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1.
Artigo em Inglês | MEDLINE | ID: mdl-33138353

RESUMO

Conjugated polymers synthesized through random terpolymerization have recently attracted great research interest due to the synergetic effect on the polymer's crystallinity and semiconducting properties. Several studies have demonstrated the efficacy of random terpolymerization in fine-tuning the aggregation behavior and optoelectronic property of conjugated polymers to yield enhanced device performance. However, as an influential approach of backbone engineering, its efficacy in modulating the mobility-stretchability property of high-performance conjugated polymers has not been fuller explored to date. Herein, a series of random terpolymers based on the diketopyrrolopyrrole-bithiophene (DPP-2T) backbone incorporating different amounts of isoindigo (IID) unit are synthesized, and their structure-mobility-stretchability correlation is thoroughly investigated. Our results reveal that random terpolymers containing a low IID content (DPP95 and DPP90) show enhanced interchain packing and solid-state aggregation to result in improved charge-transporting performance (can reach 4 order higher) compared to the parent polymer DPP100. In addition, owing to the enriched amorphous feature, DPP95 and DPP90 deliver an improved orthogonal mobility (µh) of >0.01 cm2 V-1 s-1 under a 100% strain, higher than the value (∼0.002 cm2 V-1 s-1) of DPP100. Moreover, DPP95 even yields 20% enhanced orthogonal µh retention after 800 stretching-releasing cycles with 60% strain. As concluded from a series of analyses, the improved mobility-stretchability property exerted by random terpolymerization arises from the enriched amorphous feature and enhanced aggregation behavior imposed by the geometry mismatch between different acceptors (DPP and IID). This study demonstrates that backbone engineering through rational random terpolymerization not only enhances the mobility-stretchability of a conjugated polymer but also realizes a better mechanical endurance, providing a new perspective for the design of high-performance stretchable conjugated polymers.

2.
Sci Rep ; 10(1): 19277, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159159

RESUMO

To improve the systematics and taxonomy of Patellogastropoda within the evolution of gastropods, we determined the complete mitochondrial genome sequences of Lottia goshimai and Nipponacmea fuscoviridis in the family Lottiidae, which presented sizes of 18,192 bp and 18,720 bp, respectively. In addition to 37 common genes among metazoa, we observed duplication of the trnM gene in L. goshimai and the trnM and trnW genes in N. fuscoviridis. The highest A + T contents of the two species were found within protein-coding genes (59.95% and 54.55%), followed by rRNAs (56.50% and 52.44%) and tRNAs (56.42% and 52.41%). trnS1 and trnS2 could not form the canonical cloverleaf secondary structure due to the lack of a dihydrouracil arm in both species. The gene arrangements in all Patellogastropoda compared with those of ancestral gastropods showed different levels of gene rearrangement, including the shuffling, translocation and inversion of single genes or gene fragments. This kind of irregular rearrangement is particularly obvious in the Lottiidae family. The results of phylogenetic and gene rearrangement analyses showed that L. goshimai and Lottia digitalis clustered into one group, which in turn clustered with N. fuscoviridis in Patellogastropoda. This study demonstrates the significance of complete mitogenomes for phylogenetic analysis and enhances our understanding of the evolution of Patellogastropoda.

3.
Org Biomol Chem ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33150922

RESUMO

A distinct copper-catalyzed boroacylation of allenes with acyl chlorides and bis(pinacolato)diboron is developed. For aromatic acyl chlorides, 1,2-boroacylation of allenes readily takes place, leading to the formation of tetrasubstituted vinylboronates with exclusive (E)-stereoselectivity. In comparison, the employment of alkyl acyl chlorides as electrophiles alters the selectivity to 2,3-boroacylated products. Additionally, the product can easily undergo Suzuki-Miyaura cross-coupling to afford tetrasubstituted alkene with complete retention of the configuration.

4.
J Vasc Interv Radiol ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33153865

RESUMO

PURPOSE: To report early and midterm outcomes of treating thoracic aortic aneurysm (TAA) and aortic dissection (AD) involving zone 1 and zone 0 with multiple parallel stent grafts (PSGs). MATERIALS AND METHODS: From February 2011 to August 2018, 31 of 1,806 patients (1.7%) who underwent thoracic endovascular aortic repair (TEVAR) with double PSGs (DPSGs) (n = 20) or triple PSGs (TPSGs) (n = 11) were retrospectively reviewed. Procedures were performed in high-risk patients who had TAA or AD involving zone 1 or zone 0. RESULTS: Fifteen patients (48.4%) who presented with symptomatic or impending rupture underwent urgent or emergent TEVAR with DPSGs or TPSGs. Nineteen patients (61.3%) were treated for zone 0 disease. Technical and clinical success rates were 70.0% for DPSG cohort and 45.5% for TPSG cohort. Intraoperative type Ia endoleak was observed in 30% of DPSG cohort and 45.5% of TPSG cohort. One patient in the DPSG cohort died of aortic sinus rupture intraoperatively. Minor stroke during the 30-day postoperative period was more frequent in the TPSG cohort (P = .042). Mean duration of follow-up was 28.9 months ± 17.7. The TPSG cohort had a higher incidence of major adverse events (72.7% vs 25.0%, P = .021). The most common adverse events were endoleaks (12.9%), endograft migration (9.7%), PSG stenosis or occlusion (6.5%), retrograde dissection (6.5%), and stroke (3.2%). Endograft migrations were more common in TPSG cohort (27.3%, P = .037). Overall mortality rate was 16.1% (5/31) perioperatively and during follow-up. There were no statistical differences in overall survival and reintervention-free survival. CONCLUSIONS: In the context of TEVAR with multiple PSGs for aortic arch repair, TPSGs may have a high risk of major complications.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33169961

RESUMO

Solutions or sols are commonly employed as the starting materials for the preparation of supramolecular hydrogels; however, suspension-based synthesis has been much less reported because of inhomogeneity and quick sedimentation of large particles in a suspension. Further, it remains a technical challenge to derive supramolecular aerogels directly from the parental hydrogels owing to the ease of structural collapse during water removal. Herein, we report a suspension-gel transition for the ultrafast synthesis of a new supramolecular hydrogel simply by adding AgNO3 into the aqueous suspension of cyanuric acid-melamine (CAM) aggregates. With the activation of preadded ammonia, Ag ions instantly reacted with the CAM particles, transforming into N-Ag(I)-N coordinating bonded supramolecular nanofibers; simultaneously, the suspension converted to a hydrogel without the use of polymer cross-linkers or external stimulus. Upon simple freeze-drying, a highly crystalline fibrous aerogel with a cellular network was obtained, which possessed a porosity up to 99.7% and a density as low as 4.8 mg/cm3, enabling remarkable oil uptake capacities (100 times of its weight). The supramolecular aerogel demonstrated intrinsic elasticity, which should arise from the cellular structure and elastic character of the nanofiber skeletons. Notably, the aerogel showed high compatibility to incorporate a range of external substances for further functionalization exemplified by polymeric carbon nitride (PCN, a metal-free semiconductor) included gels. The loaded PCN resulted in enhanced mechanical strength and endowed the aerogel unique photoactivity, i.e., in situ reducing Ag(I) into Ag nanoparticles upon light illumination and thus forming a plasmonic shell over the aerogel with potential applications in sensing and catalysis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33051848

RESUMO

Nonnegligible emission of bioaerosols usually occurs during aeration of wastewater in aerator tanks in wastewater treatment plants (WWTPs). Literature had shown that the respiratory and intestinal diseases of workers at WWTPs are related to bioaerosols. Thus, quantitative microbial risk assessment (QMRA) based on Monte Carlo simulation was utilized in this research to assess the health risks of Gram-negative bacteria bioaerosol (GNBB) and Staphylococcus aureus bioaerosol (SAB) among academic visitors and staffs. Results showed that the concentrations of GNBB and SAB in the inverted umbrella aeration mode were consistently higher than those in the microporous aeration mode under all six size distribution ranges of the Anderson six-stage impactor. Thus, GNBB and SAB can be highly threatening to the weasand and first bronchus (or alveoli and third bronchus) for the exposure populations. The health risks (annual probability of infection (Py) and disease burden (DB)) of males were constantly higher than those of females for each certain exposure scenario. The health risks of staffs were higher than those of academic visitors when assessed by Monte Carlo simulation. The wearing of mask is an effective measure to minimize health risks through reducing the bioaerosol concentration intake. Especially, for the academic visitors and staffs exposed to GNBB, all their DB failed to meet the World Health Organization DB benchmark under various credible intervals when they were without a mask on. In a word, the results of health risk assessment in this research can be utilized as an educational tool and policy basis to facilitate the implementation of efficacious prevention measures to protect the public health from bioaerosol health threats in WWTPs.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1648-1653, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067968

RESUMO

OBJECTIVE: To investigate the transfusion effectiveness of suspended leucocyte depleted red blood cells (sld RBC) and fresh and irradiated apheresis platelets (fia Plt) in patients with myelodysplastic syndromes (MDS), and to explore the causes and mechanisms of ineffective platelet transfusion in patients with MDS. METHODS: Clinical data of 37 patients with confirmed MDS (WHO standard) such as the sex, age, Hb levels, Plt count, hemorrhage and coagulation functions, TEG and so on, were retrospectively analyzed. RESULTS: Among the 37 patients, 15 patients (40.5%) received only sld RBC transfusion, 9 patients (24.3%) received only fia Plt transfusion, and 13 patients (35.1%) received both transfusion. Among the 15 patients with only red blood cell transfusion, 3 patients were ineffective and the ineffectual transfusion rate was 20.0%. Among the 9 patients with only received platelet transfusion, 5 patients were ineffective and the ineffectual transfusion rate was 55.6%, there were significant statistical differences between the two groups (P﹤0.01). The red blood cell transfusion ineffective were 3 patients (23.1%) , the platelet transfusion ineffective were 8 patients (61.5%) and the both transfusion ineffective were 2 patients (15.4%) among the patients both transfusion . The positive rate of platelet antibody in MDS patients with ineffective platelet transfusion was 23.1%. Compared with the normal control group, Human P selectin (P-SelectinCD62P) (P<0.001) and human anti-thrombin 3 antibody (AT-III Ab) (P<0.001) significantly increased and human tissue factor pathway inhibitor (TFPI) significantly decreased (P<0.05) in MDS patients with ineffective platelet transfusion. CONCLUSION: In the process of component transfusion for MDS patients, compared with the transfusion of red blood cells, the inefficiencies of platelet transfusion significantly increased, mainly due to the disorder of blood coagulation and the generation of platelet antibodies in MDS patients with ineffective platelet transfusion. Compared with the normal control group, human P selectin and human anti-thrombin 3 antibody significantly increase and human tissue factor pathway inhibitor significantly decreases in MDS patients with ineffective platelet transfusion. Human P selectin, human anti-thrombin 3 antibody and human tissue factor pathway inhibitor in molecular markers and fibrinolytic markers can be used as indicators of platelet transfusion time and efficiency in patients with MDS.


Assuntos
Transfusão de Sangue , Síndromes Mielodisplásicas , Transfusão de Eritrócitos , Humanos , Síndromes Mielodisplásicas/terapia , Transfusão de Plaquetas , Estudos Retrospectivos
8.
Cell Cycle ; : 1-18, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064976

RESUMO

Prostate cancer (PC) is the most common malignancy in men. As per recent findings, microRNA-300 (miR-300) were found to be overexpressed in numerous types of cancers. In this study, we aimed to explore the effects of miR-300 on the adhesion, invasion, and migration of PC cells by targeting Disabled 1 (DAB1). Firstly, the regulatory role of miRNAs on DAB1 was predicted by screening PC-related differentially expressed genes (DEGs). Immunohistochemistry was applied to determine the positive protein expression of DAB1, after which the target relationship between miR-300 and DAB1 was examined. Loss-of-function and gain-of-function experiments were conducted to determine cell proliferation, adhesion, migration, invasion capability, and cell cycle of PC cells. Our data illustrated that DAB1 had a low expression, while miR-300 was expressed at a relatively high level in PC tissues. Moreover, our clinicopathological analysis revealed that there was a correlation between miR-300 and tumor, node, metastases stage, Gleason score, and lymph node metastasis of PC patients. DAB1 was also found to be poorly expressed in PC based on the findings from the microarray analysis. The results from dual-luciferase reporter gene assay corroborated that miR-300 interacts with DAB1. Importantly, overexpression of miR-300 and/or si-DAB1 resulted in the enhancement of RAC1, MMP2, MMP9, CyclinD1, and CyclinE expressions, whereas the expression of DAB1 and Rap was reduced in PC cells, thus suggesting that down-regulated miR-300 suppressed proliferation, adhesion, migration, and invasion of PC cells. Collectively, our results provided evidence that down-regulation of miR-300 inhibits the adhesion, migration, and invasion of PC cells.

9.
Sensors (Basel) ; 20(19)2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33020401

RESUMO

Due to the growing public awareness of cardiovascular disease (CVD), blood pressure (BP) estimation models have been developed based on physiological parameters extracted from both electrocardiograms (ECGs) and photoplethysmograms (PPGs). Still, in order to enhance the usability as well as reduce the sensor cost, researchers endeavor to establish a generalized BP estimation model using only PPG signals. In this paper, we propose a deep neural network model capable of extracting 32 features exclusively from PPG signals for BP estimation. The effectiveness and accuracy of our proposed model was evaluated by the root mean square error (RMSE), mean absolute error (MAE), the Association for the Advancement of Medical Instrumentation (AAMI) standard and the British Hypertension Society (BHS) standard. Experimental results showed that the RMSEs in systolic blood pressure (SBP) and diastolic blood pressure (DBP) are 4.643 mmHg and 3.307 mmHg, respectively, across 9000 subjects, with 80.63% of absolute errors among estimated SBP records lower than 5 mmHg and 90.19% of absolute errors among estimated DBP records lower than 5 mmHg. We demonstrated that our proposed model has remarkably high accuracy on the largest BP database found in the literature, which shows its effectiveness compared to some prior works.

10.
Sci Total Environ ; 755(Pt 2): 142615, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33038813

RESUMO

Wastewater treatment plants (WWTPs) could emit a large amount of bioaerosols containing pathogenic bacteria. Assessing the health risks of exposure to these bioaerosols by using quantitative microbial risk assessment (QMRA) is important to protect workers in WWTPs. However, the relative impacts of the stochastic input variables on the health risks determined in QMRA remain vague. Hence, this study performed a Monte Carlo simulation-based QMRA case study for workers exposing to S. aureus or E. coli bioaerosols and a sensitivity analysis in two WWTPs with various aeration modes. Results showed that when workers equipped without personal protective equipment (PPE) were exposed to S. aureus or E. coli bioaerosol in the two WWTPs, the annual probability of infection considerably exceeded the U.S. EPA benchmark (≤10E-4 pppy), and the disease burden did not satisfy the WHO benchmark (≤10E-6 DALYs pppy) (except exposure to E. coli bioaerosol for disease health risk burden). Nevertheless, the use of PPE effectively reduced the annual infection health risk to an acceptable level and converted the disease health risk burden to a highly acceptable level. Referring to the sensitivity analysis, the contribution of mechanical aeration modes to the variability of the health risks was absolutely dominated in the WWTPs. On the aeration mode that showed high exposure concentration, the three input exposure parameters (exposure time, aerosol ingestion rate, and breathing rate) had a great impact on health risks. The health risks were also prone to being highly influenced by the various choices of the dose-response model and related parameters. Current research systematically delivered new data and a novel perspective on the sensitivity analysis of QMRA. Then, management decisions could be executed by authorities on the basis of the results of this sensitivity analysis to reduce related occupational health risks of workers in WWTPs.

11.
J Inorg Biochem ; 212: 111208, 2020 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-33065383

RESUMO

Two new copper(II) complexes, 9-PMAH-Cu (1) and 9-FPMAH-Cu (2), of anthrahydrazone were synthesized and structurally characterized, in which 9-FPMAH (9-(4'-trifluoromethyl)-pyrimidine anthrahydrazone) is the 4'-CF3 derivative of 9-PMAH (9-pyrimidine anthrahydrazone). Both complexes 1 and 2 showed similar intercalative binding modes towards DNA and might compete with the typical DNA intercalator, GelRed, in the same binding site. They could also act as topoisomerase (type I) suppressor to effectively inhibit its activity, in which complex 1 was more effective than 2. The in vitro antitumor screening indicated that complex 1 displayed much higher antiproliferative ability than 2 and cisplatin towards all the tested tumor cell lines. On the other hand, complex 1 also showed high cytotoxicity against human normal liver cell line HL-7702, suggesting it is a potential high cytotoxic antitumor candidate. While it was also suggested that the loss of activity of complex 2 might be due to the presence of 4'-CF3 on the pyrimidine ring. Studies on the cellular level showed that complex 1 could arrest the cell cycle of the most sensitive T-24 cells at G2/M phase and induced cell apoptosis. Complex 1 further showed a significant suppression on the tumor growth on the T-24 tumor xenograft mouse model, but not reduced the body weight. Especially, complex 1 could retain its coordination state in H2O even in the presence of HSA. The results suggests that complex 1 is of enough safety to be considered as a promising anticancer candidate by combining the bioactive Cu(II) and the anthrahydrazone pharmacophore.

12.
J Nat Prod ; 83(10): 2940-2949, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-32951423

RESUMO

In a continuing search for potential inhibitors against human carboxylesterases 1A1 and 2A1 (hCES1A1 and hCES2A1), an EtOAc extract of the roots of Paeonia lactiflora showed strong hCES inhibition activity. Bioassay-guided fractionation led to the isolation of 26 terpenoids including 12 new ones (1-5, 7-12, and 26). Among these, sesquiterpenoids 1 and 6, monoterpenoids 10, 11, and 13-15, and triterpenoids 18-20, 22, and 24-26 contributed to the hCES2A1 inhibition, in the IC50 range of 1.9-14.5 µM, while the pentacyclic triterpenoids 18-26 were responsible for the potent inhibitory activity against hCES1A1, with IC50 values less than 5.0 µM. The structures of all the compounds were elucidated using MS and 1D and 2D NMR data, and the absolute configurations of the new compounds were resolved via specific rotation, experimental and calculated ECD spectra, and single-crystal X-ray diffraction analysis. The structure-activity relationship analysis highlighted that the free HO-3 group in the pentacyclic triterpenoids is crucial for their potent inhibitory activity against hCES1A1.

13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(5): 636-642, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-32975077

RESUMO

Objective: To study the neuroprotective effect of inhalation of volatile oil of Cang Ai (VOCA) on cerebral ischemia-reperfusion injury model by MRI diffusion tensor imaging. Methods: Twenty-four healthy adult male SD rats were randomly divided into sham operation group, model (middle cerebral artery occlusion (MCAO) ) group and VOCA group. Evaluated the degree of neurological impairment of rats in each group immediately after successful establishment of model or 7 d later according to Zea Longa scoring. Coronal diffusion tensor imaging (DTI) scan was performed at 3 h, 3 d, and 7 d after the model successfully established by using 7.0 T magnetic resonance imaging. Measured the apparent diffusion coefficient (ADC) and anisotropy score (FA) of the DTI in the striatal region and the motion flat zone of the maximum infarct level and then calculate the relative apparent diffusion coefficient (rADC) and relative anisotropy score (rFA). TTC staining was used to evaluate the cerebral infarction volume of rats in each group at 7 d post model establishment, and the correlation analysis of rFA, rADC and neural score was performed. Results: No neurological defect was detected in mice in the sham operation group. The MCAO group and the VOCA group showed neurological defect to different degrees. The neurological function score of the VOCA group was obviously lower than that of MCAO group at 7 th day (P<0.05). The DTI scan results showed that the rADC value of striatum of rats in VOCA group was higher than that in MCAO group at 3 h and 3 d after modeling (P<0.05), while there was no significant difference between the three groups at 7 th day. The rADC value of the motor cortex in the VOCA group was higher than that in the MCAO group at 3 h after modeling (P<0.01), and there was no significant difference at 3 rdday and 7 thday. The rFA value of striatum in VOCA group was higher than that in MCAO group at 3 rd day and 7 th day after modeling (P<0.05). There were no significant differences in rFA value between the MCAO and the VOCA group at three time points. TTC staining results showed that there was no infarcted area in the sham operation group, and the infarct volume in the VOCA group was smaller than that of the MCAO group (P<0.05). Correlation analysis showed that the striatum rFA value was highly correlated with neurological scores (r=-0.847, P<0.01). Conclusion: For the first time, we found that VOCA can effectively protect the neurological function of MCAO rats by reducing the toxic edema of cells in the ischemic area and accelerating the recovery of nerve fiber bundles after cerebral ischemia and reperfusion. rFA and rADC values can be used as effective indicators to evaluate the recovery of nerve function after cerebral ischemia and reperfusion.

15.
J Opt Soc Am A Opt Image Sci Vis ; 37(9): 1448-1455, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32902435

RESUMO

Recently, a new form of laser beam, called the "centrosymmetric optical vortex" (CSOV), has been proposed. We employ the modified calculation method for studying the propagation of the CSOV beam, which is constructed via four canonical optical vortices with different topological charges. The speed of calculation is more convenient and faster than the usual means by using the diffraction integral directly. With a modified calculation method, the propagation properties of the CSOV in free space are illustrated and analyzed using numerical examples. Several parameters influencing the CSOV beams and the ABCD optical system are discussed in detail. Our experimental results are consistent with theoretical predictions. Furthermore, the orbital angular momentum states and density are also studied. The research results are expected to provide a basis for the application of CSOV beams in beam reshaping, optical trapping, and rotating microparticle manipulation, particularly in separating cells.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32990397

RESUMO

Transition metal catalyzed decarbonylation offers a distinct synthetic strategy for new chemical bond formation. However, the π-backbonding between CO π* orbitals and metal center d-orbitals impedes ligand dissociation to regenerate the catalyst under mild reaction conditions. Developed here is visible light induced rhodium catalysis for decarbonylative coupling of imides with alkynes under ambient conditions. Initial mechanistic studies suggest that the rhodium complex simultaneously serves as the catalytic center and photosensitizer for decarbonylation. This visible light promoted catalytic decarbonylation strategy offers new opportunities for reviewing old transformations with ligand dissociation as a rate-determining step.

17.
BMC Med Genet ; 21(1): 166, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32819290

RESUMO

BACKGROUND: Propionic acidemia (PA)(OMIM#606054) is an inborn error of branched-chain amino acid metabolism, caused by defects in the propionyl-CoA carboxylase (PCC) enzyme which encoded by the PCCA and PCCB genes. CASE PRESENTATION: Here we report a Chinese neonate diagnosed with suspected PA based on the clinical symptoms, gas chromatography-mass spectrometry (GC/MS), and brain imaging tests. Targeted next-generation sequencing (NGS) was performed on the proband. We detected only one heterozygous recurrent nonsense variant (c.937C > T, p.Arg313Ter) in the PCCA gene. When we manually checked the binary alignment map (BAM) diagram of PCCA gene, we found a heterozygous deletion chr13:100915039-100915132delinsAA (c.773_819 + 47delinsAA) (GRCh37.p13) inside the exon 10 in the PCCA gene. The results were validated by Sanger sequencing and qPCR method in the family: the variant (c.937C > T, p.Arg313Ter) was in the maternal allele, and the delins was in the paternal allele. When the mother was pregnant again, prenatal diagnosis was carried out through amniocentesis at 18 weeks gestation, the fetus carried neither of the two mutations. After birth, newborn screening was undertaken, the result was negative. CONCLUSIONS: We identified a recurrent c.937C > T and a novel c.773_819 + 47delinsAA mutations in the PCCA gene, which may be the genetic cause of the phenotype of this patient. Our findings expanded the spectrum of causative genotype-phenotype of the PCCA gene. For the cases, the NGS results revealed only a heterozygous mutation in autosomal recessive disease when the gene is associated with phenotypes, it is necessary to manually check the BAM diagram to improve the detection rate. Targeted NGS is an effective technique to detect the various genetic lesions responsible for the PA in one step. Genetic testing is essential for genetic counselling and prenatal diagnosis in the family to avoid birth defects.


Assuntos
Carbono-Carbono Ligases/genética , Mutação/genética , Acidemia Propiônica/enzimologia , Acidemia Propiônica/genética , Sequência de Bases , Humanos , Recém-Nascido , Masculino , Triagem Neonatal , Diagnóstico Pré-Natal , Acidemia Propiônica/diagnóstico
18.
J Med Chem ; 63(17): 9154-9167, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32794745

RESUMO

Myeloid cell leukemia 1 (Mcl-1), which belongs to the Bcl-2 family of prosurvival proteins, is a key regulator of cancer cell survival. To date, few drug-like Mcl-1 inhibitors have been reported. Herein, we report the preparation of 10 copper complexes with 9-substituted ß-carboline ligands that act as metal-based Mcl-1 inhibitors. Complex 14 was identified as a potent and selective Mcl-1 inhibitor with strong in vitro antitumor activity. Mechanistic studies demonstrated that complex 14 disrupted Mcl-1-Bax/Bak heterodimerization and induced Bax/Bak-dependent apoptosis. In addition, complex 14 significantly (P < 0.001) inhibited tumor growth in vivo, induced tumor necrosis, and extended survival time in an NCI-H460 xenograft model. Furthermore, complex 14 showed no apparent toxicity in mice. Together, these findings indicate that complex 14 is a copper-based Mcl-1 inhibitor with high efficacy and low toxicity that could be developed for the treatment of Mcl-1-related cancers.

19.
J Ultrasound Med ; 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32856729

RESUMO

OBJECTIVES: To explore the inter- and intra-observer reliability of Sonography-based Volume Computer Aided Diagnosis (SonoVCAD) in the display of 8 diagnostic planes of fetal echocardiography and to evaluate its efficiency. METHODS: Three-dimensional volume data sets of the 56 normal singleton fetuses were acquired from a 4-chamber view by using a volume probe. After processing the data sets by using SonoVCAD, 8 cardiac diagnostic planes were displayed automatically. Three doctors with different experiences of performing fetal echocardiography evaluated each diagnostic plane and the success rates of 8 diagnostic planes were calculated. Inter-observer and intra-observer reliabilities were estimated by Cohen's kappa statistics. RESULTS: A total of 276 volume data sets acquired from the 56 normal fetuses were used for SonoVCAD analysis and display. The success rate of each diagnostic section was more than 90%, ranging from 90.6% to 99.6%. Among 276 volumes, 81.5% (225/276) of volumes were able to generate all 8 diagnostic views successfully. Moderate to substantial agreement (kappa, 0.509-0.794) was found between 2 less experienced operators. Moderate to near-perfect agreement (kappa, 0.439-0.933) was found between an expert and 2 less experienced sonographers. Intra-observer reliability was substantial to near-perfect (kappa, 0.602-0.903). The efficiency of SonoVCAD was assessed. The expert spent less time than 2 less experienced examiners (P < 0.001) but no significant difference was found between 2 less experienced examiners (P = 0.176). Besides, SonoVCAD consumed significantly less time than 2-dimensional ultrasound (P < 0.001). CONCLUSIONS: SonoVCAD can significantly improve the success rates of 8 diagnostic planes in fetal echocardiography with low operator dependency, good reproducibility and high efficiency.

20.
J Mech Behav Biomed Mater ; 112: 104018, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32818859

RESUMO

Nacre is a natural composite featuring exceptional mechanical properties such as high strength and high toughness. Its unique structure is now universally applied in engineering bioinspired materials. On the other hand, it is still a technical challenge to investigate its interfacial strength and fracture mechanisms at micro or nano-scale. In this work, the interfacial strength and fracture mechanism of the 'brick-mortar' structure in nacre are investigated using micro-sized cantilever beam and bend samples. As compared to previous works, a high aragonite/biopolymer interfacial strength is observed (~298 MPa). The crack propagation path is investigated via experiment and finite element modelling and compared with the fracture mechanics analysis. It is confirmed that crack deflection to the aragonite/biopolymer interface contributes to a high overall toughness. This work provides a better understanding of the toughening mechanism in nacre and other bioinspired composites.

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