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1.
Magn Reson Med ; 2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33934396

RESUMO

PURPOSE: Benchmarking of flow and perfusion MR techniques on standardized phantoms can facilitate the use of advanced angiography and perfusion-mapping techniques across multiple sites, field strength, and vendors. Here, MRA and perfusion mapping by arterial spin labeling (ASL) using Fourier transform (FT)-based velocity-selective saturation and inversion pulse trains were evaluated on a commercial perfusion phantom. METHODS: The FT velocity-selective saturation-based MRA and FT velocity-selective inversion-based ASL perfusion imaging were compared with time-of-flight and pseudo-continuous ASL at 3 T on the perfusion phantom at two controlled flow rates, 175 mL/min and 350 mL/min. Velocity-selective MRA (VSMRA) and velocity-selective ASL (VSASL) were each performed with three velocity-encoding directions: foot-head, left-right, and oblique 45°. The contrast-to-noise ratio for MRA scans and perfusion-weighted signal, as well as labeling efficiency for ASL methods, were quantified. RESULTS: On this phantom with feeding tubes having only vertical and transverse flow directions, VSMRA and VSASL exhibited the dependence of velocity-encoding directions. The foot-head-encoded VSMRA and VSASL generated similar signal contrasts as time of flight and pseudo-continuous ASL for the two flow rates, respectively. The oblique 45°-encoded VSMRA yielded more uniform contrast-to-noise ratio across slices than foot-head and left-right-encoded VSMRA scans. The oblique 45°-encoded VSASL elevated labeling efficiency from 0.22-0.68 to 0.82-0.90 through more uniform labeling of the entire feeding tubes. CONCLUSION: Both FT velocity-selective saturation-based VSMRA and FT velocity-selective inversion-based VSASL were characterized on a commercial perfusion phantom. Careful selection of velocity-encoding directions along the major vessels is recommended for their applications in various organs.

2.
Chem Commun (Camb) ; 57(31): 3801-3804, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33876126

RESUMO

The mechanism underlying the strong adhesion between DNA with consecutive adenines (polyA) and Au nanoparticles (AuNPs) is experimentally and theoretically studied. We elucidate that the consecutive adenines collectively result in hydrophobic collapse in the adhesion process, which plays a pivotal role for the high adhesion affinity and specificity.

3.
J Oral Pathol Med ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33880801

RESUMO

BACKGROUND: Early detection and prognostic prediction are crucial in improving the survival of patients with head and neck squamous cell carcinoma (HNSCC). Therefore, we provided potential molecular markers in this study for early diagnosis and prognosis of this cancer based on the The Cancer Genome Atlas (TCGA) database analysis and experimental validations. METHODS: Differentially expressed genes (DEGs) between HNSCC tumor and normal samples were identified by TCGA database-based analyses. Univariate and multivariate Cox regression analyses was applied respectively to identify survival-related DEGs and independent prognostic factors in HNSCC. Further, RT-qPCR was employed to verify expression of DEGs in cancer and adjacent tissues from HNSCC patients recruited in our hospital, in which we also clarified the correlation between candidate genes and clinicopathological characteristics and prognosis of HNSCC patients. RESULTS: TCGA data analyses yielded 59 DEGs. Cox analyses identified 13 candidate genes closely related to prognosis of HNSCC patients and established a five-gene signature comprising AC103702.2, LINC00941, RPL29, FOXL2 and CCL11. This five-gene signature could classify patients into high- and low-risk groups. The survival rate of the high-risk group was significantly lower than that of the low-risk group. Clinical tissue experiments further confirmed that AC103702.2, LINC00941, CCL11 and RPL29P19 genes were inversely associated with the prognosis of HNSCC patients, while CCL11 gene was positively associated. We also found that high-risk HNSCC patients presented a higher incidence of lymph-node metastasis. CONCLUSION: Five prognostic marker genes (AC103702.2, LINC00941, CCL11, RPL29P19 and FOXL2) as a gene cluster may serve as prognostic marker genes in HNSCC.

4.
Huan Jing Ke Xue ; 42(5): 2240-2250, 2021 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-33884793

RESUMO

To reveal the hydrochemical characteristics of karst wetland located in a subtropical area and at lower elevations in China, 27 surface water samples were collected during three periods (wet, normal, and dry) in the Huixian karst wetland to investigate the distributions, pollution, and irrigation application of 12 inorganic ions and 10 heavy metals. Based on their concentrations, the Nemerow index and the four evaluation systems of the sodium adsorption ratio (SAR), sodium concentration (SC), permeability index (PI), and residual sodium carbonate (RSC) were applied to evaluate the pollution characteristics and irrigation application. It was found that the water type in this area was Ca2+-HCO3- and weakly alkaline. Regarding the 12 inorganic ions and 10 heavy metals, NH4+ exceeded the Chinese standards for drinking water with an exceedance rate of 25.93%, and the exceedance rates of Al, Mn, and Hg were 11.11%, 44.44%, and 37.04%, respectively. The spatiotemporal scaling effect on inorganic ions was lower than that of heavy metals, and the distributions of the inorganic ions and heavy metals were in the order of wet period > normal period > dry period. However, the surface water quality in the Huixian karst wetland was generally well-protected based on the pollution assessment. The Nemerow index ranged from 0.75 to 2.69, which recognized the main pollution contributors as NH4+, Mn, Al, and Hg with the contamination grade from slight pollution to moderate pollution, especially in the core area during the wet period. According to the limits of standards for irrigation water quality and environmental quality for surface water, as well as the evaluation results of the SAR, SC, PI, and RSC, the surface water in the Huixian karst wetland was generally suitable for irrigation, and the water quality in the dry period was better than that in the wet and normal periods. The surface water from site PH1 during the normal period with 19.1 µg·L-1 of Hg and site FH8 during the wet period with 13.7 mg·L-1 of NH4+ were not suitable for agricultural irrigation.

5.
Chin Med J (Engl) ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33928916

RESUMO

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18-59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 µg/dose or 10 µg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 µg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-µg vaccine (n = 24), 10-µg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-µg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-µg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and 7 (58%) participants reported at least one adverse event (AE) after receiving 5-µg vaccine, 10-µg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and 9 (18%) 0/14-regimen participants reported at least one AE after receiving 5-µg vaccine, 10-µg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-µg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).

6.
Genome Biol ; 22(1): 125, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926529

RESUMO

BACKGROUND: Medulloblastoma (MB) is the most common malignant pediatric brain tumor that originates in the cerebellum and brainstem. Frequent somatic mutations and deregulated expression of epigenetic regulators in MB highlight the substantial role of epigenetic alterations. 5-hydroxymethylcytosine (5hmC) is a highly abundant cytosine modification in the developing cerebellum and is regulated by ten-eleven translocation (TET) enzymes. RESULTS: We investigate the alterations of 5hmC and TET enzymes in MB and their significance to cerebellar cancer formation. We show total abundance of 5hmC is reduced in MB, but identify significant enrichment of MB-specific 5hmC marks at regulatory regions of genes implicated in stem-like properties and Nanog-binding motifs. While TET1 and TET2 levels are high in MBs, only knockout of Tet1 in the smoothened (SmoA1) mouse model attenuates uncontrolled proliferation, leading to a favorable prognosis. The pharmacological Tet1 inhibition reduces cell viability and platelet-derived growth factor signaling pathway-associated genes. CONCLUSIONS: These results together suggest a potential key role of 5hmC and indicate an oncogenic nature for TET1 in MB tumorigenesis, suggesting it as a potential therapeutic target for MBs.

7.
Sci Rep ; 11(1): 8842, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893350

RESUMO

To evaluate the effect of age and parity on maternal cardiac diastolic function in second trimester among pregnant women with normal left ventricular ejection fraction. To analyze the correlation between impaired diastolic function and pre-eclampsia. It had been suggested that maternal cardiac adaptations during pregnancy differed between nulliparous and primiparous women and also varied according to age. Impaired cardiac function may precede pre-eclampsia. Therefore, we examined the effects of parity and age on cardiac diastolic function during pregnancy and whether impaired diastolic function during the second trimester correlates with pre-eclampsia. Women with singleton pregnancies at 13 + 0 to 27 + 6 weeks' gestation and left ventricular ejection fraction (LVEF) ≥ 50% were retrospectively identified. Diastolic function parameters were assessed using transthoracic echocardiography. Pre-eclampsia was identified from medical records. The effect of age and parity on maternal cardiac diastolic function as well as the correlation between impaired diastolic function and occurrence rate of pre-eclampsia were examined. 376 pregnant women were included (median age: 30 years; median gestational age: 14 weeks; 171 primiparous women). LVEF was 66%. Impaired cardiac diastolic function was seen in 7.8% of pregnant women < 35 years compared with 28.6% of those ≥ 35 years (p = 0.000). ROC curve showed women with maternal age over 32 began to have a higher rate of impaired cardiac diastolic function (AUC = 0.704, p = 0.000, sensitivity = 54.5%, specificity = 75.3%). There was no difference in diastolic function indices between maternal women grouped by parity. Higher maternal age was an independent risk factor of declining Em (p < 0.05). Em < 13 cm/s was significantly associated with pre-eclampsia occurrence (HR 8.56; 95% CI 3.40-21.57) after being adjusted for confounders. Maternal age is an independent risk factor for diastolic function decline. There is no difference in cardiac diastolic function between nulliparous women and primiparous women. Pre-eclampsia occurrence is significantly higher in patients with impaired diastolic function at mid-gestation. The application of risk grading using diastolic function at mid-gestation may improve the survival outcomes of pregnant women.

8.
Neuroscience ; 463: 174-183, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33836246

RESUMO

Major depressive disorder is a serious and complex mental illness, and multiple brain regions are involved in its pathogenesis. There is increasing evidence that the amygdala is involved in depression; however, the underlying molecular mechanisms remain unclear. In this study, we applied a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomic and isobaric tags for relative and absolute quantitation (iTRAQ) proteomic to study changes in the amygdala in a chronic unpredictable mild stress (CUMS) rat model of depression. Differential analysis identified 42 metabolites and 171 proteins that were differentially expressed in the CUMS and control groups. Integrated analyses revealed two major changes in the amygdala of CUMS rats: (1) perturbations in amino acids and carbohydrate metabolism, transport-/catabolism-related proteins activity, and metabolic enzyme activity; (2) abnormal expression of synaptogenesis and oxidative phosphorylation-associated proteins.

9.
J Am Mosq Control Assoc ; 37(1): 38-40, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33857314

RESUMO

Microbiota are vital for the development, physiology, and vectorial capacity of mosquitoes. The composition and role of microbiota in Anopheles species, especially Anopheles gambiae and Anopheles stephensi, have been extensively studied, but little is known about the microbiota of Anopheles species in China. We characterized the microbial communities of Anopheles dirus, Anopheles sinensis, and Anopheles lesteri by 16S rRNA sequencing. There were distinct differences in the composition of microbiota in An. lesteri and the other 2 species. The discriminatory genera in the 3 species were analyzed by the linear discriminant analysis effect size method. Our results provide an overview of the population structure of microbiota in 3 native Anopheles species and will pave the way for further understanding of their role in mosquito physiology and vector competence.

10.
J Clin Invest ; 131(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33720050

RESUMO

Glioblastoma (GBM) is composed of heterogeneous tumor cell populations, including those with stem cell properties, termed glioma stem cells (GSCs). GSCs are innately less radiation sensitive than the tumor bulk and are believed to drive GBM formation and recurrence after repeated irradiation. However, it is unclear how GSCs adapt to escape the toxicity of repeated irradiation used in clinical practice. To identify important mediators of adaptive radioresistance in GBM, we generated radioresistant human and mouse GSCs by exposing them to repeat cycles of irradiation. Surviving subpopulations acquired strong radioresistance in vivo, which was accompanied by a reduction in cell proliferation and an increase in cell-cell adhesion and N-cadherin expression. Increasing N-cadherin expression rendered parental GSCs radioresistant, reduced their proliferation, and increased their stemness and intercellular adhesive properties. Conversely, radioresistant GSCs lost their acquired phenotypes upon CRISPR/Cas9-mediated knockout of N-cadherin. Mechanistically, elevated N-cadherin expression resulted in the accumulation of ß-catenin at the cell surface, which suppressed Wnt/ß-catenin proliferative signaling, reduced neural differentiation, and protected against apoptosis through Clusterin secretion. N-cadherin upregulation was induced by radiation-induced IGF1 secretion, and the radiation resistance phenotype could be reverted with picropodophyllin, a clinically applicable blood-brain-barrier permeable IGF1 receptor inhibitor, supporting clinical translation.

11.
Huan Jing Ke Xue ; 42(4): 1750-1760, 2021 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742810

RESUMO

To investigate the major ionic chemical characteristics and seasonal variations, 27 groundwater samples were collected from the wet season, flat season, and dry season during 2018-2019 in the Huixian Karst wetland, which is the largest low-altitude karst wetland in China. The single pollution standard index was applied to evaluate the groundwater pollution during different periods, and the major ionic factors of the karst groundwater were analyzed using the statistical analysis method, Gibbs diagram, and ion ratio. The results revealed that the groundwater samples were a weakly alkaline fresh water that were rich in Ca2+ and HCO3-. The average concentrations of the primary ions followed the order of flat season > wet season > dry season; meanwhile, the water quality in the dry season was better than that in the wet and flat seasons. The K+ and NO3- in the karst groundwater were mostly affected by the spatial distributions of the aquifers, and the Mg2+, SO42-, NO2-, NH4+, and TDS were related to the space-season scale. Na+, Ca2+, HCO3-, and Cl- were relatively stable ions in the karst groundwater. The hydrochemical characteristics were primarily determined by carbonate rock dissolution and were found to be the HCO3-Ca type, which accounted for 77.78%, 77.78%, and 88.89% in the wet season, flat season, and dry season, respectively. The karst groundwater was predominantly polluted by SO42-, NO3-, and NO2-; particularly, NO3- exhibited serious pollution points, and SO42- had heavy pollution points in the wet and flat seasons. The chemical composition of the karst groundwater was controlled mostly by water-rock interactions. Ca2+ and HCO3- primarily came from calcite dissolution, and the high concentrations of Mg2+ and SO42- in a few number of points were controlled by dolomite, dolomitic limestone, and pyrite. K+, Na+, SO42-, NO3-, and Cl- partly came from atmospheric precipitation, and Na+ and Cl- partly came from human activities; K+ was related to potash fertilizer, and the main source of NO3- was chemical fertilizer.

12.
Adv Clin Exp Med ; 30(2): 157-163, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33650330

RESUMO

BACKGROUND: This study investigated liver expression of paraoxonase 3 (PON3), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and nuclear factor (NF)-κB in a rat model of type-2 diabetes mellitus (T2DM), and assessed the effect of liraglutide treatment. OBJECTIVES: To investigate liver PON3 expression in rats withT2DM assess its role in disease pathogenesis, and determine the effect of liraglutide on its expression. MATERIAL AND METHODS: Type 2 diabetes mellitus was induced in 3 groups of rats: positive control group (PC; no treatment), and low-dose (LL; 100 µg/kg) and high-dose (HL; 200 µg/kg) liraglutide groups. Healthy rats served as a normal control (NC) group. Protein and mRNA expression were measured with western blot and reverse-transcriptase polymerase chain reaction (RT-PCR), respectively. RESULTS: After liraglutide treatment, fasting plasma glucose (FPG), homeostasis model assessment-insulin resistance (HOMA-IR), fasting insulin (FINS), malondialdehyde (MDA), and interleukin 6 (IL-6) levels were lower in HL rats compared with LL ones (p < 0.05). Compared to NC rats, FPG, FINS, HOMA-IR, low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and IL-6 levels were the lowest in HL rats, followed by LL and PC ones (p < 0.05). Body weight (BW) was lower in LL and HL groups than in NC and PC (p < 0.05). The liver expression of PON3, PI3K and Akt were the highest in HL rats, followed by LL and PC (p < 0.05). The NF-κB expression was the lowest in HL rats, followed by LL and PC (p < 0.05). The PON3 expression was decreased in the diabetic rat liver. CONCLUSIONS: Liraglutide can increase PI3K, Akt and PON3 expression, and decrease NF-κB expression. The effect of liraglutide on improving insulin resistance and abnormal glucolipid metabolism in T2DM rats may be associated with increased liver PON3 expression.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Animais , Arildialquilfosfatase , Glicemia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina , Liraglutida/farmacologia , Fígado , Fosfatidilinositol 3-Quinases , Ratos , Ratos Sprague-Dawley
13.
Hum Gene Ther ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33726499

RESUMO

This phase II clinical trial investigated the efficacy and safety of intramuscular injection of plasmid pUDK-HGF which encodes the human hepatocyte growth factor gene in patients with critical limb ischemia (CLI). Resting pain patients (n=119) and patients with leg ulcers (n=121) were enrolled as two cohorts and randomized to receive pUDK-HGF treatment on days 0, 14, and 28. In the resting pain cohort, the proportion of patients with complete pain relief on day 180 after receiving pUDK-HGF injection, as the primary outcome, was significantly higher than that of the placebo group on the same day (p = 0.0148). More responders with >50% pain reduction were also observed in the pUDK-HGF groups than in the placebo groups (p = 0.0168). In the ulcer cohort of patients, pUDK-HGF treatment tended to be superior to the placebo in the percentage of patients with both complete ulcer healing and >50% ulcer healing. No significant differences in the incidence of adverse events or serious adverse events were observed among the groups. The mid dose pUDK-HGF (6 mg) was the most efficacious, and is therefore an appropriate dose for use in a phase III clinical trial. Keywords Peripheral arterial disease, Critical limb ischemia, Gene therapy, Pain at rest, Ulceration, Hepatocyte growth factor, pUDK-HGF treatment, Phase II clinical trial.

14.
J Biochem Mol Toxicol ; : e22737, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33751715

RESUMO

Homocysteine (Hcy) is a sulfur-containing amino acid that originated in methionine metabolism and the elevated level of Hcy in plasma is considered to be an independent risk factor for cardiovascular diseases (CVD). Endothelial dysfunction plays a major role in the development of CVD, while the potential mechanism of Hcy-induced endothelial dysfunction is still unclear. Here, in Hcy-treated endothelial cells, we observed the destruction of mitochondrial morphology and the decline of mitochondrial membrane potential. Meanwhile, the level of ATP was reduced and the reactive oxygen species was increased. The expressions of dynamin-related protein 1 (Drp1) and phosphate-Drp1 (Ser616) were upregulated, whereas the expression of mitofusin 2 was inhibited by Hcy treatment. These findings suggested that Hcy not only triggered mitochondrial dysfunction but also incurred an imbalance of mitochondrial dynamics in endothelial cells. The expression of mitochondrial calcium uniporter (MCU) was activated by Hcy, contributing to calcium transferring into mitochondria. Interestingly, the formation of mitochondria-associated membranes (MAMs) was increased in endothelial cells after Hcy administration. The inositol 1,4,5-triphosphate receptor (IP3R)-glucose-regulated protein 75 (Grp75)-voltage-dependent anion channel (VDAC) complex, which was enriched in MAMs, was also increased. The accumulation of mitochondrial calcium could be blocked by inhibiting with the IP3R inhibitor Xestospongin C (XeC) in Hcy-treated cells. Then, we confirmed that the mitochondrial dysfunction and the increased mitochondrial fission induced by Hcy could be attenuated after Hcy and XeC co-treatment. In conclusion, Hcy-induced mitochondrial dysfunction and dynamics disorder in endothelial cells were mainly related to the increase of calcium as a result of the upregulated expressions of the MCU and the IP3R-Grp75-VDAC complex in MAMs.

15.
Acta Pharmacol Sin ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767381

RESUMO

Androgen receptor (AR), a ligand-activated transcription factor, is a master regulator in the development and progress of prostate cancer (PCa). A major challenge for the clinically used AR antagonists is the rapid emergence of resistance induced by the mutations at AR ligand binding domain (LBD), and therefore the discovery of novel anti-AR therapeutics that can combat mutation-induced resistance is quite demanding. Therein, blocking the interaction between AR and DNA represents an innovative strategy. However, the hits confirmed targeting on it so far are all structurally based on a sole chemical scaffold. In this study, an integrated docking-based virtual screening (VS) strategy based on the crystal structure of the DNA binding domain (DBD) of AR was conducted to search for novel AR antagonists with new scaffolds and 2-(2-butyl-1,3-dioxoisoindoline-5-carboxamido)-4,5-dimethoxybenzoicacid (Cpd39) was identified as a potential hit, which was competent to block the binding of AR DBD to DNA and showed decent potency against AR transcriptional activity. Furthermore, Cpd39 was safe and capable of effectively inhibiting the proliferation of PCa cell lines (i.e., LNCaP, PC3, DU145, and 22RV1) and reducing the expression of the genes regulated by not only the full-length AR but also the splice variant AR-V7. The novel AR DBD-ARE blocker Cpd39 could serve as a starting point for the development of new therapeutics for castration-resistant PCa.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33694256

RESUMO

Metallic nanocube ensembles exhibit tunable localized surface plasmon resonance to induce the light manipulation at the subwavelength scale. Nevertheless, precisely control anisotropic metallic nanocube ensembles with relative spatial directionality remains a challenge. Here, we report a DNA origami based nanoprinting (DOBNP) strategy to transfer the essential DNA strands with predefined sequences and positions to the surface of the gold nanocubes (AuNCs). These DNA strands ensured the specific linkages between AuNCs and gold nanoparticles (AuNPs) that generating the stereo-controlled AuNC-AuNP nanostructures (AANs) with controlled geometry and composition. By anchoring the single dye molecule in hot spot regions, the dramatic enhanced electromagnetic field aroused stronger surface enhanced Raman scattering (SERS) signal amplification. Our approach opens the opportunity for the fabrication of stereo-controlled metal nanostructures for designing highly sensitive photonic devices.

17.
Vaccines (Basel) ; 9(2)2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33670249

RESUMO

Infectious bronchitis virus (IBV) poses massive economic losses in the global poultry industry. Here, we firstly report the construction and immunogenicity comparison of virus-like particles (VLPs) carrying the S, M and E proteins (SME-VLPs); VLPs carrying the S and M proteins (SM-VLPs); and VLPs carrying the M and E proteins (ME-VLPs) from the dominant serotype representative strain GX-YL5 in China. The neutralizing antibody response induced by the SME-VLPs was similar to that induced by the inactivated oil vaccine (OEV) of GX-YL5, and higher than those induced by the SM-VLPs, ME-VLPs and commercial live vaccine H120. More importantly, the SME-VLPs elicited higher percentages of CD4+ and CD8+ T lymphocytes than the SM-VLPs, ME-VLPs and OEV of GX-YL5. Compared with the OEV of GX-YL5, higher levels of IL-4 and IFN-γ were also induced by the SME-VLPs. Moreover, the mucosal immune response (sIgA) induced by the SME-VLPs in the tear and oral swabs was comparable to that induced by the H120 vaccine and higher than that induced by the OEV of GX-YL5. In the challenge experiment, the SME-VLPs resulted in significantly lower viral RNA levels in the trachea and higher protection scores than the OEV of GX-YL5 and H120 vaccines, and induced comparable viral RNA levels in the kidneys, and tear and oral swabs to the OEV of GX-YL5. In summary, among the three VLPs, the SME-VLPs carrying the S, M and E proteins of IBV could stimulate the strongest humoral, cellular and mucosal immune responses and provide effective protection, indicating that it would be an attractive vaccine candidate for IB.

18.
Head Neck ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33783893

RESUMO

BACKGROUND: To describe the indications, technique, and preliminary experience in the application of the superior thyroid artery perforator flap (STAPF) for the reconstruction of various medium-sized intraoral defects. METHODS: From September 2018 to September 2019, 12 consecutive cases of oral squamous cell carcinoma underwent reconstruction with a STAPF. Clinical details were collected, and postoperative function was analyzed. RESULTS: The venous drainage of the STAPF is variable with drainage into the internal jugular vein in six cases, into both the internal and external jugular veins in four cases, and into the external jugular vein in two cases. Ten cases were harvested as pedicled flaps, while two cases required a venous anastomosis due to inadequate length of the venous pedicle. Ten flaps survived completely, whereas two flaps had partial necrosis that ultimately resolved with secondary healing. CONCLUSIONS: STAPF is a reliable method for the reconstruction of medium-sized intraoral defects.

19.
Minerva Med ; 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33723973

RESUMO

BACKGROUND: To explore the application value of Stachys sieboldii Miq granules which is a kind of traditional Chinese medicine (TCM) in stable chronic obstructive pulmonary disease (COPD) patients. METHODS: Randomized double blind method was used to select 160 patients with stable COPD. The patients were randomly divided into placebo group and Stachys sieboldii Miq group. Both groups underwent test items for 2 months, detected plasma cytokines, Saint George Respiratory Questionnaire (SGRQ) scores, pulmonary function, and the frequency of acute exacerbation (AE) at week 12. Follow-up was done every 12 weeks till 48 weeks to record the frequency of AE. RESULTS: A total of 120 patients with 60 in each group were included. At week 12, there were significant differences in the plasma concentrations of TH17, IL-17A, IFN-γ and IL-10 between the two groups (All p=0.000). The proinflammatory factors TH17 and IL-17A were significantly lower in control group, while the anti-inflammatory factors IFN-γ and IL-10 were higher in the control group . And the SGRQ score of Stachys sieboldii Miq group was significantly lower. There was no significant difference in lung function (FEV1, FVC, and FEV1/FVC) between the two groups (p=0.510, 0.529, and 0.843). Within 48 weeks, the AE frequency and change with time showed significant differences between the two groups (p=0.029), and the incidence of AE was reduced by 47.9% in Stachys sieboldii Miq group. CONCLUSIONS: Stachys sieboldii Miq granules reduced proinflammatory factors and increased anti-inflammatory factors in stable COPD patients, reducing the probability of inducing AE.treatment.

20.
BMC Pediatr ; 21(1): 104, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648480

RESUMO

BACKGROUND: Chorioamnionitis is associated with various neonatal short- and long-term morbidities. The effect of chorioamnionitis on premature children's outcomes remains controversial. The aim of this study is to investigate the relationship between histological chorioamnionitis (HCA) and physiological development, wheezing, and atopic diseases in preterm children. METHODS: Singleton, preterm children (< 34 weeks), whose mother underwent pathological placental examinations, were retrospectively enrolled and the outcomes were assessed at 24-40 months during follow-up. Wheezing and atopic diseases including eczema, food allergies, and allergic rhinitis were screened by a questionnaire along with medical diagnosis. Anthropometric indexes and blood pressure were measured. Cognitive and behavioural developments were assessed by the Gesell Development and Diagnosis Scale. Blood IgE and routine examination were analyzed with venous blood and serum metabolomic profiling was assessed via liquid chromatography-mass spectrometry (LC-MS). A multivariate logistic regression model was used to estimate the association between HCA and the current outcomes. RESULTS: Among the 115 enrolled children, 47 were exposed to HCA. The incidence of wheezing was significantly higher in children exposed to HCA, as 38.30% of children who were exposed to HCA and 16.18% of children who were not had been diagnosed with wheezing. After adjusting for related confounders in the multivariate logistic regression model, there remained a 2.72-fold increased risk of wheezing in children with HCA (adjusted odds ratio, aOR, 2.72; 95% confidence interval, 1.02-7.23). Moreover, 163 differential metabolites, such as butanoic acid, annotemoyin 1 and charine, were identified in the HCA exposed children's serum. Enrichment analysis revealed that these compounds participated in diverse key metabolomic pathways relating to physical and neuro- developments, including glycerophospholipid, alpha-linolenic acid and choline metabolisms. There were no significant differences in atopic diseases, serum IgE, eosinophils' level, anthropometric indexes, blood pressure, or cognitive or behavioural developments between the two groups. CONCLUSION: HCA exposure is associated with an increased risk of wheezing in preterm children less than 34 gestational weeks.

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