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1.
Artigo em Inglês | MEDLINE | ID: mdl-31472072

RESUMO

Uterus torsion is an unusual and dangerous complication of pregnancy that has been rarely reported in medical literature. It has been defined as a rotation of the uterus by more than 45 degrees around its long axis. In such cases, perinatal mortality is high if early diagnosis is missed. The present case aims to increase awareness of uterus torsion as a differential diagnosis in obstetric emergency and highlights an early diagnosis and treatment of uterus torsion.

2.
Brain Struct Funct ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515678

RESUMO

A resting-state network centered at the precuneus has been recently proposed as a precuneus network (PCUN) or "parietal memory network". Due to its spatial adjacency and overlapping with the default mode network (DMN), it is still not consensus to consider PCUN and DMN separately. Whether considering PCUN and DMN as different networks is a critical question that influences our understanding of brain functions and impairments. Previous resting-state studies using multiple methodologies have demonstrated a robust separation of the two networks. However, since there is no gold standard in justifying the functional difference between the networks in resting-state, we still lack of biological evidence to directly support the separation of the two networks. This study compared the responses and functional couplings of PCUN and DMN when participants were watching a movie and examined how the continuity of the movie context modulated the response of the networks. We identified PCUN and DMN in resting-state fMRI of 48 healthy subjects. The networks' response to a context-rich video and its context-shuffled version was characterized using the variance of temporal fluctuations and functional connectivity metrics. The results showed that (1) scrambling the contextual information altered the fluctuation level of DMN and PCUN in reversed ways; (2) compared to DMN, the FC within PCUN showed significantly higher sensitivity to the contextual continuity; (3) PCUN exhibited a significantly stronger functional network connectivity with the primary visual regions than DMN. These findings provide evidence for the distinct functional roles of PCUN and DMN in processing context-rich information and call for separately considering the functions and impairments of these networks in resting-state studies.

3.
J Zhejiang Univ Sci B ; 20(10): 838-848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489803

RESUMO

Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/ß-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ ß-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3ß (GSK-3ß), and ß-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histomorphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3ß, and ß-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/ß-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.

4.
ACS Nano ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31502821

RESUMO

Developing advanced building materials with both excellent thermal insulating and optical properties to replace common glass (thermal conductivity of ∼1 W m-1 K-1) is highly desirable for energy-efficient applications. The recent development of transparent wood suggests a promising building material with many advantages, including high optical transmittance, tunable optical haze, and excellent thermal insulation. However, previous transparent wood materials generally have a high haze (typically greater than 40%), which is a major obstacle for their practical application in the replacement of glass. In this work, we fabricate a clear wood material with an optical transmittance as high as 90% and record-low haze of 10% using a delignification and polymer infiltration method. The significant removal of wood components results in a highly porous microstructure, much thinner wood cell walls, and large voids among the cellulose fibrils, which a polymer can easily enter, leading to the dense structure of the clear wood. The separated cellulose fibrils that result from the removal of the wood components dramatically weaken light scattering in the clear wood, which combined with the highly dense structure produces both high transmittance and extremely low haze. In addition, the clear wood exhibits an excellent thermal insulation property with a low thermal conductivity of 0.35 W m-1 K-1 (one-third of ordinary glass); thus, the application of clear wood can greatly improve the energy efficiency of buildings. The developed clear wood, combining excellent thermal insulating and optical properties, represents an attractive alternative to common glass toward energy-efficient buildings.

5.
Nanoscale ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31495853

RESUMO

Lithium-sulfur (Li-S) batteries are receiving intense interest owing to their high energy densities, cost effectiveness, and the natural abundance of sulfur. However, practical applications are still limited by rapid capacity decay caused by multielectron redox reactions and complex phase transformations. Here, we include commercially available titanium silicalite-1 (TS-1) in carbon/sulfur cathodes, to introduce strong chemical interactions between the lithium polysulfides (LiPS) and TS-1 in a working Li-S battery. In situ UV-visible spectroscopy together with other experimental results confirm that incorporation of TS-1 mediators enables direct conversion between S82- and S3*- radicals during the discharge process, which effectively promotes the kinetic behaviors of soluble LiPS and regulates uniform nucleation and growth of solid sulfide precipitates. These features give our TS-1 engineered sulfur cathode an ultrahigh initial capacity of 1459 mA h g-1 at 0.1C. Moreover, the system has an impressively high areal capacity (3.84 mA h cm-2) and long cycling stability with a high sulfur loading of 4.9 mg cm-2. This novel and low-cost fabrication procedure is readily scalable and provides a promising avenue for potential industrial applications.

6.
Heart Fail Rev ; 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31446536

RESUMO

A systematic review and meta-analysis were performed to analyse the differences in clinical profiles between takotsubo syndrome (TTS) and acute coronary syndrome (ACS) patients and to consolidate the evidence regarding the mortality predictors in TTS patients. Literature search of PubMed, EMBASE and the Cochrane Central Register was made, and 55 studies with a total of 66,653 TTS patients were included. Compared with ACS subjects, TTS subjects had significantly lower left ventricle ejection fraction (LVEF) values on admission; however, cardiovascular risks were fewer and the recovery LVEF was notably higher at both discharge and follow-up in TTS patients than in ACS patients (all P < 0.05). No significant differences were observed either in-hospital mortality or long-term mortality between the two groups (both P > 0.05). Acute renal failure and malignancies were independent predictors of all-cause in-hospital mortality in TTS patients (both P < 0.05). Male sex (HR = 0.565, 95% CI 0.253-0.876, P < 0.001, I2 = 0.00%), advanced age (HR = 0.054, 95% CI 0.041 to 0.067, P < 0.001, I2 = 0.00%), shock (HR = 1.382. 95% CI 1.050 to 1.714, P < 0.001, I2 = 0.00%) and initial LVEF < 35% (HR = 0.962, 95% CI 0.948 to 0.977, P < 0.001, I2 = 16.8%) were associated with an increased risk of long-time mortality in TTS patients. In conclusion, TTS has significantly different clinical characteristics than ACS. However, the in-hospital and long-term overall mortality rates are not trivial for TTS patients, and some presenting features (underlying diseases, male sex, advanced age, low LVEF and shock) were significantly associated with all-cause mortality.

7.
Inorg Chem ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31441651

RESUMO

Mo nitrogenase (N2ase) utilizes a two-component protein system, the catalytic MoFe and its electron-transfer partner FeP, to reduce atmospheric dinitrogen (N2) to ammonia (NH3). The FeMo cofactor contained in the MoFe protein serves as the catalytic center for this reaction and has long inspired model chemistry oriented toward activating N2. This field of chemistry has relied heavily on the detailed characterization of how Mo N2ase accomplishes this feat. Understanding the reaction mechanism of Mo N2ase itself has presented one of the most challenging problems in bioinorganic chemistry because of the ephemeral nature of its catalytic intermediates, which are difficult, if not impossible, to singly isolate. This is further exacerbated by the near necessity of FeP to reduce native MoFe, rendering most traditional means of selective reduction inept. We have now investigated the first fundamental intermediate of the MoFe catalytic cycle, E1, as prepared both by low-flux turnover and radiolytic cryoreduction, using a combination of Mo Kα high-energy-resolution fluorescence detection and Fe K-edge partial-fluorescence-yield X-ray absorption spectroscopy techniques. The results demonstrate that the formation of this state is the result of an Fe-centered reduction and that Mo remains redox-innocent. Furthermore, using Fe X-ray absorption and 57Fe Mössbauer spectroscopies, we correlate a previously reported unique species formed under cryoreducing conditions to the natively formed E1 state through annealing, demonstrating the viability of cryoreduction in studying the catalytic intermediates of MoFe.

8.
Phys Chem Chem Phys ; 21(34): 18559-18568, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31411206

RESUMO

The development of lithium-sulfur (Li-S) batteries is hindered by capacity loss due to lithium polysulfide (LIPS) dissolution into electrolyte solutions (known as the "shuttle effect"). MXenes with excellent electrical conductivity, high mechanical strength and multiple possible active two-dimensional surface terminations are attracting much attention as anchoring materials of Li-S batteries. Here, the S-functionalized V2C (V2CS2) is designed and demonstrated to have not only dynamic and thermal stability, but also metallic character. Compared with bare V2C and V2CO2, V2CS2 exhibits a moderate adsorption effect to suppress the "shuttle effect" and can preserve the structure of LIPSs without any decomposition. Moreover, the metallic properties of V2CS2 are maintained after LIPSs are adsorbed, which can promote the electrochemical activity during the charge and discharge process. The low energy barriers of Li2S decomposition and Li diffusion on the V2CS2 surface promise the phase transformation of LIPSs and assist the electrochemical process. Based on these remarkable results, we can conclude that V2CS2 is a promising anchoring material for lithium-sulfur batteries. Our work may also inspire the exploration of other MXenes and new surface functionalization methods to improve the performance of MXenes as host materials for high performance Li-S batteries.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1227-1231, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418384

RESUMO

OBJECTIVE: To investigate the genetic carrier rate of thalassemia and its gene mutation types as well as the distribution characteristics among the people in Lingshui Li autonomous county of Hainan province, so as to provide the basis for making the prevention programs of thalassemia in administrative departments. METHODS: Samples were collected from couples undergoing premarital and pregestational screenings, in which the positive ones in preliminary screening were further tested by genetic diagnoses and the genotypes were analyzed. RESULTS: The rate of thalassemia gene carriers was 19.41% (274/1412) of the couples of childbearing age in Lingshui Li autonomous County of Hainan Province. In these carriers,α-thalassemia accounted for 83.21%(228/274), ß-thalassemia for 8.03%(22/274), and both α-and ß-thalassemia gene accounted for 8.76% (28/274). CONCLUSION: The carrying rate of thalassemia gene in population Lingshui Li autonomous county of Hainan province is high, and its distribution has geographical characteristics,the major type is α-thalassemia. Blood screening and genetic diagnosis of thalassemia should be strengthened, and corresponding measures should be taken to reduce its gene frequency.


Assuntos
Talassemia alfa , Talassemia beta , China , Testes Genéticos , Genótipo , Heterozigoto , Humanos
10.
J Chem Inf Model ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31430151

RESUMO

Aggregation has been posing a great challenge in drug discovery. Current computational approaches aiming to filter out aggregated molecules based on their similarity to known aggregators, such as Aggregator Advisor, have low prediction accuracy, and therefore development of reliable in silico models to detect aggregators is highly desirable. In this study, we built a data set consisting of 12 119 aggregators and 24 172 drugs or drug candidates and then developed a group of classification models based on the combination of two ensemble learning approaches and five types of molecular representations. The best model yielded an accuracy of 0.950 and an area under the curve (AUC) value of 0.987 for the training set, and an accuracy of 0.937 and an AUC of 0.976 for the test set. The best model also gave reliable predictions to the external validation set with 5681 aggregators since 80% of molecules were predicted to be aggregators with a prediction probability higher than 0.9. More importantly, we explored the relationship between colloidal aggregation and molecular features, and generalized a set of simple rules to detect aggregators. Molecular features, such as log D, the number of hydroxyl groups, the number of aromatic carbons attached to a hydrogen atom, and the number of sulfur atoms in aromatic heterocycles, would be helpful to distinguish aggregators from nonaggregators. A comparison with numerous existing druglikeness and aggregation filtering rules and models used in virtual screening verified the high reliability of the model and rules proposed in this study. We also used the model to screen several curated chemical databases, and almost 20% of molecules in the evaluated databases were predicted as aggregators, highlighting the potential high risk of aggregation in screening. Finally, we developed an online Web server of ChemAGG ( http://admet.scbdd.com/ChemAGG/index ), which offers a freely available tool to detect aggregators.

11.
Autophagy ; : 1-14, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31462126

RESUMO

Long noncoding RNAs (lncRNAs) are proved to be critical regulators in numerous cellular processes. However, the potential involvement of lncRNAs in macroautophagy/autophagy is largely unknown. Autophagy is a highly regulated cellular degradation system, and its dysregulation is involved in many human diseases, including cancers. Here, we show that the lncRNA ZNNT1 is induced by PP242 and MTORC1 selective inhibitor rapamycin in uveal melanoma (UM) cells. Overexpression of ZNNT1 promotes autophagy by upregulating ATG12 expression, whereas knockdown of ZNNT1 attenuates PP242-induced autophagy. Overexpression of ZNNT1 inhibits tumorigenesis and the migration of UM cells, and knockdown of ATG12 can partially rescue the ZNNT1-induced inhibition of UM tumorigenesis. In summary, our study reveals that ZNNT1 acts as a potential tumor suppressor in UM by inducing autophagy. Abbreviations: ADCD: autophagy dependent cell death; ANXA2R: annexin A2 receptor; ATG12: autophagy- related 12; ATG5: autophagy -related 5; ceRNA: competing endogenous RNAs; CQ: chloroquine; iTRAQ: isobaric tags for relative and absolute quantitation; lncRNA: long noncoding RNA; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; MTORC2: MTOR cmplex 2; PP242: Torkinib; RACE: rapid amplification of cDNA ends; SQSTM1/p62: sequestosome 1; UM: uveal melanoma.

12.
Sci Rep ; 9(1): 11148, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366951

RESUMO

To determine the feasibility of deformation analysis in the right ventricle (RV) using cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) in type 2 diabetes mellitus (T2DM) patients. We enrolled 104 T2DM patients, including 14 with impaired right ventricular ejection fraction (RVEF) and 90 with preserved RVEF, and 26 healthy controls in this prospective study. CMR was used to determine RV feature-tracking parameters. RV strain parameters were compared among the controls, patients with preserved and reduced RVEF. Binary logistic regression was used to predict RV dysfunction. Receiver operating characteristic analysis was used to assess the diagnostic accuracy. The agreement was tested by Bland-Altman analysis. Compared with controls, longitudinal and circumferential global peak strain (PS) and PS at mid-ventricular, apical slices were significantly decreased in T2DM patients with or without reduced RVEF (p < 0.05). Within the T2DM patients, the global longitudinal PS (GLPS) and the longitudinal PS at mid-ventricular segments were significantly reduced in the reduced RVEF group than in preserved RVEF groups (p < 0.05). GLPS was an independent predictor of RV dysfunction (odds ratio: 1.246, 95% CI: 1.037-1.496; p = 0.019). The GLPS demonstrated greater diagnostic accuracy (area under curve: 0.716) to predict RV dysfunction. On Bland-Altman analysis, global circumferential PS and GLPS had the best intra- and inter-observer agreement, respectively. In T2DM patients, CMR-FT could quantify RV deformation and identify subclinical RV dysfunction in those with normal RVEF. Further, RV strain parameters are potential predictors for RV dysfunction in T2DM patients.

13.
Aging Cell ; : e13024, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31389140

RESUMO

Prolonging the ovarian lifespan is attractive and challenging. An optimal clinical strategy must be safe, long-acting, simple, and economical. Allotransplantation of brown adipose tissue (BAT), which is most abundant and robust in infants, has been utilized to treat various mouse models of human disease. Could we use BAT to prolong the ovarian lifespan of aging mice? Could we try BAT xenotransplantation to alleviate the clinical need for allogeneic BAT due to the lack of voluntary infant donors? In the current study, we found that a single rat-to-mouse (RTM) BAT xenotransplantation did not cause systemic immune rejection but did significantly increase the fertility of mice and was effective for more than 5 months (equivalent to 10 years in humans). Next, we did a series of analysis including follicle counting; AMH level; estrous cycle; mTOR activity; GDF9, BMP15, LHR, Sirt1, and Cyp19a level; ROS and annexin V level; IL6 and adiponectin level; biochemical blood indices; body temperature; transcriptome; and DNA methylation studies. From these, we proposed that rat BAT xenotransplantation rescued multiple indices indicative of follicle and oocyte quality; rat BAT also improved the metabolism and general health of the aging mice; and transcriptional and epigenetic (DNA methylation) improvement in F0 mice could benefit F1 mice; and multiple KEGG pathways and GO classified biological processes the differentially expressed genes (DEGs) or differentially methylated regions (DMRs) involved were identical between F0 and F1. This study could be a helpful reference for clinical BAT xenotransplantation from close human relatives to the woman.

14.
Sci Rep ; 9(1): 11656, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31406129

RESUMO

To evaluate the value of dual-source computed tomography (DSCT) compared with transthoracic echocardiography (TTE) in assessing intracardiac and extracardiac anomalies in patients with coarctation of aorta (CoA) and interrupted aortic arch (IAA). Seventy-five patients (63 with CoA and 12 with IAA) who received preoperative DSCT and TTE were retrospectively studied. Intracardiac and extracardiac anomalies were recorded and compared by DSCT and TTE, in reference to surgical or cardiac catheterization findings. A total of 155 associated anomalies were finally found. Collateral circulation (56, 74.70%), patent ductus arteriosus (PDA; 41, 54.67%) were the most common anomalies. PDA, aortopulmonary window, and collateral circulation were more frequently present in patients with IAA than those with CoA (100% vs. 46.03%, 16.67% vs. 0%, and 100% vs. 69.84%, respectively, all p < 0.05). DSCT was superior to TTE in assessing associated extracardiac-vascular anomalies (sensitivity: 100% vs. 39.81%; specificity: 100% vs. 100%; positive predictive value: 100% vs. 100%; negative predictive value: 100% vs. 76.06%). Extracardiac-vascular anomalies, including collateral circulation and PDA, were the most common anomalies in patients with IAA and CoA. Compared with TTE, DSCT is more reliable in providing an overall preoperative evaluation of morphological features and extracardiac anomalies for surgical planning.

15.
Inorg Chem ; 58(16): 10625-10628, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31390189

RESUMO

Carbenes are known as donor molecules to form with chloroalane adducts, which enhances their aerobic and thermal stabilities. In contrast, the insertion products (cAACH)AlCl2(cAAC) (1) and (cAACH)AlHCl(THF) (2; THF = tetrahydrofuran) have been formed in the reaction of a cyclic alkyl(amino)carbene (cAAC:) with HAlCl2, and H2AlCl, respectively. PhC(NtBu)2Li as the precursor for the reaction with HAlCl2 in a molar ratio of 2:1 can easily form compound [PhC(NtBu)2]2AlH (3) with five-coordinate aluminum. The new products have been studied by spectroscopic methods and single-crystal X-ray diffraction.

16.
Molecules ; 24(16)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31408988

RESUMO

As a folk medicine of the Jingpo minority in Yunnan province, the venom of Vespa magnifica has been commonly used for the treatment of rheumatoid arthritis. Quality standardization of the wasp venom is a necessary step for its pharmaceutical research and development. To control the quality of the wasp venom, a method based on high-performance liquid chromatography (HPLC) was developed for chemical fingerprint analysis. In the chromatographic fingerprinting, chemometrics procedures, including similarity analysis (SA), hierarchical clustering analysis (HCA), and principal component analysis (PCA), were applied to classify 134 batches (S1-S134) of wasp venom from different origins. The HPLC fingerprint method displayed good precision (Relative standard deviation, RSD < 0.27%), stability (in 16 h, RSD < 0.34%), and repeatability (RSD < 1.00%). Simultaneously, four compounds (VMS1, VMS2, VMS3, and VMS4) in the wasp venom were purified and identified. VMS1 was 5-hydroxytryptamine, and the other compounds were three peptides that were sequenced as follows: Gly-Arg-Pro-Hyp-Gly-Phe-Ser-Pro-Phe-Arg-Ile-Asp-NH2 (VMS2), Ile-Asn-Leu-Lys-Ala-Ile-Ala-Ala-Leu-Ala-Lys-Lys-Leu-Leu-NH2 (VMS3), and Phe-Leu-Pro-Ile-Ile-Gly-Lys-Leu-Leu-Ser-Gly-Leu-Leu-NH2 (VMS4). The quantifications for these components were 110.2 mg/g, 26.9 mg/g, 216.3 mg/g, and 58.0 mg/g, respectively. The results of this work indicated that the combination of the chemical fingerprint and quantitative analysis offers a reasonable way to evaluate the quality of wasp venom.

17.
Cancer Immunol Res ; 7(9): 1511-1522, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31383650

RESUMO

Ligand-receptor complexes play a central role in mediating a range of processes in immunology and cancer biology. The ability to directly quantify the fraction of receptors occupied by a ligand in a given biospecimen, as opposed to assessing the concentration of ligand and receptor separately, could provide an additional and valuable clinical and research tool for assessing whether receptors are occupied by a ligand. To address this need, a biomarker platform was developed to quantify the fraction of receptors occupied by a ligand using pairs of RNA aptamers, where one aptamer binds preferentially to the unoccupied receptor and the other to the ligand-receptor complex. Bound aptamer was quantified using RT-qPCR colorimetric probes specific for each aptamer. The binding ratio of aptamer correlated with the fraction of receptors occupied by a ligand. This assay, termed as LIRECAP (LIgand-REceptor Complex-binding APtamer) assay, was used to determine the fraction of soluble CD25 occupied by IL2 in the serum from subjects with B-cell lymphoma. No correlation was found between the type of lymphoma and total soluble CD25 or IL2 independently. In contrast, the fraction of soluble CD25 occupied by IL2 was significantly higher in follicular lymphoma patient serum compared with diffuse large B-cell lymphoma patient serum. We conclude that this technology has the potential to serve as a high-throughput biomarker platform to quantify the fraction of receptors occupied by a ligand.

18.
NMR Biomed ; : e4158, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31393647

RESUMO

We developed a novel manganese (Mn2+ ) chelate for magnetic resonance imaging (MRI) assessment of myocardial viability in acute and chronic myocardial infarct (MI) models, and compared it with Gadolinium-based delay enhancement MRI (Gd3+ -DEMRI) and histology. MI was induced in 14 rabbits by permanent occlusion of the left circumflex coronary artery. Gd3+ -DEMRI and Mn2+ chelate-based delayed enhancement MRI (Mn2+ chelate-DEMRI) were performed at 7 days (acute MI, n = 8) or 8 weeks (chronic MI, n = 6) after surgery with sequential injection of 0.15 mmol/kg Gd3+ and Mn2+ chelate. The biodistribution of Mn2+ in tissues and blood was measured at 1.5 and 24 h. Blood pressure, heart rate (HR), left ventricular (LV) function, and infarct fraction (IF) were analyzed, and IF was compared with the histology. The Mn2+ chelate group maintained a stable hemodynamic status during experiment. For acute and chronic MI, all rabbits survived without significant differences in HR or LV function before and after injection of Mn2+ chelate or Gd3+ (p > 0.05). Mn2+ chelate mainly accumulated in the kidney, liver, spleen, and heart at 1.5 h, with low tissue uptake and urine residue at 24 h after injection. In the acute MI group, there was no significant difference in IF between Mn2+ chelate-DEMRI and histology (22.92 ± 2.21% vs. 21.79 ± 2.25%, respectively, p = 0.87), while Gd3+ -DEMRI overestimated IF, as compared with histology (24.54 ± 1.73%, p = 0.04). In the chronic MI group, there was no significant difference in IF between the Mn2+ chelate-DEMRI, Gd3+ -DEMRI, and histology (29.50 ± 11.39%, 29.95 ± 9.40%, and 29.00 ± 10.44%, respectively, p > 0.05), and all three were well correlated (r = 0.92-0.96, p < 0.01). We conclude that the use of Mn2+ chelate-DEMRI is reliable for MI visualization and identifies acute MI more accurately than Gd3+ -DEMRI.

19.
Insect Biochem Mol Biol ; 113: 103212, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31425853

RESUMO

Larvae of the leaf beetle Phaedon cochleariae synthesize the iridoid chysomelidial via the mevalonate pathway to repel predators. The normal terpenoid biosynthesis is integrated into the dedicated defensive pathway by the ω-hydroxylation of geraniol to (2E,6E)-2,6-dimethylocta-2,6-diene-1,8-diol (ω-OH-geraniol). Here we identify and characterize the P450 monooxygenase CYP6BH5 as the geraniol hydroxylase using integrated transcriptomics, proteomics and RNA interference (RNAi). In the fat body, 73 cytochrome P450s were identified, and CYP6BH5 was among those that were expressed specifically in fat body. Double stranded RNA mediated knockdown of CYP6BH5 led to a significant reduction of ω-hydroxygeraniol glucoside in the hemolymph and, later, of the chrysomelidial in the defensive secretion. Heterologously expressed CYP6BH5 converted geraniol to ω-OH-geraniol. In addition to geraniol, CYP6BH5 also catalyzes hydroxylation of other monoterpenols, such as nerol and citronellol to the corresponding α,ω-dihydroxy compounds.

20.
Bioorg Med Chem Lett ; 29(16): 2178-2181, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31257084

RESUMO

Here we reported the development of a novel immuno-SPECT tracer, namely 99mTc-JS001, to non-invasively image PD-1 expression in mice. The JS001 antibody was directly labeled by the most widely used SPECT radionuclide 99mTc with a radiochemical yield of 90%, and the specific activity was ≤74 GBq/mmol. After the radiolabeling, 99mTc-JS001 exhibited a similar immnuoaffinity to PD-1 in vitro. 99mTc-conjugated JS001 maintained intact in 5% HSA system for 24 h. S180 sarcoma xenograft-bearing Kunming mice and BGC823 gastric cancer orthotopic tumor model were built. Bio-distribution and/or immuno-SPECT studies with 99mTc-JS001 showed the antibody maintained in the blood, liver, kidneys and tumors at 1.5 ID%/g, 1.4 ID%/g, 2.0 ID%/g and 0.5 ID%/g, respectively. Also, there was a higher uptake in the BGC823 orthotopic tumor than that in the adjunct stomach. These results demonstrated that 99mTc-JS001 might have capacity to monitor the PD-1 expression in vivo, which might facilitate the anti-PD-1 antibodies treatment in preclinical models.

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