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1.
J Cell Biochem ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31595563

RESUMO

BACKGROUND: Toll-like receptor-7 (TLR7) is functionally involved in the pathogenesis of Hunner-type interstitial cystitis (HIC). In addition, maternally expressed gene 3 (MEG3) is implicated in many urethral diseases. In this study, we aimed to verify the hypothesis that exosomal MEG3 in urine can be used as a novel diagnostic biomarker for HIC. METHODS: Electron microscopy was utilized to observe the distribution of urinary exosomes between the case group and the control group. Receiver operating characteristic analysis was utilized to compare the diagnostic values of MEG3 and miR-19a-3p. Computational analysis and luciferase assay were conducted to identify the correlation between MEG3 and miR-19a-3p as well as between TLR7 and miR-19a-3p. In addition, real-time polymerase chain reaction and Western blot were performed to establish the signaling pathways implicated in the pathogenesis of HIC. RESULTS: When age and gender distributions are excluded, urinary exosomes were equally distributed between case and control groups. The area under the curve of MEG3 was larger than that of miR-19a-3p, indicating that MEG3 has a better value in the diagnosis of HIC. In addition, patients with HIC showed elevated MEG3 expression and inhibited miR-19a-3p expression, thus establishing a negative correlation between MEG3 and miR-19a-3p. MEG3 and TLR7 were both identified as targets of miR-19a-3p, establishing a MEG3/miR-19a-3p/TLR7 signaling pathway, in which MEG3 enhances the expression of TLR7 via inhibiting the expression of miR-19a-3p. CONCLUSION: MEG3 level was upregulated in patients with HIC. In addition, MEG3 downregulated miR-19a-3p expression while upregulating TLR7 expression. Furthermore, MEG3 contributes to the pathogenesis of HIC. Therefore, exosomal MEG3 in urine can be used as a biomarker for HIC diagnosis.

2.
Cancer Biol Ther ; : 1-8, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597506

RESUMO

People who suffers renal angiomyolipoma (AML) has a low quality of life. It is widely known that genetic factors including TSC2 mutation contribute to certain populations of renal AML-bearing patients. In this study, we are the first to identify novel TSC2 mutations in one Chinese renal epithelioid AML patient: c.2652C>A; c.2688G>A based on sequencing result from biopsy tissue. These two somatic mutations cause a translational stop of TSC2, which leads to mTORC1 activation. Given the fact that activation of mTORC1 ensures cell growth and survival, we applied its inhibitor, FDA-approved everolimus, to this woman. After months of treatment with everolimus, Computer-Tomography (CT) scan results showed that everolimus successfully reduced tumor growth and distal metastasis and achieved partial response (PR) to everolimu according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Further Blood Routine Examination results showed the concentration of red cell mass, hemoglobin, white blood cell (WBC), platelets and hematocrit (HCT) significantly returned to normal levels indicating patients with these two TSC2 mutations could be effectively treated by everolimus.

3.
Lancet Oncol ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31591062

RESUMO

BACKGROUND: Upper gastrointestinal cancers (including oesophageal cancer and gastric cancer) are the most common cancers worldwide. Artificial intelligence platforms using deep learning algorithms have made remarkable progress in medical imaging but their application in upper gastrointestinal cancers has been limited. We aimed to develop and validate the Gastrointestinal Artificial Intelligence Diagnostic System (GRAIDS) for the diagnosis of upper gastrointestinal cancers through analysis of imaging data from clinical endoscopies. METHODS: This multicentre, case-control, diagnostic study was done in six hospitals of different tiers (ie, municipal, provincial, and national) in China. The images of consecutive participants, aged 18 years or older, who had not had a previous endoscopy were retrieved from all participating hospitals. All patients with upper gastrointestinal cancer lesions (including oesophageal cancer and gastric cancer) that were histologically proven malignancies were eligible for this study. Only images with standard white light were deemed eligible. The images from Sun Yat-sen University Cancer Center were randomly assigned (8:1:1) to the training and intrinsic verification datasets for developing GRAIDS, and the internal validation dataset for evaluating the performance of GRAIDS. Its diagnostic performance was evaluated using an internal and prospective validation set from Sun Yat-sen University Cancer Center (a national hospital) and additional external validation sets from five primary care hospitals. The performance of GRAIDS was also compared with endoscopists with three degrees of expertise: expert, competent, and trainee. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of GRAIDS and endoscopists for the identification of cancerous lesions were evaluated by calculating the 95% CIs using the Clopper-Pearson method. FINDINGS: 1 036 496 endoscopy images from 84 424 individuals were used to develop and test GRAIDS. The diagnostic accuracy in identifying upper gastrointestinal cancers was 0·955 (95% CI 0·952-0·957) in the internal validation set, 0·927 (0·925-0·929) in the prospective set, and ranged from 0·915 (0·913-0·917) to 0·977 (0·977-0·978) in the five external validation sets. GRAIDS achieved diagnostic sensitivity similar to that of the expert endoscopist (0·942 [95% CI 0·924-0·957] vs 0·945 [0·927-0·959]; p=0·692) and superior sensitivity compared with competent (0·858 [0·832-0·880], p<0·0001) and trainee (0·722 [0·691-0·752], p<0·0001) endoscopists. The positive predictive value was 0·814 (95% CI 0·788-0·838) for GRAIDS, 0·932 (0·913-0·948) for the expert endoscopist, 0·974 (0·960-0·984) for the competent endoscopist, and 0·824 (0·795-0·850) for the trainee endoscopist. The negative predictive value was 0·978 (95% CI 0·971-0·984) for GRAIDS, 0·980 (0·974-0·985) for the expert endoscopist, 0·951 (0·942-0·959) for the competent endoscopist, and 0·904 (0·893-0·916) for the trainee endoscopist. INTERPRETATION: GRAIDS achieved high diagnostic accuracy in detecting upper gastrointestinal cancers, with sensitivity similar to that of expert endoscopists and was superior to that of non-expert endoscopists. This system could assist community-based hospitals in improving their effectiveness in upper gastrointestinal cancer diagnoses. FUNDING: The National Key R&D Program of China, the Natural Science Foundation of Guangdong Province, the Science and Technology Program of Guangdong, the Science and Technology Program of Guangzhou, and the Fundamental Research Funds for the Central Universities.

4.
Retina ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31584558

RESUMO

PURPOSE: To determine the ability of nonperfusion, vessel density, and morphologic measurements using projection-resolved optical coherence tomography angiography to detect early retinal microvasculature impairments in diabetes mellitus. METHODS: A retrospective review was performed on Type 2 diabetes mellitus patients with no diabetic retinopathy (DR) or mild nonproliferative DR and age-matched controls imaged with optical coherence tomography angiography. Foveal avascular zone-related metrics and extrafoveal avascular area were measured in optical coherence tomography angiography images. Vessel density and fractal dimension were calculated with and without a skeletonization process. The vessel diameter index and vessel tortuosity were computed. The area under the receiver operating characteristic curve (AUC) estimated diagnostic performances. RESULTS: Dilated capillary diameter was observed in the deep capillary plexus in the diabetic groups. Vessel density and fractal dimension of skeletonized deep capillary plexus significantly and progressively decreased in the no DR and mild nonproliferative DR groups compared with controls. Superficial extrafoveal avascular area, vessel density, and fractal dimension of the skeletonized deep capillary plexus had the highest diagnostic performance to differentiate mild nonproliferative DR from control eyes, with AUCs of 0.885, 0.876, and 0.876, respectively. CONCLUSION: Vessel density and fractal dimension from the skeletonized deep capillary network may be the most sensitive for detecting early retinal capillary loss in diabetes mellitus.

5.
Nanoscale ; 11(42): 20245-20251, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31621764

RESUMO

Recent studies have demonstrated that tellurene is a van der Waals (vdW) two-dimensional material with potential optoelectronic and thermoelectric applications as a result of its pseudo-one-dimensional structure and properties. Here, we report on the pressure induced anomalous phase transition of tellurium nanoribbons. The observation of clean phase transitions was made possible with high quality single crystalline Te nanoribbons that are synthesized by hydrothermal reaction growth. The results show that phase transition has a large pressure hysteresis and multiple competing phases: during compression, the phase transition is sudden and takes place from trigonal to orthorhombic phase at 6.5 GPa. Orthorhombic phase remains stable up to higher pressures (15 GPa). In contrast, phase transition is not sudden during decompression, but orthorhombic and trigonal phases co-exist between 6.9 to 3.4 GPa. Grüneisen parameter calculations further confirm the presence of co-existing phases and suggest hysteretic phase change behavior. Finally, orthorhombic to trigonal phase transition occurs at 3.4 GPa which means overall pressure hysteresis is around 3.1 GPa.

6.
Org Lett ; 21(21): 8789-8794, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622106

RESUMO

Acyl radical triggered difunctionalizations of aryl olefins have been realized using oxime ester as the acyl precursor for the first time. Irradiation of fac-Ir(ppy)3 and oxime ester by visible light caused scission into three components, which recombined with olefins to yield significant ß-carbonyl imides showing good functional group tolerance and high atom economy. Control experiments as well as spectroscopic and electrochemical studies revealed the efficient intermolecular reorganization of oxime ester into styrene with the aid of solvent exchange.

7.
Cytokine ; 126: 154871, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31629104

RESUMO

OBJECTIVE: Chronic activation of the innate immune system plays a central role in HIV-1 disease progression. Negative regulation of innate immunity is critical in preventing the effects of this excessive activation; however, the molecules involved in this process remain to be identified. In this study, we compared the expression of immune regulation genes between HIV-1 infected individuals and healthy control participants to identify genes involved in the regulation of innate immunity in HIV-1 infection. METHODS: We conducted gene expression analysis of a series of immune regulatory genes in viremic treatment-naïve HIV-positive donors, patients receiving highly active antiretroviral therapy (HAART) and HIV-negative healthy control participants. Reverse transcription-quantitative PCR (RT-qPCR) was conducted to determine the expression levels of genes in peripheral blood mononuclear cells isolated from all participants. The spearman correlation test and linear regression analysis were performed to evaluate the correlation between gene expression level and viral load. RESULTS: The following differentially expressed genes were identified: A20, CYLD, DDX24, MARCH5, MKRN2, PTP1B, RNF125, S1PR1, SOCS1, IFI35, RBCK1, TTLL12 and USP18. The three most differentially expressed genes were A20, S1PR1, and USP18. USP18 correlated positively with viral load. CONCLUSION: Thirteen immune regulation genes were identified in comparisons of viremic treatment-naïve HIV-positive donors, HAART-treated patients and healthy control participants, indicating the potential of these genes as therapeutic targets.

8.
Org Lett ; 21(21): 8537-8542, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31642686

RESUMO

A highly efficient, chemo-, and regioselective approach has been developed for the switchable synthesis of tetrasubstituted alkenyl sulfones and naphthyl sulfones from homopropargylic alcohols via sulfonylation/1,4-aryl migration and sulfonylation/cyclization. The present switchable processes are characterized by mild and metal-free conditions, high selectivities, good functional group tolerance, the use of inexpensive and easily handled sulfonyl hydrazides as sulfonyl sources, and the release of the nontoxic byproducts H2O and N2.

9.
J Ethnopharmacol ; : 112317, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31629862

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Arnebiae Radix, a common herbal medicine in China, is often utilized to treat blood-heat syndrome and has been reported to exert an effect on the heart. AIM OF THE STUDY: The combination of acetylcholine (Ach) and CaCl2 has been widely used to induce atrial fibrillation (AF) in animals. However, whether Arnebiae Radix displays any preventive action on Ach-CaCl2 induced AF in rats remains uncertain. In our study, we attempted to investigate the protective effects of Arnebiae Radix on Ach-CaCl2 induced AF compared to amiodarone, which was employed as the positive control. MATERIALS AND METHODS: To establish the AF model, SD rats were treated with a mixture of 0.1 mL/100 g Ach-CaCl2 (60 µg/mL Ach and 10 mg/mL CaCl2) by tail vein injection for 7 days. Rats were also given a gavage of Arnebiae Radix (0.18 g/mL) one week before or concurrently with the establishment of the AF model. At the end of the experimental period, the induction, duration and timing of AF were monitored using electrocardiogram recordings. Left atrial tissues were stained to observe the level of fibrosis. Electrophysiological measurements were used to examine atrial size and function. RESULTS: In Ach-CaCl2-induced AF rats, Arnebiae Radix decreased AF induction, duration and susceptibility to AF. In addition, Arnebiae Radix significantly reduced atrial fibrosis and inhibited atrial enlargement induced by Ach-CaCl2. Moreover, there was an apparent improvement in cardiac function in the Arnebiae Radix-treated group. CONCLUSIONS: Our findings indicate that Arnebiae Radix treatment can attenuate Ach-CaCl2-induced atrial injury and serve as an effective therapeutic strategy for the treatment of AF in the future.

10.
Magn Reson Imaging ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31654738

RESUMO

Atheroembolic renal disease (AERD) is the major cause of renal insufficiency in the elderly, and particularly, the diagnose of AERD is often delayed and even missed due to its nonspecific presentation and the sudden occurrence of an embolic event. To investigate the feasibility of the view-shared compressed sensing (VCS) based dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in the assessment of AERD in animal models. The reproducibility of VCS DCE-MRI based glomerular filtration rate (GFR) estimation was first evaluated using the three healthy rabbits. Animal models of unilateral AERD were then conducted. All the rabbits underwent VCS DCE-MRI and the GFR maps were estimated by a commonly used cortical-compartment model. The whole kidney and suspicious lesion region GFR values of embolized kidneys were then compared with the corresponding values of normal kidneys. Finally, the suspicious lesion regions were confirmed by the corresponding renal specimens and histological findings. The reproducibility of GFR measurements was analyzed using the coefficient of variation and Bland-Altman analysis. The GFR values of normal and embolized kidneys were compared using the Student t-test. Contrast-enhanced images with sufficient diagnostic quality and reduced motion artifacts are obtained at a temporal resolution of 2.5 s. The Bland-Altman plot indicated close agreement between the GFR values estimated from between-day scans in healthy rabbits. Besides, there existed significant differences between the pixel-wise GFR values of normal and AERD kidneys in region-based comparison(P < 0.0001). The suspicious lesions are consistent well with the renal specimen and histological findings. The preliminary animal study verified the feasibility of VCS DCE-MRI for renal function evaluation, and the strategy could potentially provide a valuable tool to identify AERD.

11.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3798-3805, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602956

RESUMO

Based on metabolomics,the metabolites of larvae zebrafish with overdose of Panax notoginseng saponins( PNS) were compared with those in normal group of larvae zebrafish to investigate the possible toxicity mechanism of overdose PNS in larvae zebrafish. An experimental animal model of long-term toxicity induced by PNS overdose was established by administering 1-6 dpf at low,medium and high doses of PNS,respectively. The ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry( UPLC-Q-TOF-MS) technique was combined with principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA) to screen and identify biomarkers associated with toxicity,and then the MetaboAnalyst database was used to analyze metabolism-related pathways. The results showed that the metabolites of each group could be distinguished distinctly,and they deviated more from the normal group in a time and dose dependent manner. Twenty-nine potential biomarkers related to toxicity( VIP>1,P<0. 05) were identified preliminarily,mainly involving six metabolic pathways. From the metabonomics point of view,the toxicity mechanism of overdose PNS may be related to the disorders of lipid metabolism,amino acid metabolism and energy metabolism.


Assuntos
Metabolômica , Panax notoginseng/toxicidade , Saponinas/toxicidade , Aminoácidos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Metabolismo Energético , Larva/efeitos dos fármacos , Metabolismo dos Lipídeos , Espectrometria de Massas , Testes de Toxicidade Aguda , Peixe-Zebra
12.
Sci Data ; 6(1): 201, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615985

RESUMO

The identification of novel disease associations using big-data for patient care has had limited success. In this study, we created a longitudinal disease network of traced readmissions (disease trajectories), merging data from over 10.4 million inpatients through the Healthcare Cost and Utilization Project, which allowed the representation of disease progression mapping over 300 diseases. From these disease trajectories, we discovered an interesting association between schizophrenia and rhabdomyolysis, a rare muscle disease (incidence < 1E-04) (relative risk, 2.21 [1.80-2.71, confidence interval = 0.95], P-value 9.54E-15). We validated this association by using independent electronic medical records from over 830,000 patients at the University of California, San Francisco (UCSF) medical center. A case review of 29 rhabdomyolysis incidents in schizophrenia patients at UCSF demonstrated that 62% are idiopathic, without the use of any drug known to lead to this adverse event, suggesting a warning to physicians to watch for this unexpected risk of schizophrenia. Large-scale analysis of disease trajectories can help physicians understand potential sequential events in their patients.

13.
ACS Nano ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31625718

RESUMO

We present here a detailed study of the wettability of surfaces nanostructured with amorphous and crystalline nanoparticles (NPs) derived from the phase-change material Ge2Sb2Te5 (GST). Particular attention was devoted to the effect of airborne surface hydrocarbons on surface wetting. Our analysis illustrates that a reversible hydrophilic-hydrophobic wettability switch is revealed by combined ultraviolet-ozone (UV-O3) treatments and exposure to hydrocarbon atmospheres. Indeed, the as-prepared surfaces exhibited a hydrophilic state after thermal annealing or UV-O3 treatment which can partially remove hydrocarbon contaminants, while a hydrophobic state was realized after exposure to hydrocarbon atmosphere. Using high-angle annular dark-field scanning transmission electron microscopy for the specially designed GST NP decorated graphene substrates, a network of hydrocarbon connecting GST NPs was observed. Our findings indicate that airborne hydrocarbons can significantly enhance the hydrophobicity of nanostructured surfaces. Finally, the experiments reveal that previously defined hydrophilic materials can be used for the design of hydrophobic surfaces even if the meniscus is highly adhered to a solid surface, which is in agreement with our qualitative model involving the contribution of the nanomeniscus formed between the substrate and a decorating NP.

14.
Medicine (Baltimore) ; 98(39): e17373, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574886

RESUMO

Ionizing radiation can induce deoxyribonucleic acid (DNA) methylation pattern change, and ionizing radiation-induced oxidative damage may also affect DNA methylation status. However, the influence of low-dose ionizing radiation, such as occupational radiation exposure, on DNA methylation is still controversial.By investigating the relationship between occupational radiation exposure and DNA methylation changes, we evaluated whether radiation-induced oxidative damage was related to DNA methylation alterations and then determined the relationship among occupational radiation level, DNA methylation status, and oxidative damage in interventional physicians.The study population included 117 interventional physicians and 117 controls. We measured global methylation levels of peripheral blood leukocyte DNA and expression level of DNA methyltransferase (Dnmts) and homocysteine (Hcy) in serum to assess the DNA methylation status of the body. We measured 8-hydroxy-2'-deoxyguanosine (8-OHDG) and 4-hydroxynonenal (4-HNE) levels as indices of oxidative damage. Relevance analysis between multiple indices can reflect the relationship among occupational radiation exposure, DNA methylation changes, and oxidative damage in interventional physicians.The expression levels of Dnmts, 4-HNE, and 8-OHDG in interventional physicians were higher than those in controls, while there was no statistical difference in total DNA methylation rate and expression of Hcy between interventional physicians and controls. Total cumulative personal dose equivalent in interventional physicians was positively correlated with the expression levels of Dnmts, 8-OHDG, and 4-HNE. The expression levels of 8-OHDG in interventional physicians were negatively correlated with global DNA methylation levels and positively correlated with the expression levels of Hcy.Occupational radiation exposure of interventional physicians has a certain effect on the expression of related enzymes in the process of DNA methylation, while ionizing radiation-induced oxidative damage also has a certain effect on DNA methylation. However, there was no evidence that dose burden of occupational exposure was associated to changes of DNA methylation status of interventional physicians, since it is rather unclear which differences are observed among the effects produced by radiation exposure and oxidative damage.


Assuntos
Dano ao DNA/efeitos da radiação , Metilação de DNA/efeitos da radiação , Exposição Ocupacional/análise , Estresse Oxidativo/efeitos da radiação , Exposição à Radiação/análise , Radiologia Intervencionista/estatística & dados numéricos , Adulto , Aldeídos/sangue , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Feminino , Homocisteína/sangue , Humanos , Leucócitos/metabolismo , Masculino , Metiltransferases/sangue , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Médicos/estatística & dados numéricos , Exposição à Radiação/efeitos adversos
15.
Nat Commun ; 10(1): 4807, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641126

RESUMO

The upgrading of CO2/CO feedstocks to higher-value chemicals via energy-efficient electrochemical processes enables carbon utilization and renewable energy storage. Substantial progress has been made to improve performance at the cathodic side; whereas less progress has been made on improving anodic electro-oxidation reactions to generate value. Here we report the efficient electroproduction of value-added multi-carbon dimethyl carbonate (DMC) from CO and methanol via oxidative carbonylation. We find that, compared to pure palladium controls, boron-doped palladium (Pd-B) tunes the binding strength of intermediates along this reaction pathway and favors DMC formation. We implement this doping strategy and report the selective electrosynthesis of DMC experimentally. We achieve a DMC Faradaic efficiency of 83 ± 5%, fully a 3x increase in performance compared to the corresponding pure Pd electrocatalyst.

16.
Int J Biol Markers ; 34(3): 213-220, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31507240

RESUMO

BACKGROUND: Preoperative estimation of microvascular invasion is of great significance for the clinical decision making in hepatocellular carcinoma. Neutrophil-lymphocyte ratio (NLR) has been reported to be correlated with the poor prognosis of hepatocellular carcinoma. However, the conclusions are conflicting on whether high preoperative NLR level is associated with the presence of microvascular invasion. AIM: To evaluate the association between preoperative NLR level and the risk of microvascular invasion in hepatocellular carcinoma. METHODS: Relevant studies were identified by searching PubMed and Embase through February 2019. Fixed or random models were applied to analyze the data based on the heterogeneity. Subgroup, sensitivity, and publication bias analyses were performed. Review Manager 5.3 and STATA software were used for the meta-analysis. RESULTS: A total of 15 studies were eventually included in this meta-analysis. Pooled data based on retrospective cohort studies showed there are more hepatocellular carcinoma patients with vascular invasion (OR 1.74; 95% Cl 1.42, 2.12; P < 0.001) and microvascular invasion (OR 1.62 95% Cl 1.39, 1.89; P < 0.001) in the high NLR group than in the low NLR group. Of case-control studies, a higher preoperative NLR level was found in the microvascular invasion positive group than in the microvascular invasion negative group (OR 0.62; 95% Cl 0.35, 0.90; P < 0.001). The subgroup, sensitivity, and publication bias analyses did not change the results. CONCLUSION: A higher preoperative NLR level is positively correlated with the risk of microvascular invasion in hepatocellular carcinoma.

18.
Cell ; 179(1): 251-267.e24, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31539496

RESUMO

In situ transgenesis methods such as viruses and electroporation can rapidly create somatic transgenic mice but lack control over copy number, zygosity, and locus specificity. Here we establish mosaic analysis by dual recombinase-mediated cassette exchange (MADR), which permits stable labeling of mutant cells expressing transgenic elements from precisely defined chromosomal loci. We provide a toolkit of MADR elements for combination labeling, inducible and reversible transgene manipulation, VCre recombinase expression, and transgenesis of human cells. Further, we demonstrate the versatility of MADR by creating glioma models with mixed reporter-identified zygosity or with "personalized" driver mutations from pediatric glioma. MADR is extensible to thousands of existing mouse lines, providing a flexible platform to democratize the generation of somatic mosaic mice. VIDEO ABSTRACT.

19.
J Orthop Surg (Hong Kong) ; 27(3): 2309499019876073, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31554466

RESUMO

OBJECTIVE: Although the optimal screw tightening sequence is a common question orthopaedists encounter during fractures fixation with a dynamic compression plate (DCP), the effect of the screw tightening sequence on the stability of the plate has never been explored. This study explores the effect of the screw tightening sequence on the stress distribution of a DCP using a finite element method. METHODS: Idealized finite element analysis models of the femoral diaphysis with six-hole or eight-hole DCPs were constructed. The screw tightening preload was simulated using 'bolt load' in ABAQUS. Two screw tightening sequences were studied for the six-hole plate and six sequences were studied for the eight-hole plate. U magnitude and Von Mises stress were used to evaluate the deformation and stress distribution of the plate, respectively. Deformation and stress distribution plots from different sequences were compared. RESULTS: The different screw tightening sequences showed different deformation processes, while all had the same final deformation after all the screws were tightened. Each screw tightening step of different tightening sequences showed different stress distributions in the plate, while all had the same stress distribution after all the screws were tightened. CONCLUSION: Using different screw tightening sequences to fix the same DCP can produce the same stability, which means in terms of fixation stability, after the two screws nearest to the fracture line are tightened, surgeons do not need to hesitate about the order in which the rest screws should be inserted during the surgery.

20.
Environ Sci Technol ; 53(20): 11960-11968, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31532631

RESUMO

Urban growth comes with significant warming impacts and related increases in air pollution concentrations, so many cities have implemented growth management to minimize "sprawl" and its environmental consequences. However, controlling the amount of growth is costly. Therefore, in this Article, we focus on urban warming and investigate whether climate-conscious urban growth planning (CUGP), that is, urban growth with the same magnitude but optimized spatial arrangements, brings significant mitigation effects. First, the classical spatial multiobjective land-use optimization (SMOLA) model is improved by integrating the spatially, diurnally, and compositionally varying associations between land-use and their warming impacts. We then solve the improved model using the nondominated genetic algorithm (NSGA-II) to generate urban growth plans with minimal warming impacts and minimal cost of change without reducing the amount of urban growth. Results show that climate-conscious urban growth brings 33.3 ± 4.6% less warming impacts as compared to unplanned urban growth in Shenzhen, China, and suggest a compact and spatially equalized development pattern. This study provides evidence that spatial planning tools such as the CUGP can help mitigate human impacts on the environment. Meanwhile, the improved SMOLA model could be applied to balance urban development and other environmental consequences such as air pollution.

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