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1.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21265032

RESUMO

SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. In China, over 85% of individuals aged [>=]12 years have been vaccinated against COVID-19 (albeit with vaccines developed against historical lineages), while children aged 0-11 years are currently not eligible for vaccination (as of September 2021). The aim of this work is to assess whether the importation of Delta variant infections will shift the COVID-19 burden from adults to children. We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission dynamics to simulate the epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalisations, intensive care unit (ICU) admissions, and deaths. In the context of the vaccination programme targeting individuals aged [≥]12 years (as of September 2021), and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could lead to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 97% across the currently eligible age groups. The symptomatic SARS-CoV-2 infections and hospitalisation are projected to shift towards children and young adolescents, with 13% of symptomatic infections and 30% of hospitalisations occurring in those aged 0-11 years. Extending the vaccination roll-out to include children aged 3-11 years is estimated to dramatically decrease the burden of symptomatic infections and hospitalisations within this age group (54% and 81%, respectively), but would have a low impact on protecting infants (aged 0-2 years). Our findings highlight the need to strengthen vaccination efforts by simultaneously extending the target population and elevating vaccine effectiveness. Author summaryOlder age groups have the highest risk of severe illness and fatality from SARS-CoV-2 infection. While the vaccination coverage in China is highly skewed towards older age groups. No study has quantified to what extent the spread of Delta variant infections and lack of vaccination in younger age groups will shift the COVID-19 burden towards younger age groups and how this will affect the return to normal. To this end, we developed an age-structured transmission model to mimic the epidemics triggered by imported Delta variant infections in China. In the context of the vaccination programme targeting individuals aged [≥]12 years as of September 2021, and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections would lead to substantial disease burden, which will shift towards the 0-11-year age group. Extending the vaccination to children aged 3-11 years, for whom the currently available vaccines have been licensed, is projected to dramatically decrease symptomatic infections and hospitalisations within this age group but would have a low impact in protecting infants aged 0-2 years. This study highlights the value of extending vaccination to children aged 3-11 years and protecting infants 0-2 years by vaccinating their contacts.

2.
J Cardiothorac Surg ; 16(1): 306, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663402

RESUMO

BACKGROUND: For thoracic surgeons, three-dimensional computed tomography bronchography and angiography (3-DCTBA) is a convenient way to analyze pulmonary variations before segmentectomy. Mediastinal lingular artery (MLA) is one of the representative variations. METHODS: The 3-DCTBA data of left upper lobe (LUL) were collected from patients who underwent pulmonary surgery from January 2018 to December 2019. We reviewed the patterns of bronchi and pulmonary vessels and grouped them according to different classifications. RESULTS: Among all the 404 cases of 3-DCTBA, mediastinal lingular artery (MLA) was found in 107 cases (26.49%). The patterns of B3 and the vein in left upper division (LUD) are distinct between mediastinal (M-type) group and interlobar (IL-type) group. The patterns of bronchi and veins in lingular division, as well as the pattern of pulmonary artery in LUD, have no differences between M-type and IL-type groups. CONCLUSIONS: Mediastinal lingular artery is speculated to originate from the variation of B3, and the MLA independently influences the venous pattern in LUD in turn.


Assuntos
Pulmão , Artéria Pulmonar , Brônquios/diagnóstico por imagem , Humanos , Mediastino/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Tomografia Computadorizada por Raios X
3.
Ying Yong Sheng Tai Xue Bao ; 32(10): 3771-3780, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34676740

RESUMO

Large volcanic eruption is an important factor affecting global climate change. In the past few decades, many researchers reconstructed a number of climate series based on tree rings on the Tibetan Plateau, and examined the impacts of large volcanic eruptions on the climate. The results showed that these tree-ring sites used to examined the influences of large volcanic eruptions on climate change were primarily located in the eastern Tibetan Plateau. In addition, the series comparison and the superposed epoch analysis were main methods for studying the climate effects of large volcanic eruptions. Based on the results analyzed using two methods, we suggested that the large volcanic eruptions in low-mid latitudes had a significant impact on temperature and dry/wet variation. Cooling or drought occurred after large volcanic eruptions in the subsequent 1-2 years. How-ever, the large volcanic eruptions in high latitudes had minor impacts on climate change. Furthermore, consecutive multiple volcanic eruptions could result in cooling at the decades scale. The factors influencing the climate effects of large volcanic eruptions included the location of the volcanic eruptions, intensity of the volcanic eruptions, atmospheric circulation, etc. Finally, we proposed research projects that need to be carried out in the future.

4.
Bioresour Technol ; 341: 125866, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34523551

RESUMO

Biochar prepared from pineapple peel was facially combined with polyurethane sponges for the first time to form homogeneous biocompatible biocarriers, which can enhance denitrification performance in an anoxic MBBR. The experiments showed that a higher NO3--N removal efficiency (96.24 ± 1.3%) and kinetic constant (0.26 h-1) were obtained in the MBBR employing these new biocarriers (B-MBBR), compared with a control MBBR with polyurethane sponges (C-MBBR). The attached and suspended biomass of the B-MBBR was increased by 47% and 26%, respectively. Biochar significantly enhanced the abundance of functional bacteria in terms of promoting biofilm (i.e., Leptonema), denitrifying bacteria (i.e., Thauera, Enterobacter and Pseudomonas) and electroactive bacteria (i.e., Geobacter) in the B-MBBR. Meanwhile, based on the content of coenzyme I (NADH) and denitrifying enzymes, biochar would also enhance electron transport activity for denitrification. Consequently, these facial prepared biocarriers are effective to enhance denitrification performance in MBBR with application significance.


Assuntos
Biofilmes , Desnitrificação , Reatores Biológicos , Carvão Vegetal , Nitrogênio/análise , Eliminação de Resíduos Líquidos , Águas Residuárias
5.
Front Pharmacol ; 12: 636204, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34588976

RESUMO

Rationale: Nonalcoholic fatty liver disease (NAFLD) is a kind of metabolic disease characterized by liver steatosis. Excessive reactive oxygen species (ROS) originating from dysfunctional mitochondria is the major pathophysiological contributor in the development of NAFLD and is thought to be a promising therapeutic target. A few reports demonstrate the antioxidative treatments for NAFLD. Methods: Male C57 mice were fed on a normal chow diet (ND) or high-fat diet (HFD) for 8 weeks. PBS or N-acetyl cysteine (NAC) was gavaged to mice. LO2 human liver cell line treated with palmitic acid (PA) was applied as a cellular model. Western blot, immunofluorescence, biochemistry assay, and pathological staining were used to investigate the mechanism of suppressing lipid accumulation of NAC. Results: NAC treatment was able to prevent HFD-induced NAFLD, as evidenced by less hepatic triglyceride accumulation and lipid droplet formation compared with that of mice in the HFD group. NAC could preserve mitochondrial function by inhibiting excessive mitophagy and promoting mitochondria biogenesis to prevent ROS production. NAC also activated Sirt1 and preserved its protein level and subsequently promoted mitochondria biogenesis via deacetylating PGC1a. Conclusion: We demonstrated that NAC may be an effective drug to treat NAFLD, which was related to its antioxidative and mitochondrial protective effect.

6.
Oxid Med Cell Longev ; 2021: 9397960, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552687

RESUMO

Objectives: In glaucomatous eyes, the main aqueous humor (AH) outflow pathway is damaged by accumulated oxidative stress arising from the microenvironment, vascular dysregulation, and aging, which results in increased outflow resistance and ocular hypertension. Schlemm's canal (SC) serves as the final filtration barrier of the main AH outflow pathway. The present study is aimed at investigating the possible regulation of vasoactive intestinal peptide (VIP) on the cytoskeleton by stabilizing ZO-1 in SC. Methods: Model of chronic ocular hypertension (COH) induced by episcleral venous cauterization was treated with topical VIP. The ultrastructure of junctions, ZO-1 levels, and permeability of the SC inner wall to FITC-dextran (70 kDa) were detected in the COH models. The F-actin distribution, F/G-actin ratio, and ZO-1 degradation pathway in human umbilical vein endothelial cells (HUVECs) and HEK 293 cells were investigated. Results: ZO-1 in the outer wall of the SC was less than that in the inner wall. COH elicited junction disruption, ZO-1 reduction, and increased permeability of the SC inner wall to FITC-dextran in rats. ZO-1 plays an essential role in maintaining the F/G-actin ratio and F-actin distribution. VIP treatment attenuated the downregulation of ZO-1 associated with COH or H2O2-induced oxidative damage. In H2O2-stimulated HUVECs, the caspase-3 inhibitor prevents ZO-1 disruption. Caspase-3 activation promoted endolysosomal degradation of ZO-1. Furthermore, a decrease in caspase-3 activation and cytoskeleton redistribution was demonstrated in VIP + H2O2-treated cells. The knockdown of ZO-1 or the overexpression of caspase-3 blocked the effect of VIP on the cytoskeleton. Conclusion: This study provides insights into the role of VIP in stabilizing the interaction between the actin cytoskeleton and cell junctions and may provide a promising targeted strategy for glaucoma treatment.

7.
Math Biosci Eng ; 18(5): 6652-6671, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34517550

RESUMO

The image super-resolution reconstruction method can improve the image quality in the Internet of Things (IoT). It improves the data transmission efficiency, and is of great significance to data transmission encryption. Aiming at the problem of low image quality in image super-resolution using neural networks, a self-attention-based image reconstruction method is proposed for secure data transmission in IoT environment. The network model is improved, and the residual network structure and sub-pixel convolution are used to extract the feature of the image. The self-attention module is used extract detailed information in the image. Using generative confrontation method and image feature perception method to improve the image reconstruction effect. The experimental results on the public data set show that the improved network model improves the quality of the reconstructed image and can effectively restore the details of the image.


Assuntos
Processamento de Imagem Assistida por Computador , Internet das Coisas , Redes Neurais de Computação
8.
Comput Intell Neurosci ; 2021: 8387382, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475949

RESUMO

Image style transfer can realize the mutual transfer between different styles of images and is an essential application for big data systems. The use of neural network-based image data mining technology can effectively mine the useful information in the image and improve the utilization rate of information. However, when using the deep learning method to transform the image style, the content information is often lost. To address this problem, this paper introduces L1 loss on the basis of the VGG-19 network to reduce the difference between image style and content and adds perceptual loss to calculate the semantic information of the feature map to improve the model's perceptual ability. Experiments show that the proposal in this paper improves the ability of style transfer, while maintaining image content information. The stylization of the improved model can better meet people's requirements for stylization, and the evaluation indexes of structural similarity, cosine similarity, and mutual information value have increased by 0.323%, 0.094%, and 3.591%, respectively.


Assuntos
Sistemas de Dados , Redes Neurais de Computação , Humanos , Semântica
9.
Antonie Van Leeuwenhoek ; 114(10): 1735-1744, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34392432

RESUMO

A Gram-positive, acid-fast and rapidly growing rod, designated S2-37 T, that could form yellowish colonies was isolated from one soil sample collected from cotton cropping field located in the Xinjiang region of China. Genomic analyses indicated that strain S2-37 T harbored T7SS secretion system and was very likely able to produce mycolic acid, which were typical features of pathogenetic mycobacterial species. 16S rRNA-directed phylogenetic analysis referred that strain S2-37 T was closely related to bacterial species belonging to the genus Mycolicibacterium, which was further confirmed by pan-genome phylogenetic analysis. Digital DNA-DNA hybridization and the average nucleotide identity presented that strain S2-37 T displayed the highest values of 39.1% (35.7-42.6%) and 81.28% with M. litorale CGMCC 4.5724 T, respectively. And characterization of conserved molecular signatures further supported the taxonomic position of strain S2-37 T belonging to the genus Mycolicibacterium. The main fatty acids were identified as C16:0, C18:0, C20:3ω3 and C22:6ω3. In addition, polar lipids profile was mainly composed of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. Phylogenetic analyses, distinct fatty aids and antimicrobial resistance profiles indicated that strain S2-37 T represented genetically and phenotypically distinct from its closest phylogenetic neighbour, M. litorale CGMCC 4.5724 T. Here, we propose a novel species of the genus Mycolicibacterium: Mycolicibacterium gossypii sp. nov. with the type strain S2-37 T (= JCM 34327 T = CGMCC 1.18817 T).


Assuntos
Mycobacterium , Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/análise , Genômica , Fosfolipídeos/análise , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Microbiologia do Solo
10.
Biochim Biophys Acta Mol Basis Dis ; 1867(11): 166237, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34339838

RESUMO

R-loops are naturally occurring transcriptional intermediates containing RNA/DNA hybrids. Excessive R-loops cause genomic instability, DNA damage, and replication stress. Senataxin-associated exonuclease (San1) is a protein that interacts with Senataxin (SETX), a helicase resolving R-loops. It remains unknown if R-loops-induced DNA damage plays a role in the heart, especially in the proliferative neonatal cardiomyocytes (CMs). San1-/- mice were generated using the CRISPR/Cas9 technique. The newborn San1-/- mice show no overt phenotype, but their hearts were smaller with larger, yet fewer CMs. CM proliferation was impaired with reduced cell cycle-related transcripts and proteins. S9.6 staining revealed that excessive R-loops accumulated in the nucleus of neonatal San1-/- CMs. Increased γH2AX staining on newborn and adult heart sections exhibited increased DNA damage. Similarly, San1-/- AC16-cardiomyocytes showed cumulative R-loops and DNA damage, leading to the activation of cell cycle checkpoint kinase ATR and PARP1 hyperactivity, arresting G2/M cell-cycle and CM proliferation. Together, the present study uncovers an essential role of San1 in resolving excessive R-loops that lead to DNA damage and repressing CM proliferation, providing new insights into a novel biological function of San1 in the neonatal heart. San1 may serve as a novel therapeutic target for the treatment of hypoplastic cardiac disorders.

11.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21261544

RESUMO

ImportanceWhether herd immunity through mass vaccination is sufficient to curb SARS-CoV-2 transmission requires an understanding of the duration of vaccine-induced immunity, and the necessity and timing of booster doses. Objective: To evaluate immune persistence of two priming doses of CoronaVac, and immunogenicity and safety of a third dose in healthy adults [≥]60 years. Design, setting, and participants: We conducted a vaccine booster study built on a single-center, randomized, double-blind phase 1/2 trial of the two-dose schedule of CoronaVac among healthy adults[≥]60 years in Hebei, China. We examined neutralizing antibody titres six months or more after the second dose in all participants. We provided a third dose to 303 participants recruited in phase 2 trial to assess their immune responses. InterventionsTwo formulations (3 g, and 6 g) were used in phase 1 trial, and an additional formulation of 1.5 g was used in phase 2 trial. All participants were given two doses 28 days apart and followed up 6 months after the second dose. Participants in phase 2 received a third dose 8 months after the second dose. Main outcomes and measuresGeometric mean titres (GMT) of neutralizing antibodies to live SARS-CoV-2 and adverse events were assessed at multiple time points following vaccination. ResultsNeutralizing antibody titres dropped below the seropositive cutoff of 8 at 6 months after the primary vaccination in all vaccine groups in the phase 1/2 trial. A third dose given 8 months or more after the second dose significantly increased neutralizing antibody levels. In the 3 g group (the licensed formulation), GMT increased to 305 [95%CI 215.3-432.0] on day 7 following the third dose, an approximately 7-fold increase compared with the GMT 28 days after the second dose. All solicited adverse reactions reported within 28 days after a booster dose were of grade 1 or 2 severity. Conclusion and relevanceNeutralizing antibody titres declined substantially six months after two doses of CoronaVac among older adults. A booster dose rapidly induces robust immune responses. This evidence could help policymakers determine the necessity and the timing of a booster dose for older adults. Trial registrationClinicalTrials.gov (NCT04383574).

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1011-1018, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362476

RESUMO

OBJECTIVE: To the clinical characteristics and prognostic value of the patients with complete deletion of TET_JBP domain (ΔJBP) in TET2 acute myeloid leukemia (AML). METHODS: Next Generation Sequencing technology was used to determine the mutations of 34 AML-related genes (including TET2 gene). The I-TASSER tool was used to predict the tertiary structure of the full-length TET2 protein and TET_JBP structure deletion. RESULTS: Among 38 AML patients with TET2 mutations, 22(57.9%) showed truncation mutations, of which 16 (72.7%) produced TET2ΔJBP truncation mutants. Protein structure prediction showed that the deletion of TET_JBP domain lead to the significant changes of tertiary structure in TET2 protein. Compared with the patients in non-ΔJBP group, the age of patients in ΔJBP group were older (63 vs 54 years old, P=0.047), and the occurrence rate of CEBPA double mutation (CEBPAdm) were more frequency (31.3% vs 0, P=0.009), the complete remission (CR) rate after induction chemotherapy(37.5% vs 81.8%, P=0.008) were lower, the median EFS (5 vs 19 months, P=0.000) and median OS (16 vs 22 months, P=0.041) were shorter. Univariate analysis showed that platelets <50×109/L (P=0.004) and CEBPAdm (P=0.001) were related to the shorter OS of the patients. Further COX multivariate analysis showed that CEBPAdm is an independent prognostic factors of OS in TET2ΔJBP patients (P=0.010). In addition, ΔJBP patients with CEBPAdm showed lower hemoglobin levels (62 vs 75g/L, P=0.030) and lower median OS (9 months vs 18 months, P=0.000) than the patients without CEBPAdm. CONCLUSION: AML patients with TET2ΔJBP truncation mutant shows lower CR rate, shorter EFS and OS after induction chemotherapy, which may be related to the poor prognosis, and co-mutation with CEBPAdm, which is the independent prognostic factors of OS in AML patients with TET2ΔJBP.


Assuntos
Leucemia Mieloide Aguda , Proteínas de Ligação a DNA/genética , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas/genética , Indução de Remissão
13.
Artigo em Inglês | MEDLINE | ID: mdl-34343063

RESUMO

A Gram-negative bacterium, designated S1-65T, was isolated from soil samples collected from a cotton field located in the Xinjiang region of PR China. Results of 16S rRNA gene sequence analysis revealed that strain S1-65T was affiliated to the genus Steroidobacter with its closest phylogenetic relatives being 'Steroidobacter cummioxidans' 35Y (98.4 %), 'Steroidobacter agaridevorans' SA29-B (98.3 %) and Steroidobacter agariperforans KA5-BT (98.3 %). 16S rRNA-directed phylogenetic analysis showed that strain S1-65T formed a unique phylogenetic subclade next to 'S. agaridevorans' SA29-B and S. agariperforans KA5-BT, suggesting that strain S1-65T should be identified as a member of the genus Steroidobacter. Further, substantial differences between the genotypic properties of strain S1-65T and the members of the genus Steroidobacter, including average nucleotide identity and digital DNA-DNA hybridization, resolved the taxonomic position of strain S1-65T and suggested its positioning as representing a novel species of the genus Steroidobacter. The DNA G+C content of strain S1-65T was 62.5 mol%, based on its draft genome sequence. The predominant respiratory quinone was ubiquinone-8. The main fatty acids were identified as summed feature 3 (C16:1ω6c/C16:1ω7c), C16 : 0 and iso-C15 : 0. In addition, its polar lipid profile was composed of aminophospholipid, diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. Here, we propose a novel species of the genus Steroidobacter: Steroidobacter gossypii sp. nov. with the type strain S1-65T (=JCM 34287T=CGMCC 1.18736T).


Assuntos
Gammaproteobacteria/classificação , Gossypium/microbiologia , Filogenia , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Gammaproteobacteria/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/química
14.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3687-3693, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402293

RESUMO

A LC-MS/MS method was developed for the rapid and simultaneous determination of genipin-1-ß-D-gentiobioside,geniposide,naringin,hesperidin and neohesperidin in SD rat plasma.The linear relationships of these five constituents in rats were validated,and the specificity,accuracy,precision and stability met the requirements.Their pharmacokinetic parameters were calculated by DAS 3.2.2,and the results showed that the metabolic process in vivo of the five constituents accorded with the characteristics of noncompartmental model.Their main pharmacokinetic parameters were listed as follows:(1) genipin-1-ß-D-gentiobioside:t_(1/2)(3.20±0.51)h,C_(max)(403.15±96.93)µg·L~(-1)and AUC_(0-t)(612.56±148.50)µg·L~(-1)·h for the model group,while t_(1/2)(3.07±0.75) h,C_(max)(229.50±60.63)µg·L~(-1)and AUC_(0-t)(413.14±76.37)µg·L~(-1)·h for the normal group;(2) geniposide:t_(1/2)(3.24±0.68) h,C_(max)(2 961.40±688.02)µg·L~(-1),and AUC_(0-t)(10 972.87±1 992.96)µg·L~(-1)·h for the model group,while t_(1/2)(4.56±0.96) h,C_(max)(1 833.27±558.13)µg·L~(-1),and AUC_(0-t)(8 996.27±3 053.48)µg·L~(-1)·h for the normal group;(3) naringin:t_(1/2)(1.64±0.59) h,C_(max)(415.13±259.54)µg·L~(-1),and AUC_(0-t)(608.62±289.05)µg·L~(-1)·h for the model group,while t_(1/2)(1.02±0.25) h,C_(max)(355.08±180.00)µg·L~(-1),and AUC_(0-t)(501.07±242.68)µg·L~(-1)·h for the normal group;(4) hesperidin:t_(1/2)(0.86±0.29) h,C_(max)(95.17±22.80)µg·L~(-1)and AUC_(0-t)(141.19±54.63)µg·L~(-1)·h for the model group,while t_(1/2)(0.95±0.31) h,C_(max)(46.48±18.33)µg·L~(-1)and AUC_(0-t)(69.51±14.73)µg·L~(-1)·h for the normal group;(5) neohesperidin:t_(1/2)(0.89±0.29) h,C_(max)(828.78±361.56)µg·L~(-1)and AUC_(0-t)(1 292.29±553.73)µg·L~(-1)·h for the model group,while t_(1/2)(0.90±0.31) h,C_(max)(314.68±172.45)µg·L~(-1)and AUC_(0-t)(385.99±138.55)µg·L~(-1)·h for the normal group.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Ratos , Ratos Sprague-Dawley
15.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21261013

RESUMO

BackgroundTo allow a return to a pre-COVID-19 lifestyle, virtually every country has initiated a vaccination program to mitigate severe disease burden and control transmission. However, it remains to be seen whether herd immunity will be within reach of these programs. MethodsWe developed a data-driven model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. The model is calibrated considering COVID-19 natural history and the estimated transmissibility of the Delta variant. Three vaccination programs are tested, including the one currently enacted in China and model-based estimates of the herd immunity level are provided. ResultsWe found that it is unlike to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021, the exclusion of underage individuals from the targeted population, and the lack of prior natural immunity. We estimate that, assuming a vaccine efficacy of 90% against the infection, vaccine-induced herd immunity would require a coverage of 93% or higher of the Chinese population. However, even when vaccine-induced herd immunity is not reached, we estimated that vaccination programs can reduce SARS-CoV-2 infections by 53-58% in case of an epidemic starts to unfold in the fall of 2021. ConclusionsEfforts should be taken to increase populations confidence and willingness to be vaccinated and to guarantee highly efficacious vaccines for a wider age range.

16.
J Nanobiotechnology ; 19(1): 210, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261493

RESUMO

BACKGROUND: We investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma. METHODS: Raw264.7 cells were harvested to extract EVs for the preparation of ICG/PTX@RGE-EV by electroporation and click chemistry. We evaluated the success of modifying Neuropilin-1 targeting peptide (RGE) on the EV membrane of ICG/PTX@RGE-EV using super-resolution fluorescence microscopy and flow cytometry. Spectrophotometry and high performance liquid chromatography (HPLC) were implemented for qualitative and quantitative analysis of the ICG and PTX loaded in EVs. Photothermal properties of the vesicles were evaluated by exposing to 808-nm laser light. Western blot analysis, cell counting kit 8 (CCK-8), Calcein Acetoxymethyl Ester/propidium iodide (Calcein-AM/PI) staining, and flow cytometry were utilized for assessing effects of vesicle treatment on cellular behaviors. A nude mouse model bearing glioma was established to test the targeting ability and anti-tumor action of ICG/PTX@RGE-EV in vivo. RESULTS: Under exposure to 808-nm laser light, ICG/PTX@RGE-EV showed good photothermal properties and promotion of PTX release from EVs. ICG/PTX@RGE-EV effectively targeted U251 cells, with activation of the Caspase-3 pathway and elevated apoptosis in U251 cells through chemotherapy combined with hyperthermia. The anti-tumor function of ICG/PTX@RGE-EV was confirmed in the glioma mice via increased accumulation of PTX in the ICG/PTX@RGE-EV group and an increased median survival of 48 days in the ICG/PTX@RGE-EV group as compared to 25 days in the PBS group. CONCLUSION: ICG/PTX@RGE-EV might actively target glioma to repress tumor growth by accelerating glioma cell apoptosis through combined chemotherapy-hyperthermia.

17.
Biomolecules ; 11(3)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33807040

RESUMO

The melanocortin-4 receptor (MC4R) plays an important role in the regulation of food intake and energy expenditure. Melanocortin-2 receptor accessory protein 2 (MRAP2) modulates trafficking, ligand binding, and signaling of MC4R. The Northern snakehead (Channa argus) is an economically important freshwater fish native to East Asia. To explore potential interaction between snakehead MC4R and MRAP2, herein we cloned snakehead mc4r and mrap2. The snakehead mc4r consisted of a 984 bp open reading frame encoding a protein of 327 amino acids, while snakehead mrap2 contained a 693 bp open reading frame encoding a protein of 230 amino acids. Synteny analysis indicated that mc4r was highly conserved with similar gene arrangement, while mrap2 contained two isoforms in teleost with different gene orders. Snakehead mc4r was primarily expressed in the brain, whereas mrap2 was expressed in the brain and intestine. Snakehead mc4r and mrap2 expression was modulated by fasting and refeeding. Further pharmacological experiments showed that the cloned snakehead MC4R was functional, capable of binding to peptide agonists and increasing intracellular cAMP production in a dose-dependent manner. Snakehead MC4R exhibited high constitutive activity. MRAP2 significantly decreased basal and agonist-stimulated cAMP signaling. These findings suggest that snakehead MC4R might be involved in energy balance regulation by interacting with MRAP2. Further studies are needed to elucidate MC4R in regulating diverse physiological processes in snakehead.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Peixes/metabolismo , Peixes/metabolismo , Receptor Tipo 4 de Melanocortina/metabolismo , Animais , Ligação Proteica , Transdução de Sinais
18.
Enzyme Microb Technol ; 146: 109778, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33812566

RESUMO

Microtuning the substrate-binding pocket (SBP) of EHs has emerged as an effective approach to manipulate their enantio- or regio-selectivities and activities towards target substrates. Here, the enantioselectivity (enantiomeric ratio, E) of AuEH2 towards a racemic (rac-) ortho-trifluoromethyl styrene oxide (o-TFMSO) was improved via microtuning its SBP. Based on the analysis on the crystal structure of AuEH2, its specific residues I192, Y216, R322 and L344 lining the SBP in close to the catalytic triad were identified for site-saturation mutagenesis. After screening, five single-site mutants were selected with E values elevated from 8 to 12-25 towards rac-o-TFMSO. To further improve E, four double-site mutants were constructed by combinatorial mutagenesis of AuEH2R322V separately with AuEH2I192V, AuEH2Y216F, AuEH2L344A and AuEH2L344C. Among all the mutants, AuEH2R322V/L344C possessed the largest E of 83 with activity of 67 U/g wet cell. The kinetic resolution of 200 mM rac-o-TFMSO was conducted at 0 °C for 5.5 h using 80 mg/mL wet cells of E. coli/Aueh2R322V/L344C, a transformant expressing AuEH2R322V/L344C, retaining (S)-o-TFMSO with 98.4 % ees and 49.3 % yields. Furthermore, the molecular docking simulation analysis indicated that AuEH2R322V/L344C more enantiopreferentially attacks the terminal carbon (Cß) in the oxirane ring of (R)-o-TFMSO than AuEH2.


Assuntos
Epóxido Hidrolases , Escherichia coli , Aspergillus , Epóxido Hidrolases/genética , Compostos de Epóxi , Escherichia coli/genética , Simulação de Acoplamento Molecular , Estereoisomerismo
19.
Front Med ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33909260

RESUMO

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.

20.
Biotechnol Adv ; 48: 107725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33727145

RESUMO

As fungus-like protists, thraustochytrids have been increasingly studied for their faster growth rates and high lipid content. In the 1990s, thraustochytrids were used as docosahexaenoic acid (DHA) producers for the first time. Thraustochytrids genera, such as Thraustochytrium, Schizochytrium, and Aurantiochytrium have been developed and patented as industrial strains for DHA production. The high DHA yield is attributed to its unique and efficient polyketide-like synthase (PKS) pathway. Moreover, thraustochytrids possess a completed mevalonate (MVA) pathway, so it can be used as host for terpenoid production. In order to improve strain performance, the metabolic engineering strategies have been applied to promote or disrupt intracellular metabolic pathways, such as genetic engineering and addition of chemical activators. However, it is difficult to realize industrialization only by improving strain performance. Various operation strategies were developed to enlarge the production quantities from the laboratory-scale, including two-stage cultivation strategies, scale-up technologies and bioreactor design. Moreover, an economical and effective downstream process is also an important consideration for the industrial application of thraustochytrids. Downstream costs accounts for 20-60% of the overall process costs, which represents an attractive target for increasing the cost-competitiveness of thraustochytrids, including how to improve the efficiency of lipid extraction and the further application of biomass residues. This review aims to overview the whole lipid biotechnology of thraustochytrids to provide the background information for researchers.


Assuntos
Estramenópilas , Terpenos , Reatores Biológicos , Biotecnologia , Ácidos Docosa-Hexaenoicos
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