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1.
Radiology ; : 203998, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33434112

RESUMO

Background It is unknown if there are cardiac abnormalities in participants recovered from COVID-19 without cardiac symptoms and those who have normal biomarkers and normal ECGs. Purpose To evaluate cardiac involvement in participants recovered from COVID-19 without clinical evidence of cardiac involvement using cardiac MRI Materials and methods In this prospective observational cohort study, 40 participants recovered from COVID-19 with moderate(n=24) or severe(n=16) pneumonia and no cardiovascular medical history, without cardiac symptoms, with normal ECG, normal serological cardiac enzyme levels, and discharged > 90 days between May and September 2020. Demographic characteristics, serum cardiac enzymes, and cardiac MRI were obtained. Cardiac function, native T1, ECV and Two-dimensional (2D) strain were quantitatively evaluated and compared with controls (n = 25).The Comparison among the 3 groups were performed using one-way analysis of variance (ANOVA) with Bonferroni corrected post-hoc comparisons(for normal distribution) or Kruskal-Wallis tests with post-hoc pairwise comparisons(for non-normal distribution). Results Forty participants (54±12 years; 24 men) enrolled with a mean time between admission and CMR of 158 ±18 days and discharge and CMR examination of 124 ±17 days. There was no LV and RV size or functional differences among participants recovered from COVID-19 and healthy controls. Only one (3%) participants had positive LGE located at the mid inferior wall. Global ECV values were elevated in both participants recovered from COVID-19 with moderate or severe pneumonia, compared to the healthy controls [median ECV (IQR)], [29.7% (28.0%-32.9%), versus 31.4% (29.3%-34.0%), versus 25.0% (23.7%-26.0%); both p<.001]. The 2D-global LV longitudinal stains (GLS) were reduced in both groups of participants [COVID-19 moderate group,-12.5%(-10.7%--15.5%), COVID-19 severe group, -12.5%(-8.7%--15.4%) compared to healthy control group -15.4%(-14.6%-17.6%), p=.002 and p=.001, respectively]. Conclusion CMR myocardial tissue and strain imaging parameters suggest that a proportion of participants recovered from COVID-19 had subclinical myocardial abnormalities detectable months after recovery.

2.
Nat Commun ; 12(1): 117, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402692

RESUMO

Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even in high-income countries the 5-year survival rate for stage IV NPC is less than 40%. Here we report high somatostatin receptor 2 (SSTR2) expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that SSTR2 expression is induced by the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) via the NF-κB pathway. Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rates of survival and report in vivo uptake of the SSTR2-binding 68Ga-DOTA-peptide radioconjugate in PET-CT scanning in a clinical trial of NPC patients (NCT03670342). These findings reveal a key role in EBV-associated NPC for SSTR2 in infection, imaging, targeted therapy and survival.


Assuntos
Infecções por Vírus Epstein-Barr/genética , Regulação Neoplásica da Expressão Gênica , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Recidiva Local de Neoplasia/genética , Receptores de Somatostatina/genética , Proteínas da Matriz Viral/genética , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/crescimento & desenvolvimento , Herpesvirus Humano 4/patogenicidade , Interações Hospedeiro-Patógeno/genética , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Terapia de Alvo Molecular , NF-kappa B/genética , NF-kappa B/metabolismo , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/virologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/virologia , Octreotida/farmacologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Receptores de Somatostatina/antagonistas & inibidores , Receptores de Somatostatina/metabolismo , Transdução de Sinais , Análise de Sobrevida , Proteínas da Matriz Viral/antagonistas & inibidores , Proteínas da Matriz Viral/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Theranostics ; 11(4): 1672-1689, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33408774

RESUMO

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and devastating cancers without effective treatments. Amplified in breast cancer 1 (AIB1) is a member of the steroid receptor coactivator family that mediates the transcriptional activities of nuclear receptors. While AIB1 is associated with the initiation and progression of multiple cancers, the mechanism by which AIB1 contributes to PDAC progression remains unknown. In this study, we aimed to explore the role of AIB1 in the progression of PDAC and elucidate the underlying mechanisms. Methods: The clinical significance and mRNA level of AIB1 in PDAC were studied by database analysis. To demonstrate whether AIB1 mediates the malignant features of PDAC cells, namely, proliferation, migration, invasion, we performed real-time PCR and Western blot analysis, established xenograft models and used in vivo metastasis assay. With insights into the mechanism of AIB1, we performed RNA sequencing (Seq), ChIP-Seq, luciferase reporter assays and pull-down assays. Furthermore, we analyzed the relationship between AIB1 expression and its target expression in PDAC cells and patients and explored whether PDAC cells with high AIB1 levels are sensitive to inhibitors of its target. Results: We found that AIB1 was significantly upregulated in PDAC and associated with its malignancy. Silencing AIB1 impaired hedgehog (Hh) activation by reducing the expression of smoothened (SMO), leading to cell cycle arrest and the inhibition of PDAC cell proliferation. In addition, AIB1, via upregulation of integrin αv (ITGAV) expression, promoted extracellular matrix (ECM) signaling, which played an important role in PDAC progression. Further studies showed that AIB1 preferably bound to AP-1 related elements and served as a coactivator for enhancing the transcriptional activity of MafB, which promoted the expression of SMO and ITGAV. PDAC cells with high AIB1 levels were sensitive to Hh signaling inhibitors, suggesting that blocking Hh activation is an effective treatment against PDAC with high AIB1 expression. Conclusions: These findings reveal that AIB1 is a crucial oncogenic regulator associated with PDAC progression via Hh and ECM signaling and suggest potential therapeutic targets for PDAC treatment.

4.
Int J Biol Macromol ; 167: 415-422, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33278433

RESUMO

Foodborne nanoparticles have attracted considerable interest due to their distinctive fluorescence and physicochemical properties. The discovery of vinegar carbon dots (VCDs) has drawn our attention to study their effect on human plasma protein. Herein, spectral, constructional, morphological, and enzymatic activity assessments were carried out to investigate the interaction of VCDs with human hemoglobin (HHb). The intrinsic fluorescence of HHb was quenched significantly by the VCDs through a static quenching process. Furthermore, binding constants and important thermodynamic parameters were calculated, the negative enthalpy and entropy changes were accompanied by a negative Gibbs energy, which proposed the binding between VCDs with HHb was spontaneous. Moreover, negative enthalpy and entropy change corroborated the involvement of van der Waals force and hydrogen bonds in the binding process. Results from FTIR, atomic force microscopy and circular dichroism revealed change of HHB after binding with VCDs although their essential morphological features were unaffected. The esterase activity of HHb decreased after VCDs treatment in a dose-dependent manner, which further confirmed the effect of VCDs on HHb. The results offered detailed information about the interaction between VCDs and HHb.

5.
Free Radic Biol Med ; 163: 281-296, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33359910

RESUMO

Inhibition of phosphodiesterase 4 (PDE4) protects against neuronal apoptosis induced by cerebral ischemia. However, the exact mechanisms responsible for the protection of PDE4 inhibition have not been completely clarified. Roflumilast (Roflu) is an FDA-approved PDE4 inhibitor for the treatment of chronic obstructive pulmonary disease. The potential protective role of Roflu against ischemic stroke-associated neuronal injury remains unexplored. In this study, we investigated the effect and mechanism of Roflu against ischemic stroke using in vitro oxygen-glucose deprivation reperfusion (OGD/R) and in vivo rat middle cerebral artery occlusion (MCAO) models. We demonstrated that Roflu significantly reduced the apoptosis of HT-22 cells exposed to OGD/R, enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2), and reduced oxidative stress. Treatment with Roflu increased the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase 3ß (GSK3ß) but decreased the level of phosphorylated inositol requiring enzyme 1α (IRE1α). Interestingly, constitutively active GSK3ß (S9A) mutation abolished the effects of Roflu on oxidative stress and IRE1α phosphorylation. Moreover, Roflu decreased the binding of IRE1α to tumor necrosis factor receptor-associated factor 2 (TRAF2) and attenuated the phosphorylation of c-Jun N-terminal kinase (JNK). We also found that PDE4B knockdown reduced the phosphorylation of both IRE1α and JNK, while overexpression of PDE4B antagonized the role of PDE4B knockdown on the activation of IRE1α and JNK. Besides, the inhibition of PDE4 by Roflu produced similar effects in primary cultured neurons. Finally, Roflu ameliorated MCAO-induced cerebral injury by decreasing infarct volume, restoring neurological score, and reducing the phosphorylation of IRE1α and JNK. Collectively, these data suggest that Roflu protects neurons from cerebral ischemia reperfusion-mediated injury via the activation of GSK3ß/Nrf-2 signaling and suppression of the IRE1α/TRAF2/JNK pathway. Roflu has the potential as a protective drug for the treatment of cerebral ischemia.

6.
Am J Infect Control ; 49(1): 65-69, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32599099

RESUMO

BACKGROUND: The incidence of Klebsiella pneumoniae (KP) infections is worrisome. Previous studies have shown that increased antibiotic treatment might affect the resistance profile of this organism. The objective of this study was to describe the resistance profile of KP strains and to correlate it with antibiotics consumption. METHODS: A retrospective observational analysis was performed to examine exposure to antibiotics and resistant profile, comparing the results of different measuring outcomes of resistance (the incidence and the percentage of resistant KP) during January 2012 to June 2019 by using the autoregressive integrated moving average and transfer function model. RESULTS: During the study period, the use of some third-generation cephalosporins and carbapenems continued to increase and a total of 5,519 KP isolates were collected. There were positive relationships between amikacin-resistant KP, ciprofloxacin-resistant KP, and corresponding antibiotic use in the transfer function models; both for the incidence rate and the resistant rate (time lag = 0) (P < .05). CONCLUSIONS: The present study confirms that the history of amikacin or ciprofloxacin use influences the susceptibility of these agents against KP with no delay. Similar results were obtained with different measuring outcomes of resistance.

7.
Sci Total Environ ; 759: 143557, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33198999

RESUMO

BACKGROUND: Many studies have explored the association between meteorological factors and infectious diarrhea (ID) transmission but with inconsistent results, in particular the roles from temperatures. We aimed to explore the effects of temperatures on the transmission of category C ID, to identify its potential heterogeneity in different climate zones of China, and to provide scientific evidence to health authorities and local communities for necessary public health actions. METHODS: Daily category C ID counts and meteorological variables were collected from 270 cities in China over the period of 2014-16. Distributed lag non-linear models (DLNMs) were applied in each city to obtain the city-specific temperature-disease associations, then a multivariate meta-analysis was implemented to pool the city-specific effects. Multivariate meta-regression was conducted to explore the potential effect modifiers. Attributable fraction was calculated for both low and high temperatures, defined as temperatures below the 5th percentile of temperature or above the 95th percentile of temperature. RESULTS: A total of 2,715,544 category C ID cases were reported during the study period. Overall, a M-shaped curve relationship was observed between temperature and category C ID, with a peak at the 81st percentile of temperatures (RR = 1.723, 95% CI: 1.579-1.881) compared to 50th percentile of temperatures. The pooled associations were generally stronger at high temperatures compared to low ambient temperatures, and the attributable fraction due to heat was higher than cold. Latitude was identified as a possible effect modifier. CONCLUSIONS: The overall positive pooled associations between temperature and category C ID in China suggest the increasing temperature could bring about more category C infectious diarrhea cases, which warrants further public health measurements.


Assuntos
Temperatura Baixa , Temperatura Alta , China/epidemiologia , Cidades/epidemiologia , Diarreia/epidemiologia , Humanos , Temperatura
8.
J Trace Elem Med Biol ; 64: 126686, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33249375

RESUMO

BACKGROUND: Ceruloplasmin (Cp) is a major copper-binding protein produced in the liver and delivers copper to extrahepatic organs. Patients with myocardial infarction are often featured by an elevation of serum copper concentrations due to copper efflux from ischemic hearts. The present study was undertaken to test the hypothesis that serum copper elevation leads to up-regulation of hepatic Cp in myocardial infarction. METHODS: Adult male Sprague-Dawley rats were subjected to left anterior descending (LAD) coronary artery ligation to induce myocardial infarction. Serum copper and Cp levels, as well as changes in hepatic Cp and copper-transporting P-type ATPase (Atp7b), were determined from blood and liver samples collected on day 1, 4, or 7 after the operation. RESULTS: Serum copper concentrations were significantly increased on day 4 after LAD ligation, accompanied by an increase in serum Cp levels and activities. Concomitantly, the protein levels of Cp and copper exporter, Atp7b, were also significantly increased in the liver. Furthermore, inhibiting the increase of serum copper by a copper chelator, triethylenetetramine (TETA), effectively abolished the elevated Cp activity after LAD ligation. CONCLUSION: These results indicate that serum Cp elevation in response to myocardial ischemia most likely resulted from the increased hepatic Cp production, which in turn was more responsive to serum copper elevation than inflammatory response following myocardial ischemia.

9.
Food Chem ; 338: 127832, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32818868

RESUMO

Food-borne carbon dots (CDs) may cause health risks due to their unique properties. However, previous efforts were mainly focused on the characterization of their physicochemical properties, their effects on cellular metabolism are not entirely revealed. Herein, the features and potential toxicity of CDs from lamb baked for 15, 30, and 45 min were evaluated, their cytotoxicity increased with the extension of baking time. Furthermore, the metabolic responses of PC12 cells after exposure to CDs from lamb baked for 45 min were investigated. The CDs perturbed purine metabolism, causing reactive oxygen species accumulation. Meanwhile, the CDs down-regulated glycolysis and TCA cycle, led to a significant decrease in ATP. Additionally, the CDs induced triglyceride accumulation, mainly through enhanced fatty acid biosynthesis. The adverse effects of CDs from baked lamb involved the perturbation of energy production, purine metabolism, and triglyceride biosynthesis, which provided additional information about the risks of CDs from food items.


Assuntos
Carbono/química , Metabolismo Energético/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Carne Vermelha/efeitos adversos , Trifosfato de Adenosina/metabolismo , Animais , Carbono/toxicidade , Culinária , Regulação da Expressão Gênica/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Células PC12 , Purinas/metabolismo , Pontos Quânticos/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , Carneiro Doméstico , Triglicerídeos/metabolismo
10.
Nanotechnology ; 32(10): 105706, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33232953

RESUMO

Herein, Ag/In2S3/ZnO nanorods (NRs) composite photocatalysts were successfully prepared via simple methods. Significantly, hydroxyl radical active substances were found in the electron spin resonance tests of In2S3/ZnO NRs and Ag/In2S3/ZnO NRs, which indicates that the oxidation reaction that oxidizes water or hydroxide ions into hydroxyl radicals occurs on the valence band of ZnO NRs. It suggests that Z-scheme heterojunction was successfully constructed. In the photocatalytic experiments of degrading 4-nitrophenol (PNP), the Ag/In2S3/ZnO NRs composite exhibits higher photocatalytic activity than ZnO NRs, In2S3, Ag/ZnO NRs and In2S3/ZnO NRs. The characteristic peak of PNP disappears completely in 50 min. The enhanced photocatalytic performance can be attributed to the formation of Z-scheme heterojunction between ZnO NRs and In2S3. In addition, local surface plasmon resonance of Ag and Schottky junction formed between Ag and In2S3 also promote the photocatalytic activity.

11.
J Environ Sci (China) ; 101: 361-372, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33334531

RESUMO

Chemical speciation can fundamentally affect the potential toxicity and bioavailability of heavy metals. The transformation of heavy metal speciation and change of bioavailability were investigated in an anaerobic digestion (AD) system using four different substrates (pig manure (PM), cattle manure (CAM), chicken manure (CHM) and rice straw (RS)). The results obtained indicated that the total contents of heavy metals in PM, CHM and CAM were higher than in RS and decreased in the order Zn > Cu > Ni > Pb > As > Cd in all substrates. Moreover, the speciation with the largest proportion for each heavy metal was the same both in the different substrates and the biogas residues. Among them, Zn, Ni, Cd and As were mainly in the reducible fraction (F2), while Cu was mainly in the oxidizable fraction (F3) and Pb occurred predominantly in the residual fraction (F4). Our results further indicated that the AD process had a greater effect on the speciation of heavy metals in CHM and PM, but less on CAM and RS. The rates of change in bioavailability followed the order PM > CHM > CAM > RS. Changes in organic matter, humic acid or local metal ion environment as a result of AD were inferred as likely mechanisms leading to the transformation of heavy metal speciation. These results enhanced our understanding of the behavior of heavy metals in AD and provided a new perspective for the treatment and disposal of the substrates.


Assuntos
Metais Pesados , Anaerobiose , Animais , Disponibilidade Biológica , Bovinos , Substâncias Húmicas , Esterco , Suínos
12.
Microorganisms ; 8(12)2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33260576

RESUMO

Swine are regarded as promising biomedical models, but the dynamics of their gastrointestinal microbiome have been much less investigated than that of humans or mice. The aim of this study was to establish an integrated multi-omics protocol to investigate the fecal microbiome of healthy swine. To this end, a preparation and analysis protocol including integrated sample preparation for meta-omics analyses of deep-frozen feces was developed. Subsequent data integration linked microbiome composition with function, and metabolic activity with protein inventories, i.e., 16S rRNA data and expressed proteins, and identified proteins with corresponding metabolites. 16S rRNA gene amplicon and metaproteomics analyses revealed a fecal microbiome dominated by Prevotellaceae, Lactobacillaceae, Lachnospiraceae, Ruminococcaceae and Clostridiaceae. Similar microbiome compositions in feces and colon, but not ileum samples, were observed, showing that feces can serve as minimal-invasive proxy for porcine colon microbiomes. Longitudinal dynamics in composition, e.g., temporal decreased abundance of Lactobacillaceae and Streptococcaceae during the experiment, were not reflected in microbiome function. Instead, metaproteomics and metabolomics showed a rather stable functional state, as evident from short-chain fatty acids (SCFA) profiles and associated metaproteome functions, pointing towards functional redundancy among microbiome constituents. In conclusion, our pipeline generates congruent data from different omics approaches on the taxonomy and functionality of the intestinal microbiome of swine.

13.
Foods ; 9(12)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33261175

RESUMO

Cadmium contamination is a severe threat to food safety. Therefore, the development of sensitive and selective cadmium detection strategies is urgently required. The elimination of background autofluorescence generated from the food matrix is critical to the optical assay for cadmium detection. Herein, a time-resolved phosphorescence sensor based on an "on-off" strategy was developed for cadmium determination in food samples. The phosphorescence nanoparticles were used as a luminous material to minimize the interference of background autofluorescence. The cadmium-binding aptamer was immobilized onto the magnetic beads and combined with a black hole quencher 1 (BHQ1) with complementary DNA as the target recognition element. With the presence of cadmium, the cadmium-binding aptamer bound to cadmium specifically and resulted in the release of BHQ1. The free BHQ1 remained in the solution after magnetic separation and quenched the phosphorescence. The phosphorescence intensity was negatively related to the concentration of cadmium. Under optimal conditions, the time-resolved phosphorescence sensor showed a linear response to cadmium concentration within a range from 0.05 to 5 ng mL-1 and with a detection limit of 0.04 ng mL-1. This "on-off" time-resolved phosphorescence sensor was successfully applied for cadmium detection in spring water and clam samples, which provided a rapid and straightforward method.

14.
World J Clin Cases ; 8(21): 5188-5202, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33269255

RESUMO

BACKGROUND: Pneumonia of uncertain cause has been reported in Wuhan, China since the beginning of early December 2019. In early January 2020, a novel strain of ß-coronavirus was identified by the Chinese Center for Disease Control and Prevention from the pharyngeal swab specimens of patients, which was recently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is evidence of human-to-human transmission and familial cluster outbreak of SARS-CoV-2 infection. The World Health Organization(WHO) recently declared the SARS-CoV-2 epidemic a global health emergency. As of February 17, 2020, 71329 laboratory-confirmed cases (in 25 countries, including the United States and Germany) have been reported globally. Other than its rapid transmission, the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) remain unclear. In December 2019, coronavirus disease (named COVID-19 by the WHO) associated with the SARS-CoV-2 emerged in Wuhan, China and spread quickly across the country. AIM: To analyze the epidemiological and clinical characteristics of confirmed cases of this disease in Liaoning province, a Chinese region about 1800 km north of Wuhan. METHODS: The clinical data of 56 laboratory-confirmed COVID-19 cases due to 2019-nCoV infection were analyzed. The cases originated from eight cities in Liaoning province. RESULTS: The median age of the patients was 45 years, and 57.1% of them were male. No patient had been in direct contact with wild animals. Among them, 23 patients (41.1%) had resided in or traveled to Wuhan, 27 cases (48.2%) had been in contact with confirmed COVID-19 patients, 5 cases (8.9%) had been in contact with confirmed patients with a contact history to COVID-19 patients, and 1 case (1.8%) had no apparent history of exposure. Fever (75.0%) and cough (60.7%) were the most common symptoms. The typical manifestations in lung computed tomography (CT) included ground-glass opacity and patchy shadows, with 67.8% of them being bilateral. Among the patients in the cohort, 78.6% showed reduction in their lymphocyte counts, 57.1% showed increases in their C-reactive protein levels, and 50.0% showed decreases in their blood albumin levels. Eleven patients (19.6%) were admitted to intensive care unit, 2 patients (3.5%) progressed to acute respiratory distress syndrome, 4 patients (7.1%) were equipped with non-invasive mechanical ventilation, and 1 patient (1.8) received extracorporeal membrane oxygenation support. There were 5 mild cases (5/56, 8.9%), 40 moderate cases (40/56, 71.4%), 10 severe cases (10/56, 17.9%), and 1 critical case (1/56, 1.8%). No deaths were reported. CONCLUSION: SARS-CoV-2 can be transmitted among humans. Most COVID-19 patients show symptoms of fever, cough, lymphocyte reduction, and typical lung CT manifestations. Most are moderate cases. The seriousness of the disease (as indicated by blood oxygen saturation, respiratory rate, oxygenation index, blood lymphocyte count, and lesions shown in lung CT) is related to history of living in or traveling to Wuhan, underlying diseases, admittance to intensive care unit, and mechanical ventilation.

15.
Adv Sci (Weinh) ; 7(23): 2001914, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33304752

RESUMO

Resistance to therapeutic drugs occurs in virtually all types of cancers, and the tolerance to one drug frequently becomes broad therapy resistance; however, the underlying mechanism remains elusive. Combining a whole whole-genome-wide RNA interference screening and an evolutionary drug pressure model with MDA-MB-231 cells, it is found that enhanced protein damage clearance and reduced mitochondrial respiratory activity are responsible for cisplatin resistance. Screening drug-resistant cancer cells and human patient-derived organoids for breast and colon cancers with many anticancer drugs indicates that activation of mitochondrion protein import surveillance system enhances proteasome activity and minimizes caspase activation, leading to broad drug resistance that can be overcome by co-treatment with a proteasome inhibitor, bortezomib. It is further demonstrated that cisplatin and bortezomib encapsulated into nanoparticle further enhance their therapeutic efficacy and alleviate side effects induced by drug combination treatment. These data demonstrate a feasibility for eliminating broad drug resistance by targeting its common mechanism to achieve effective therapy for multiple cancers.

16.
J Glob Health ; 10(2): 020513, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33312506

RESUMO

Background: The COVID-19 pandemic is challenging the public health response system worldwide, especially in poverty-stricken, war-torn, and least developed countries (LDCs). Methods: We characterized the epidemiological features and spread dynamics of COVID-19 in Niger, quantified the effective reproduction number (Rt ), evaluated the impact of public health control measures, and estimated the disease burden. Results: As of 4 July 2020, COVID-19 has affected 29 communes of Niger with 1093 confirmed cases, among whom 741 (67.8%) were males. Of them 89 cases died, resulting in a case fatality rate (CFR) of 8.1%. Both attack rates and CFRs were increased with age (P < 0.0001). Health care workers accounted for 12.8% cases. Among the reported cases, 39.3% were isolated and treated at home, and 42.3% were asymptomatic. 74.6% cases were clustered in Niamey, the capital of Niger. The Rt fluctuated in correlation to control measures at different outbreak stages. After the authorities initiated the national response and implemented the strictest control measures, Rt quickly dropped to below the epidemic threshold (<1), and maintained low level afterward. The national disability-adjusted life years attributable to COVID-19 was 1267.38 years in total, of which years of life lost accounted for over 99.1%. Conclusions: Classic public health control measures such as prohibition of public gatherings, travelling ban, contact tracing, and isolation and quarantine at home, are proved to be effective to contain the outbreak in Niger, and provide guidance for controlling the ongoing COVID-19 pandemic in LDCs.


Assuntos
/epidemiologia , Controle de Doenças Transmissíveis/organização & administração , Adulto , Países em Desenvolvimento , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Níger/epidemiologia , Pandemias , Fatores Socioeconômicos
17.
EMBO Mol Med ; 12(12): e12109, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33259138

RESUMO

Pathological new bone formation is a typical pathological feature in ankylosing spondylitis (AS), and the underlying molecular mechanism remains elusive. Previous studies have shown that the calcium-sensing receptor (CaSR) is critical for osteogenic differentiation while also being highly involved in many inflammatory diseases. However, whether it plays a role in pathological new bone formation of AS has not been reported. Here, we report the first piece of evidence that expression of CaSR is aberrantly upregulated in entheseal tissues collected from AS patients and animal models with different hypothetical types of pathogenesis. Systemic inhibition of CaSR reduced the incidence of pathological new bone formation and the severity of the ankylosing phenotype in animal models. Activation of PLCγ signalling by CaSR promoted bone formation both in vitro and in vivo. In addition, various inflammatory cytokines induced upregulation of CaSR through NF-κB/p65 and JAK/Stat3 pathways in osteoblasts. These novel findings suggest that inflammation-induced aberrant upregulation of CaSR and activation of CaSR-PLCγ signalling in osteoblasts act as mediators of inflammation, affecting pathological new bone formation in AS.

18.
Nanotechnology ; 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33316789

RESUMO

Researches in the plasma actuation are increasingly scrutinizing the methodology to enhance the thrust density for the application in the aerodynamic flow control. In this paper, a new method has been proposed and experimentally evaluated. This method is based on the deposition of nanoscaled structures on the electrode surface and the tuning of the applied voltages and frequency. It is found that the thrust enhancement rate resulted from the incorporation of the nanostructures could be approximately 78 \%, relative to the controlled group, under 14kV and 7kHz. However, a threshold effect has been founded across all of the tested samples, where lower applied voltage and frequency could lead to the decrease in the thrust generation. Capacitor charging effects are basically not sensitive to the introduction of the nanostructures in electrical characteristic. Other experimental features and electric filed simulation results also indicate the effectiveness of introducing nanoscaled structures into DBD plasma actuators, thus providing a new way to improve mechanical performance.

19.
Zootaxa ; 4878(1): zootaxa.4878.1.4, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33311168

RESUMO

Four new species of amblyceran chewing lice of the genus Myrsidea Waterston, 1915 are described from hosts of the babbler families Leiothrichidae, Paradoxornithidae and Timaliidae in China. They are: Myrsidea attenuata n. sp. from Garrulax maesi maesi (Oustalet, 1890), Myrsidea zhangae n. sp. from Ianthocincla berthemyi (Oustalet, 1876), Myrsidea liopari n. sp. from Lioparus chrysotis amoenus (Mayr, 1941) and L. chrysotis swinhoii (Verreaux, 1871), and Myrsidea suthorae n. sp. from Suthora verreauxi verreauxi Sharpe, 1883. A checklist of host-louse associations for identified and unidentified Myrsidea species known from babblers is provided.


Assuntos
Amblíceros , Doenças das Aves , Infestações por Piolhos , Passeriformes , Animais , Humanos
20.
J Agric Food Chem ; 68(50): 14996-15004, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33270443

RESUMO

Consumption of seafood is a common route of cadmium ion (Cd2+) exposure to consumers. The seafood matrices may alter the toxicity profile of Cd2+ due to the interaction between Cd2+ and biomacromolecules in seafood. In this study, enhanced cytotoxicity of Cd2+ was found in the presence of an abalone gonad sulfated polysaccharide (AGSP) and the mechanism was investigated at a metabolic level. The formation of the AGSP-Cd2+ complex was demonstrated by isothermal titration calorimetry. The level of reactive oxygen species (ROS) increased and mitochondrial membrane potential reduced upon exposure to the AGSP-Cd2+ complex as compared with those of Cd2+ exposure. The decreased cell viability after incubation with the AGSP-Cd2+ complex also suggested enhanced Cd2+ toxicity induced by AGSP. The metabolomics and lipidomics analysis revealed that, compared with the Cd2+ group, the AGSP-Cd2+ downregulated the phospholipid metabolism and resulted in more serious damage in the cellular membrane. The lipid metabolism disorder, in turn, amplified the generation of ROS, leading to a decrease in cell viability. These results provided new evidence of the enhanced Cd2+ toxicity upon interaction with seafood polysaccharides, and much attention should be paid to the effect of food ingredients on heavy metal ion toxicity.

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