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1.
Mol Med Rep ; 22(5): 3723-3734, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000187

RESUMO

The cellular and molecular mechanisms via which MK2206, an AKT inhibitor, prevents the activation of AKT in toluene diisocyanate (TDI)­induced asthma remain unclear. Thus, the present study aimed to evaluate the potential effects of MK2206 on airway AKT activation, inflammation and remodeling in a TDI­induced mouse model of asthma. A total of 24 BALB/c mice were selected and randomly divided into untreated (AOO), asthma (TDI), MK2206 (TDI + MK2206), and dexamethasone (TDI + DEX) groups. Phosphorylated AKT (p­AKT), total AKT, airway remodeling indices, α­smooth muscle actin (α­SMA) and collagen I levels in pulmonary tissue were measured using western blotting. Airway inflammation factors, including interleukin (IL)­4, ­5, ­6, and ­13 in bronchoalveolar lavage fluid (BALF) and IgE in serum, were determined using ELISA. Additionally, the airway hyperresponsiveness (AHR) and pulmonary pathology of all groups were evaluated. The results of the present study demonstrated that p­AKT levels in lung protein lysate were upregulated, and neutrophil, eosinophil and lymphocyte counts were increased in the lungs obtained from the asthma group compared with the AOO group. Both MK2206 and DEX treatment in TDI­induced mice resulted not only in the attenuation of AKT phosphorylation, but also reductions in neutrophil, eosinophil and lymphocyte counts in the lungs of mice in the asthma group. Consistently, increases in the levels of the inflammatory cytokines IL­4, ­5, ­6 and ­13 analyzed in BALF, and serum IgE in the TDI group were demonstrated to be attenuated in the TDI + MK2206 and TDI + DEX groups. Furthermore, α­SMA and AHR were significantly attenuated in the TDI + MK2206 group compared with the TDI group. These results revealed that MK2206 not only inhibited AKT activation, but also served a role in downregulating airway inflammation and airway remodeling in chemical­induced asthma. Therefore, the findings of the present study may provide important insight into further combination therapy.

2.
J Mech Behav Biomed Mater ; 113: 104114, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33045517

RESUMO

The poor elasticity of wound dressings often leads to wound healing failure due to rupture and fall off. In this study, the composite films of zein and hydrogel poly (acrylic acid) were developed in order to obtain stretchable wound dressing for skin burn repair. The mechanical test revealed that the maximum elongation of break of composite films could reach 349.76% when the mass ratio of zein to poly (acrylic acid) was 1.5. SEM and FTIR analysis demonstrated the good elasticity of composite films might be due to the formation of a dense structure and the strong interaction between zein and poly (acrylic acid). Interestingly, the composite films exhibited great adhesiveness to human finger skin and stretchable ability under strenuous joint exercise. CCK-8 assay and fluorescence staining showed that the composite films and their extract had good cytocompatibility on human foreskin fibroblasts (L929) cells. The in vivo experiment on rat's skin burning model indicated that the composite films could promote wound healing and collagen synthesis by comparison with commercial gauze. It could be concluded that the stretchable composite films of zein and hydrogel poly (acrylic acid) had the potential as the wound dressing.

3.
J Stroke Cerebrovasc Dis ; 29(11): 105232, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066931

RESUMO

BACKGROUND: The prognosis of acute ischemic stroke is related to collateral circulation, which is different with different pathogenesis. OBJECTIVE: To explore the prognosis of acute large atherosclerotic (LAA) cerebral infarction with different pathogenesis by assessing the establishment of collateral circulation. METHODS: 108 patients with acute LAA cerebral infarction in our hospital, who failed to thrombolytic or thrombectomy in the acute phase were selected and classified by Chinese ischemic stroke subclassification (CISS). They were evaluated by National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). CT angiography (CTA) of head and neck were used to evaluate the collateral circulation for patients with large vessel stenosis or occlusion within one week of admission. The CTA collateral scores (CS) were recorded in a dichotomized fashion (ie, poor vs good). RESULTS: Patients with good CS had significantly lower NIHSS score and good prognosis at 2 weeks and 3 months than patients with poor CS (P < 0.001). The arterial-to-arterial embolization mechanism was the highest in the ratio of good CS and good prognosis at 3 months (P < 0.001). Multivariate Logistic regression analysis showed that baseline NIHSS score (OR=1.407, 95%CI:1.153-1.717, P=0.001) was an independent factor affecting poor CS. The NIHSS score at baseline (OR=0.604, 95%CI:0.436-0.837, P=0.002) and good CS (OR=39.552, 95%CI:8.908-175.618, P=0.000) were important predictors of good prognosis at 3 months. CONCLUSION: The prognosis and collateral circulation of acute LAA cerebral infarction with different pathogenesis was different. Baseline NIHSS score and collateral circulation had great impact on prognosis at 3 months.

4.
Elife ; 92020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064077

RESUMO

In plants, establishment of de novo DNA methylation is regulated by the RNA-directed DNA methylation (RdDM) pathway. RdDM machinery is known to concentrate in the Cajal body, but the biological significance of this localization has remained elusive. Here, we show that the antiviral methylation of the Tomato yellow leaf curl virus (TYLCV) genome requires the Cajal body in Nicotiana benthamiana cells. Methylation of the viral genome is countered by a virus-encoded protein, V2, which interacts with the central RdDM component AGO4, interfering with its binding to the viral DNA; Cajal body localization of the V2-AGO4 interaction is necessary for the viral protein to exert this function. Taken together, our results draw a long sought-after functional connection between RdDM, the Cajal body, and antiviral DNA methylation, paving the way for a deeper understanding of DNA methylation and antiviral defences in plants.

5.
J Cell Physiol ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33090488

RESUMO

The aim of this study was to investigate the role of scoparone (SCO) in hepatic fibrosis. For this, we conducted in vivo and in vitro experiments. In vivo rats that were divided into six groups, control, carbon tetrachloride, and colchicine, as well as SCO groups, SCO50, SCO100, and SCO200 treated with 50, 100, and 200 mg/kg SCO doses, respectively. Furthermore, SCO was shown to inhibit Toll-like receptor-4 (TLR-4)/nuclear factor kappa-B (NF-κB; TLR-4/NF-κB) signals by inhibiting TLR-4, which in turn downregulates the expression of MyD88, promotes NF-κB inhibitor-α, NF-κB inhibitor-ß, and NF-κB inhibitor-ε activation, while inhibiting NF-κB inhibitor-ζ. Subsequently, the decrease of phosphorylation of nuclear factor-κB levels leads to the downregulation of the downstream inflammatory factors' tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 beta, thus weakening hepatic fibrosis. Notably, the SCO200 treated group presented the most significant improvement. Hence, we conclude that SCO alleviates hepatic fibrosis by inhibiting TLR-4/NF-κB signals.

6.
Med Mal Infect ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007402

RESUMO

OBJECTIVE: To investigate the prevalence of different human papillomavirus (HPV) subtypes and their association with human leukocyte antigen (HLA) class II alleles in China. PATIENTS AND METHODS: A total of 16,168 married Chinese women in Maoming City of Guangdong province were tested for high-risk HPV infection. High-resolution typing of HLA-DRB1/DQB1 alleles was also performed on samples found to be infected with HPV. RESULTS: All in all, HPV-52, -58, -16, -18, and -53 were the five most common subtypes of HPV, with an incidence of high-risk HPV infection of 7.14%. Among women at high-risk of HPV infection, -DRB1*0403 (3.12% vs. 1.67%, odds ratio [OR] 1.894), -DQB1*0602 (3.74% vs. 1.82%, OR 2.094), and -DQB1*0609 (2.02% vs. 0.91%, OR 2.249) frequencies were higher than in controls. In contrast, -DQB1*0402 (0.31% vs. 1.29%, OR 0.239) in women with high-risk HPV infection exhibited a significantly decreased frequency compared to the controls. CONCLUSION: Our results strongly support previous findings from other populations that -DRB1*0403 and -DQB1*0602 may be risk factors for HPV infection and subsequent development of cervical cancer. Moreover, unlike the European population, -DQB1*0402 may protect rather than render Maoming women susceptible to HPV infection.

7.
Clin Infect Dis ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068430

RESUMO

BACKGROUND: The growing epidemics of severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne disease in East Asia, and its high case fatality rate have raised serious public health concerns. METHODS: Surveillance data on laboratory-confirmed SFTS cases in China were collected. The spatiotemporal dynamics and epidemiological features were explored. The socioeconomic and environmental drivers were identified for SFTS diffusion using survival analysis and for SFTS persistence using a two-stage generalized boosted regression tree model. RESULTS: During 2010‒2018, a total of 7,721 laboratory-confirmed SFTS cases were reported in China, with an overall CFR of 10.5%. The average annual incidence increased >20 times and endemic areas expanded from 27 to 1,574 townships, whereas the CFR declined from 19% to 10% during this period. Four geographical clusters, the Changbai Mountain area, the Jiaodong Peninsula, the Taishan Mountain area and the Huaiyangshan Mountain area, were identified. Diffusion and persistence of the disease were both driven by elevation, high coverages of woods, crops and shrub, and the vicinity of habitats of migratory birds, but had different meteorological drivers. Residents ≥60 years old in rural areas with crop fields and tea farms were at increased risk to SFTS. CONCLUSIONS: Surveillance of SFTS and intervention programs need to be targeted at areas with ecologically suitability for vector ticks and in the vicinity of migratory birds to curb the growing epidemic.

8.
Cell Stem Cell ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33049217

RESUMO

Differentiated somatic cells can be reprogrammed to totipotent embryos through somatic cell nuclear transfer (SCNT) with low efficiency. The histone deacetylase inhibitor trichostatin A (TSA) has been found to improve SCNT efficiency, but the underlying mechanism remains undetermined. Here, we examined genome-wide H3K9ac during SCNT embryo development and found that aberrant H3K9ac regions resulted in reduced 2-cell genome activation. TSA treatment largely corrects aberrant acetylation in SCNT embryos with an efficiency that is dictated by the native epigenetic environment. We further identified that the overexpression of Dux greatly improves SCNT efficiency by correcting the aberrant H3K9ac signal at its target sites, ensuring appropriate 2-cell genome activation. Intriguingly, the improvement in development mediated by TSA and Kdm4b is impeded by Dux knockout in SCNT embryos. Together, our study reveals that reprogramming of H3K9ac is important for optimal SCNT efficiency and identifies Dux as a crucial transcription factor in this process.

11.
Perfusion ; : 267659120960310, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33016239

RESUMO

BACKGROUND: Redo coronary artery bypass grafting (redo CABG) is associated with increased mortality and morbidity. The aim of this study was to systematically evaluate the evidence comparing the outcomes of off-pump with on-pump redo CABG. METHODS: Studies were systematically searched and identified using PubMed, EMBASE, the Cochrane Library, and the International Clinical Trials Registry Platform (ICTRP) by two researchers independently. The primary outcome was 30-day mortality, and the secondary outcomes were in-hospital mortality, post-operative complications, completeness of revascularization, blood transfusion rate, duration of mechanical ventilation, intensive care unit and hospital stays. RESULTS: The 21 studies including 4,889 patients were enrolled in our meta-analysis. Compared with on-pump, the off-pump technique was associated with significantly reduced 30-day mortality (odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.26-0.72, p = 0.001). Moreover, a notably decreased in-hospital mortality (OR = 0.55, 95% CI = 0.39-0.76, p = 0.0004) and incidence of post-operative new-onset atrial fibrillation, myocardial infarction, acute kidney injury, low cardiac output state, blood transfusion rate (OR = 0.46, 95% CI = 0.35-0.60, p < 0.00001; OR = 0.54, 95% CI = 0.38-0.78, p = 0.0007; OR = 0.51, 95% CI = 0.37-0.70, p < 0.0001; OR = 0.31, 95% CI = 0.20-0.47, p < 0.00001; OR = 0.29, 95% CI = 0.14-0.61, p = 0.001) and significantly shortened duration of mechanical ventilation, intensive care unit and hospital stays (mean difference [MD] = -8.21 h, 95% CI = -11.74 to -4.68, p < 0.00001; MD = -0.77 d, 95% CI = -0.81 to -0.73, p < 0.00001; MD = -2.24 d, 95% CI = -3.17 to -1.32, p < 0.00001) could be observed when comparing the outcomes of off-pump with on-pump redo CABG. There was nonsignificant difference between off-pump and on-pump redo CABG in completeness of revascularization. CONCLUSION: In patients undergoing redo CABG surgery, the off-pump technique was associated with decreased mortality, less post-operative complications when compared to on-pump.

12.
PLoS One ; 15(10): e0240076, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33022019

RESUMO

Public health emergency of SARS-CoV-2 has facilitated diagnostic testing as a related medical countermeasure against COVID-19 outbreak. Numerous serologic antibody tests have become available through an expedited federal emergency use only process. This paper highlights the analytical characteristic of an ELISA based assay by AnshLabs and three random access immunoassay (RAIA) by DiaSorin, Roche, and Abbott that have been approved for emergency use authorization (EUA), at a tertiary academic center in a low disease-prevalence area. The AnshLabs gave higher estimates of sero-prevalence, over the three RAIA methods. For positive results, AnshLabs had 93.3% and 100% agreement with DiaSorin or Abbott and Roche respectively. For negative results, AnshLabs had 74.3% and 78.3% agreement with DiaSorin and Roche or Abbott respectively. All discrepant samples that were positive by AnshLabs and negative by RAIA tested positive by all-in-one step SARS-CoV-2 Total (COV2T) assay performed on the automated Siemens Advia Centaur XPT analyzer. None of these methods, however, are useful in early diagnosis of SARS-CoV-2.

13.
Plant Dis ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074071

RESUMO

Sisal (Agave sisalana Perrine) is an important hard fiber crop that is widely planted in Guangxi, Guangdong, Hainan, Yunnan, and Fujian provinces, China. In July 2019, a new leaf disease of sisal with a disease incident of about 36% was found in Guangxi (Fig.1a~d). The oval or circular black lesions were 2.3 cm to 15.9 cm in length and 1.6 cm to 5.5 cm in width on both sides of the diseased leaves. The central part of the lesions was slightly hollow. The lesions continuously enlarged and ultimately penetrated the leaves. Reddish brown and dark mucus was secreted from the lesions. The junction of lesions and healthy parts was reddish brown to yellow. The diseased leaf fiber and mesophyll tissues were reddish brown and necrotic. Fresh leaf yield was reduced about 30% by the disease, and fiber quality was significantly compromised every year in Guangxi. Six kinds of fungi distinguished by their morphology, size and color of the colonies were isolated from diseased leaf tissues of 60 sisal plants sampled from five different farms in Guangxi. Isolate JMHB1 was isolated at a rate of 95.67%. The isolate JMHB1 was initially white with dense and hairy aerial mycelium, gradually turning dark grey to olive green on PDA (Fig. 2). Conidia, arthrospores, and chlamydospores were observed on PDA in culture (Fig. 3). The conidia formed arthric chains, disarticulating, cylindrical-truncate, oblong-obtuse to doliiform, colorless and transparent, zero- to one-septate, and averaging 4.4 to 13.8 µm × 2.2 to 5.6 µm (n=100). Arthrospores were short columnar, pigmented and transparent, single or formed arthric chains, averaging 5.5 to 17.9 µm × 2.1 to 3.5 µm (n=100). Chlamydospores were dark brown, round or oval, averaging 4.5 to 9.6 µm × 4.5 to 8.6 µm (n=100). Pathogenicity testing was conducted by inoculating 3-year-old healthy sisal plants with PDA plugs (5 × 5 mm) on which the fungus had grown for 5 days. Nine healthy plants were wounded on the leaves with a sterile needle, and mycelial plugs were placed on the wounds, covered with sterile moist cotton, and wrapped with parafilm. Nine control plants were wounded and treated with PDA plugs as the negative control. The test was repeated three times. All treated plants were kept in a greenhouse at ~28 ℃ and 40% RH. After 5 days, only leaves inoculated with isolate JMHB1 showed lesions similar to symptoms observed in the field (Fig.1e~f). The fungus was re-isolated from all nine diseased plants, and no symptoms were observed on the leaves of control plants. Molecular identification of the fungus was made by PCR amplification of the internal transcribed spacer (ITS) region of rDNA, EF1-α gene and ß-tubulin gene using primers ITS1/ITS4 (White et al. 1990), EFl-728F/EF1-986R (Carbone and Kohn 1999), TUB2Fd/TUB4Rd (Aveskamp et al. 2009) respectively. The ITS (MT705646), EF1-α (MT733516) and ß-tubulin (MT773603) sequences of JMHB1 were similar to the ITS (AY819727), EF1-α (EU144063) and ß-tubulin (KF531800) sequences of the epitype of Neoscytalidium dimidiatum (CBS 499.66) with 100%, 99.65% and 99.02% identity, respectively. Based on pathogenicity testing, morphological characteristics, and molecular identification, the pathogen of sisal causing black spot was identified as N. dimidiatum (Penz.) Crous & Slippers (Crous et al. 2006). To our knowledge, this is the first report of black spot caused by N. dimidiatum on sisal in China. Sisal is the main economic crop in arid and semi-arid areas that is widely planted in several provinces of southern China. The serious occurrence of the disease caused by N. dimidiatum has greatly affected the development of sisal industry and local economic income in China. Identification of the pathogen of the disease is of great significance to guide disease control, increase farmers' income and promote the development of sisal industry. References: Aveskamp, M. M., et al. 2009. Mycologia, 101: 363. https://doi.org/10.3852/08-199. Carbone, I., and Kohn, L. M. 1999. Mycologia, 91:553. https://doi.org/10.1080/00275514.1999. 12061051. Crous, P. W., et al. 2006. Stud. Mycol. 55:235. https://doi.org/10.3114/sim.55.1.235. White, T. J., et al. 1990. PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, Page 315. doi.org/10.1002/mrd.1080280418. Supplemental photographs: Fig. 1 Symptoms of sisal black spot disease a, b, c, d showed symptoms in the field, e and f were symptoms after inoculating Neoscytalidium dimidiatum JMHB1. a, c, and e were the front of the lesions, b, d, and f were the back of the lesions. Fig. 2 Primary colony (a) and old colony (b) of Neoscytalidium dimidiatum JMHB1 Fig. 3 Arthrospores (a), conidia and chlamydospores (b) of Neoscytalidium dimidiatum JMHB1.

15.
Cell Death Dis ; 11(10): 898, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093458

RESUMO

Currently, only a few available targeted drugs are considered to be effective in stomach adenocarcinoma (STAD) treatment. The PARP inhibitor olaparib is a molecularly targeted drug that continues to be investigated in BRCA-mutated tumors. However, in tumors without BRCA gene mutations, particularly in STAD, the effect and molecular mechanism of olaparib are unclear, which largely restricts the use of olaparib in STAD treatment. In this study, the in vitro results showed that olaparib specifically inhibited cell growth and migration, exerting antitumor effect in STAD cell lines. In addition, a ClC-3/SGK1 regulatory axis was identified and validated in STAD cells. We then found that the down-regulation of ClC-3/SGK1 axis attenuated olaparib-induced cell growth and migration inhibition. On the contrary, the up-regulation of ClC-3/SGK1 axis enhanced olaparib-induced cell growth and migration inhibition, and the enhancement effect could be attenuated by SGK1 knockdown. Consistently, the whole-cell recorded chloride current activated by olaparib presented the same variation trend. Next, the clinical data showed that ClC-3 and SGK1 were highly expressed in human STAD tissues and positively correlated (r = 0.276, P = 0.009). Furthermore, high protein expression of both ClC-3 (P = 0.030) and SGK1 (P = 0.006) was associated with poor survival rate in STAD patients, and positive correlations between ClC-3/SGK1 and their downstream molecules in STAD tissues were demonstrated via the GEPIA datasets. Finally, our results suggested that olaparib inhibited the PI3K/AKT pathway in STAD cells, and up-regulation of ClC-3/SGK1 axis enhanced olaparib-induced PI3K/AKT pathway inhibition. The animal experiments indicated that olaparib also exerted antitumor effect in vivo. Altogether, our findings illustrate that olaparib exerts antitumor effect in human STAD, and ClC-3/SGK1 regulatory axis enhances the olaparib-induced antitumor effect. Up-regulation of the ClC-3/SGK1 axis may provide promising therapeutic potential for the clinical application of olaparib in STAD treatment.

16.
Talanta ; 219: 121343, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32887072

RESUMO

N-acylated homoserine lactones (AHLs), a class of auto-inducers produced by Gram-negative bacteria, are typical signaling molecules in quorum sensing (QS) systems. Importantly, AHLs play a key role in determining the virulence of foodborne pathogens and reflect the activity of spoilage bacteria. In this study, an eco-friendly fluorescence-sensing platform for the rapid and sensitive detection of AHLs was developed and characterized. Molecularly imprinted polymers embedded with yellow-emitting carbon quantum dots (CQDs) were obtained via the sol-gel process using furanone as an alternative template molecule, and long-wave-emitting CQDs with excellent optical properties were used as signal conversion materials. After template elution, the blotting cavities on the surface of the CQD@MIPs (molecularly imprinted polymers) were able to selectively recognize AHLs, demonstrating a stronger fluorescence response compared with the corresponding CQD@NIPs (non-imprinted polymers). Under optimal test conditions, a good linear relationship between the concentration of analyte and the relative fluorescence intensity of the CQD@MIPs was observed. The linear detection range was 0-2.0 µM, and the limit of detection (LOD) was 0.067 µM. Importantly, the proposed sensing platform functioned as an optical detection strategy that responded quickly (2 min) to AHLs. Additionally, this sensing platform was applied to the analysis of AHLs in bacterial supernatant samples with satisfactory results. More interestingly, the 3D-printing CQD@MIPs were tentative explored in this work, which was personalized and portable, has an advantage of point of care testing (POCT) detection in the future. Based on these results, this detection strategy has demonstrated substantial potential for application in and the field of food safety.

17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(5): 495-500, 2020 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879096

RESUMO

OBJECTIVES: To summarize the emergency management of the kidney transplantation for a large tertiary first-class hospital in response to the epidemic of coronavirus disease 2019 (COVID-19). METHODS: The clinical data of inpatients in the Department of Kidney Transplantation from January 24, 2020 to February 29, 2020 were retrospectively analyzed. Since the outbreak of COVID-19, we conducted telephone, Wechat follow-up, and online education for kidney transplant recipients and patients on waiting-list for kidney transplantation one by one. We also strictly screened for COVID-19 in outpatients. To guarantee the security of medical staff and recipients and to reduce the transmission risk of COVID-19, we have made detailed approaches to prevent COVID-19, which mainly included 6 aspects of preventive approaches, such as kidney transplant clinic, kidney transplant ward, patients on waiting-list for kidney transplantation, kidney transplant operation, medical staff self-protection, and postoperative follow-up of kidney transplant recipients. RESULTS: There were altogether 47 inpatients which included 20 recipients who had just received kidney transplantation in the meantime, 2 577 kidney transplant recipients, 1 689 patients on waiting-list for kidney transplantation, and 794 outpatients in our hospital. No case of COVID-19 occurred in this period. CONCLUSIONS: Through strictly implementing proactive and preventive approaches, we avoid the occurrence of COVID-19 in carrying out kidney transplantation in the epidemic period.


Assuntos
Infecções por Coronavirus/epidemiologia , Transplante de Rim , Pneumonia Viral/epidemiologia , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Estudos Retrospectivos , Centros de Atenção Terciária , Transplantados , Listas de Espera
18.
Med Ultrason ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32905560

RESUMO

AIMS: To compare the diagnostic value of S-Detect (a computer aided diagnosis system using deep learning) in differentiating thyroid nodules in radiologists with different experience and to assess if S-Detect can improve the diagnostic performance of radiologists. MATERIALS AND METHODS: Between February 2018 and October 2019, 204 thyroid nodules in 181 patients were included. An experienced radiologist performed ultrasound for thyroid nodules and obtained the result of S-Detect. Four radiologists with different experience on thyroid ultrasound (Radiologist 1, 2, 3, 4 with 1, 4, 9, 20 years, respectively) analyzed the conventional ultrasound images of each thyroid nodule and made a diagnosis of "benign" or "malignant" based on the TI-RADS category. After referring to S-Detect results, they re-evaluated the diagnoses. The diagnostic performance of radiologists was analyzed before and after referring to the results of S-Detect. RESULTS: The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of S-Detect were 77.0, 91.3, 65.2, 68.3 and 90.1%, respectively. In comparison with the less experienced radiologists (radiologist 1 and 2), S-Detect had a higher area under receiver operating characteristic curve (AUC), accuracy and specificity (p <0.05). In comparison with the most experienced radiologist, the diagnostic accuracy and AUC were lower (p<0.05). In the less experienced radiologists, the diagnostic accuracy, specificity and AUC were significantly improved when combined with S-Detect (p<0.05), but not for experienced radiologists (radiologist 3 and 4) (p>0.05). CONCLUSIONS: S-Detect may become an additional diagnostic method for the diagnosis of thyroid nodules and improve the diagnostic performance of less experienced radiologists.

19.
J Clin Invest ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32910804

RESUMO

Homeostasis of bone metabolism is regulated by the central nervous system and mood disorders such as anxiety are associated with bone metabolism abnormalities, yet our understanding of the central neural circuits regulating bone metabolism is limited. Here, we demonstrate that chronic stress in crewmembers resulted in decreased bone density and elevated anxiety in an isolated habitat mimicking a space station. We then used a mouse model to demonstrate that GABAergic neural circuitry in the ventromedial hypothalamus (VMH) mediates chronic stress-induced bone loss. We show that GABAergic inputs in the VMHdm arise from a specific group of somatostatin neurons in the posterior region of bed nucleus of the stria terminalis (BNST), which is indispensable for stress-induced bone loss and is able to trigger bone loss in the absence of stressors. In addition, the sympathetic system and glutamatergic neurons in nucleus tractus solitaries (NTS) were employed to regulate stress-induced bone loss. Our study has therefore identified the central neural mechanism by which chronic stress induced mood disorders, such as anxiety, influence bone metabolism.

20.
Plant Mol Biol ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32915351

RESUMO

KEY MESSAGE: SsLOS directly catalyzed formation of the sesquiterpenoid ether liguloxide in the medicinal plant Senecio scandens. Terpene synthases determine the diversity of terpene skeletons and corresponding terpenoid natural products. Oxygenated groups introduced in catalysis of terpene synthases are important for solubility, potential bioactivity and further elaboration of terpenoids. Here we identified one terpene synthase, SsLOS, in the Chinese medicinal plant Senecio scandens. SsLOS acted as the sesquiterpene synthase and utilized (E,E)-farnesyl diphosphate as the substrate to produce a blend of sesquiterpenoids. GC-MS analysis and NMR structure identification demonstrated that SsLOS directly produced the sesquiterpenoid ether, liguloxide, as well as its alcoholic isomer, 6-epi-guaia-2(3)-en-11-ol. Homology modeling and site-directed mutagenesis were combined to explore the catalytic mechanism of SsLOS. A few key residues were identified in the active site and hedycaryol was identified as the neutral intermediate of SsLOS catalysis. The plausible catalytic mechanism was proposed as well. Altogether, SsLOS was identified and characterized as the sesquiterpenoid ether synthase, which is the second terpenoid ether synthase after 1,8-cineol synthase, suggesting some insights for the universal mechanism of terpene synthases using the water molecule in the catalytic cavity.

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