluted regions, which indicated the complexity for explaining the BCC variation in the studied region. The partial Mantel test revealed stronger spatial effects on beta diversity than those of local environmental factors, which indicated that dispersal limitation accounted more for the beta diversity than environmental heterogeneity. Furthermore, variation partitioning analysis (VPA) conducted by combining the environmental variables, linear trends, and principal coordinates of the variables from neighbor matrices (PCNM) showed that it was the joint effects of environmental and spatial factors contributed to the explained variation of BCC in the studied area. Considering the special human geography characteristics of Bohai Bay, the unmeasured biotic/abiotic factors, stochastic factors, and anthropogenic disturbances may be responsible for the unexplained variation of the BCC.

14.
Plant Sci ; 293: 110438, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32081275

RESUMO

MicroRNAs (miRNAs) participate in plant development and defence through post-transcriptional regulation of the target genes. However, few miRNAs were reported to regulate cotton plant disease resistance. Here, we characterized the cotton miR164-NAC100 module in the later induction stage response of the plant to Verticillium dahliae infection. The results of GUS fusing reporter and transcript identity showed that ghr-miR164 can directly cleave the mRNA of GhNAC100 in the post-transcriptional process. The ghr-miR164 positively regulated the cotton plant resistance to V. dahliae according to analyses of its over-expression and knockdown. In link with results, the knockdown of GhNAC100 increased the plant resistance to V. dahliae. Based on LUC reporter, expression analyses and yeast one-hybrid (Y1H) assays, GhNAC100 bound to the CGTA-box of GhPR3 promoter and repressed its expression, negatively regulating plant disease resistance. These results showed that the ghr-miR164 and GhNAC100 module fine-tunes plant defence through the post-transcriptional regulation, which documented that miRNAs play important roles in plant resistance to vascular disease.

15.
Hepatology ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32083759

RESUMO

Glycogen storage disease type Ia (GSD Ia) is an inborn error of metabolism caused by defective glucose-6-phosphatase (G6PC) activity. GSD Ia patients exhibit severe hepatomegaly due to glycogen and triglyceride (TG) accumulation in the liver. We have previously shown that the activity of Carbohydrate Response Element Binding Protein (ChREBP), a key regulator of glycolysis and de novo lipogenesis, is increased in GSD Ia. In the current study we assessed the contribution of ChREBP to non-alcoholic fatty liver disease (NAFLD) development in a mouse model for hepatic GSD Ia. Liver-specific G6pc knockout (L-G6pc-/- ) mice were treated with AAV2/8-shChREBP to normalize hepatic ChREBP activity to levels observed in wildtype (L-G6pc+/+ ) mice receiving AAV8-shScramble. Hepatic ChREBP knockdown markedly increased liver weight and hepatocyte size in L-G6pc-/- mice. This was associated with hepatic accumulation of G6P, glycogen and lipids, while the expression of glycolytic and lipogenic genes was reduced. Enzyme activities, flux measurements, hepatic metabolite analysis and VLDL-TG secretion assays revealed that hepatic ChREBP knockdown reduced downstream glycolysis and de novo lipogenesis, but also strongly suppressed hepatic VLDL lipidation hence promoting the storage of 'old fat'. Interestingly, enhanced VLDL-TG secretion in shScramble-treated L-G6pc-/- mice associated with a ChREBP-dependent induction of the VLDL lipidation proteins MTTP and TM6SF2, the latter being confirmed by ChIP-PCR. CONCLUSION: Attenuation of hepatic ChREBP induction in GSD Ia liver aggravates hepatomegaly due to further accumulation of glycogen and lipids as a result of reduced glycolysis and suppressed VLDL-TG secretion. TM6SF2, critical for VLDL formation, was identified as a novel ChREBP target in mouse liver. Altogether, our data show that enhanced ChREBP activity limits NAFLD development in GSD Ia by balancing hepatic TG production and -secretion.

16.
Mater Sci Eng C Mater Biol Appl ; 108: 110189, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31924023

RESUMO

Particulate pollution in the air has strong links with increased morbidity of cardiopulmonary diseases. Iron is one of the major carcinogens in air pollution and can produce hydroxyl radical which induce oxidative stress, lead to cell damage and even to cancer. In this work, a novel nitronyl nitroxide radical NITPh(OMe)2 (2-(2,4-dimethoxyphenyl) -4,4,5,5- tetramethylimidazoline- 1- oxyl-3- oxide) was prepared and characterized by electron spin-resonance spectroscopy (ESR), X-ray crystal diffraction, Fourier transform infrared (IR), X-ray powder diffraction (XRD), elemental analysis, ultraviolet and visible spectra (UV-Vis), and the electronic transition processes was also calculated by time-dependent density functional theory (TDDFT) to analysis UV-Vis spectrum. In vitro cell model of oxidative damage was established by ferric ammonium citrate (FAC) overload, and NITPh(OMe)2 was studied as a free radical scavenger to protect peroxidation of A549 cells. Results showed that NITPh(OMe)2 could significantly alleviate the damage of A549 cells by iron overload in cell morphology, cell viability, cell proliferation and cell apoptosis. The apoptotic signaling pathway of A549 cells induced by FAC and the protection mechanism of NITPh(OMe)2 were all discussed through the expression of three relating proteins, Bcl-2, Bax and DDIT3. This work confirms that nitroxide radicals are effective antioxidants, and have potential application in clinical practice as therapeutic agents.

17.
J Chem Phys ; 152(2): 024710, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31941318

RESUMO

Pt-Pd bimetallic nanoparticles were synthesized on TiO2 support on the planar substrate as well as on high surface area SiO2 gel by atomic layer deposition to identify the catalytic performance improvement after the formation of Pt-Pd bimetallic nanoparticles by surface analysis techniques. From X-ray absorption near edge spectra of Pt-Pd bimetallic nanoparticles, d-orbital hybridization between Pt 5d and Pd 4d was observed, which is responsible for charge transfer from Pt to Pd. Moreover, it was found from the in situ grazing incidence X-ray absorption spectroscopy study that Pt-Pd nanoparticles have a Pd shell/Pt core structure with CO adsorption. Resonant photoemission spectroscopy on Pt-Pd bimetallic nanoparticles showed that Pd resonant intensity is enhanced compared to that of Pd monometallic nanoparticles because of d-orbital hybridization and electronic states broadening of Pt and Pd compared monometallic catalysts, which results in catalytic performance improvement.

18.
Bioorg Chem ; 95: 103564, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31927335

RESUMO

Xanthine oxidase (XO) is a critical target for the therapy of hyperuricemia and gout. In this study, a number of 3-[4-alkoxy-3-(1H-tetrazol-1-yl) phenyl]-1,2,4-oxadiazol-5(4H)-ones (3a-3w) were newly designed by a bioisosteric replacement and hybrid strategy with the hope of obtaining novel and effective nonpurine XO inhibitors. Subsequently, these compounds were synthesized through a three-step procedure, with good yields. In addition, the in vitro bovine XO inhibitions were measured by spectrophotometric determination of uric acid formation at 295 nm using allopurinol as a positive control. As a result, compound 3j was found to be the most potent XO inhibitor, with an IC50 value of 0.121 µM, which was approximately 63-fold more potent than allopurinol, and the analysis of the structure-activity relationships indicated that the hydrophobic group at 4'-position was essential for inhibitory potency. Additionally, the molecular modeling results showed that the 1,2,4-oxadiazol-5(4H)-one moiety binds to XO active site via various hydrogen bonds with Arg880 and Thr1010. Moreover, the compound 3j was demonstrated to be a mixed-type nonpurine XO inhibitor. Furthermore, the hypouricemic studies on a rat model, induced by potassium oxonate, demonstrated that serum uric acid levels could be effectually reduced by compound 3j at an oral dose of 15 mg/kg. Therefore, compound 3j could be a promising lead compound for the treatment of hyperuricemia and gout.

19.
Eur J Pharmacol ; 876: 172946, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31996320

RESUMO

Liver fibrosis is involved in the progression of most chronic liver diseases. Even though we have made a huge progress in order to understand the pathogenesis of liver fibrosis, however, there is still a lack of productive treatments. Being a traditional Chinese medicine, Platycodin D (PD), an oleanane kind of triterpenoid saponin has been put to extensive use for treating different kinds of illnesses that include not just anti-nociceptive, but also antiviral, anti-inflammatory, and anti-cancer for thousands of years. Nonetheless, there has been no clarification made for its effects on the progression of liver fibrosis. In this manner, we carried out in vitro studies for the purpose of investigating the anti-fibrosis impact of PD. Activation of hepatic stellate cells was evaluated by means of the detection of the proliferation of HSCs and the expression of specific proteins. We discovered the fact that PD had the potential of activating HSCs. Thereafter, we detected the apoptosis and autophagy of the HSCs; as the results suggested, PD induced apoptosis and autophagy of the HSCs. It augmented the expression level of apoptotic proteins that included Bax, Cytochrome C (cyto-c), cleaved caspase3 and cleaved caspase9, in addition to the autophagy relevant proteins, for instance, LC3II, beclin1, Atg5 and Atg9. Further research was carried out for the investigation of the underlying molecular mechanism, and discovered that PD promoted the phosphorylation of JNK and c-Jun. Treating the JNK inhibitor P600125 inhibited the effect of PD, confirming the impact of PD on the regulation of JNK/c-Jun pathway. Thus, we speculated that PD alleviates liver fibrosis and activation of hepatic stellate via promoting phosphorylation of JNK and c-Jun and further altering the autophagy along with apoptosis of HSCs.

20.
J Xray Sci Technol ; 28(1): 71-82, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31904001

RESUMO

BACKGROUND: Versa HD linear accelerators (linacs) are used for stereotactic radiosurgery treatment. However, the mechanical accuracy of such systems remains a concern. OBJECTIVE: The purpose of this study was to evaluate the accuracy of an Elekta Versa HD linac. METHODS: We performed measurements with a ball bearing phantom to calculate the rotational isocenter radii of the linac's gantry, collimator, and table, and determine the relative locations of those isocenters. We evaluated the accuracy of the cone-beam computed tomography (CBCT) guidance with a film-embedding head phantom and circular cone-collimated radiation beams. We also performed dosimetric simulations to study the effects of the linac mechanical uncertainties on non-coplanar cone arc delivery. RESULTS: The mechanical uncertainty of the linac gantry rotation was 0.78 mm in radius, whereas that of the collimator and the table was <0.1 mm and 0.33 mm, respectively. The axes of rotation of the collimator and the table were coinciding with and 0.13 mm away from the gantry isocenter, respectively. Experiments with test plans demonstrated the limited dosimetric consequences on the circular arc delivery given the aforementioned mechanical uncertainties. End-to-end measurements determined that the uncertainty of the CBCT guidance was≤1 mm in each direction with respect to the reference CT image. CONCLUSIONS: In arc delivery, the mechanical uncertainties associated with the gantry and the table do not require remarkable increases in geometric margins. If large enough, the residual setup errors following CBCT guidance will dominate the overall dosimetric consequence. Therefore, the Versa HD linac is a valid system for stereotactic radiosurgery using non-coplanar arc delivery.

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