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1.
Front Immunol ; 12: 673693, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408744

RESUMO

Background: Thymosin alpha 1 (Tα1) is widely used to treat patients with COVID-19 in China; however, its efficacy remains unclear. This study aimed to explore the efficacy of Tα1 as a COVID-19 therapy. Methods: We performed a multicenter cohort study in five tertiary hospitals in the Hubei province of China between December 2019 and March 2020. The patient non-recovery rate was used as the primary outcome. Results: All crude outcomes, including non-recovery rate (65/306 vs. 290/1,976, p = 0.003), in-hospital mortality rate (62/306 vs. 271/1,976, p = 0.003), intubation rate (31/306 vs. 106/1,976, p = 0.001), acute respiratory distress syndrome (ARDS) incidence (104/306 vs. 499/1,976, p = 0.001), acute kidney injury (AKI) incidence (26/306 vs. 66/1,976, p < 0.001), and length of intensive care unit (ICU) stay (14.9 ± 12.7 vs. 8.7 ± 8.2 days, p < 0.001), were significantly higher in the Tα1 treatment group. After adjusting for confounding factors, Tα1 use was found to be significantly associated with a higher non-recovery rate than non-Tα1 use (OR 1.5, 95% CI 1.1-2.1, p = 0.028). An increased risk of non-recovery rate associated with Tα1 use was observed in the patient subgroups with maximum sequential organ failure assessment (SOFA) scores ≥2 (OR 2.0, 95%CI 1.4-2.9, p = 0.024), a record of ICU admission (OR 5.4, 95%CI 2.1-14.0, p < 0.001), and lower PaO2/FiO2 values (OR 1.9, 95%CI 1.1-3.4, p = 0.046). Furthermore, later initiation of Tα1 use was associated with a higher non-recovery rate. Conclusion: Tα1 use in COVID-19 patients was associated with an increased non-recovery rate, especially in those with greater disease severity.


Assuntos
COVID-19/tratamento farmacológico , Síndrome do Desconforto Respiratório/epidemiologia , Timalfasina/efeitos adversos , Adulto , Idoso , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prognóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/prevenção & controle , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Timalfasina/administração & dosagem , Resultado do Tratamento
2.
J Magn Reson Imaging ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34327763

RESUMO

BACKGROUND: Chemical exchange saturation transfer (CEST) is an emerging metabolic MRI technique to map creatine distribution in the myocardium. PURPOSE: To investigate the feasibility of using a contrast-free CEST technique to evaluate cardiac involvement in amyloid light-chain (AL) amyloidosis. STUDY TYPE: Prospective. POPULATION: Forty patients with biopsy-proven AL amyloidosis (age 57.6 ± 9.1 years, 31 males) and 20 healthy controls (age 42.8 ± 13.8 years, 13 males). FIELD STRENGTH/SEQUENCE: A 3.0 T, CEST imaging using a single-shot FLASH sequence, T1 mapping with a modified Look-Locker inversion recovery sequence and late gadolinium enhancement (LGE) imaging with a phase-sensitive inversion recovery gradient echo sequence. ASSESSMENT: The average CEST was calculated in the basal short-axis slice of the entire left ventricle and septum. LGE was assessed subjectively (none/patchy/global) and extracellular volume (ECV), CEST and T1 maps generated. STATISTICAL TESTS: Comparison between patient groups and healthy controls was performed by one-way analysis of variance with post hoc Bonferroni correction. Correlation was assessed using the Pearson's r correlation or Spearman ρ correlation. Statistical significance was defined as P < 0.05. RESULTS: Global (0.09 ± 0.03 vs. 0.11 ± 0.02) and septal (0.09 ± 0.03 vs. 0.11 ± 0.03) basal short-axis CEST was significantly decreased in patients with AL amyloidosis compared to the controls. Global CEST correlated significantly with Mayo stage (ρ = -0.508), NYHA Class (ρ = -0.430), LVEF (r = 0.511), mass index (r = -0.373), LGE (ρ = -0.537), ECV (r = -0.544), and T2 (r = -0.396). Septal CEST correlated significantly with LVEF (r = 0.395), LGE (ρ = -0.330), and ECV (r = -0.391). DATA CONCLUSIONS: This study highlights the potential of CEST MRI to identify cardiac involvement and evaluate disease burden and to give insight into cellular changes intermediary between function and structure in AL amyloidosis patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

3.
PLoS One ; 16(6): e0252662, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34077462

RESUMO

Breast cancer cells were reported to up-regulate human prolactin receptor (PRLR) to assist their growth through the utilization of prolactin (PRL) as the growth factor, which makes PRLR a potential therapeutic target for breast cancer. On the other hand, advanced cancer cells tend to down-regulate or shed off stress signal proteins to evade immune surveillance and elimination. In this report, we created a fusion protein consisting of the extracellular domain of MHC class I chain-related protein (MICA), a stress signal protein and ligand of the activating receptor NKG2D of natural killer (NK) cells, and G129R, an antagonistic variant of PRL. We hypothesize that the MICA portion of the fusion protein binds to NKG2D to activate NK cells and the G129R portion binds to PRLR on breast cancer cells, so that the activated NK cells will kill the PRLR-positive breast cancer cells. We demonstrated that the MICA-G129R fusion protein not only binds to human natural killer NK-92 cells and PRLR-positive human breast cancer T-47D cells, but also promotes NK cells to release granzyme B and IFN-γ and enhances the cytotoxicity of NK cells specifically on PRLR-positive cells. The fusion protein, therefore, represents a new approach for the development of breast cancer specific immunotherapy.

4.
Clin Microbiol Infect ; 27(10): 1488-1493, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34020032

RESUMO

OBJECTIVES: Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients. METHODS: This retrospective multicentre study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting (IPW) were used to control confounding factors. RESULTS: The study included 850 patients (421 IVIG-treated patients and 429 non-IVIG-treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (average treatment effect (ATE) = 0.008, 95% CI -0.081 to 0.097, p 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy and extracorporeal membrane oxygenation except for prone position ventilation (ATE = -0.022, 95% CI -0.041 to -0.002, p 0.028). DISCUSSION: IVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies.

5.
Cancer Treat Res Commun ; 27: 100377, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33945921

RESUMO

Non-small cell lung cancer (NSCLC) patients with oncogenic ROS1 rearrangements would inevitably develop drug resistance and disease progression after receiving targeted oncogene therapy. Here, we present a metastatic lung adenocarcinoma patient harboring a CD74-ROS1 fusion who initially responded to crizotinib and then developed resistance after acquiring a rarely reported BRAF V600E mutation.

6.
Phytochem Anal ; 32(6): 1152-1161, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33977590

RESUMO

INTRODUCTION: Citri Reticulatae Pericarpium Viride (Qing Pi in Chinese) is a clinically effective Chinese herb, which contains biologically valuable flavonoids. Qing Pi is divided into two commodity specifications, Si Hua Qing Pi (SHQP) and Ge Qing Pi (GQP), based on the harvesting time. The flavonoid contents in Qing Pi from different origins and commodity specifications may vary significantly, which will affect their therapeutic functions. Thus, it is crucial to set up a reliable and comprehensive quality evaluation method for flavonoid analysis in Qing Pi. OBJECTIVES: We aimed to establish a rapid and sensitive ultrahigh-performance liquid chromatography method coupled with diode-array detection and high-resolution mass spectrometry (UPLC-DAD-HRMS) for identification and quantification of ten flavonoids in Qing Pi. Chemometric methods were further applied to distinguish Qing Pi of different origins and specifications. METHODOLOGY: An UPLC-DAD-HRMS method was developed for the simultaneous separation and quantification of ten flavonoids in 46 batches of Qing Pi samples from different sources in China. Chemometric approaches were applied to discriminate Qing Pi from different origins and commodity specifications. RESULTS: The chemometric procedures (i.e., hierarchical clustering analysis and principal component analysis) were employed to identify the differences of Qing Pi samples with different origins and commodity specifications. The results showed that the contents of ten flavonoids in Qing Pi samples of different origins were significantly different, and the same results were found out between SHQP and GQP. CONCLUSIONS: This study provides a chemical basis for quality control of Qing Pi.


Assuntos
Citrus , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Flavonoides/análise , Espectrometria de Massas em Tandem
7.
Anal Chim Acta ; 1167: 338578, 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34049630

RESUMO

Exosomes are membrane-bound, cell-secreted vesicles, with sizes ranging from 30 to 150 nm. Exosomes in blood plasma have become proposed targets as measurable indicators of disease conditions. Current methods for plasma-based exosome isolation are time-consuming, complex, and have high operational costs. One of the most commonly reported shortcomings of current isolation protocols is the co-extraction of lipoproteins (e.g. low-density lipoproteins, LDLs) with the target exosomes. This report describes the use of a rapid, single-operation hydrophobic interaction chromatography (HIC) procedure on a polyester (PET) capillary-channeled polymer (C-CP) fiber column, demonstrating the ability to efficiently purify exosomes. The method has previously been demonstrated for isolation of exosomes from diverse biological matrices, but questions were raised about the potential co-elution of LDLs. In the method described herein, a step-gradient procedure sequentially elutes spiked lipoproteins and blood plasma-originating exosomes in 10 min, with the LDLs excluded from the desired exosome fraction. Mass spectrometry (MS) was used to characterize an impurity in the primary LDL material, identifying the presence of exosomal material. Transmission electron microscopy (TEM) and an enzyme-linked immunosorbent assay (ELISA) were used to identify the various elution components. The method serves both as a rapid means of high purity exosome isolation as well as a screening tool for the purity of LDL samples with respect to extracellular vesicles.


Assuntos
Exossomos , Cromatografia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lipoproteínas LDL , Plasma , Poliésteres , Polímeros
8.
BMC Infect Dis ; 21(1): 398, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926377

RESUMO

BACKGROUND: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammatory event and a fatal complication of viral infections. Whether sHLH may also be observed in patients with a cytokine storm induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still uncertain. We aimed to determine the incidence of sHLH in severe COVID-19 patients and evaluate the underlying risk factors. METHOD: Four hundred fifteen severe COVID-19 adult patients were retrospectively assessed for hemophagocytosis score (HScore). A subset of 7 patients were unable to be conclusively scored due to insufficient patient data. RESULTS: In 408 patients, 41 (10.04%) had an HScore ≥169 and were characterized as "suspected sHLH positive". Compared with patients below a HScore threshold of 98, the suspected sHLH positive group had higher D-dimer, total bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine, triglycerides, ferritin, interleukin-6, C-reactive protein, procalcitonin, lactate dehydrogenase, creatine kinase isoenzyme, troponin, Sequential Organ Failure Assessment (SOFA) score, while leukocyte, hemoglobin, platelets, lymphocyte, fibrinogen, pre-albumin, albumin levels were significantly lower (all P < 0.05). Multivariable logistic regression revealed that high ferritin (>1922.58 ng/mL), low platelets (<101 × 109/L) and high triglycerides (>2.28 mmol/L) were independent risk factors for suspected sHLH in COVID-19 patients. Importantly, COVID-19 patients that were suspected sHLH positive had significantly more multi-organ failure. Additionally, a high HScore (>98) was an independent predictor for mortality in COVID-19. CONCLUSIONS: HScore should be measured as a prognostic biomarker in COVID-19 patients. In particular, it is important that HScore is assessed in patients with high ferritin, triglycerides and low platelets to improve the detection of suspected sHLH.


Assuntos
COVID-19/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Adulto , Idoso , Aspartato Aminotransferases/sangue , COVID-19/epidemiologia , COVID-19/terapia , China/epidemiologia , Comorbidade , Síndrome da Liberação de Citocina/complicações , Síndrome da Liberação de Citocina/virologia , Feminino , Ferritinas/sangue , Humanos , Incidência , Contagem de Linfócitos , Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Retrospectivos , Fatores de Risco
10.
Anal Bioanal Chem ; 413(11): 2985-2994, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33608753

RESUMO

Lentiviruses are increasingly used as gene delivery vehicles for vaccines and immunotherapies. However, the purification of clinical-grade lentivirus vectors for therapeutic use is still troublesome and limits preclinical and clinical experiments. Current purification methods such as ultracentrifugation and ultrafiltration are time consuming and do not remove all of the impurities such as cellular debris, membrane fragments, and denatured proteins from the lentiviruses. The same challenges exist in terms of their analytical characterization. Presented here is the novel demonstration of the chromatographic isolation of virus particles from culture media based on the hydrophobicity characteristics of the vesicles. A method was developed to isolate lentivirus from media using a hydrophobic interaction chromatography (HIC) method performed on a polyester, capillary-channeled polymer (PET C-CP) stationary phase and a standard liquid chromatography apparatus. The method is an extension of the approach developed in this laboratory for the isolation of extracellular vesicles (EVs). Quantitative polymerase chain reaction (qPCR) was used to verify and quantify lentiviruses in elution fractions. Load and elution mobile phase compositions were optimized to affect high efficiency and throughput. The process has been visualized via scanning electron microscopy (SEM) of the fiber surfaces following media injection, the elution of proteinaceous material, and the elution of lentiviruses. This effort has yielded a rapid (<10 min), low-cost (< $15 per column, providing multiple separations), and efficient method for the isolation/purification of lentivirus particles from cell culture media at the analytical scale.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Lentivirus/isolamento & purificação , Poliésteres/química , Polímeros/química , Células HEK293 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Reação em Cadeia da Polimerase em Tempo Real , Espectrofotometria Ultravioleta
11.
Electrophoresis ; 42(3): 245-256, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33169421

RESUMO

We have developed a rapid, low-cost, and simple separation strategy to separate extracellular vesicles (EVs) from a small amount of serum (i.e.,<100 µL) with minimal contamination by serum proteins and lipoprotein particles to meet the high purity requirement for EV proteome analysis. EVs were separated by a novel polyester capillary channel polymer (PET C-CP) fiber phase/hydrophobic interaction chromatography (HIC) method which is rapid and can process small size samples. The collected EV fractions were subjected to a post-column cleanup protocol using a centrifugal filter to perform buffer exchange and eliminate potential coeluting non-EV proteins while minimizing EV sample loss. Downstream characterization demonstrated that our current strategy can separate EVs with the anticipated exosome-like particle size distribution and high yield (∼1 × 1011 EV particles per mL of serum) in approximately 15 min. Proteome profiling of the EVs reveals that a group of genuine EV components were identified that have significantly less high-abundance blood proteins and lipoprotein particle contamination in comparison to traditional separation methods. The use of this methodology appears to address the major challenges facing EV separation for proteomics analysis. In addition, the EV post-column cleanup protocol proposed in the current work has the potential to be combined with other separation methods, such as ultracentrifugation (UC), to further purify the separated EV samples.

12.
Melanoma Res ; 31(2): 119-129, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347048

RESUMO

Although germline mutations in BRCA-associated protein-1 (BAP1) predispose to cutaneous melanoma (CM), BAP1 is rarely mutated in primary CM outside the familial context. The role of BAP1 in the pathogenesis of CM remains obscure. Here, we discovered an unexpected role of BAP1 in suppressing CM growth and metastasis. BAP1 deletion by CRISPR-Cas9 system severely compromises colony-forming capability of murine CM cell line B16-F10 and human CM cell lines, SK-MEL-28 and A375. Furthermore, BAP1 loss abrogates tumor growth and lung metastasis in murine syngeneic tumor models. Deletion of BAP1 in B16-F10 cells leads to preferential downregulation of genes accompanied with increased H2A ubiquitination at lysine 119. Transcriptomic characterization of BAP1 deletion reveals multiple deregulated cellular functions including extracellular matrix-receptor interaction and MAPK signaling pathway which may contribute to BAP1's effect on metastasis and proliferation. Our findings indicate that BAP1 could be a potential therapeutic target for CM.


Assuntos
Melanoma/genética , Neoplasias Cutâneas/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismo , Animais , Humanos , Camundongos , Camundongos Nus , Metástase Neoplásica , Transfecção
13.
J Clin Invest ; 130(12): 6417-6428, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33141117

RESUMO

BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P < 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P < 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P < 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (>200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.


Assuntos
Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , COVID-19/tratamento farmacológico , COVID-19/mortalidade , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/mortalidade , Idoso , COVID-19/complicações , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/etiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida
14.
Ann Intensive Care ; 10(1): 99, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737627

RESUMO

BACKGROUND: Since December 2019, an outbreak of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) initially emerged in Wuhan, China, and has spread worldwide now. Clinical features of patients with COVID-19 have been described. However, risk factors leading to in-hospital deterioration and poor prognosis in COVID-19 patients with severe disease have not been well identified. METHODS: In this retrospective, single-center cohort study, 1190 adult inpatients (≥ 18 years old) with laboratory-confirmed COVID-19 and determined outcomes (discharged or died) were included from Wuhan Infectious Disease Hospital from December 29, 2019 to February 28, 2020. The final follow-up date was March 2, 2020. Clinical data including characteristics, laboratory and imaging information as well as treatments were extracted from electronic medical records and compared. A multivariable logistic regression model was used to explore the potential predictors associated with in-hospital deterioration and death. RESULTS: 1190 patients with confirmed COVID-19 were included. Their median age was 57 years (interquartile range 47-67 years). Two hundred and sixty-one patients (22%) developed a severe illness after admission. Multivariable logistic regression demonstrated that higher SOFA score (OR 1.32, 95% CI 1.22-1.43, per score increase, p < 0.001 for deterioration and OR 1.30, 95% CI 1.11-1.53, per score increase, p = 0.001 for death), lymphocytopenia (OR 1.81, 95% CI 1.13-2.89 p = 0.013 for deterioration; OR 4.44, 95% CI 1.26-15.87, p = 0.021 for death) on admission were independent risk factors for in-hospital deterioration from not severe to severe disease and for death in severe patients. On admission D-dimer greater than 1 µg/L (OR 3.28, 95% CI 1.19-9.04, p = 0.021), leukocytopenia (OR 5.10, 95% CI 1.25-20.78), thrombocytopenia (OR 8.37, 95% CI 2.04-34.44) and history of diabetes (OR 11.16, 95% CI 1.87-66.57, p = 0.008) were also associated with higher risks of in-hospital death in severe COVID-19 patients. Shorter time interval from illness onset to non-invasive mechanical ventilation in the survivors with severe disease was observed compared with non-survivors (10.5 days, IQR 9.25-11.0 vs. 16.0 days, IQR 11.0-19.0 days, p = 0.030). Treatment with glucocorticoids increased the risk of progression from not severe to severe disease (OR 3.79, 95% CI 2.39-6.01, p < 0.001). Administration of antiviral drugs especially oseltamivir or ganciclovir is associated with a decreased risk of death in severe patients (OR 0.17, 95% CI 0.05-0.64, p < 0.001). CONCLUSIONS: High SOFA score and lymphocytopenia on admission could predict that not severe patients would develop severe disease in-hospital. On admission elevated D-dimer, leukocytopenia, thrombocytopenia and diabetes were independent risk factors of in-hospital death in severe patients with COVID-19. Administration of oseltamivir or ganciclovir might be beneficial for reducing mortality in severe patients.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32784792

RESUMO

Background: Scant attention has been paid to how risk perceptions of public health crises may affect people's mental health. Aims: The aims of this study are to (1) construct a conceptual framework for risk perception and depression of people in public health crises, (2) examine how the mental health of people in the crisis of Coronavirus Disease 2019 (COVID-19) is affected by risk perception and its associated factors, including distance perception of the crisis and support of prevention and control policies, and (3) propose policy recommendations on how to deal with psychological problems in the current COVID-19 crisis. Methods: Online questionnaire survey was implemented. A total of 6373 people visited the questionnaire online, 1115 people completed the questionnaire, and the number of valid questionnaires was 1081. Structural equation modeling was employed for data analysis. Results: Risk perception and its associated factors significantly affect the mental health of people in public health crises. Specifically, (1) distance perception of public health crises is negatively associated with depression among people, (2) affective risk perception is positively associated with depression of people in public health crises, (3) cognitive risk perception is negatively associated with depression of people in public health crises, and (4) support of prevention and control policies is negatively associated with depression of people in public health crises. Conclusion: The findings of this study suggest that risk perception plays an important role in affecting the mental health of people in a public health crisis. Therefore, health policies aiming to improve the psychological wellbeing of the people in a public health crisis should take risk perception into consideration.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/psicologia , Saúde Mental , Desastres Naturais , Pneumonia Viral/epidemiologia , Pneumonia Viral/psicologia , Adulto , Betacoronavirus , COVID-19 , China/epidemiologia , Controle de Doenças Transmissíveis/organização & administração , Coronavirus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Saúde Pública , Medição de Risco , SARS-CoV-2 , Fatores Socioeconômicos
16.
Micromachines (Basel) ; 11(8)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32752053

RESUMO

To solve the problem of vibration motor fault detection accuracy and inefficiency in smartphone components, this paper proposes a fault diagnosis method based on the wavelet packet and improves long and short-term memory network. First, the voltage signal of the vibration motor is decomposed by a wavelet packet to reconstruct the signal. Secondly, the reconstructed signal is input into the improved three-layer LSTM network as a feature vector. The memory characteristics of the LSTM network are used to fully learn the time-series fault feature information in the unsteady state signal, and then, the model is used to diagnose the motor fault. Finally, the feasibility of the proposed method is verified through experiments and can be applied to engineering practice. Compared with the existing motor fault diagnosis method, the improved WP-LSTM diagnosis method has a better diagnosis effect and improves fault diagnosis.

17.
Biotechnol Prog ; 36(5): e2998, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32246744

RESUMO

Exosomes are membrane-secreted vesicles, with sizes ranging from 30 to 150 nm, which play key roles in intercellular communication. There is intense interest in developing methods to isolate and quantify exosomes toward clinical diagnostics, fundamental studies of intercellular processes, and use of exosomes as delivery vehicles for therapeutic agents. Current methods for exosomes isolation and quantification are time consuming and have operational high costs; few combine isolation and quantification into a singular operation unit. This report describes the use of hydrophobic interaction chromatography on a polyester capillary-channeled polymer fiber column, employing a step gradient for exosome elution, including use of glycerol as a solvent modifier. The entire procedure is completed in 8 min, while maintaining the structural integrity and biological activity of the isolated exosomes. Electron microscopy was used to verify the size and structural fidelity of single exosomes. Absorbance response curves for a commercial exosome sample were used for exosome quantification in the chromatographic separations. In order to determine the dynamic loading capacity for exosomes, different volumes of Dictyostelium discoideum cell culture milieu supernatant were loaded at different column lengths (5-30 cm) and loading flow rates (0.2-0.5 ml/min). A loading capacity of 5.4 × 1012 exosomes derived from D. discoideum milieu was obtained on a 0.8 × 300 mm column; yielding recoveries of over 80%. It is believed that this isolation and purification strategy holds many advantages toward the use of exosomes across a wide breadth of medical and biotechnology applications.

18.
PLoS One ; 15(2): e0229159, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32059028

RESUMO

Durum wheat, genetic resource with favorable alleles is considered as natural gene pool for wheat breeding. Kernel size and weight are important factors affecting grain yield in crops. Here, association analysis was performed to dissect the genetic constitution of kernel-related traits in 150 lines collected from 46 countries and regions using a set of EST-derived and genome-wide SNP markers with five consecutive years of data. Total 109 significant associations for eight kernel-related traits were detected under a mix linear model, generating 54 unique SNP markers distributed on 13 of 14 chromosomes. Of which, 19 marker-trait associations were identified in two or more environments, including one stable and pleiotropic SNP BE500291_5_A_37 on chromosome 5A correlated with six kernel traits. Although most of our SNP loci were overlapped with the previously known kernel weight QTLs, several novel loci for kernel traits in durum were reported. Correlation analysis implied that the moderate climatic variables during growth and development of durum are needed for the large grain size and high grain weight. Combined with our previous studies, we found that chromosome 5A might play an important role in durum growth and development.


Assuntos
Polimorfismo de Nucleotídeo Único , Triticum/genética , Cromossomos de Plantas/genética , Fenótipo , Triticum/crescimento & desenvolvimento
19.
Toxicology ; 435: 152408, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32057834

RESUMO

PURPOSE: To investigate the effects and mechanisms of NADPH on Kainic acid (KA)-induced excitotoxicity. METHODS: KA, a non-N-methyl-d-aspartate glutamate receptor agonist, was exposed to adult SD rats via intrastriatal injection and rat primary cortical neurons to establish excitotoxic models in vivo and in vitro, respectively. To determine the effects of NADPH on KA-induced excitotoxicity, neuronal survival, neurologically behavioral score and oxidative stress were evaluated. To explore the mechanisms of neuroprotective effects of NADPH, the autophagy-lysosome pathway related proteins were detected. RESULTS: In vivo, NADPH (1 mg/kg or 2 mg/kg) diminished KA (2.5 nmol)-induced enlargement of lesion size in striatum, improved KA-induced dyskinesia and reversed KA-induced activation of glial cells. Nevertheless, the neuroprotective effect of NADPH was not significant under the condition of autophagy activation. NADPH (2 mg/kg) inhibited KA (2.5 nmol)-induced down-regulation of TP-53 induced glycolysis and apoptosis regulator (TIGAR) and p62, and up-regulation of the protein levels of LC3-II/LC3-I, Beclin-1 and Atg5. In vitro, the excitotoxic neuronal injury was induced after KA (50 µM, 100 µM or 200 µM) treatment as demonstrated by decreased cell viability. Moreover, KA (100 µM) increased the intracellular levels of calcium and reactive oxygen species (ROS) and declined the levels of the reduced form of glutathione (GSH). Pretreatment of NADPH (10 µM) effectively reversed these changes. Meanwhile NADPH (10 µM) inhibited KA (100 µM)-induced down-regulation of TIGAR and p62, and up-regulation of the ratio of LC3-II/LC3-I, Beclin-1, Atg5, active-cathepsin B and active-cathepsin D. CONCLUSIONS: Our data provide a possible mechanism that NADPH ameliorates KA-induced excitotoxicity by blocking the autophagy-lysosome pathway and up-regulating TIGAR along with its antioxidant properties.


Assuntos
Autofagia/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/toxicidade , Ácido Caínico/toxicidade , Lisossomos/efeitos dos fármacos , NADP/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/metabolismo , Comportamento Animal/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Lisossomos/metabolismo , Lisossomos/patologia , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Atividade Motora/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Monoéster Fosfórico Hidrolases/metabolismo , Ratos Sprague-Dawley , Proteína Sequestossoma-1/metabolismo
20.
Anal Chim Acta ; 1082: 186-193, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472708

RESUMO

Exosomes are one class of extracellular vesicles (30-150 nm diameter) that are secreted by cells. These small vesicles hold a great deal of promise in disease diagnostics, as they display the same protein biomarkers as their originating cell. On a cellular level, exosomes are attributed to playing a key role in intercellular communication, and may eventually be exploited for targeted drug delivery. In order for exosomes to become useful in disease diagnostics, and as burgeoning drug delivery platforms, they must be isolated efficiently and effectively without compromising their structure. Plasma from peripheral blood is an excellent source of exosomes, as it is easily collected and the process does not normally cause undue discomfort to the patient. Unfortunately, blood plasma content is complex, containing abundant amounts of soluble proteins and aggregates, making exosomes extremely difficult to isolate in high purity from plasma. Most current exosome isolation methods have practical challenges including being too time-consuming and labor intensive, destructive to the exosomes, or too costly for use in clinical settings. To this end, this study examines the use of poly(ethylene terephthalate) (PET) capillary-channeled polymer (C-CP) fibers in a hydrophobic interaction chromatography (HIC) protocol to isolate exosomes from a human plasma sample. Initial results demonstrate the ability to isolate exosomes with comparable yields and size distributions and on a much faster time scale when compared to traditional isolation methods, while also alleviating concomitant proteins and other impurities. As a demonstration of the potential quantitative utility of the approach, a linear response (particles injected on-column vs peak area) using a commercial exosome standard was established using a standard UV absorbance detector. Based on the calibration function, the concentration of the original human plasma sample was determined and subsequently confirmed by NTA measurement. The potential for scalable separations covering sub-milliliter spin-down solid phase extraction tips to the preparative scale is anticipated.


Assuntos
Células Sanguíneas , Exossomos , Cromatografia/instrumentação , Cromatografia/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Polietilenotereftalatos/química
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