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1.
Diabetologia ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608769

RESUMO

AIMS/HYPOTHESIS: We aimed to determine associations of regression to normal glucose tolerance (NGT), maintaining impaired glucose tolerance (IGT) or progression to diabetes with subsequent risks of CVD and microvascular disease among Chinese adults with IGT. METHODS: We conducted an observational study among 540 participants in the Da Qing Diabetes Prevention Study, a 6 year lifestyle intervention trial in people with IGT, defined by 1985 WHO criteria as fasting plasma glucose <7.8 mmol/l and 2 h post-load plasma glucose ≥7.8 and <11.1 mmol/l. At the end of the trial, the groups that had regressed to NGT, remained with IGT or progressed to diabetes were identified. Participants were then followed for 24 years after completion of the trial, during which we compared the incidence and hazard ratios for CVD and microvascular disease in each group and estimated the differences in their median time to onset from parametric Weibull distribution models. RESULTS: At the end of the 6 year trial, 252 (46.7%) participants had developed diabetes, 114 (21.1%) had remained with IGT and 174 (32.2%) had regressed to NGT. Compared with those who developed diabetes during the trial, the median time to onset of diabetes was delayed by 14.86 years (95% CI 12.49, 17.25) in the NGT and 9.87 years (95% CI 8.12, 11.68) in the IGT groups. After completion of the trial, among those with diabetes, IGT and NGT, the 24 year cumulative incidence of CVD was 64.5%, 48.5% and 45.1%, respectively, and 36.8%, 21.7% and 16.5% for microvascular diseases. Compared with participants who had progressed to diabetes during the trial, those who regressed to NGT had a 37% (HR 0.63; 95% CI 0.47, 0.85) reduction in CVD incidence and a median delay of 7.45 years (95% CI 1.91, 12.99) in onset, and those who remained with IGT had a 34% (HR 0.66; 95% CI 0.47, 0.91) lower CVD incidence with a median delay in onset of 5.69 years (95% CI 1.0, 10.38). Participants with NGT had a 66% (HR 0.34; 95% CI 0.20, 0.56) lower incidence of microvascular diseases and a median delay in the onset of 18.66 years (95% CI 6.08, 31.24), and those remaining with IGT had a 52% (HR 0.48; 95% CI 0.29, 0.81) lower incidence with a median delay of 12.56 years (95% CI 2.49, 22.63). CONCLUSIONS/INTERPRETATION: People with IGT who reverted to NGT or remained with IGT at the end of the 6 year trial subsequently had significantly lower incidences of CVD and microvascular disease than those who had developed diabetes.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33604715

RESUMO

PURPOSE: Results of previous studies on the associations between Forkhead box A1 (FOXA1) expression in breast cancer tissues and the prognosis varied depending on the follow-up durations. The present study would investigate whether there is a time-varying effect of FOXA1 in breast cancer tissues on the prognosis. METHODS: FOXA1 expressions were evaluated in 1041 primary invasive breast tumors with tissue microarrays by immunohistochemistry. Cox models with restricted cubic splines and Kaplan-Meier survival analysis were used to examine the associations between FOXA1 and the prognosis. Flexible parametric models were applied to explore the time-varying effect of FOXA1. RESULTS: Overall, the association between FOXA1 expression and the prognosis was not significant but varied on the time of follow-up. Compared to FOXA1 ≤ 270 of H-score, the hazard ratios (HRs) of death for those with 271-285 of FOXA1 expression increased from 0.35 (95% CI 0.14-0.86) at 6 months after diagnosis to 2.88 (95% CI 1.35-6.15) at 120 months with a crossover at around 36 months. Similar patterns were also observed for FOXA1 > 285 of H-score and for progression free survival (PFS). Moreover, when allowed both FOXA1 and estrogen receptor (ER) to change over time in the model (considering that ER had a similar time-varying effect), these time-varying effects remained for FOXA1 on both overall survival (OS) (P < 0.01) and PFS (P = 0.01) but were attenuated for ER (P = 0.13 for OS). CONCLUSIONS: This study revealed an independent time-varying effect of FOXA1 on breast cancer prognosis, which would provide an insight into the roles of FOXA1 as a marker of breast cancer prognosis and may help optimize the medication strategies.

3.
Stem Cell Res ; 51: 102174, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33485183

RESUMO

Human induced pluripotent stem cell (hiPSC)-derived endothelial cell (hiPSC-EC) transplantation is a promising therapy for treating peripheral artery disease (PAD). However, the poor differentiation of hiPSCs limits their clinical application. Therefore, finding key factors that regulate cellular differentiation is crucial for improving the therapeutic efficacy of hiPSC-EC transplantation. Sterol regulatory element binding protein 1 (SREBP1) is a key regulator of lipid metabolism and stem cell differentiation. However, it remains unknown whether SREPBP1 modulates hiPSC differentiation. In this study, we showed that SREBP1 expression was negatively associated with hiPSC differentiation and EC function. The results show that SREBP1 binds to the promoter region of miR199b-5p and suppresses its transcription, resulting in the activation of Notch1 signaling. Blocking SREBP1 increased both hiPSC differentiation and EC angiogenesis. These findings demonstrate a novel role for SREBP1 in hiPSC differentiation and EC angiogenesis.

4.
Diabetes Res Clin Pract ; 173: 108668, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33453295

RESUMO

AIMS: To examine whether high-sensitivity C-reactive protein (hs-CRP) can predict all-cause death in Chinese adults with hyperglycemia. METHODS: All the 237 diabetes and 49 prediabetes recruited in the study were evolved from the participants with impaired glucose tolerance in the original Da Qing Diabetes Study. Blood hs-CRP level was measured at 2006. Ten-year outcome of death was traced from 2006 to 2016. Cox model was used to analyse the association between hs-CRP level and the risk of all-cause death occurred over the subsequent 10 years. RESULTS: During the follow-up, death occurred in 36 (37.9%) subjects in the highest hs-CRP tertile group (hs-CRP > 2.16 mg/L) and 19 (20.0%) in the lowest hs-CRP tertile group (hs-CRP < 0.82 mg/L, p < 0.05). The corresponding incidence of all-cause death (per 1,000 person-years) was 44.7 (95% CI 30.1-59.3) and 21.6 (95% CI 11.9-31.3) in the two groups respectively (p < 0.0001). The highest hs-CRP tertile was associated with the increased risk of all-cause death significantly (hazard ratio 1.88, 95% CI 1.07-3.32) after controlling for traditional risk factors. CONCLUSIONS: Serum hs-CRP was predictive of 10-year all-cause death in Chinese adults with hyperglycemia, suggesting the impact of low-grade inflammation on mortality deserves more attention.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33513964

RESUMO

Urban greenways improve green coverage rates in urban environments and transform these environments in a people-oriented manner. This study adopted semantic differential (SD) methods and an importance-performance analysis (IPA) model to evaluate resident perceptions and preferences of riverside greenways. A survey of 588 residents was conducted on typical natural greenways, built greenways, and mixed greenways along the Huangpu River in Shanghai. The results showed that resident perceptions of style, space, and distance differed markedly, whereas their perceptions of environmental and psychological characteristics were relatively similar. There were strong correlations between residents' characteristics and their perceptions, especially for their perceptions of greenway style, sense of order, and distance from the river. By comparison, most residents preferred mixed greenways. Additionally, respondents from areas with natural and mixed greenways believed that they benefited, whereas those from areas with built greenways displayed a potential sense of deprivation. The results of IPA analysis provide further support for the above conclusions. As a whole, the relatively simple methods demonstrated here could be useful to quantitatively analyze the subjective perceptions of urban residents.

7.
Biochem Biophys Res Commun ; 535: 33-38, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33340763

RESUMO

Nano titanium implants induce osteogenesis, but how osteoblasts respond to this physical stimulation remains unclear. In this study, we tried to reveal the role of the mitochondrial fission-fusion of osteoblasts in response to a nano titanium surface during the process of osteogenesis, which is important for the design of the surface structure of titanium implants. A TiO2 nanotube array (nano titanium, NT) was fabricated by anodization, and a smooth surface (smooth titanium, ST) was used as a control. We investigated changes in the mitochondrial fission-fusion (MFF) dynamics in MC3T3-E1 cells on the NT surface with those on the ST surface by performing transmission electron microscopy (TEM), confocal laser scanning microscope (CLSM) and real-time PCR. At the same time, we also detected changes in the MFF and osteogenic differentiation of MC3T3-E1 cells after DRP1 downregulation with RNA interference. Cells on the NT surface exhibited more mitochondrial fusion than those on the ST surface, and DRP1 was the key regulatory molecule. Interestingly, DRP1 increased for only a short time at the early stage on the NT surface, and when DRP1 was inhibited by siRNA at the early stage, the osteogenic differentiation of MC3T3-E1 cells significantly decreased. In conclusion, DRP1-regulated mitochondrial dynamics played a key role in the nanotopography-accelerated osteogenic differentiation of MC3T3-E1 cells.

8.
Fungal Biol ; 125(1): 49-61, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33317776

RESUMO

Flowers' fungal and bacterial communities can exert great impacts on host plant wellness and reproductive success-both directly and indirectly through species interactions. However, information about community structure and co-occurrence patterns in floral microbiome remains scarce. Here, using culture-independent methods, we investigated fungal and bacterial communities associated with stamens and pistils of four plant species (Scaevola taccada, Ipomoea cairica, Ipomoea pes-caprae, and Mussaenda kwangtungensis) growing together under the same environment conditions in an island located in South China. Plant species identity significantly influenced community composition of floral fungi but not bacteria. Stamen and pistil microbiomes did not differ in community composition, but differed in co-occurrence network topological features. Compared with the stamen network, pistil counterpart had fewer links between bacteria and fungi and showed more modular but less concentrated and connected structure. In addition, degree distribution of microbial network in each host species and each microhabitat (stamen or pistil) followed a significant power-law pattern. These results enhance our understanding in the assembly principles and ecological interactions of floral microbial communities.

9.
Eur J Med Chem ; 211: 113083, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33340911

RESUMO

In the past five years, our team had been committed to click chemistry research, exploring the biological activity of 1,2,3-triazole by synthesizing different target inhibitors. In this study, a series of novel indole-2-one derivatives based on 1,2,3-triazole scaffolds were synthesized for the first time, and their inhibitory activity on vascular endothelial growth factor receptor-2 (VEGFR-2) was tested. Most of the compounds had shown promising activity in the VEGFR-2 kinase assay and had low toxicity to human umbilical vein endothelial cells (HUVECs). The compound 13d (IC50 = 26.38 nM) had better kinase activity inhibition ability than sunitinib (IC50 = 83.20 nM) and was less toxic to HUVECs. Moreover, it had an excellent inhibitory effect on HT-29 and MKN-45 cells. On the one hand, by tube formation assay, transwell, and Western blot analysis, compound 13d could inhibit VEGFR-2 protein phosphorylate on HUVECs, thereby inhibiting HUVECs migration and tube formation. In vivo study, the zebrafish model with VEGFR-2 labeling also verified that compound 13d had more anti-angiogenesis ability than sunitinib. On the other hand, molecular docking and molecular dynamics (MD) simulation results showed that compound 13d could stably bind to the active site of VEGFR-2. Based on the above findings, compound 13d could be considered an effective anti-angiogenesis drug and has more development value than sunitinib.

10.
Chin Med J (Engl) ; 134(1): 73-80, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33323827

RESUMO

BACKGROUND: Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy. METHODS: In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1. RESULTS: The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein. CONCLUSION: Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.

11.
Eur J Med Chem ; : 112988, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33189438

RESUMO

The molecular chaperone heat shock protein 90 (Hsp90) is a promising target for cancer therapy. Natural product aconitine is a potential Hsp90 inhibitor reported in our previous work. In this study, we designed and synthesized a series of 2-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-2-azabicyclo[3.2.1]octan-3-one derivatives as potent Hsp90 inhibitors by simplifying and modifying aconitine scaffold. Among these compounds, 14t exhibited an excellent antiproliferative activity against LoVo cells with an IC50 value of 0.02 µM and a significant Hsp90α inhibitory activity with an IC50 value of 0.71 nM. Molecular docking studies provided a rational binding model of 14t in complex with Hsp90α. The following cell cycle and apoptosis assays revealed that compound 14t could arrest cell cycle at G1/S phase and induce cell apoptosis via up-regulation of bax and cleaved-caspase 3 protein expressions while inhibiting the expressions of bcl-2. Moreover, 14t could inhibit cell migration in LoVo and SW620 cell lines. Consistent with in vitro results, 14t significantly repressed tumor growth in the SW620 xenograft mouse model.

12.
Transl Oncol ; 14(1): 100907, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33217646

RESUMO

Early diagnosis has been proved to improve survival rate of lung cancer patients. The availability of blood-based screening could increase early lung cancer patient uptake. Our present study attempted to discover Chinese patients' plasma metabolites as diagnostic biomarkers for lung cancer. In this work, we use a pioneering interdisciplinary mechanism, which is firstly applied to lung cancer, to detect early lung cancer diagnostic biomarkers by combining metabolomics and machine learning methods. We collected total 110 lung cancer patients and 43 healthy individuals in our study. Levels of 61 plasma metabolites were from targeted metabolomic study using LC-MS/MS. A specific combination of six metabolic biomarkers note-worthily enabling the discrimination between stage I lung cancer patients and healthy individuals (AUC = 0.989, Sensitivity = 98.1%, Specificity = 100.0%). And the top 5 relative importance metabolic biomarkers developed by FCBF algorithm also could be potential screening biomarkers for early detection of lung cancer. Naïve Bayes is recommended as an exploitable tool for early lung tumor prediction. This research will provide strong support for the feasibility of blood-based screening, and bring a more accurate, quick and integrated application tool for early lung cancer diagnostic. The proposed interdisciplinary method could be adapted to other cancer beyond lung cancer.

13.
J Adv Res ; 26: 95-110, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33133686

RESUMO

Introduction: The development of a new type of Thymidylate synthase (TS) inhibitor that could inhibit cancer cells' proliferation and anti-angiogenesis is of great significance for cancer's clinical treatment. Objectives: Our research hopes to develop a TS inhibitor that is more effective than the current first-line clinical treatment of pemetrexed (PTX) and provide a new reference for the clinical treatment of non-small cell lung cancer (NSCLC). Methods: We obtained a series of novel TS inhibitors by chemical synthesis. Moreover, TS assay and molecular docking to verify the target compound's inhibitory mode. Use MTT assay, colony-forming assay, flow cytometry, and western blot to verify the compound's inhibitory effect on cancer cell proliferation and its mechanism; and explore the compound's effect on angiogenesis in vitro and in vivo. Further, explore the hit compound's anti-cancer ability through the xenograft tumor model and the orthotopic cancer murine model. Results: A series of N-(3-(5-phenyl-1,3,4-oxadiazole-2-yl) phenyl)-2,4-dihydroxypyrimidine-5-sulfamide derivatives were synthesized as TS inhibitors for the first time. All target compounds significantly inhibited hTS enzyme activity and demonstrated significant antitumor activity against five cancer cell lines. Notably, 7f had a high selectivity index (SI) and unique inhibitory effects on eight NSCLC cells. In-depth research indicated that 7f could induce apoptosis by the mitochondrial pathway in A549 and PC-9 cells through the upregulation of wild-type P53 protein expression. Additionally, 7f was shown to inhibit angiogenesis in vitro and in vivo. In vivo studies, compared to PTX, 7f significantly inhibited tumor growth in A549 cell xenografts and had a higher therapeutic index (TGI). Moreover, 7f could prolong the survival of the orthotopic lung cancer murine model more effectively than PTX. Conclusion: The anti-angiogenic effect of 7f provides a new reference for the development of TS inhibitors and the clinical treatment of NSCLC.

14.
Ecol Evol ; 10(20): 11304-11321, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33144966

RESUMO

Generally, island populations are predicted to have less genetic variation than their mainland relatives. However, a growing number of studies have nevertheless reported exceptions, indicating that the relationships were impacted by several factors, for example, historical processes. In the present study, we chose a group of subtropical islands located in South China as the study system, which are quite younger and much closer to the mainland than most of the previous studied island systems, to test the hypothesis that in situ glacial survival contributes to high levels of genetic diversity in island populations. We conducted a comparison of genetic variation between 12 island and 11 nearby mainland populations of Mussaenda kwangtungensis using eleven nuclear microsatellite and three chloroplast markers, evaluated effects of the island area and distance to mainland on genetic diversity of island populations, and simulated the potential distribution over the past by ecological niche modeling, together with the genetic data to detect the role of islands during the glacial periods. The island populations displayed comparable levels of genetic diversity and differentiation with mainland populations, overall high levels of unique polymorphisms, and the greatest values of specific within-population genetic diversity. No significant correlation was detected between genetic diversity of island populations and distance to mainland, as well as area of islands, except that allelic richness was significantly positively correlated with the area of islands. Nuclear microsatellites revealed two main clusters, largely corresponding to islands and inland populations, which divergence dated to a time of island formation by ABC analysis. Ecological niche modeling predicted a highly climatic suitability on islands during the last glacial maximum (LGM). Our results suggest that the islands have acted as refugia during the LGM and highlight the role of in situ glacial survival in maintaining high levels of genetic diversity of M. kwangtungensis in continental islands of subtropical China.

15.
Life Sci ; 263: 118597, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33075373

RESUMO

AIMS: To explore the biological function and mechanism of Syntaxin2 (STX2) in Colorectal cancer (CRC) proliferation. MAIN METHODS: A series of gain- and loss-of-function analysis were conducted the to explore the biological function of STX2 in CRC proliferation in vivo and in vitro. Western blot, Co-immunoprecipitation (Co-IP) and the functional analyses were taken to analyze the regulative role of STX2 on Exosome Complex 4 (EXOSC4) in CRC proliferation; Immunohistochemistry (IHC) and Real-time quantitative polymerase chain reaction (qPCR) were used to further verify the relationship between the expression of STX2 and EXOSC4 in human CRC samples. KEY FINDINGS: Our study revealed that the over-expression of STX2 promoted CRC proliferation, while knockdown of STX2 repressed CRC proliferation; STX2 promoted CRC proliferation via increasing EXOSC4 protein; There was a positive correlation between STX2 and EXOSC4 expression. SIGNIFICANCE: The current data verify that STX2 drives the proliferation of CRC via increasing the expression of EXOSC4.

16.
Medicine (Baltimore) ; 99(42): e22577, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080692

RESUMO

RATIONALE: The new coronavirus pneumonia Corona Virus Disease 2019 (COVID-19) has become a global pandemic. Patients with critically COVID-19 usually require invasive respiratory support, and the airway management is particularly important and the prognosis is poor. PATIENT CONCERNS: A 64-year-old man with an anastomotic fistula after radical treatment of esophageal cancer and right-side encapsulated pyopneumothorax was admitted with cough and dyspnea. DIAGNOSIS: The patient was diagnosed with novel coronavirus pneumonia and right-side encapsulated pyopneumothorax by pharyngeal swab nucleic acid test in combination with chest computed tomography (CT). INTERVENTIONS: The patient was treated with antibiotics, antiviral and antibacterial medications, respiratory support, expectorant nebulization, and nutritional support. But he expressed progressive deterioration. Endotracheal intubation and mechanical ventilation were performed since the onset of the type - respiratory failure on the 13th day of admission. The patient had persistent refractory hypercapnia after mechanical ventilation. Based on the treatment mentioned above, combined with repeated bronchoalveolar lavage by using N-acetylcysteine (NAC) inhalation solution, the patients refractory hypercapnia was gradually improved. OUTCOMES: The patient was cured and discharged after being given the mechanical ventilation for 26 days as well as 46 days of hospitalization, currently is surviving well. LESSONS: Patients with severe conditions of novel coronavirus pneumonia often encounter bacterial infection in their later illness-stages. They may suffer respiratory failure and refractory hypercapnia that is difficult to improve due to excessive mucus secretion leading to small airway obstruction. This study provided a new insight on the proper treatment severe COVID-19 patients. The use of reasonable antibiotics and symptomatic respiratory support and other treatment, timely artificial airway and repeated bronchoalveolar NAC inhalation solution lavage, expectorant and other airway management are essential for such patients.


Assuntos
Acetilcisteína/uso terapêutico , Manuseio das Vias Aéreas/métodos , Lavagem Broncoalveolar/métodos , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Acetilcisteína/administração & dosagem , Administração por Inalação , Anastomose Cirúrgica , Betacoronavirus , Infecções por Coronavirus/complicações , Humanos , Intubação Intratraqueal/métodos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumotórax/complicações , Respiração Artificial
17.
Atherosclerosis ; 313: 102-110, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33038663

RESUMO

BACKGROUND AND AIMS: Phenotypic switch of vascular smooth muscle cells (VSMC) plays a key role in the pathogenesis of atherosclerosis and restenosis after artery intervention. Transcription repressor element 1-silencing transcription factor (REST) has been identified as key regulator of VSMC proliferation. In the present study, we sought to investigate the potential association of E3-ubiquitin ligase ß-TRCP mediated REST protein degradation with Kv1.3 expression during VSMC phenotypic switch. METHODS: Protein and mRNA expression was measured in ex vivo and in vitro models. Protein interaction and ubiquitination were analyzed by immunoprecipitation assays. ChIP assays were performed to assess the relationship between REST and targeted DNA binding site. RESULTS: We found that the expression level of E3-ubiquitin ligase ß-TRCP is significantly increased during VSMC phenotypic switch. REST protein ubiquitination mediated by ß-TRCP is critical for VSMC proliferation and migration. We also found that the gene KCNA3 encoding potassium channel protein Kv1.3 contains a functional REST binding site and is repressed by REST. Downregulation of REST by ß-TRCP and consequently upregulation of Kv1.3 are important events during VSMC phenotypic switch. Furthermore, upregulated Kv1.3 accelerates ß-TRCP modulated REST degradation through Erk1/2 signaling. CONCLUSIONS: Our results reveal a fundamental role for regulatory interactions between ß-TRCP modulated REST degradation and Kv1.3 in the control of the multilayered regulatory programs required for VSMC phenotype switch.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33031033

RESUMO

Accurate ground-truth pose is essential to the training of most existing head pose estimation methods. However, in many cases, the "ground truth" pose is obtained in rather subjective ways, such as asking the subjects to stare at different markers on the wall. Thus it is better to use soft labels rather than explicit hard labels to indicate the pose of a face image. This paper proposes to associate a Multivariate Label Distribution (MLD) to each image. An MLD covers a neighborhood around the original pose. Labeling the images with MLD can not only alleviate the problem of inaccurate pose labels, but also boost the training examples associated to each pose without actually increasing the total amount of training examples. Four algorithms are proposed to learn from MLD. Furthermore, an extension of MLD with the hierarchical structure is proposed to deal with fine-grained head pose estimation, which is named Hierarchical Multivariate Label Distribution (HMLD). Experimental results show that the MLD-based methods perform significantly better than the compared state-of-the-art head pose estimation algorithms. Moreover, the MLD-based methods appear much more robust against the label noise in the training set than the compared baseline methods.

19.
Abdom Radiol (NY) ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025152

RESUMO

PURPOSE: To investigate the safety and effectiveness of superselective prostatic artery embolization (PAE) in patients with benign prostatic hyperplasia (BPH). METHODS: Sixty-five patients diagnosed with BPH in Fujian Provincial Hospital between December 2014 and July 2019 were included. Patients with ineffective drug treatment after 6 months, who refused surgery, or who were unsuitable for surgery were included. We observed postoperative complications, followed up at 1, 3, and 6 months, compared clinical symptoms, and monitored changes in prostate-specific antigen (PSA) and prostatic volume (PV) before and after treatment. RESULTS: Of the 65 patients, 58 (89.23%) successfully received PAE; 44 and 14 bilateral and unilateral embolization, respectively. Clinical efficacy was 94.83% (55/58) after the 6-month follow-up. Postoperative PV, International Prostate Symptom Score, quality of life, maximum flow rate, and post-void residual significantly improved after 6 months (P < 0.05). One month after PAE, the serum total PSA increased by 1.47 (10.84/7.37) times and dropped 3 months later to a level lower than that before surgery (P < 0.05). Six months after PAE, the degree of relief from obstructive symptoms was more apparent than that of irritative symptoms. No serious complications were observed after PAE. CONCLUSION: PAE was safe and effective for the treatment of BPH. The efficacy of bilateral PAE was better than that of unilateral PAE.

20.
Sci Rep ; 10(1): 17492, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060796

RESUMO

The novel SARS-CoV-2 outbreak has swiftly spread worldwide. The rapid genome sequencing of SARS-CoV-2 strains has become a helpful tool for better understanding the genomic characteristics and origin of the virus. To obtain virus whole-genome sequences directly from clinical specimens, we performed nanopore sequencing using a modified ARTIC protocol in a portable nanopore sequencer and validated a routine 8-h workflow and a 5-h rapid pipeline. We conducted some optimization to improve the genome sequencing workflow. The sensitivity of the workflow was also tested by serially diluting RNA from clinical samples. The optimized pipeline was finally applied to obtain the whole genomes of 29 clinical specimens collected in Hangzhou from January to March 2020. In the 29 obtained complete genomes of SARS-CoV-2, 33 variations were identified and analyzed. The genomic variations and phylogenetic analysis hinted at multiple sources and different transmission patterns during the COVID-19 epidemic in Hangzhou, China. In conclusion, the genomic characteristics and origin of the virus can be quickly determined by nanopore sequencing following our workflows.


Assuntos
Betacoronavirus/genética , Genoma Viral , Sequenciamento por Nanoporos/métodos , Adolescente , Adulto , Betacoronavirus/classificação , Betacoronavirus/isolamento & purificação , Criança , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Pandemias , Filogenia , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Análise de Sequência de DNA , Adulto Jovem
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