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1.
Sci Total Environ ; 751: 141777, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32871317

RESUMO

Cells have inherent anti-fouling properties. The mechanisms underpinning these natural properties inform the design of an anti-biosorption coating for a polyethersulfone microfiltration membrane, which includes polydopamine and chitosan layers. This tri-layered membrane is created using quick and easy synthesis method. Its ability to resist bio-adsorption and membrane extracellular polymeric substances (EPS) formation is investigated using the bacterium E. coli (ATCC 11775, 1.5 × 107 CFU/mL). In addition, the proliferative bio-adsorption process is explored on the microfiltration membrane surface, using natural water under static and shaken conditions, while monitoring the bio-adsorption kinetics and EPS dynamic changes. The characterization results show that the modification by polydopamine and chitosan change the membrane surface morphology and increase its hydrophilicity. After 10 min dipping in 5 g/L chitosan solution, the pure water flux of the modified membrane is 5469 ± 30 L/(m2·h) (0.2 bar) and the contact angle decreases to 36.7 ± 1.0°, compared with 9889 ± 23 L/(m2·h) (0.2 bar) and 60.3 ± 1.5° for the unmodified polyethersulfone membrane, respectively. In proliferative bio-adsorption tests, the modified membrane is shown to decrease bio-adsorption by 0.4-2.3 orders of magnitude. However, no antimicrobial function is observed, probably due to the alkaline environment and insufficient functional amino groups. A series of linear and non-linear kinetic models is applied to fit the proliferative bio-adsorption process. The pseudo-second-order model is found to describe the proliferative bio-adsorption process best. Neither total organic carbon (TOC) nor protein is detected on the modified membrane surface. In contrast, on the unmodified PES membrane the ratios of protein/TOC (%), TOC/abundance ((µg/cm2)/CFU (log)) and protein/abundance ((µg/cm2)/CFU(log)) are 10%-16%, 0.17-0.28 and 0.02-0.04, respectively. No significant difference (p > 0.05) is found between static and shaken conditions. All these results point to improved anti-biosorption properties for water treatment applications, encouraging further studies on this membrane.


Assuntos
Escherichia coli , Purificação da Água , Adsorção , Interações Hidrofóbicas e Hidrofílicas , Membranas Artificiais
2.
Nat Commun ; 11(1): 5838, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203860

RESUMO

Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.

3.
IEEE Trans Cybern ; PP2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33156799

RESUMO

In this article, we present a multiagent framework for real-time large-scale 3-D reconstruction applications. In SLAM, researchers usually build and update a 3-D map after applying nonlinear pose graph optimization techniques. Moreover, many multiagent systems are prevalently using odometry information from additional sensors. These methods generally involve extensive computer vision algorithms and are tightly coupled with various sensors. We develop a generic method for the key challenging scenarios in multiagent 3-D mapping based on different camera systems. The proposed framework performs actively in terms of localizing each agent after the first loop closure between them. It is shown that the proposed system only uses monocular cameras to yield real-time multiagent large-scale localization and 3-D global mapping. Based on the initial matching, our system can calculate the optimal scale difference between multiple 3-D maps and then estimate an accurate relative pose transformation for large-scale global mapping.

4.
Nanoscale ; 12(43): 22317-22329, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33146638

RESUMO

The reactive oxygen species (ROS)-mediated anti-cancer therapy that shows the advantages of tumor specificity, high curative effect, and less toxic side-effects has powerful potential for cancer treatment. However, hypoxia in the tumor microenvironment (TME) and low penetrability of photosensitizers further limit their clinical application. Here, we present a composite core-shell-structured nanozyme (MS-ICG@MnO2@PEG) that consists of a mesoporous silica nanoparticle (MS) core and a MnO2 shell loaded with the photosensitizer indocyanine green (ICG) and then coated with PEG as the photodynamic/chemodynamic therapeutic agent for the ROS-mediated cancer treatment. On the one hand, MS-ICG@MnO2@PEG catalyzes H2O2 to produce O2 for enhanced photodynamic therapy (PDT), and on the other hand, it consumes GSH to trigger a Fenton-like reaction that generates *OH, thus enhancing the chemodynamic therapy (CDT). At the cellular level, MS-ICG@MnO2@PEG nanozymes exhibit good biocompatibility and induce the production of ROS in 4T1 tumor cells. It disrupts the redox balance in tumor cells affecting the mitochondrial function, and specifically kills the tumor cells. In vivo, the MS-ICG@MnO2@PEG nanozymes selectively accumulate at tumor sites and inhibit tumor growth and metastasis in 4T1 tumor-bearing mice. Accordingly, this study shows that the core-shell nanozymes can serve as an effective platform for the ROS-mediated breast cancer treatment by enhancing the combination of PDT and CDT.

5.
Food Funct ; 11(11): 9585-9598, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33151233

RESUMO

The objective of this study is to assess the potential anti-obesity effects of black garlic melanoidins (MLDs) and gut microbiota changes in an animal model, hypothesizing that the effects of oral administration of MLDs can be partially mediated by the modulation of intestinal microbiota via inhibiting the formation of lipopolysaccharides (LPS) and promoting the production of short-chain fatty acids (SCFAs). The effects of MLDs in C57BL/6J mice with high-fat diet (HFD)-induced obesity were investigated for 12 weeks with low (50 mg kg-1 day-1), medium (100 mg kg-1 day-1) and high (200 mg kg-1 day-1) doses. The results indicated that oral administration of MLDs markedly reduced high fat diet-induced weight gain and white adipose tissue weights and reversed glucose tolerance, especially at high doses. Besides, MLDs could alleviate dyslipidaemia, significantly suppress hepatic lipid accumulation and steatosis and effectively ameliorate lipid metabolism. The plasma LPS reduced significantly and the SCFAs increased in a dose-dependent manner. The MLDs could down-regulate the expression of fatty acid synthase (FAS) and interleukin-6 (IL-6) and up-regulate the expression of adipose triacylglyceride lipase (ATGL) and hormone sensitive lipase (HSL) in adipose tissues and livers at mRNA levels. Moreover, after the oral administration of MLDs, the intestinal microbial environment improved in the sense that bacterial diversity and richness increased. Intervention with MLDs modified the gut microbiota in mice with HFD-induced obesity, increasing the number of SCFA-producing bacteria (Bacteroidaceae) and reducing opportunistic pathogens (Enterobacteriaceae and Desulfovibrionaceae). An increased abundance of other probiotics including Lactobacillaceae and Akkermansiaceae was also observed. In conclusion, MLDs could improve glucose tolerance, induce the production of SCFAs and inhibit the production of endotoxin LPS, most likely mediated by modulating the gut microbiota. Therefore, it seems that MLDs exhibit anti-obesity effects and might be used as potential agents against obesity.

6.
Virulence ; 11(1): 1569-1581, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33172355

RESUMO

A pandemic designated as Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Up to date, there is no efficient biomarker for the timely prediction of the disease progression in patients. To analyze the inflammatory profiles of COVID-19 patients and demonstrate their implications for the illness progression of COVID-19. Retrospective analysis of 3,265 confirmed COVID-19 cases hospitalized between 10 January 2020, and 26 March 2020 in three medical centers in Wuhan, China. Patients were diagnosed as COVID-19 and hospitalized in Leishenshan Hospital, Zhongnan Hospital of Wuhan University and The Seventh Hospital of Wuhan, China. Univariable and multivariable logistic regression models were used to determine the possible risk factors for disease progression. Moreover, cutoff values, the sensitivity and specificity of inflammatory parameters for disease progression were determined by MedCalc Version 19.2.0. Age (95%CI, 1.017 to 1.048; P < 0.001), serum amyloid A protein (SAA) (95%CI, 1.216 to 1.396; P < 0.001) and erythrocyte sedimentation rate (ESR) (95%CI, 1.006 to 1.045; P < 0.001) were likely the risk factors for the disease progression. The Area under the curve (AUC) of SAA for the progression of COVID-19 was 0.923, with the best predictive cutoff value of SAA of 12.4 mg/L, with a sensitivity of 83.9% and a specificity of 97.67%. SAA-containing parameters are novel promising ones for predicting disease progression in COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Idoso , Área Sob a Curva , Betacoronavirus/genética , Biomarcadores , Sedimentação Sanguínea , Proteína C-Reativa/análise , China , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Laringe/virologia , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Valor Preditivo dos Testes , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Proteína Amiloide A Sérica/análise
7.
Food Funct ; 11(11): 9662-9674, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33211056

RESUMO

The aim of this study was to determine the effects of wheat germ polysaccharides (WGPs), which are indigestible carbohydrate fibers, on mice in early life, and the changes leading to long-lasting consequences. We determined the influences of early life ceftriaxone and WGP treatment on intestinal microbiota and immunity both in newborn and adulthood mice. The results showed that ceftriaxone significantly altered the intestinal microbiota, short-chain fatty acids' (SCFAs) metabolism, organ index, and serum OVA-specific IgE levels in newborn mice. Comparing adulthood mice to ceftriaxone-treated mice, the diversity and composition of intestinal microbiota were significantly improved after WGP treatment. In addition, the levels of OVA-specific IgE in the WGP-treated mice were significantly decreased, and the expression of cytokines (IL-2, IL-4, IL-6, IFN-γ, and TNF-α) were obviously increased. Therefore, we speculate that the mechanism of action of the indigestible carbohydrate fibers of WGPs is through maintaining immune homeostasis in newborns, which may partly last into adulthood. More importantly, this may be closely related to alterations in the intestinal microbiota.

8.
Plant Cell ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037144

RESUMO

The plant defense hormone salicylic acid (SA) is perceived by two classes of receptors, NPR1 and NPR3/NPR4. They function in two parallel pathways to regulate SA-induced defense gene expression. To better understand the roles of the SA receptors in plant defense, we systematically analyzed their contributions to different aspects of plant immunity using the SA-insensitive npr1-1 npr4-4D double mutant. We found that perception of SA by NPR1 and NPR4 is required for activation of N-hydroxypipecolic acid (NHP) biosynthesis, which is essential for inducing systemic acquired resistance (SAR). In addition, both pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) are severely compromised in the npr1-1 npr4-4D double mutant. Interestingly, the PTI and ETI attenuation in npr1-1 npr4-4D is more dramatic compared to the SA-induction deficient 2-1 (sid2-1) mutant, suggesting that perception of residual levels of SA in sid2-1 also contributes to immunity. Furthermore, NPR1 and NPR4 are involved in positive feedback amplification of SA biosynthesis and regulation of SA homeostasis through modifications including 5-hydroxylation and glycosylation. Thus, the SA receptors NPR1 and NPR4 play broad roles in plant immunity.

9.
J Ethnopharmacol ; : 113490, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33091501

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis Calyx seu Fructus is typically used to treat inflammatory diseases such as upper respiratory tract infection and acute tonsillitis in clinical practice of China. Physalin A, a main active ingredient of this traditional Chinese medicine (TCM), has been reported for its significant anti-tumor activity. However, most reports focused on the studies of its anti-tumor activity, the anti-inflammatory activity of physalin A and its molecular mechanism are still not elucidated clearly. AIM OF THE STUDY: The aim of the study was to investigate the anti-inflammatory activities both in vitro and in vivo and molecular mechanism of physalin A. MATERIALS AND METHODS: The potential anti-inflammatory properties of physalin A were evaluated in vitro by lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells, and in vivo via two typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by enzyme-linked immuno sorbent assay (ELISA) and Western blotting. RESULTS: The results showed that physalin A inhibited carrageenan-induced paw edema of rats and capillary permeability of mice induced by acetic acid in vivo. Furthermore, physalin A also significantly reduced the release of inflammatory mediators nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in RAW 264.7 in vitro. Further investigations indicated that physalin A can down-regulate the high expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Physalin A remarkably blocked the degradation of inhibitor of nuclear factor kappa B alpha (IκB-α) and the nuclear translocation of nuclear factor-κB (NF-κB) p65 induced by LPS in RAW 264.7 cells. However, physalin A did not significantly inhibit the phosphorylation of mitogen-activated protein kinases (MAPKs) family proteins c-Jun N-terminal kinase (JNK) or extracellular signal-regulated kinase (ERK) or p38. CONCLUSIONS: All the results clearly illustrated that the anti-inflammatory action of physalin A is due to the inactivation of NF-κB signal pathway, but is irrelevant to the MAPKs pathway.

10.
Food Chem ; : 128175, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33097332

RESUMO

Although aged fragrance is the most outstanding quality characteristic of dark tea, its formation still is not much clear. Thus, the volatiles of Qingzhuan tea (QZT) during the whole post-fermentation process were investigated at an industrial scale. The results showed that most of volatiles increased during pile-fermentation of QZT and weakened during aging storage, but some new volatiles were produced through aging storage. Hexanal, (E)-2-hexenal, (E)-2-decenal, 2,6,6-trimethyl-1-cyclohexene-1-carboxaldehyde, heptanal, (E)-2-octenal, (R)-5,6,7,7a-tetrahydro-4,4,7a-trimethyl-2(4H)-benzofuranone, ionone, 2-heptanone, 3-ethyl-4-methyl-1H-pyrrole-2,5-dione, (R,S)-5-ethyl-6-methyl-3-hepten-2-one, cis-5-ethenyltetrahydro-5-trimethyl-2-furanmethanol, and linalool generated by pile-fermentation should be the basic volatiles of aged fragrance in QZT, and 4-(2,4,4-trimethyl-cyclohexa-1,5-dienyl)-but-3-en-2-one, 6-methyl-5-heptene-2-one, safranal, guaiene, trans-2-(2-propynyloxy)-cyclohexanol, nonanal, and 4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-butanone formed during aging storage should be the transformed volatiles of aged fragrance in QZT, which together constitute the characteristic components of aged fragrance. Notably, 4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-butanone, 6-methyl-5-heptene-2-one, and safranal were selected as the key volatiles of QZT. These results contribute to understand better the formation of agedfragrance in dark tea.

11.
Int J Dev Neurosci ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33118216

RESUMO

BACKGROUND: Perinatal brain injury affects around 300,000 neonates in China each year, early diagnosis and active intervention are also crucial for timely treatment and better prognoses. As hearing is the earliest as well as the most sensitive sense to develop in neonates, we propose that the ability to differentiate among different emotional prosodies may differ between neonates with and without brain injuries. METHODS: We enrolled full-term neonates admitted to the neonatology department of Peking University First Hospital from January 2016 to December 2016, conducted functional near-infrared spectroscopy (fNIRS) monitoring within 24 hr of admission, and analyzed changes in oxyhemoglobin (ΔHbO2 ) and deoxyhemoglobin (ΔHb) to study the ability of neonates to differentiate among emotional prosodies. The neonates were followed up to 36 months for neurological outcome evaluation. RESULTS AND CONCLUSIONS: We found that neonates showed the early ability to differentiate among emotional prosodies, responding most sensitively to positive emotions, and this ability may have been impaired following brain injury.

12.
Br J Cancer ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33122847

RESUMO

BACKGROUND: Cyclin-dependent kinase 9 (CDK9) is a promising prognostic marker and therapeutic target in cancers. Bufalin is an effective anti-tumour agent; however, the clinical application of bufalin is limited due to its high toxicity. Acetyl-bufalin, the bufalin prodrug, was designed and synthesised with higher efficiency and lower toxicity. METHODS: Three non-small-cell lung cancer (NSCLC) cell lines, a xenograft model and a patient-derived xenograft (PDX) model were used to examine the effects of acetyl-bufalin. CDK9/STAT3 involvement was investigated by knockdown with siRNA, proteome microarray assay, western blot analysis and co-immunoprecipitation experiments. Acute toxicity test and pharmacokinetics (PK) study were conducted to assess the safety and PK. The human NSCLC tissues were analysed to verify high CDK9 expression. RESULTS: We showed that CDK9 induced NSCLC cell proliferation and that this effect was associated with STAT3 activation, specifically an increase in STAT3 phosphorylation and transcription factor activity. Acetyl-bufalin is an effective and safety inhibitor of the CDK9/STAT3 pathway, leading to the impediment of various oncogenic processes in NSCLC. Molecular docking and high-throughput proteomics platform analysis uncovered acetyl-bufalin directly binds to CDK9. Consequently, acetyl-bufalin impaired the complex formation of CDK9 and STAT3, decreased the expressions of P-STAT3, and transcribed target genes such as cyclin B1, CDC2, MCL-1, Survivin, VEGF, BCL2, and it upregulated the expression levels of BAX and caspase-3 activity. Acetyl-bufalin inhibited tumour growth in NSCLC xenograft and PDX models. CONCLUSIONS: Acetyl-bufalin is a novel blocker of the CDK9/STAT3 pathway thus may have potential in therapy of NSCLC and other cancers.

13.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(8): 1112-1118, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895171

RESUMO

OBJECTIVE: To analyze the clinical features of severe or critical ill adult patients with coronavirus disease (COVID-19). METHODS: The clinical data of 75 patients with severe or critical COVID-19 in Honghu People's Hospital from January to March in 2020 were collected. RESULTS: Of the 75 patients with COVID-19 pneumonia, 41 were male (54.67%) and 34 were female (45.33%) with a mean age of 67.53 ±12.37 years; 43 patients had severe and 32 had critical COVID-19, and 49.3% of the patients had underlying diseases. The main clinical manifestations included fever (78.67%) and coughing (70.67%). Compared with the severe patients, the critically ill patients had higher proportions of patients over 60 years old with elevated white blood cell count, increased prothrombin time, and higher levels of hsCRP, PCT, D-dimer, ALT, LDH, cTnI and NT-proBNP. Univariate logistic regression analysis showed that an age over 60 years, leukocytosis, hs-CRP elevation, prolonged prothrombin time, and increased levels of D-dimer, NT-proBNP and cTnI were associated with severe COVID-19. Multivariate logistic regression showed that an age over 60 years (OR=8.165, 95% CI: 1.483-45.576, P=0.017), prolonged prothrombin time (OR=7.516, 95% CI: 2.568-21.998, P=0.006) and elevated NT-proBNP (OR=6.194, 95% CI: 1.305-29.404, P=0.022) were independent risk factors for critical type of COVID-19. CONCLUSIONS: An age over 60 years, a prolonged prothrombin time and elevated NT-proBNP level are important clinical features of critically ill patients with COVID-19, and can be deemed as early warning signals for critical conditions of the disease.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Idoso , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(5): 723-726, 2020 May 30.
Artigo em Chinês | MEDLINE | ID: mdl-32897208

RESUMO

OBJECTIVE: To evaluate the clinical efficacy of ultrasound subgingival scaling combined with manual root planing for treatment of chronic periodontitis in elderly patients. METHODS: Forty elderly patients with chronic periodontitis were randomly divided into test group for treatment with ultrasound and Gracey subgingival curette for subgingival scaling combined with manual root planing and control group treated with ultrasound subgingival curette scaling (n=20). We compared plaque index (PLI), bleeding index (BI), probing depth (PD), and attachment loss (AL) between the two groups before and at 6 weeks and 12 weeks after the treatment. RESULTS: After periodontal treatment, PLI, BI, PD and AL all decreased significantly in both groups compared with the levels before the treatment (P < 0.05). The patients in the test group showed significantly more obvious decrease of PD and AL than those in the control group (P < 0.05), but the reduction of PLI and BI was comparable between the two groups (P>0.05). CONCLUSIONS: Ultrasound subgingival scaling combined with manual root planing produces better therapeutic effect than ultrasonic subgingival scaling alone for treatment of chronic periodontitis in elderly patients.


Assuntos
Periodontite Crônica , Idoso , Periodontite Crônica/terapia , Raspagem Dentária , Humanos , Aplainamento Radicular , Resultado do Tratamento , Ultrassonografia
15.
Medicine (Baltimore) ; 99(36): e20976, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32898990

RESUMO

BACKGROUND: Adequate bowel preparation is essential for the detection of pathological lesions during colonoscopy. However, it has been found to be inadequate in approximately 20% to 30% of colonoscopy examinations. Educational interventions focused on health staff, such as physicians and nurses, may improve the patients' understanding of the bowel preparation instructions, and consequently, increase the quality of bowel preparation. OBJECTIVES: To investigate whether enhanced education of ward nurses could improve the bowel preparation quality in inpatients undergoing colonoscopy. DESIGN: This was a single-center randomized controlled study. METHODS: A total of 190 consecutive inpatients scheduled to undergo colonoscopy from March 2019 to March 2020 were randomized to the educated (nurses with enhanced education) or control group (nurses without enhanced education). We assessed the bowel preparation quality using the Boston bowel preparation scale. RESULTS: There were 89 patients in the educated group and 101 patients in the control group. The proportion of colonoscopies with adequate bowel preparation was 83.1% in the educated group and 69.3% in the control group. Patients' compliance with bowel preparation in the educated group was superior to that in the control group. Furthermore, significantly better sleep quality was found in the educated group. The multivariate logistic regression analysis identified the ward nurses-focused enhanced educational intervention as a risk factor for bowel preparation quality. CONCLUSIONS: The ward nurses-focused educational intervention improved the bowel preparation quality and reduced the adverse event rates in inpatients undergoing colonoscopy. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry under number ChiCTR2000030366.


Assuntos
Catárticos/uso terapêutico , Colonoscopia/normas , Recursos Humanos de Enfermagem no Hospital/educação , Cooperação do Paciente/estatística & dados numéricos , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório
16.
Genet Test Mol Biomarkers ; 24(10): 625-631, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32991201

RESUMO

Background: Mutations within the myotubularin-related protein 9 gene (MTMR9) have been identified in several families with nonsyndromic intellectual disability (NSID), a generalized neurodevelopmental disorder; however, the relationship between MTMR9 and NSID needs to be verified using a larger sample size. Aim: To explore whether genetic variants in the MTMR9 gene are linked to susceptibility of NSID among the Chinese population. Materials and Methods: Seven single nucleotide polymorphisms (SNPs) of the MTMR9 gene (rs4559208, rs3824211, rs2164272, rs2164273, rs1897951, rs6991606, and rs7815802) were analyzed using family-based association testing among 258 Han Chinese NSID families. Results: Three SNPs of MTMR9 were significantly associated with NSID (z = 2.152, p = 0.031 for rs4559208; z = 2.403, p = 0.016 for rs2164273; and z = 2.758, p = 0.006 for rs7815802). Three alleles of these SNPs were more likely to be transferred from the carrier parents to the affected offspring. Haplotypes constructed using these SNPs also showed a similar transmitting trend (z = 2.505, p = 0.012, χ2(3) = 8.835, and global p = 0.032). Carriers with the G-G-C haplotype showed a higher risk of NSID (odds ratio = 1.46, 95% confidence interval [1.01-2.09], p = 0.04) than others. In silico functional predictions supported an etiological role for these three SNPs in NSID biology. Conclusions: This study provides additional insights into the association of NSID with specific alleles, and haplotypes within the MTMR9 gene. Genotypic analyses of the MTMR9 gene should be considered for patients presenting with NSID of unknown etiology.

17.
Chemistry ; 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32888220

RESUMO

ß-Phase anhydrous guanine (ß-AG) crystals are one of the most widespread organic crystals to construct optical structures in organisms. Currently, no synthetic method is available that allows for producing guanine crystals with similar control in size, morphology, and crystallography as in biological ones. Herein, a facile one-step synthesis route to fabricate bio-inspired guanine microplatelets with (100) exposing planes in almost pure ß-phase is reported. The synthesis is based on a precipitation process of a guanine sodium hydroxide solution in formamide with poly(1-vinylpyrrolidone-co-vinyl acetate) as a morphological additive. Due to their uniform size (ca. 20 µm) and thickness (ca. 110 nm), the crystals represent the first synthetic guanine microplatelets that exhibit strong structural coloration and pearlescent lusters. Moreover, this synthesis route was utilized as a model system to investigate the effects of guanine analogues, including uric acid, hypoxanthine, xanthine, adenine, and guanosine, during the crystallization process. Our results indicate that the introduction of guanine analogues not only can reduce the required synthesis temperature but also provide a versatile control in crystal morphology and polymorph selection between the α-phase AG (α-AG) and ß-AG. Turbidity experiments show that the ß-AG microplatelets are formed with a fast precipitation rate in comparison to α-AG, suggesting that the formation of ß-AG crystals follows a kinetically driven process.

19.
J Virol ; 94(22)2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32900822

RESUMO

Animal models recapitulating human COVID-19 disease, especially severe disease, are urgently needed to understand pathogenesis and to evaluate candidate vaccines and therapeutics. Here, we develop novel severe-disease animal models for COVID-19 involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or RAG2 knockout (KO) hamsters were exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the respiratory route. Both the CyP-treated and RAG2 KO hamsters developed clinical signs of disease that were more severe than those in immunocompetent hamsters, notably weight loss, viral loads, and fatality (RAG2 KO only). Disease was prolonged in transiently immunosuppressed hamsters and was uniformly lethal in RAG2 KO hamsters. We evaluated the protective efficacy of a neutralizing monoclonal antibody and found that pretreatment, even in immunosuppressed animals, limited infection. Our results suggest that functional B and/or T cells are not only important for the clearance of SARS-CoV-2 but also play an early role in protection from acute disease.IMPORTANCE Syrian hamsters are in use as a model of disease caused by SARS-CoV-2. Pathology is pronounced in the upper and lower respiratory tract, and disease signs and endpoints include weight loss and viral RNA and/or infectious virus in swabs and organs (e.g., lungs). However, a high dose of virus is needed to produce disease, and the disease resolves rapidly. Here, we demonstrate that immunosuppressed hamsters are susceptible to low doses of virus and develop more severe and prolonged disease. We demonstrate the efficacy of a novel neutralizing monoclonal antibody using the cyclophosphamide transient suppression model. Furthermore, we demonstrate that RAG2 knockout hamsters develop severe/fatal disease when exposed to SARS-CoV-2. These immunosuppressed hamster models provide researchers with new tools for evaluating therapies and vaccines and understanding COVID-19 pathogenesis.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Modelos Animais de Doenças , Mesocricetus , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Imunidade Adaptativa , Animais , Animais Geneticamente Modificados , Betacoronavirus/fisiologia , Ciclofosfamida , Proteínas de Ligação a DNA/genética , Técnicas de Inativação de Genes , Imunossupressores , Pandemias , Índice de Gravidade de Doença
20.
Soft Matter ; 16(43): 9844-9856, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-32996949

RESUMO

The transport of bio-particles in viscous flows exhibits a rich variety of dynamical behaviour, such as morphological transitions, complex orientation dynamics or deformations. Characterising such complex behaviour under well controlled flows is key to understanding the microscopic mechanical properties of biological particles as well as the rheological properties of their suspensions. While generating regions of simple shear flow in microfluidic devices is relatively straightforward, generating straining flows in which the strain rate is maintained constant for a sufficiently long time to observe the objects' morphologic evolution is far from trivial. In this work, we propose an innovative approach based on optimised design of microfluidic converging-diverging channels coupled with a microscope-based tracking method to characterise the dynamic behaviour of individual bio-particles under homogeneous straining flow. The tracking algorithm, combining a motorised stage and a microscopy imaging system controlled by external signals, allows us to follow individual bio-particles transported over long-distances with high-quality images. We demonstrate experimentally the ability of the numerically optimised microchannels to provide linear velocity streamwise gradients along the centreline of the device, allowing for extended consecutive regions of homogeneous elongation and compression. We selected three test cases (DNA, actin filaments and protein aggregates) to highlight the ability of our approach for investigating dynamics of objects with a wide range of sizes, characteristics and behaviours of relevance in the biological world.

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