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1.
Genome Biol ; 21(1): 107, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381040

RESUMO

BACKGROUND: Tumors comprise a complex microenvironment of interacting malignant and stromal cell types. Much of our understanding of the tumor microenvironment comes from in vitro studies isolating the interactions between malignant cells and a single stromal cell type, often along a single pathway. RESULT: To develop a deeper understanding of the interactions between cells within human lung tumors, we perform RNA-seq profiling of flow-sorted malignant cells, endothelial cells, immune cells, fibroblasts, and bulk cells from freshly resected human primary non-small-cell lung tumors. We map the cell-specific differential expression of prognostically associated secreted factors and cell surface genes, and computationally reconstruct cross-talk between these cell types to generate a novel resource called the Lung Tumor Microenvironment Interactome (LTMI). Using this resource, we identify and validate a prognostically unfavorable influence of Gremlin-1 production by fibroblasts on proliferation of malignant lung adenocarcinoma cells. We also find a prognostically favorable association between infiltration of mast cells and less aggressive tumor cell behavior. CONCLUSION: These results illustrate the utility of the LTMI as a resource for generating hypotheses concerning tumor-microenvironment interactions that may have prognostic and therapeutic relevance.

2.
J Med Internet Res ; 22(5): e18718, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396516

RESUMO

BACKGROUND: In early 2020, over 80,000 cases of coronavirus disease (COVID-19) were confirmed in China. Public prevention and control measures, along with efforts from all sectors of society, were undertaken to control and eliminate disease transmission. OBJECTIVE: This paper describes Chinese citizens' response to the epidemic, the preventive measures they implemented to avoid being infected, and the public strategies that were carried out by the government, health workers, etc. We also discuss the efficacy of these measures in controlling the epidemic in China. METHODS: Information on the responses and behaviors of Chinese citizens were collected through a cross-sectional, internet-based survey using Dingxiang Doctor's public account on WeChat. Information on public strategies implemented by all sectors of society to control the epidemic and data on new COVID-19 cases were collected from the internet, mainly from government websites. Standard descriptive statistics and multivariate logistic regression analyses were conducted to analyze the data. RESULTS: A total of 10,304 participants responded to the survey, with 10,198 valid responses; 74.1% (n=7557) were female and 25.9% (n=2641) were male. Overall, 98.2% (n=10,013) of participants paid high or very high attention to the epidemic, with WeChat being their main information source (n=9400, 92.2%). Over half the participants (n=5878, 57.7%) were confident that the epidemic could be curbed in China; 92.4% (n=9427) opened windows for ventilation more frequently than usual; 97.9% (n=9986) used masks in public; 95.7% (n=9759) avoided large crowds and stayed at home as much as possible; and 97.9% (n=9988) washed their hands more often than usual. Women were more likely to practice these behaviors than men (P<.001). With a series of strict public control measures, like nationwide health education campaigns, holiday extensions, the Examine and Approve Policy on the resumption of work, close management of working and living quarters, a health QR (Quick Response) code system, community screening, and social distancing policies, the number of new cases have decreased dramatically since February 12, 2020. CONCLUSIONS: The methods employed by Chinese citizens and authorities have effectively curtailed the spread of COVID-19, demonstrating that this pandemic can be brought under control as long as the right measures are taken.

3.
Neurosci Lett ; 729: 135007, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32371156

RESUMO

Intracerebral hemorrhage (ICH) causes neurological function deficit due to the loss of neurons surrounding the hematoma. Increased neurogenesis of endogenous neural stem cells (EnNSCs) is believed to increase cell proliferation and differentiation, thereby improving the neurological deficit. However, there are still limited drugs that are effective for treating neurological deficit. So, the effects of compound K (CK) in EnNSCs were measured after thrombin-induced mice models both in vivo and in vitro, and investigated the probable mechanisms of CK during pro-neurogenesis. The results revealed that 10 µM CK promotes neurogenesis, proliferation and reduces apoptosis of EnNSCs after induction by thrombin. After that, CK treatment increased the neurogenesis of EnNSCs through liver X receptor α (LXRα) signaling pathway using adeno-associated virus knockdown and knocked out mice of LXRα gene. Finally, intraperitoneal injection of 10 mg/kg CK improved the neurogenesis of subventricular zone (SVZ), myelin repair and behavioral deficit after stereotaxic injection of thrombin in the basal ganglia of mice, and this process involved LXRα. These observations provided evidence regarding the effect of CK in pro-neurogenesis via LXRα activation, and suggested further evaluation of it due to its potential role as an effective modulator in the treatment of ICH.

4.
Proc Natl Acad Sci U S A ; 117(20): 10865-10875, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32366666

RESUMO

Cell-to-cell transmission of misfolding-prone α-synuclein (α-Syn) has emerged as a key pathological event in Parkinson's disease. This process is initiated when α-Syn-bearing fibrils enter cells via clathrin-mediated endocytosis, but the underlying mechanisms are unclear. Using a CRISPR-mediated knockout screen, we identify SLC35B2 and myosin-7B (MYO7B) as critical endocytosis regulators for α-Syn preformed fibrils (PFFs). We show that SLC35B2, as a key regulator of heparan sulfate proteoglycan (HSPG) biosynthesis, is essential for recruiting α-Syn PFFs to the cell surface because this process is mediated by interactions between negatively charged sugar moieties of HSPGs and clustered K-T-K motifs in α-Syn PFFs. By contrast, MYO7B regulates α-Syn PFF cell entry by maintaining a plasma membrane-associated actin network that controls membrane dynamics. Without MYO7B or actin filaments, many clathrin-coated pits fail to be severed from the membrane, causing accumulation of large clathrin-containing "scars" on the cell surface. Intriguingly, the requirement for MYO7B in endocytosis is restricted to α-Syn PFFs and other polycation-bearing cargos that enter cells via HSPGs. Thus, our study not only defines regulatory factors for α-Syn PFF endocytosis, but also reveals a previously unknown endocytosis mechanism for HSPG-binding cargos in general, which requires forces generated by MYO7B and actin filaments.

5.
Nanomedicine ; : 102224, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32428675

RESUMO

Anlotinib is a new type of small-molecule multi-target tyrosine kinase inhibitor with inhibitory effects against angiogenesis and tumor growth. An effective targeted nano-delivery system is urgently needed to effectively utilize anlotinib for the treatment of melanoma and lung metastases. In this study, an anlotinib-loaded reduction-sensitive nanomicelle, cyclic RGD peptide (cRGDyk)-anlotinib-reduction sensitive micelles (cARM), was developed as a tumor microenvironment-responsive delivery platform. The micelle carrier was formed by the self-assembly of reduction-sensitive amphiphilic copolymers DSPE-SS-PEG2k and DSPE-PEG2k-cRGDyk. The disulfide bonds in the amphiphilic block of micelles are responsive to elevated GSH in tumor cells for controlled drug release. In a B16F10 tumor-bearing mouse model, cRGDyk-anlotinib-RM (cARM) showed better tumor tissue accumulation and internalization than those for non-reduction-sensitive micelles. Therefore, this reduction-sensitive drug delivery system benefits from its specificity, prolonged blood circulation time, effective absorption by tumor cells, and rapid release of intracellular drugs and is therefore a promising strategy.

6.
J Pineal Res ; : e12660, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323368

RESUMO

Choroidal neovascularization (CNV) is an important characteristic of advanced wet age-related macular degeneration (AMD) and leads to severe visual impairment among elderly patients. Previous studies have demonstrated that melatonin induces several biological effects related to antioxidation, anti-inflammation, and anti-angiogenesis. However, the role of melatonin in CNV, and its underlying mechanisms, has not been investigated thus far. In this study, we found that melatonin administration significantly reduced the scale and volume of CNV lesions, suppressed vascular leakage, and inhibited the capacity of vascular proliferation in the laser-induced mouse CNV model. Additionally, the results also show that the melatonin-treated retinal microglia in the laser-induced mice exhibited enhanced expression of M1-type markers, such as iNOS, CCL-3, CCL-5, and TNF-α, as well as decreased production of M2-type markers, such as Arg-1, Fizz-1, IL-10, YM-1, and CD206, indicating that melatonin switched the macrophage/microglia polarization from pro-angiogenic M2 phenotype to anti-angiogenic M1 phenotype. Furthermore, the RhoA/ROCK signaling pathway was activated during CNV formation, yet was suppressed after an intraperitoneal injection of melatonin. In conclusion, melatonin attenuated CNV, reduced vascular leakage, and inhibited vascular proliferation by switching the macrophage/microglia polarization from M2 phenotype to M1 phenotype via inhibition of RhoA/ROCK signaling pathway in CNV. This suggests that melatonin could be a novel agent for the treatment of AMD.

7.
Anal Chem ; 92(10): 6941-6948, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32329602

RESUMO

For surface-enhanced Raman scattering (SERS) analysis, only analytes that can be absorbed spontaneously onto a noble metal surface can be detected effectively. Therefore, getting nonadsorptive molecules close enough to the surface has always been a key challenge in SERS analysis. Here absorbance measurements show that the liquid-interfacial array (LIA) does not adsorb or enrich benzopyrene (Bap) molecules, which lack effective functional groups that can interact with the noble metal surfaces. But the SERS intensity of 0.1 ppm Bap on the LIA is 10 times larger than that of 10 ppm Bap on traditional solid substrate, i.e., 3 orders of magnitude of enhancement. The LIA overcomes the restriction of affinity between Bap molecules and the metal surface, and the Bap molecules can easily enter nanogaps without steric hindrance. Furthermore, both adsorptive and nonadsorptive molecules were used to observe the SERS enhancement behavior on the LIA platforms. In multiple detection, competitive SERS signal changes could be observed between adsorptive and nonadsorptive molecules or between nonadsorptive and nonadsorptive molecules. A theoretical scheme was profiled for localized surface plasmon resonance (SPR) properties of the LIA. Finite difference-time domain (FDTD) simulation shows that the LIAs have biphasic and accessible asymmetric hotspots, and the electric field enhancement in the CHCl3 (O) phase is approximately four times larger than that of the water (W) phase. In addition, the position and relative strength of the electromagnetic field depend on the spatial position of gold nanoparticles (GNPs) relative to the liquid-liquid interface (LLI), i.e., when the GNP dimer is completely immersed in a certain phase, the electromagnetic field enhancement of the CHCl3 phase is approximately 7 times larger than that of the W phase. We speculate that dual-phase-accessible hotspots and the hydrophobic environment provided by CHCl3 are two important factors contributing to successful detection of four common polycyclic aromatic hydrocarbons (PAHs) with a detection limit of 10 ppb. Finally, the LIA platform successfully realizes simultaneous detection of multiple PAHs in both plant and animal oils with good stability. This study provides a new direction for the development of high-efficiency and practical SERS technology for nonadsorptive molecules.

8.
Proc Natl Acad Sci U S A ; 117(19): 10357-10367, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32345720

RESUMO

Cystic fibrosis (CF) is a recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The most common symptoms include progressive lung disease and chronic digestive conditions. CF is the first human genetic disease to benefit from having five different species of animal models. Despite the phenotypic differences among the animal models and human CF, these models have provided invaluable insight into understanding disease mechanisms at the organ-system level. Here, we identify a member of the ABCC4 family, CG5789, that has the structural and functional properties expected for encoding the Drosophila equivalent of human CFTR, and thus refer to it as Drosophila CFTR (Dmel\CFTR). We show that knockdown of Dmel\CFTR in the adult intestine disrupts osmotic homeostasis and displays CF-like phenotypes that lead to intestinal stem cell hyperplasia. We also show that expression of wild-type human CFTR, but not mutant variants of CFTR that prevent plasma membrane expression, rescues the mutant phenotypes of Dmel\CFTR Furthermore, we performed RNA sequencing (RNA-Seq)-based transcriptomic analysis using Dmel\CFTR fly intestine and identified a mucin gene, Muc68D, which is required for proper intestinal barrier protection. Altogether, our findings suggest that Drosophila can be a powerful model organism for studying CF pathophysiology.

9.
Chin Med Sci J ; 35(1): 85-91, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32299541

RESUMO

Objective To investigate the association between total homocysteine (tHcy) level in plasma and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus (T2DM) accompanied by dyslipidemia. Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively. Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C. Plasma tHcy and lipid levels were measured as well. The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test. Plasma tHcy level of T2DM patients who carried the different genotypes was compared by Student's t test. Results Finally, 82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study. There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism in T2DM patients (t=2.27, P=0.02). Moreover, the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677 TT genotype was significantly higher than that in those with CT+CC genotype (13.62±6.97 vs. 10.95±3.62 µmol/L, t=2.20, P=0.03); while for patients without dyslipidemia, comparison of the tHcy level between those who carried the above two alleles showed no significantly difference (13.34±6.03 vs. 12.04±5.09 µmol/L, t=1.08, P=0.29). Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.

10.
Am J Transplant ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32243709

RESUMO

Approximately 33.6% of nondiabetic solid organ transplant recipients who received tacrolimus developed hyperglycemia. Whether the tacrolimus-induced gut microbiota is involved in the regulation of hyperglycemia has not been reported. Hyperglycemia was observed in a tacrolimus-treated mouse model, with reduction in taxonomic abundance of butyrate-producing bacteria and decreased butyric acid concentration in the cecum. This tacrolimus-induced glucose metabolic disorder was caused by the gut microbiota, as confirmed by a broad-spectrum antibiotic model. Furthermore, oral supplementation with butyrate, whether for remedy or prevention, significantly increased the butyric acid content in the cecum and arrested hyperglycemia through the regulation of glucose-regulating hormones, including glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and insulin, in serum. The butyrate-G-protein-coupled receptor 43-GLP-1 pathway in the intestinal crypts may be involved in the pathogenesis of normalization of hyperglycemia caused by the tacrolimus. Therefore, tacrolimus affects glucose metabolism through the butyrate-associated GLP-1 pathway in the gut, and oral supplementation with butyrate provides new insights for the prevention and treatment of tacrolimus-induced hyperglycemia in transplant recipients.

11.
Appl Opt ; 59(9): 2739-2745, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32225823

RESUMO

A novel three-observation-window time-gated algorithm that combines overlapped windows and discrete windows together is developed for accurate fluorescence lifetime extraction. The new algorithm adopting a rapid lifetime determination strategy can offer an excellent ability to precisely detect long fluorescence lifetime for fluorescence lifetime imaging microscopy. Monte Carlo simulation indicates that an extremely small relative standard deviation below 0.4% is obtained over a wide fluorescence lifetime range from 5 ns to 30 ns. The detection error of the short fluorescence lifetime less than 5 ns is further reduced by means of an adaptive window width method. In contrast to other algorithms, such as time-correlated single-photon counting and traditional gated-window methods, not only the detection range but also the measurement accuracy is dramatically enhanced.

12.
BMC Gastroenterol ; 20(1): 101, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32276605

RESUMO

BACKGROUND: Jejunogastric intussusception (JGI) is a rare but severe complication after gastric surgery. JGI can occur from a few days to 55 years postoperatively and has a reported incidence of < 0.1% in patients who undergo gastric surgery. We firstly report a male patient with duodenal cancer who underwent Whipple's procedure with side-to-side gastrojejunostomy and who subsequently developed JGI. A literature review is provided. CASE PRESENTATION: A 68-year-old man was admitted to our emergency department with left upper quadrant abdominal pain and hematemesis of 4 h' duration. He had undergone Whipple's procedure (duct-to-mucosa pancreaticojejunostomy and side-to-side gastrojejunostomy) with B-II reconstruction for duodenal papillary adenocarcinoma 5 years earlier. His vital signs were stable with a blood pressure of 163/93 mmHg, temperature of 37.0 °C; and heart and respiratory rates of 86 per/min and 20 per/min, respectively. Physical assessment showed mild tenderness in the left upper quadrant, only. A complete blood count showed white cell and platelet counts of 11.69 × 103/L and 196 × 103/L, respectively, and a hemoglobin level of 13.5 g/L. Abdominal computed tomography (CT) suggested a retrograde intussusception of the intestines into the stomach with dilatation of the remnant stomach. The patient immediately underwent exploratory laparotomy, which revealed a 20-cm retrograde efferent limb at the remnant stomach that had travelled through the previous gastrojejunostomy. There was no evidence of malignancy. We manually reduced the intussuscepted loop using gentle traction, and the viability of the intestinal loop was preserved. The patient had an uneventful postoperative recovery. CONCLUSION: JGI is a rare but potentially fatal complication after gastric surgery, especially following Whipple's procedure. Early diagnosis and treatment are crucial, and surgery is considered the most effective treatment for JGI.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32306090

RESUMO

PURPOSE: Most studies have concentrated on the changes in contact pressure and area on the tibiofemoral joint. This study compared the contact mechanics underneath the medial meniscus of a repaired vertical longitudinal tear with that of the intact or the torn ones. METHODS: In this controlled laboratory study, a 1000 N compressive axial load was applied to eight fresh-frozen cadaveric knees at four flexion angles and four loading conditions using a custom testing apparatus attached to a material testing machine. Intact knees, knees with a medial meniscus vertical longitudinal tear, and knees after meniscal repair were tested. The peak contact pressure and area underneath the meniscus were measured using Fuji pressure-sensitive film. RESULTS: A medial meniscus vertical longitudinal tear significantly increased the contact pressure and decreased contact area underneath the meniscus compared with those at the intact meniscus under all tested biomechanical conditions, and repair of the tear can restore the contact pressure and area in most conditions. While the repaired group showed a significantly higher or similar contact pressure compared with the tear group at 90° neutral knee position and at 60°, 90° 5 N·m-external rotation and 134 N-anterior tibial translation, and 5 N·m-internal rotation at all flexion angles. The contact area corresponding to the aberrant result of the contact pressure in the repaired group was lower than in the intact meniscus group. CONCLUSIONS: The contact mechanics underneath the meniscus of the repaired medial meniscus vertical longitudinal tear were significantly improved compared with the corresponding tear conditions in most cases, while the contact pressure and area at some certain status after repair were not significantly different from those of the corresponding tear conditions.

14.
Environ Pollut ; 262: 114139, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32120253

RESUMO

We investigated the levels and distributions of organochlorine pesticides (OCPs) in 159 background soil samples collected from 30 forested mountain sites across China. The sum of DDT was the most abundant OCP, with the concentrations of 0.197-207 ng/g and 0.033-122 ng/g in the O-horizon and A-horizon, respectively. High concentrations of OCPs usually occur near agricultural regions or high consumption areas. The spatial distribution was mainly influenced by the emission sources and soil total organic contents (TOC). The chiral compounds were generally nonracemic in the soils and showed preferential degradation of (-) o,p'- dichlorodiphenyltrichloroethane, (+) trans-chlordane, and (-) cis-chlordane in both the O- and A-horizons. The enantiomeric fraction (EF) distributions of chiral OCPs displayed no differences across the forest sites in the O-horizon or the A-horizon. Comparing the deviation of EFs from racemic (DEVrac = absolute value of 0.500 - EF) with environmental parameters, we found that DEVrac of cis-chlordane demonstrated a strong positive correlation with TOC (p < 0.05) and the C/N ratio (p < 0.01). This relationship suggests that these factors could affect the microbial activity and significantly impact the extent of enantioselective degradation of chiral compounds in the soils. Fresh and historical applications of DDT and historical chlordane and endosulfan uses may be prominent sources of OCP accumulation in Chinese forest soils.

15.
Environ Pollut ; 262: 114267, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32179224

RESUMO

Multiple types of persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), and hexachlorobenzene (HCB), can be unintentionally released from combustion or thermal industrial processes, which are speculated to be the main sources of these contaminants, as they were banned on production and use since several decades ago. In this study, concentrations and sources of 40 PCBs, 39 PCNs, and HCB were analyzed in air samples collected during the period 2012-2015 at a background site in east China. ΣPCBs, ΣPCNs, and HCB were in the range of 9-341 pg/m3, 6-143 pg/m3, and 14-522 pg/m3, respectively. Seasonal characteristics with high levels in winter and low levels in summer were observed for PCNs and HCB. PCBs also exhibited slightly higher levels in winter. Source apportionment was conducted, using polycyclic aromatic hydrocarbons (PAHs) as combustion sources indicator, combined with principal component analysis (PCA) and positive matrix factorization (PMF) model. The results indicated that the legacy of past produced and used commercial PCBs was the dominant contributor (∼56%) to the selected PCBs in the atmosphere in east China. PCNs were mainly emitted from combustion sources (∼64%), whereas HCB almost entirely originated from combustion process (>90%).

16.
Artigo em Inglês | MEDLINE | ID: mdl-32210915

RESUMO

Background: Turner syndrome (TS) is a sex chromosome aneuploidy with a variable spectrum of symptoms including short stature, ovarian failure and skeletal abnormalities. The etiology of TS is complex, and the mechanisms driving its pathogenesis remain unclear. Methods: In our study, we used the online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE46687 to identify differentially expressed genes (DEGs) between monosomy X TS patients and normal female individuals. The relevant data on 26 subjects with TS (45,XO) and 10 subjects with the normal karyotype (46,XX) was investigated. Then, tissue-specific gene expression, functional enrichment, and protein-protein interaction (PPI) network analyses were performed, and the key modules were identified. Results: In total, 25 upregulated and 60 downregulated genes were identified in the differential expression analysis. The tissue-specific gene expression analysis of the DEGs revealed that the system with the most highly enriched tissue-specific gene expression was the hematologic/immune system, followed by the skin/skeletal muscle and neurologic systems. The PPI network analysis, construction of key modules and manual screening of tissue-specific gene expression resulted in the identification of the following five genes of interest: CD99, CSF2RA, MYL9, MYLPF, and IGFBP2. CD99 and CSF2RA are involved in the hematologic/immune system, MYL9 and MYLPF are related to the circulatory system, and IGFBP2 is related to skeletal abnormalities. In addition, several genes of interest with possible roles in the pathogenesis of TS were identified as being associated with the hematologic/immune system or metabolism. Conclusion: This discovery-driven analysis may be a useful method for elucidating novel mechanisms underlying TS. However, more experiments are needed to further explore the relationships between these genes and TS in the future.

17.
Sci Rep ; 10(1): 5157, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198373

RESUMO

The gold standard for prostate cancer (PCa) diagnosis is prostate biopsy. However, it remines controversial as an invasive mean for patients with PSA levels in the gray zone (4-10 ng/mL). This study aimed to develop strategy to reduce the unnecessary prostate biopsy. We retrospectively identified 235 patients with serum total PSA testing in the gray zone before prostate biopsy between 2014 and 2018. Age, PSA derivates, prostate volume and multiparametric magnetic imaging (mpMRI) examination were assessed as predictors for PCa and clinically significant PCa with Gleason score ≥ 7 (CSPCa). Univariate analysis showed that prostate volume, PSAD, and mpMRI examination were significant predictors of PCa and CSPCa (P < 0.05). The differences of diagnostic accuracy between mpMRI examination (AUC = 0.69) and other clinical parameters in diagnostic accuracy for PCa were not statistically significant. However, mpMRI examination (AUC = 0.79) outperformed prostate volume and PSAD in diagnosis of CSPCa. The multivariate models (AUC = 0.79 and 0.84 for PCa and CSPCa) performed significantly better than mpMRI examination for detection of PCa (P = 0.003) and CSPCa (P = 0.036) among patients with PSA level in the gray zone. At the same level of sensitivity as the mpMRI examination to diagnose PCa, applying the multivariate models could reduce the number of biopsies by 5% compared with mpMRI examination. Overall, our results supported the view that the multivariate model could reduce unnecessary biopsies without compromising the ability to diagnose PCa and CSPCa. Further prospective validation is required.

18.
Anal Chem ; 92(6): 4419-4426, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32053360

RESUMO

Cancer cells rely on fatty acid synthase (FASN), a key enzyme for de novo biosynthesis of long chain fatty acids, to sustain their proliferative potential and drive invasion. Unfortunately, conventional FASN assays are technically inadequate for discerning otherwise elusive FASN activity in complex biological milieux, which has hindered progress in the functional study of FASN and development of its inhibitors. Here, we describe a chemical probe with unprecedented selectivity and sensitivity for the labeling of active FASN in living cells, thus demonstrating a new analytical modality for visualizing endogenous FASN activity and exploring opportunities for drug discovery.

19.
Orthod Craniofac Res ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32011803

RESUMO

OBJECTS: To simulate and compare salivary flow patterns over a tooth surface bonded with different orthodontic appliances using computational fluid dynamics (CFD) and investigate the impact of bracket design on salivary flow in relation to peri-bracket bacterial accumulation. SETTING AND SAMPLE POPULATION: The models were constructed using computed tomography (CT) data of 81 patients scheduled for fixed orthodontic treatment: 27 patients (10 males, 17 females) for the metal Victory MBT™ bracket; 27 patients (seven males, 20 females) for the ceramic Clarity MBT™ bracket; 27 patients (15 males, 12 females) for the Mini Uni-Twin (MUT) bracket. METHODS: The salivary flow patterns were simulated by CFD and compared between the groups and the model predictions were validated using a bacteriological experiment. RESULTS: The MUT bracket was associated with the greatest number of low salivary velocity areas, as it is designed with a connector between double tie wings and a right contact angle between tooth surface and bracket base. After archwire placement, the centred slot in the bracket and the bilateral sites around the bracket had higher bacterial retention and needed special oral hygiene measures. The obtuse contact angle of the ceramic bracket formed a pocket structure in the tie-wing area, retarding salivary flow and contributing to bacteria retention. CONCLUSION: With the evaluation of CFD models, we demonstrate that salivary flow patterns over a tooth surface with a bracket vary with bracket designs and further promote bacterial retention in specific locations, suggesting the need for additional oral hygiene measures for specific bracket types.

20.
Org Lett ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32077704

RESUMO

Described herein is a visible-light mediated intermolecular radical cyclization approach to access heterocycles. Heteroatom radicals, such as silicon and phosphorus atom radicals, were generated via direct hydrogen atom abstraction by the photoexcited catalyst species with hydro-silanes and phosphine oxides. The radical addition/cyclization/HAT (hydrogen atom transfer) reaction sequences of 1,6-enynes and 1,6-dienes were highly efficient delivering the desired heterocycles in good yields.

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