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1.
Nat Metab ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895578

RESUMO

Not all individuals age at the same rate. Methods such as the 'methylation clock' are invasive, rely on expensive assays of tissue samples and infer the ageing rate by training on chronological age, which is used as a reference for prediction errors. Here, we develop models based on convoluted neural networks through training on non-invasive three-dimensional (3D) facial images of approximately 5,000 Han Chinese individuals that achieve an average difference between chronological or perceived age and predicted age of ±2.8 and 2.9 yr, respectively. We further profile blood transcriptomes from 280 individuals and infer the molecular regulators mediating the impact of lifestyle on the facial-ageing rate through a causal-inference model. These relationships have been deposited and visualized in the Human Blood Gene Expression-3D Facial Image (HuB-Fi) database. Overall, we find that humans age at different rates both in the blood and in the face, but do so coherently and with heterogeneity peaking at middle age. Our study provides an example of how artificial intelligence can be leveraged to determine the perceived age of humans as a marker of biological age, while no longer relying on prediction errors of chronological age, and to estimate the heterogeneity of ageing rates within a population.

2.
Angiology ; : 3319720953044, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32911955

RESUMO

Iodixanol is associated with lower rates of contrast-induced acute kidney injury (CI-AKI). However, the effects of high volumes of iodixanol on renal function after percutaneous coronary intervention (PCI) have not been fully elucidated. This study evaluates the effects of high-dose (>300 mL) iodixanol on renal function within 72 hours of PCI. We retrospectively reviewed 676 consecutive patients who received high-dose (>300 mL) iodixanol during PCI between October 2015 and December 2017 in 4 centers. Logistic regression analysis was used to identify significant independent predictors for CI-AKI. The incidence of CI-AKI was 3.5% (23/651). In patients administered 300 to 500 mL and >500 mL iodixanol, the incidence of CI-AKI was 3.9% and 1.7%, respectively. In patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, the incidence of CI-AKI was 2.6%. In high-risk and very high-risk patients, stratified by the Mehran risk score, the incidence of CI-AKI was 3.3% and 4.3%, respectively. In patients received high-dose iodixanol (>300 mL), logistic regression analysis demonstrated that female sex, chronic kidney disease, and eGFR were independent risk factors for CI-AKI, but contrast volume was not. The administration of high (300-500 mL) and very high (>500 mL) dose of iodixanol is associated with low rates of CI-AKI.

3.
Chem Commun (Camb) ; 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32808607

RESUMO

We discovered two antibacterial bimetallic nanoparticles (AuRh and AuRu NPs), that possess antibacterial activities against multi-drug resistant (MDR) Gram-negative bacteria and can cure wound infections. None of the nanoparticles comprising just one of these metals elements shows any antibiotic activities.

4.
Nat Prod Res ; : 1-5, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32779484

RESUMO

2-hydroxy-6-tridecylbenzoic acid is alkylsalicylic acid monomer compound, abundantly existed in the ginkgo biloba extracts, however, the underlying mechanism of its anti-migration and anti-invasion effects in triple-negative breast cancer (TNBC) is not clear. Here, 2-hydroxy-6 -tridecylbenzoic acid inhibited MDA-MB-231 and 4 T-1 cells growth without toxicity to MCF-10A normal breast cells. Meanwhile, 2-hydroxy-6-tridecylbenzoic acid inhibited cells migration and invasion as well as EMT with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, Vimentin, Snail, MMP-2 and MMP-9 expression. The inhibition was further demonstrated by the enhancement of cytochrome P450 (CYP) 1B1 expression through the activation of AMP activated protein kinase (AMPK) in MDA-MB-231 and 4 T-1 cells. Silencing of CYP1B1 and AMPK with siRNA blocked the inhibitory effects of migration and invasion, and reversed the EMT related genes. These findings may provide a novel mechanism of the 2-hydroxy-6-tridecylbenzoic acid as a molecular-targeted therapeutic drug for TNBC patients.

5.
Curr Med Res Opin ; 36(9): 1541-1548, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32609549

RESUMO

OBJECTIVE: To determine the impact of telemental health (TMH) use on total healthcare costs and mental health (MH)-related costs paid by a third party among adults with mental health conditions (MHC). METHOD: This study employed a pre-post design with a non-equivalent control group. The cohort comprised adults with MHCs identified using diagnosis codes from de-identified claims data of the Optum Clinformatics DataMart (2010 January 01 to 2017 June 30). We identified mental health (MH) service users and TMH users (N = 348) based on procedure codes. Non-users (N = 238,595) were defined as those who only used in-person MH services. A Difference-in-Differences (DID) analysis was performed within a multivariable two-part model (TPM) framework to examine the impact of TMH use on adjusted standardized costs (2018 US $) of all healthcare services and MH services. Patient-level and state-level factors were adjusted in TPM. RESULTS: TMH use was associated with significantly higher MH-related costs [Marginal effect = $461.3, 95% confidence interval: $142.4-$780.2] and an excess of $370 increase in MH-related costs at follow-up as compared to baseline. However, TMH use was not associated with an increase in total third-party healthcare costs nor with changes in total costs from baseline to follow-up. CONCLUSIONS: Despite having a higher likelihood of MH services use and MH-related costs, TMH users did not have higher total costs as compared to adults using only in-person MH services. Our findings suggest that TMH can increase access to MH care without increasing total healthcare costs among adults with MHC. Future studies exploring whether TMH use can lead to cost-savings over a longer period are warranted.

6.
Medicine (Baltimore) ; 99(28): e20930, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664089

RESUMO

Surgical lung biopsy is regarded as the golden standard for the diagnosis of idiopathic interstitial pneumonias (IIPs). Here, we attempted to show the diagnostic accuracy of multidisciplinary classifications based on transbronchial pathology including transbronchial lung cryobiopsy (TBLC) , bronchoalveolar lavage fluid (BALF) and endobronchial ultrasound-guided transbronchial needle aspiration biopsy (EBUS-TBNA).Patients with suspected interstitial lung diseases admitted from June 1, 2016 to December 31, 2018 were involved. Patients with known causes of interstitial lung diseases and typical idiopathic pulmonary fibrosis diagnosed through clinical, radiological information were excluded. Patients with atypical idiopathic pulmonary fibrosis and possible IIPs accepted transbronchial pathological evaluation. Initial multidisciplinary diagnosis (MDD) classifications were made depending on clinical, radiological and transbronchial pathological information by a multidisciplinary team (MDT). The final MDD classifications were confirmed by subsequent therapeutic effects. All patients were followed up for at least 6 months.A total of 70 patients were finally involved. The samples of lung parenchyma extracted through TBLC were enough for confirmation of pathological diagnoses in 68.6% (48/70) cases. Samples of 6 cases were extracted by EBUS-TBNA. Bacteriological diagnoses were positive in 1 case by BALF. Pathological diagnoses of 77.1% (54/70) cases were achieved through TBLC, EBUS-TBNA and BALF. During the follow up study, the pulmonary lesions of 60% patients were improved, 11.43% were relapsed when glucocorticoid was reduced to small dose or withdrawal, 14.29% were leveled off and 8.57% were progressed. The diagnoses of 4 patients with progressed clinical feature were revised. As a result, 94.3% initial MDD classifications based on transbronchial pathology were consistent with the final MDD, and the difference of diagnostic yield wasn't significant between initial and final MDD (Z = -1.414, P = .157).Classifications of IIPs based on transbronchial pathology were useful and quite agreed with final MDD.


Assuntos
Broncoscopia/métodos , Pneumonias Intersticiais Idiopáticas/classificação , Pneumonias Intersticiais Idiopáticas/patologia , Biópsia Guiada por Imagem/métodos , Idoso , Biópsia/tendências , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia/efeitos adversos , Broncoscopia/tendências , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Hospitalização , Humanos , Pneumonias Intersticiais Idiopáticas/diagnóstico por imagem , Pneumonias Intersticiais Idiopáticas/tratamento farmacológico , Fibrose Pulmonar Idiopática/patologia , Comunicação Interdisciplinar , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Tomografia Computadorizada por Raios X/métodos
7.
Biochem Biophys Res Commun ; 528(3): 554-560, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32505349

RESUMO

Tamoxifen resistance is a major roadblock in the treatment of patients with breast cancer. Ribonucleotide reductase M2 (RRM2) was found to be involved in acquired resistance of breast cancer cells (BCCs) to tamoxifen. Here, we used GW8510, which has been identified as a potential RRM2 inhibitor, to evaluate the effect of RRM2 inhibition on reversing resistance of BCCs to tamoxifen and investigate its mechanisms. We showed that RRM2 overexpression played a key role in the development of acquired tamoxifen resistance in BCCs through downregulation of autophagy level. Combination treatment with tamoxifen and GW8510 significantly inhibited survival of the tamoxifen-resistant BCCs through induction of autophagic cell death compared to either of the two drugs. Furthermore, combination of tamoxifen and GW8510 resulted in marked growth inhibition of tamoxifen-resistant BBC xenograft tumor in vivo compared to tamoxifen or GW8510 alone. In conclusion, tamoxifen in combination with GW8510 can overcome acquired tamoxifen resistance in BCCs and may be a rational therapeutic approach against breast cancer with high RRM2 expression.

8.
Nanoscale Horiz ; 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32478357

RESUMO

Piezochromic materials alter their photoluminescent (PL) colors in response to the action of external force. Such materials have attracted much attention owing to their promising applications in pressure-sensing, optoelectronic memory and anticounterfeiting. However, almost all the reported piezochromic materials were limited to the organic matters or compounds containing organic components. Here we present piezochromic materials and pressure-induced optical response based on all-inorganic core/shell InP/ZnS nanocrystals (NCs). The InP/ZnS NCs exhibit noticeable PL color changes, shifting from orange (2.08 eV) to green (2.25 eV), with the PL intensity showing slight enhancement below an applied pressure of 2.5 GPa. Further compressing to fluorescence quenching produces an ultrabroad energy tenability range up to 400 meV. Structural and time-resolved PL lifetime studies, together with first-principle calculations, reveal the weakening of strain-induced defect states in the low pressure regime, which contributes to effective excition recombination, thus ensuring high fluorescence emission of InP/ZnS NCs. This work provides a promising strategy to prepare piezochromic materials of all-inorganic semiconductors, thereby greatly increasing the choice of materials for new applications.

9.
Can J Cardiol ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: covidwho-276980

RESUMO

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased use of health care services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.

10.
Scand J Immunol ; : e12895, 2020 May 23.
Artigo em Inglês | MEDLINE | ID: covidwho-343507

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that belongs to the ß-genus, causing the outbreak of coronavirus disease 19 (COVID-19). SARS-CoV-2 infection can stimulate a pronounced immune response in the host, which embodies in the decrease of lymphocytes and aberrant increase of cytokines in COVID-19 patients. SARS-CoV-2 RNA and proteins interact with various pattern recognition receptors that switch on antiviral immune responses to regulate viral replication and spreading within the host in vivo. However, overactive and impaired immune responses also cause immune damage and subsequent tissue inflammation. This article focuses on the dual roles of immune system during SARS-CoV-2 infection, providing a theoretical basic for identifying therapeutic targets in a situation with an unfavourable immune reaction.

11.
Can J Cardiol ; 36(7): 1068-1080, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32425328

RESUMO

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased use of health care services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Infecções por Coronavirus/epidemiologia , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Doenças Cardiovasculares/terapia , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Feminino , Saúde Global , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Prevalência , Medição de Risco , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/terapia , Análise de Sobrevida
12.
Scand J Immunol ; 92(2): e12895, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32445403

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that belongs to the ß-genus, causing the outbreak of coronavirus disease 19 (COVID-19). SARS-CoV-2 infection can stimulate a pronounced immune response in the host, which embodies in the decrease of lymphocytes and aberrant increase of cytokines in COVID-19 patients. SARS-CoV-2 RNA and proteins interact with various pattern recognition receptors that switch on antiviral immune responses to regulate viral replication and spreading within the host in vivo. However, overactive and impaired immune responses also cause immune damage and subsequent tissue inflammation. This article focuses on the dual roles of immune system during SARS-CoV-2 infection, providing a theoretical basic for identifying therapeutic targets in a situation with an unfavourable immune reaction.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , RNA Viral/imunologia , Receptores de Reconhecimento de Padrão/imunologia , Proteínas Virais/imunologia , Antivirais/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Citocinas/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Pandemias , Pneumonia Viral/imunologia , Transdução de Sinais/imunologia
14.
Small ; 16(24): e2000755, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32374506

RESUMO

Utilization of microbes as the carbon source and structural template to fabricate porous carbon has incentivized great interests owing to their diverse micromorphology and intricate intracellular structure, apart from the obvious benefit of "turning waste into wealth." Challenges remain to preserve the biological structure through the harsh and laborious post-synthetic treatments, and tailor the functionality as desired. Herein, Escherichia coli is directly coated with metal-organic frameworks (MOFs) through in situ assembly to fabricate N, P co-doped porous carbon capsules expressing self-phosphorized metal phosphides. While the MOF coating serves as an armoring layer for facilitating the morphology inheritance from the bio-templates and provides metal sources for generating extra porosity and electrochemically active sites, the P-rich phospholipids and N-rich proteins from the plasma membrane enable carbon matrix doping and further yield metal phosphides. These unique structural and compositional features endow the carbon capsules with great capabilities in suppressing polysulfide shuttling and catalyzing reversible oxygen conversion, ultimately leading to the superb performance of lithium-sulfur batteries and zinc-air batteries. Combining the bio-templating strategy with hierarchical MOF assembly, this work opens a new avenue for the fabrication of highly porous and functional carbon for advanced energy applications.

15.
Phys Chem Chem Phys ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32426785

RESUMO

Two novel phenanthro[9,10-b]benzofuran and pyreno[4,5-b]benzofuran modified twistacene derivatives, 9 and 10, have been successfully synthesized via Suzuki coupling and then characterized. The photophysical properties were examined and DFT calculations were carried out in a comparative manner, and both molecules emitted strong blue light in organic solvents and in the solid state. Impressively, fabricated electroluminescent devices based on these single emitters radiate pure white light.

18.
Nat Genet ; 52(4): 428-436, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32231277

RESUMO

Adaptive changes in plant phenology are often considered to be a feature of the so-called 'domestication syndrome' that distinguishes modern crops from their wild progenitors, but little detailed evidence supports this idea. In soybean, a major legume crop, flowering time variation is well characterized within domesticated germplasm and is critical for modern production, but its importance during domestication is unclear. Here, we identify sequential contributions of two homeologous pseudo-response-regulator genes, Tof12 and Tof11, to ancient flowering time adaptation, and demonstrate that they act via LHY homologs to promote expression of the legume-specific E1 gene and delay flowering under long photoperiods. We show that Tof12-dependent acceleration of maturity accompanied a reduction in dormancy and seed dispersal during soybean domestication, possibly predisposing the incipient crop to latitudinal expansion. Better understanding of this early phase of crop evolution will help to identify functional variation lost during domestication and exploit its potential for future crop improvement.


Assuntos
Produtos Agrícolas/genética , Flores/genética , Genes de Plantas/genética , Soja/genética , Domesticação , Fabaceae/genética , Fotoperíodo , Sementes/genética
19.
Nanoscale ; 12(16): 8922-8933, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32267278

RESUMO

As continuous consumption of the world's lithium reserves is causing concern, alternative energy storage solutions based on earth-abundant elements, such as sodium-ion batteries and zinc-air batteries, have been attracting increasing attention. Herein, nanoframes of CoOx are encapsulated into carbonized microporous fibers by electrospinning zeolitic imidazolate frameworks to impart both a sodium-hosting capability and catalytic activities for reversible oxygen conversion. The ultrahigh rate performance of sodium-ion batteries up to 20 A g-1 and ultrastable cycling over 6000 cycles are attributed to a dual-buffering effect from the framework structure of CoOx and the confinement of carbon fibers that effectively accommodates cyclic volume fluctuation. Both in situ Raman and ex situ microscopic analyses unveil the reversible conversion of CoOx during the sodiation/desodiation process. The excellent ORR activity, superior to that of commercial Pt/C, is mainly ascribed to the abundant Co-N-C species and the full exposure of active sites on the microporous framework structure. Flexible and rechargeable sodium-ion full batteries and zinc-air batteries are further demonstrated with great energy efficiency and cycling stability, as well as mechanical deformability.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32302436

RESUMO

Metal oxides exposing high-index facets are potentially impactful in catalysis and adsorption processes owing to under-coordinated ions and polarities that alter their interfacial properties compared to low-index facets. Here, we report molten-salt syntheses of NiO particles exposing a variety of crystal facets. We show that for a given anion (nitrate or chloride), the alkali cation has a notable impact on the formation of crystals exposing {311}, {611}, {100}, and {111} faces. Based on a parametric analysis of synthesis conditions, we postulate that the crystallization mechanism is governed by the formation of growth units consisting of NiII complexes whose coordination numbers are determined by temperature and the selection of anion (associated to the coordination sphere) and alkali cation (associated with the outer coordination sphere). Notably, our findings reveal that high-index facets are particularly favored in chloride media and are stable under prolonged periods of catalysis and steaming.

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