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1.
J Clin Microbiol ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952598

RESUMO

While China experienced a peak and decline in coronavirus disease 2019 (COVID-19) cases at the start of 2020, in subsequent months, regional outbreaks have continuously emerged. Resurgences of COVID-19 have also been observed in many other countries. In Guangzhou, China, a small outbreak, involving less than 100 residents, emerged in March and April 2020, and comprehensive and near-real-time genomic surveillance of SARS-CoV-2 was conducted. When the numbers of confirmed cases among overseas travelers increased, public health measures were enhanced by shifting from self-quarantine to central quarantine and SARS-CoV-2 testing for all overseas travelers. In an analysis of 109 imported cases, we found diverse viral variants distributed in the global viral phylogeny, which were frequently shared within households but not among passengers on the same flight. In contrast to the viral diversity of imported cases, local transmission was predominately attributed to two specific variants imported from Africa, including local cases that reported no direct or indirect contact with imported cases. The introduction events of the virus were identified or deduced before the enhanced measures were taken. These results show that the interventions were effective in containing the spread of SARS-CoV-2, and they ruled out the possibility of cryptic transmission of viral variants from the first wave in January and February 2020. Our study provides evidence and emphasizes the importance of controls for overseas travelers in the context of the pandemic and exemplifies how viral genomic data can facilitate COVID-19 surveillance and inform public health mitigation strategies.

2.
BMC Public Health ; 21(1): 874, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33957893

RESUMO

BACKGROUND: The prevalence of chronic non-communicable diseases (NCDs) challenges the Chinese health system reform. Little is known for the differences in catastrophic health expenditure (CHE) between urban and rural households with NCD patients. This study aims to measure the differences above and quantify the contribution of each variable in explaining the urban-rural differences. METHODS: Unbalanced panel data were obtained from the China Family Panel Studies (CFPS) conducted between 2012 and 2018. The techniques of Fairlie nonlinear decomposition and Blinder-Oaxaca decomposition were employed to measure the contribution of each independent variable to the urban-rural differences. RESULTS: The CHE incidence and intensity of households with NCD patients were significantly higher in rural areas than in urban areas. The urban-rural differences in CHE incidence increased from 8.07% in 2012 to 8.18% in 2018, while the urban-rural differences in CHE intensity decreased from 2.15% in 2012 to 2.05% in 2018. From 2012 to 2018, the disparity explained by household income and self-assessed health status of household head increased to some extent. During the same period, the contribution of education attainment to the urban-rural differences in CHE incidence decreased, while the contribution of education attainment to the urban-rural differences in CHE intensity increased slightly. CONCLUSIONS: Compared with urban households with NCD patients, rural households with NCD patients had higher risk of incurring CHE and heavier economic burden of diseases. There was no substantial change in urban-rural inequality in the incidence and intensity of CHE in 2018 compared to 2012. Policy interventions should give priority to improving the household income, education attainment and health awareness of rural patients with NCDs.

3.
Psychiatry Res Neuroimaging ; 312: 111286, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33857750

RESUMO

Hippocampal volume loss is prominent in first episode schizophrenia (FES) and has been associated with poor clinical outcomes and with BDNF genotype; antidepressants are believed to reverse hippocampal volume loss via release of BDNF. In a 12-month, placebo-controlled add-on trial of the antidepressant, citalopram, during the maintenance phase of FES, negative symptoms were improved with citalopram. We now report results of structural brain imaging at baseline and 6 months in 63 FES patients (34 in citalopram group) from the trial to assess whether protection against hippocampal volume loss contributed to improved negative symptoms with citalopram. Hippocampal volumetric integrity (HVI) did not change significantly in the citalopram or placebo group and did not differ between treatment groups, whereas citalopram was associated with greater volume loss of the right CA1 subfield. Change in cortical thickness was associated with SANS change in 4 regions (left rostral anterior cingulate, right frontal pole, right cuneus, and right transverse temporal) but none differed between treatment groups. Our findings suggest that minimal hippocampal volume loss occurs after stabilization on antipsychotic treatment and that citalopram's potential benefit for negative symptoms is unlikely to result from protection against hippocampal volume loss or cortical thinning.

4.
Medicine (Baltimore) ; 100(17): e25636, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907120

RESUMO

ABSTRACT: The cartilage endplate plays an important role in the stress distribution and nutrition metabolism of the intervertebral disc. The healing morphology of the endplate after spinal fracture and its effect on the intervertebral disc degeneration are still unclear.This was a retrospective study. Patients with traumatic single-level thoracolumbar fractures treated in our orthopedic trauma service center from June 2011 to May 2019 were included and the relevant data were collected from the medical records. Based on combined computed tomography and MRI images, the endplate injury status was determined (no endplate injury, unilateral and bilateral endplate injury). According to the location of the injury, endplate injury was further divided into endplate central injury and endplate peripheral injury. The degree of posttraumatic disc lesions and disc degeneration during follow-up were classified based on the Sander classification and the Pfirrmann classification, respectively. According to the T1 image of MRI at the final follow-up, the healing morphology of endplates was determined and classified. Univariate analyses and correlation analyses were performed to evaluate the within- and between-group differences.There were in total 51 patients included in this study. Cartilage endplate fracture was significantly closely related to the degree of degeneration of the intervertebral disc (P = .003). Injuries in different parts of the endplate have no significant effect on the intervertebral disc degeneration (P = .204). The healing morphology after endplate fracture significantly affected the degree of intervertebral disc degeneration (P = .001). The comparisons of groups showed that the effects of irregular healing and traumatic Schmorl nodes on disc degeneration were not statistically significant, but were significantly significant with increased curvature.These results suggest that the irregular healing and the traumatic Schmorl nodes are closely related to intervertebral disc degeneration. The presence and severity of the endplate injury can provide valuable information for individualized clinical decision-making processes.


Assuntos
Consolidação da Fratura , Degeneração do Disco Intervertebral/patologia , Parafusos Pediculares/efeitos adversos , Complicações Pós-Operatórias/patologia , Fraturas da Coluna Vertebral/patologia , Adulto , Cartilagem Articular/patologia , Feminino , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/instrumentação , Humanos , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/etiologia , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X , Adulto Jovem
5.
Opt Lett ; 46(9): 2220-2223, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33929459

RESUMO

To exploit spatial dimension, on-chip optical modes with various spatial profiles have been utilized in optical interconnects and spatial analog computing. An integrated Fourier optical system is able to perform spatial operations. However, the reported schemes based on a subwavelength structure pose difficulty in fabrication, and the fabrication-friendly structure has been investigated only with a fundamental mode. With the complementary metal-oxide-semiconductor process, we propose an integrated 4-f system with simple geometry and a moderate minimum feature size to manipulate the mode's spatial size and position in a mode-transparent way. A size magnification of 2.5 and center-to-center position offset of 7 µm are experimentally demonstrated. Reasonable insertion loss and low inter-mode crosstalk are measured over a 30 nm bandwidth. The work in this Letter paves the way for an on-chip Fourier optical system with convenient fabrication and broadband operation.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33877731

RESUMO

Ni-promoted electrocatalytic biomass reforming has shown promising prospect in enabling high value-added product synthesis. Here, we developed a novel hybrid catalyst with Ni nanosheet forests anchored on carbon paper. The hybrid catalyst exhibits high efficiency in electrooxidation of HMF to FDCA coupling with H2 production in high purity. The Ni nanosheets have small crystal grain sizes with abundant edges, which is able to deliver an efficient HMF oxidation to FDCA (selectivity >99%) at low potential of 1.36 VRHE with high stability. The post-reaction structure analysis reveals the Ni nanosheets would transfer electrons to carbon and readily turn into NiOx and Ni(OH)x during the reaction. DFT results suggest high valence Ni species would facilitate the chemical adsorption (activation) of HMF revealing the reaction pathway. This work emphasizes the importance of the precise control of Ni activity via atomic structure engineering.

7.
Zhen Ci Yan Jiu ; 46(3): 173-9, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33798288

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture preconditioning at "Zusanli"(ST36,Lower Confluent point) and "Zhongwan"(CV12,Front-Mu point) combination on oxidative stress and inflammation-related indicators, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and inhibitor-α of nuclear transcription factor κB (IκB-α) in serum and gastric tissue of rats with stress gastric ulcer(SGU),so as to explore its mechanisms underlying prevention of SGU. METHODS: A total of 36 Wistar rats were randomly divided into blank control, model, positive drug and He-Sea-Front-Mu point combination groups (n=9 in each group). A rat model of SGU was established by restraint water-immersion stress method. Ten days before mode-ling, rats in the He-Sea-Front-Mu point combination group received electroacupuncture (2 Hz, 0.6 mA)at ST36 and CV12 for 10 min once every other day for 10 days, and those in the positive drug group was treated by gavage of omeprazole (20 mg/kg) once every other day for 10 days. The morphology of the gastric mucosa was observed by naked eyes and hematoxylin-eosin staining, and the ulcer index (UI) and lesion score were calculated. TBA and colorimetric methods, ELISA and Western blot were used to detect malondialdehyde (MDA), myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels and the relative expressions of TLR4, MyD88, and IκB-α protein, separately. RESULTS: The gastric mucosa of rats in the blank control group was smooth and intact, the cells were arranged neatly, and there was no telangiec-tasia, hyperemia and inflammatory cell infiltration. The gastric mucosal epithelial structure of rats in the model group was destroyed, and a large number of mucosal epithelial cell death and inflammatory cell infiltration were seen. The degree of gastric mucosal injury and inflammatory cell infiltration in the positive drug group and the combined point group was less than that in the model group. Compared with the blank control group, the UI and lesion score of rats in the model group were significantly increased (P<0.05), the levels of MDA and MPO in the serum and gastric tissues were significantly increased (P<0.05), GSH-Px was significantly reduced (P<0.05), the contents of TNF-α and IL-6 in serum were markedly increased (P<0.05), the expression levels of TLR4 and MyD88 proteins in gastric tissue were significantly increased (P<0.05), IκB-α was significantly reduced (P<0.05). After intervention and in comparison with the model group showed that, the UI and lesion score, the levels of MDA and MPO, contents of serum TNF-α and IL-6, expression levels of TLR4 and MyD88 proteins in positive drug and He-Sea-Front-Mu point combination groups were significantly decreased (P<0.05), while GSH-Px and IκB-α were significantly increased (P<0.05); There were no significant differences in the above indicators between the positive drug and the He-Sea-Front -Mu point combination groups (except TNF-α). CONCLUSION: Electroacupuncture preconditioning at ST36 and CV12 can prevent SGU, which may be related to its effects in anti-oxidant, anti-inflammatory and regulating TLR4/MyD88/IκB signaling pathway.


Assuntos
Terapia por Acupuntura , Preparações Farmacêuticas , Úlcera Gástrica , Pontos de Acupuntura , Animais , Fator 88 de Diferenciação Mieloide/genética , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Transdução de Sinais , Úlcera Gástrica/genética , Úlcera Gástrica/terapia , Receptor 4 Toll-Like/genética
8.
Oncoimmunology ; 10(1): 1875637, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33796401

RESUMO

This study aims to identify the density of TILs in ductal carcinoma in situ (DCIS) in terms of prognostic significance with recurrence and the benefit of whole breast irradiation (WBI). The clinicopathological data of DCIS patients from Jan 2009 to Dec 2016 who received breast-conserving surgery (BCS) were retrospectively reviewed. Cox regression analysis was used to confirm independent prognostic factors of ipsilateral breast tumor recurrence (IBTR). Kaplan-Meier method was utilized to analyze IBTR and values of WBI. Touching-tumor-infiltrating lymphocytes (TILs) were defined by TILs touching or within one lymphocyte cell thickness from the malignant ducts' basement membrane. In total, 129 patients were enrolled in this analysis with 98 patients who received WBI. After a median follow-up of 53.0 months, there were 16 IBTR events with five invasive IBTRs. Univariate and multivariate analyses showed that touching-TILs >5 were an independent prognostic factor for higher IBTR (HR = 6.17, 95%CI 1.95-19.56, p < .01). The whole cohort was classified into two subgroups: dense group (>5 touching-TILs per duct) and sparse group (≤5 touching-TILs per duct). Dense touching-TILs were associated with unfavorable biologic characteristics. The 5-y rate of IBTR between dense and sparse group was 29.0% versus 4.5% (p < .01). For the sparse group, WBI significantly reduced the rate of 5-y-IBTR risk from 13.2% to 1.7% (p = .02), but there was no benefit of WBI in the dense group. Touching-TILs density was heterogeneous in patients with DCIS. Sparse touching-TILs were associated with better prognosis and benefit from WBI. Dense touching-TILs not only were associated with a higher risk of IBTR but also lack of benefit from WBI.

9.
Bioresour Technol ; 333: 125139, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33882384

RESUMO

One of the major limitations of lignocellulose conversion is the relatively low efficiency of cellulases. Expansins can act as an accessory protein to loosen the rigid cellulose structure and promote cellulose hydrolysis. However, the synergistic action of expansin is not well understood. In this study, we employed quartz crystal microbalance with dissipation to real-time monitor the adsorption of Bacillus subtilis expansin (BsEXLX1) and endoglucanase I (Cel7B) and the hydrolysis of cellulose. The effects of pH, temperature, and zinc ions on the initial adsorption rate and adsorption capacity of BsEXLX1 were examined. When 36.5 mM of zinc ions was added, the irreversible adsorption ratio of BsEXLX1 further increased to 4.63 times the value in the absence of zinc ions, whereas the initial adsorption rate and the hydrolysis rate constants of Cel7B could reach 2.16 times and 2.05 times the values in the absence of zinc ions, respectively.

10.
J Clin Psychopharmacol ; 41(3): 244-249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33814546

RESUMO

PURPOSE/BACKGROUND: Hippocampal volume loss in early schizophrenia has been linked with markers of inflammation and oxidative stress, and with less response of negative symptoms. Aripiprazole has been reported to preserve hippocampal volume and to reduce inflammation. METHODS/PROCEDURES: Study 1 was a 12-month multicenter randomized placebo-controlled trial of citalopram added to clinician-determined second-generation antipsychotic medication in 95 patients with first-episode schizophrenia (FES), 19 of whom received aripiprazole. We compared participants taking aripiprazole with those on other antipsychotics to determine whether those on aripiprazole had less hippocampal volume loss. We also examined peripheral biomarker data from medication-naive patients with schizophrenia receiving 8 weeks of antipsychotic treatment (n = 24) to see whether markers of inflammation and oxidative stress that previously predicted hippocampal volume differed between aripiprazole (n = 9) and other antipsychotics (study 2). FINDINGS/RESULTS: Aripiprazole was associated with a mean increase in hippocampal volume of 0.35% (SD, 0.80%) compared with a 0.53% decrease (SD, 1.2%) with other antipsychotics during the first year of maintenance treatment in patients with FES. This difference was significant after adjusting for age, sex, citalopram treatment, and baseline Brief Psychiatric Rating Scale score (B = 0.0079, P = 0.03). Aripiprazole was also associated with reduced concentrations of the inflammatory cytokines interleukin-8 and tumor necrosis factor (P < 0.01) during the first 8 weeks of treatment in medication-naive patients with FES. IMPLICATIONS/CONCLUSIONS: These results suggest that aripiprazole may protect against hippocampal atrophy via an anti-inflammatory mechanism, but these results require replication in larger, randomized trials, and the clinical relevance of hippocampal volume loss is not established.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33852401

RESUMO

Frequency estimation of 2-D multicomponent sinusoidal signals is a fundamental issue in the statistical signal processing community that arises in various disciplines. In this article, we extend the DeepFreq model by modifying its network architecture and apply it to 2-D signals. We name the proposed framework 2-D ResFreq. Compared with the original DeepFreq framework, the 2-D convolutional implementation of the matched filtering module facilitates the transformation from time-domain signals to frequency-domain signals and reduces the number of network parameters. The additional upsampling layer and stacked residual blocks are designed to perform superresolution. Moreover, we introduce frequency amplitude information into the optimization function to improve the amplitude accuracy. After training, the signals in the test set are forward-mapped to 2-D accurate and high-resolution frequency representations. Frequency and amplitude estimation are achieved by measuring the locations and strengths of the spectral peaks. We conduct numerical experiments to demonstrate the superior performance of the proposed architecture in terms of its superresolution capability and estimation accuracy.

12.
Int J Clin Oncol ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844112

RESUMO

AIM: Lymphoepithelioma-like carcinoma (LELC) is a rare histological types of solid tumors. The present study aims to comprehensively describe the demographic and clinical features of LELC using surveillance, epidemiology, and end results (SEER) database, with an emphasis on the prognostic difference according to primary tumor sites of LELC. MATERIALS AND METHODS: A population cohort with histologically diagnosed LELC were identified from SEER database between 1973 and 2016. Age-adjusted incidence rates and cancer-specific survival (CSS) were determined. Cox-regression proportional hazards model was used for both univariate and multivariate analyses. RESULTS: In total, 2106 patients with LELC were identified, with the most common diagnosed primary tumor site of nasopharyngeal LELC (56.22%), followed by non-nasopharyngeal head and neck LELC (21.32%) and respiratory system (7.83%). The overall age-adjusted incidence of LELC was 0.091 per 100,000. The CSS rates of LELC patients at 5, 10, 15, and 20 years were 76%, 69%, 65%, and 61%, respectively. A tendency of decreasing incidence of LELC was observed in the past decade. Univariate analysis indicated that sex [hazard ratio (HR) 1.21, p = 0.031], year of diagnosis (HR 0.60 and 0.63, p < 0.001), race (HR 1.29, p = 0.0021), age (HR 1.25, p = 0.0072), summary tumor stage (HR 1.97, and 4.57, both p < 0.001), number of positive LN(HR2.21, p < 0.001), surgery (HR 0.58, p = 0.0033), chemotherapy (HR 1.19, p = 0.037) and primary tumor site (p < 0.001) were significant factors associated with prognosis of LELC. In multivariate analysis, age (HR 1.75, p = 0.03), distant stage (HR 6.57, p = 0.0001), number of positive LN (HR 2.63, p = 0.0015) and non-nasopharyngeal head and neck LELC (HR 0.37, p = 0.0031) were significantly independent predictors for CSS of LELC. In sub-group analysis, radiotherapy significantly improves CSS for nasopharyngeal LELC (HR 0.57, p = 0.0002), while surgery significantly improve CSS for non-nasopharyngeal LELC (HR 0.33, p < 0.0001). CONCLUSION: Based on SEER data analysis, age older than 50 years, distant stage and more than three positive LN are significantly associated with worse CSS for LELC, while the prognosis of non-nasopharyngeal head and neck LELC is significantly better than nasopharyngeal LELC. Local treatments for LELC could be recommended according to primary tumor sites.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33796915

RESUMO

BACKGROUND: The present study aims to investigate the prognostic role of systematic inflammatory and nutritional indexes in extensive-stage small-cell lung cancer (ES-SCLC) treated with first-line chemotherapy and atezolizumab. MATERIALS AND METHODS: Prospective cohort population involving 53 patients were identified from NCT03041311 trial. The following peripheral blood-derived inflammatory and nutritional indexes, including neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), prognostic nutrition index (PNI), advanced lung cancer inflammation index (ALI), and lung immune prognostic index (LIPI) were evaluated. RESULTS: The optimal cut-off values of the ALI, LMR, NLR, PLR, PNI, SII and SIRI were 323.23, 2.73, 2.57, 119.23, 48, 533.28 and 2.32, respectively. With a median follow-up of 17.1 months, the 1-year OS and PFS were 56% and 8%, respectively. Multivariate analysis showed that PLR was the only independent prognostic factors for OS among ES-SCLC patients treated with chemotherapy and atezolizumab (HR 4.63, 95%CI: 1.00-21.46, p = 0.05). K-M analysis showed that the OS and PFS for patients with high PLR (> 119.23) were significantly poorer than these with low PLR (≤ 119.23) (p = 0.0004 for OS and p = 0.014 for PFS). In external validation set, prognosis of patients with high PLR was also significantly poorer than these with low PLR in terms of OS (p = 0.038) and PFS (p = 0.028). CONCLUSION: Pre-treatment PLR could serve as a valuable independent prognostic factor for ES-SCLC who receive chemotherapy and immune checkpoint inhibitors. Further, prospective studies are still needed to confirm our findings.

14.
Front Immunol ; 12: 552429, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717057

RESUMO

Isolated central nervous system involvement in multiple myeloma (CNS-MM) is rare and carries extremely poor prognosis. Chimeric antigen receptor T cell therapy (CART) targeting B-cell maturation antigen (BCMA) is demonstrated as a promising strategy in MM treatment, but the clinical safety and efficacy of BCMA-CART against isolated CNS-MM remain elusive. Here we report on a 56-year-old male with refractory isolated CNS-MM who received autologous BCMA-CART therapy and developed grade 4 neurological complications. Cerebrospinal fluid (CSF) analyses showed significant expansion of CART cells and a substantially elevated interleukin-6 (IL-6) level. Intravenous methylprednisolone was administered and the symptoms resolved gradually. Unexpectedly, the level of IL-6 in the CSF was maintained for another 3 days even after the relief of the neurological symptoms. A partial response was achieved and sustained for 5.5 months. This is the first report describing a patient with isolated CNS-MM treated using BCMA-CART therapy. The results demonstrated that BCMA-CART cells administered intravenously trafficked into the CSF, eradicated tumor cells, and induced severe but reversible neurological adverse events. This single-patient report suggests that BCMA-CART therapy can be considered as an alternative option for isolated CNS-MM. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03196414.

15.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1866(6): 158919, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33684567

RESUMO

Adipose tissue is important for systemic metabolic homeostasis in response to environmental changes, and adipogenesis involves dynamic transcriptional regulation. Ten-eleven translocation (TET) enzymes (TET1, 2 and 3) oxidize the 5-methylcytosine (5mC) in DNA to 5-hydroxylmethylcytosine (5hmC), which associates with transcriptional activation. Step by step, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) are further generated by TETs and the cytosine can be restored through base-excision repair. It is still unclear how DNA demethylation is involved in adipogenesis. Through a phenotypic screen, we found TET inhibition decreased adipocyte differentiation from mesenchymal stem cells (MSCs). Comparing with the undifferentiated MSCs, the differentiated adipocytes exhibited much higher levels of 5hmC and slightly increased 5fC and 5caC. Higher 5hmC was associated with better differentiation at single-cell level by image analysis. TET1 is upregulated in differentiation and depletion of it significantly impaired the gain of 5hmC. Furthermore, Tet1 depletion significantly hampered the adipocyte differentiation. Using RNA-seq, 5mC and 5hmC-DNA immunoprecipitation, we found that Tet1 knockout led to lower expression of genes associated with lipid metabolism and fat cell differentiation. Genes with loss of 5mC or gain of 5hmC in adipocytes include Lipe, Bmp4 and Rxra, etc. RXRα agonist partially rescued the inhibitory effect of Tet1 knockout for adipogenesis. So, Rxra is one of the critical TET1 modulated genes. Together, TET1-mediated active DNA demethylation plays an important role in adipogenesis.

16.
Ecotoxicol Environ Saf ; 214: 112115, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33691242

RESUMO

Nanoplastics (NPs) are becoming an emerging pollutant of global concern. A potential risk of NPs is that they can serve as carriers and synergistically function with other contaminants to cause diseases. A variety of diseases such as Alzheimer's disease are related to the generation of amyloid fibrils, and insulin is typically used as a model to study the fibrillation process. In this study, we examined the fibrillation of insulin promoted by polystyrene nanoplastics (PSNPs) alone and synergistically with organic contaminants (denoted as X, X = pyrene, bisphenol A, 2,2',4,4'-tetrabromodiphenyl ether, 4,4'-dihydroxydiphenylmethane, or 4-nonylphenol) having different polarities using thioflavin T fluorescence assays, dynamic light scattering, and circular dichroism spectroscopy. The presence of PSNPs and small organic contaminants decreased the lag phase time (tlag) for insulin fibrillation from 54.6 h to 35-51 h and their combination (PS-X) enhanced this process (tlag = 21-30 h). Notably, the lag phase time for insulin fibrillation with PS-nonpolar contaminants, PS-weakly polar contaminants, and PS-polar contaminants is around 20.8, 26.7, and 30.1 h, respectively, indicating the synergistic effect of PS-nonpolar contaminants or PS-weakly polar contaminants was more obvious than that of PS-polar contaminants. Moreover, molecular dynamic simulation reveal the interactions between insulin and PSs or small organic contaminants are primarily driven by van der Waals forces and hydrophobic interactions. Overall, the findings of this study underscore the potentially significant environmental impact of small organic contaminants assisting NPs in promoting insulin fibrillation.


Assuntos
Poluentes Ambientais/química , Insulina/química , Microplásticos/química , Nanopartículas/química , Poliestirenos/química , Compostos Benzidrílicos/química , Éteres Difenil Halogenados/química , Fenóis/química , Pirenos/química
17.
Biochem Biophys Res Commun ; 547: 192-197, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33618226

RESUMO

In this study, we aimed to develop B. subtilis spore coat protein A (CotA) for the enzymatic determination of bilirubin. Firstly, molecular docking and oxidation kinetic analysis confirmed the feasibility of CotA for oxidizing bilirubin. Secondly, CotA showed pH-preferable oxidization performance to direct bilirubin (DB) in acidic conditions and an alkaline-catalytic oxidation capacity to total bilirubin (TB). Mechanism analysis results confirm that the conformational changes of CotA, DB and UB caused by pH changes are responsible for the selective oxidation of DB and TB by CotA. Then, CotA exhibits better structural characteristics and enzymatic performance than M. verrucaria-derived bilirubin oxidase (Mv-BOD). Besides, the strong anti-interference ability helps CotA adapt to complex catalytic environment in the detection of DB and TB. Our results prove that CotA can be used as a promising candidate bio-enzymatic detection reagent for DB and TB.

18.
Mar Biotechnol (NY) ; 23(2): 294-307, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33570690

RESUMO

In mammals, mature miR-122 is 22 nucleotides long and can be involved in regulating a variety of physiological and biological pathways. In this study, the expression profile and effects of grouper Epinephelus coioides miR-122 response to Singapore grouper iridovirus (SGIV) infection were investigated. The sequences of mature microRNAs (miRNAs) from different organisms are highly conserved, and miR-122 from E. coioides exhibits high similarity to that from mammals and other fish. The expression of miR-122 was up-regulated during SGIV infection. Up-regulation of miR-122 could significantly enhance the cytopathic effects (CPE) induced by SGIV, the transcription levels of viral genes (MCP, VP19, LITAF and ICP18), and viral replication; reduce the expression of inflammatory factors (TNF-a, IL-6, and IL-8), and the activity of AP-1 and NF-κB, and miR-122 can bind the target gene p38α MAPK to regulate the SGIV-induced cell apoptosis and the protease activity of caspase-3. The results indicated that SGIV infection can up-regulate the expression of E. coioides miR-122, and up-regulation of miR-122 can affect the activation of inflammatory factors, the activity of AP-1 and NF-κB, and cell apoptosis to regulate viral replication and proliferation.

19.
Thorac Cancer ; 12(8): 1180-1186, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33605068

RESUMO

BACKGROUND: This was a single institute, phase I/II study of salvage chemoradiotherapy (CRT) with simultaneous integrated boost in patients with mediastinal lymph node (LN) recurrence after esophagectomy. METHODS: Patients who presented with a clinical diagnosis of ≤5 mediastinal LN recurrence received three consecutive levels of radiotherapy dose for the recurrences. Level 1: 58.8 Gy/2.1 Gy/28 fractions, Level 2: 64.4 Gy/2.3 Gy/28 fractions and Level 3: 70 Gy/2.5 Gy/28 fractions. RESULTS: A total of 17 patients (10 patients in phase I and 7 patients in phase II) were enrolled in the present study between June 2019 and July 2020. The median duration from surgery to initial recurrence was four months (range: 3-43 months). The most common site of recurrence according to JES was 106recR, accounting for 35%. Dose-limiting toxicity was not observed during three-month follow-up after completion of irradiation. The most common hematological toxicities were leukocytopenia and anemia. The most common nonhematological toxicity was esophagitis. The ORR according to RECIST was 58.8% (CR: seven patients; PR: three patients). With a median follow-up of 15 months (95% CI: 7-16 months), all patients were still alive. Among them, two patients who received a level 1 dose and one patient who received a level III dose developed multiple lung metastases after salvage CRT, and another patient who received a level 1 dose developed an out-of-field recurrence in the left cervical lymph node area. Another patient who received a level III dose developed chest wall recurrence after salvage CRT. CONCLUSIONS: The regimen of salvage CRT using the simultaneous integrated boost (SIB) technique (70 Gy/2.5 Gy/28F) for mediastinal lymph node recurrence in ESCC patients after esophagectomy is feasible and well tolerated.

20.
ACS Nano ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33629584

RESUMO

The self-assembly of chiral metal nanoclusters into supramolecular chiral aggregates is of interest for developing advanced materials. Herein, we manipulated the self-assembly of Au nanoclusters modified by l-/d-cysteine (l-/d-AuNCs) into ordered microstructures featuring enhanced phosphorescence and optical activities. The formation of these aggregates was driven by synergistic effect of coordination and electrostatic interactions assisted by Cd2+/H+. Detailed structural characterization and theoretical studies confirmed that the compact aggregation structures are essential for the emission enhancement and the chirality amplification of l-/d-AuNCs. Interestingly, upon the formation of microflowers, the emission lifetime was prolonged to 3.34 ms with a switch from fluorescence to phosphorescence induced by aurophilic Au(I)···Au(I) interactions and intensive ligand-to-metal charge transfer (LMCT). Moreover, both the CD and photoluminescence (PL) signals of the microflowers exhibited pH-responsiveness. This dual-mode sensitive platform could be developed as a pH sensor with improved accuracy. Additionally, the pH-responsive photoluminescence ON/OFF switch of the microflowers could be employed for reliable information encryption and decryption. This study provides useful ideas for regulating the self-assembly of nanoclusters to generate desired photophysical properties with potential applications.

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