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1.
Sci Rep ; 14(1): 11026, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744903

RESUMO

Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02-1.09), vascular dementia (HR, 1.08; 95% CI 1.01-1.15), and non-Alzheimer's disease non-vascular dementia (HR, 1.09; 95% CI 1.03-1.14). No significant association was observed for Alzheimer's disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.


Assuntos
Bancos de Espécimes Biológicos , Demência , Características da Família , Humanos , Feminino , Masculino , Reino Unido/epidemiologia , Demência/epidemiologia , Demência/etiologia , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Estudos Prospectivos , Incidência , Modelos de Riscos Proporcionais , Encéfalo/patologia , Biobanco do Reino Unido
2.
Stroke ; 55(3): 660-669, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38299341

RESUMO

BACKGROUND: Our primary objective was to assess the association between joint exposure to various air pollutants and the risk of ischemic stroke (IS) and the modification of the genetic susceptibility. METHODS: This observational cohort study included 307 304 British participants from the United Kingdom Biobank, who were stroke-free and possessed comprehensive baseline data on genetics, air pollutant exposure, alcohol consumption, and dietary habits. All participants were initially enrolled between 2006 and 2010 and were followed up until 2022. An air pollution score was calculated to assess joint exposure to 5 ambient air pollutants, namely particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, as well as nitrogen oxide and nitrogen dioxide. To evaluate individual genetic risk, a polygenic risk score for IS was calculated for each participant. We adjusted for demographic, social, economic, and health covariates. Cox regression models were utilized to estimate the associations between air pollution exposure, polygenic risk score, and the incidence of IS. RESULTS: Over a median follow-up duration of 13.67 years, a total of 2476 initial IS events were detected. The hazard ratios (95% CI) of IS for per 10 µg/m3 increase in particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, nitrogen dioxide, and nitrogen oxide were 1.73 (1.33-2.14), 1.24 (0.88-1.70), 1.13 (0.89-1.33), 1.03 (0.98-1.08), and 1.04 (1.02-1.07), respectively. Furthermore, individuals in the highest quintile of the air pollution score exhibited a 29% to 66% higher risk of IS compared with those in the lowest quintile. Notably, participants with both high polygenic risk score and air pollution score had a 131% (95% CI, 85%-189%) greater risk of IS than participants with low polygenic risk score and air pollution score. CONCLUSIONS: Our findings suggested that prolonged joint exposure to air pollutants may contribute to an increased risk of IS, particularly among individuals with elevated genetic susceptibility to IS.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , AVC Isquêmico , Humanos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Dióxido de Nitrogênio/efeitos adversos , Dióxido de Nitrogênio/análise , AVC Isquêmico/induzido quimicamente , Biobanco do Reino Unido , Bancos de Espécimes Biológicos , Material Particulado/efeitos adversos , Material Particulado/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Óxidos de Nitrogênio , Óxido Nítrico , Estratificação de Risco Genético , Exposição Ambiental/efeitos adversos
3.
Angew Chem Int Ed Engl ; 62(34): e202305397, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37394690

RESUMO

Capacitive analogues of semiconductor diodes (CAPodes) present a new avenue for energy-efficient and nature-inspired next-generation computing devices. Here, we disclose the generalized concept for bias-direction-adjustable n- and p-CAPodes based on selective ion sieving. Controllable-unidirectional ion flux is realized by blocking electrolyte ions from entering sub-nanometer pores. The resulting CAPodes exhibit charge-storage characteristics with a high rectification ratio (96.29 %). The enhancement of capacitance is attributed to the high surface area and porosity of an omnisorbing carbon as counter electrode. Furthermore, we demonstrate the use of an integrated device in a logic gate circuit architecture to implement logic operations ('OR', 'AND'). This work demonstrates CAPodes as a generalized concept to achieve p-n and n-p analogue junctions based on selective ion electrosorption, provides a comprehensive understanding and highlights applications of ion-based diodes in ionologic architectures.

4.
Hepatol Int ; 17(4): 850-859, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37067675

RESUMO

BACKGROUND AND AIMS: Liver transplantation (LT) is the primary curative option for cirrhotic patients with early-stage hepatocellular carcinoma (HCC). However, tumor recurrence occurs in 15-20% of cases with unfavorable prognosis. We have developed a library of T cell receptors (TCRs) specific for different hepatitis B virus (HBV) antigens, restricted by different molecules of human leucocyte antigen (HLA)-class I, to redirect T cells against HBV antigens (Banu in Sci Rep 4:4166, 2014). We further demonstrated that these transiently functional T cells specific for HBV obtained through messenger RNA (mRNA) electroporation can eliminate HCC cells expressing HBV antigens in vitro and in vivo (Kah in J Clin Invest 127:3177-3188, 2017). A phase I clinical trial for patients with HCC recurrence post-liver transplant was conducted to assess the safety, tolerability, and anti-tumor efficacy of transiently functional HBV-TCR T cells. Here, we report the clinical findings with regard to the safety and anti-tumor efficacy of mRNA electroporated HBV-specific TCR-T cells. (ClinicalTrials.gov identifier: NCT02719782). PATIENTS AND METHODS: A total of six patients with HBV-positive recurrent HCC post-liver transplant and HLA-matched to TCR targeting hepatitis B surface antigen (HBsAg) or hepatitis B core antigen (HBcAg) (HLA-A*02:01/HBsAg, HLA-A*11:01/HBcAg, HLA-B*58:01/HBsAg or HLA-C*08:01/HBsAg) were enrolled in this study. The primary objective was to assess the safety of short-lived mRNA electroporated HBV-TCR T cells based on the incidence and severity of the adverse event (AE) graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0. The secondary objective was to determine the effectiveness of HBV-TCR T cells as per RECIST 1.1 criteria. Patients were followed up for survival for 2 years post-end of treatment. RESULTS: The median age of the six patients was 35.5 years (range: 28-47). The median number of HBV-TCR T cell infusions administered was 6.5 (range: 4-12). The treatment-related AE included grade 1 pyrexia. This study reported no cytokine release syndrome nor neurotoxicity. One patient remained alive and five were deceased at the time of the data cutoff (30 April 2020). CONCLUSION: This study has demonstrated that multiple infusions of mRNA electroporated HBV-specific TCR T cells were well-tolerated in patients with HBV-positive recurrent HCC post-liver transplant.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Adulto , Pessoa de Meia-Idade , Vírus da Hepatite B/genética , Antígenos de Superfície da Hepatite B , Neoplasias Hepáticas/patologia , Antígenos do Núcleo do Vírus da Hepatite B/uso terapêutico , RNA Mensageiro , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/complicações , Receptores de Antígenos de Linfócitos T/genética , Hepatite B/complicações
5.
Front Genet ; 14: 1331951, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38323242

RESUMO

DNA strand displacement (DSD) is an efficient technology for constructing molecular circuits. However, system computing speed and the scale of logical gate circuits remain a huge challenge. In this paper, a new method of coding DNA domains is proposed to carry out logic computation. The structure of DNA strands is designed regularly, and the rules of domain coding are described. Based on this, multiple-input and one-output logic computing modules are built, which are the basic components forming digital circuits. If the module has n inputs, it can implement 2n logic functions, which reduces the difficulty of designing and simplifies the structure of molecular logic circuits. In order to verify the superiority of this method for developing large-scale complex circuits, the square root and exponentiation molecular circuits are built. Under the same experimental conditions, compared with the dual-track circuits, the simulation results show that the molecular circuits designed based on the domain coding strategy have faster response time, simpler circuit structure, and better parallelism and scalability. The method of forming digital circuits based on domain coding provides a more effective way to realize intricate molecular control systems and promotes the development of DNA computing.

6.
Angew Chem Int Ed Engl ; 61(50): e202212250, 2022 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-36260635

RESUMO

Switchable supercapacitors (SCs) enable a reversible electrically-driven uptake/release of bioactive ions by polarizing porous carbon electrodes. Herein we demonstrate the first example of a bioactive ion-based switchable supercapacitor. Based on choline chloride and porous carbons we unravel the mechanism of physisorption vs. electrosorption by nuclear magnetic resonance, Raman, and impedance spectroscopy. Weak physisorption facilitates electrically-driven electrolyte depletion enabling the controllable uptake/release of electrolyte ions. A new 4-terminal device is proposed, with a main capacitor and a detective capacitor for monitoring bioactive ion adsorption in situ. Ion-concentration control in printed choline-based switchable SCs realizes switching down to 8.3 % residual capacitance. The exploration of adsorption mechanisms in printable microdevices will open an avenue of manipulating bioactive ions for the application of drug delivery, neuromodulation, or neuromorphic devices.


Assuntos
Carbono , Eletrólitos , Capacitância Elétrica , Íons , Eletrodos , Carbono/química
7.
Natl Sci Rev ; 9(8): nwac031, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36128048

RESUMO

The revolution of automotive vehicles (from petrol vehicles to electric vehicles) has set high demands for the performance of batteries. Lithium-metal batteries (LMBs) show great potential owing to their high energy density but encounter poor cycle life and safety issues. It is of great significance to reveal LMB failure mechanisms and understand their relationship with battery performance. This review presents an overview of the state-of-the-art Li-metal anodes, with an emphasis on two typical failure modes: capacity degradation and dendritic growth of Li metal. The critical correlations between the composition, structure and failure are explained point by point. The chemical and electrochemical stabilities of the lithium anode are discussed. Particularly, for the first time, five types of lithium-metal anodes are classified to develop a comprehensive understanding of LMBs. Furthermore, strategies are suggested to improve the practical performance of LMBs, including material innovation, electrolyte modification and advanced characterization.

8.
Front Genet ; 13: 889378, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559036

RESUMO

Background: Heart failure (HF) is the main cause of mortality in hemodialysis (HD) patients. However, it is still a challenge for the prediction of HF in HD patients. Therefore, we aimed to establish and validate a prediction model to predict HF events in HD patients. Methods: A total of 355 maintenance HD patients from two hospitals were included in this retrospective study. A total of 21 variables, including traditional demographic characteristics, medical history, and blood biochemical indicators, were used. Two classification models were established based on the extreme gradient boosting (XGBoost) algorithm and traditional linear logistic regression. The performance of the two models was evaluated based on calibration curves and area under the receiver operating characteristic curves (AUCs). Feature importance and SHapley Additive exPlanation (SHAP) were used to recognize risk factors from the variables. The Kaplan-Meier curve of each risk factor was constructed and compared with the log-rank test. Results: Compared with the traditional linear logistic regression, the XGBoost model had better performance in accuracy (78.5 vs. 74.8%), sensitivity (79.6 vs. 75.6%), specificity (78.1 vs. 74.4%), and AUC (0.814 vs. 0.722). The feature importance and SHAP value of XGBoost indicated that age, hypertension, platelet count (PLT), C-reactive protein (CRP), and white blood cell count (WBC) were risk factors of HF. These results were further confirmed by Kaplan-Meier curves. Conclusions: The HF prediction model based on XGBoost had a satisfactory performance in predicting HF events, which could prove to be a useful tool for the early prediction of HF in HD.

9.
Sci Rep ; 12(1): 8398, 2022 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-35589811

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent synovitis, in which T helper 1 (Th1) can promote the development of a pro-inflammatory microenvironment. Poly(rC)-binding protein 1 (PCBP1) has been identified as a promising biomarker of RA, while its molecular mechanisms in RA development are unknown. As a canonical RNA binding protein, we propose that PCBP1 could play roles in RA by affecting both expression and alternative splicing levels in Th1 cells. Here, microarray datasets (GSE15573 and GSE23561), including 102 peripheral blood mononuclear cell samples from 39 RA patients and 63 controls, were used to evaluate the PCBP1 expression changes in RA patients. High throughput sequencing data (GSE84702) of iron driven pathogenesis in Th1 cells were downloaded and reanalyzed, including two Pcbp1 deficiency samples and two control samples in Th1 cells. In addition, CLIP-seq data of PCBP1 in Jurkat T cells was also analyzed to investigate the regulatory mechanisms of PCBP1. We found PCBP1 were down-regulated in RA specimens compared with control. The result of differentially expressed genes (DEGs) showed that Pcbp1 silencing in Th1 cells affected the expression of genes involved in immune response pathway. Alternative splicing analysis also revealed that PCBP1-regulated alternative splicing genes (RASGs) were enriched in TNF-a/NF-κB signaling pathway, T cell activation, T cell differentiation and T cell differentiation associated immune response pathways, which were highly associated with RA. DEGs and RASGs by Pcbp1 deficiency in mice were validated in PBMCs specimens of RA patients by RT-qPCR. Investigation of the CLIP-seq data revealed PCBP1 preferred to bind to 3'UTR and intron regions. PCBP1-bound genes were also significantly associated with RASGs, identifying 102 overlapped genes of these two gene sets. These genes were significantly enriched in several immune response related pathways, including myeloid cell differentiation and positive regulation of NF-κB transcription factor activity. Two RA-related genes, PML and IRAK1, were screened from the above immune related pathways. These results together support our hypothesis that PCBP1 can regulate the expression of genes involved in immune response pathway, and can bind to and regulate the alternative splicing of immune response related genes in immune T cells, and ultimately participate in the molecular mechanism of RA, providing new research ideas and directions for clinical diagnosis and treatment.


Assuntos
Artrite Reumatoide , RNA , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Imunidade , Leucócitos Mononucleares/metabolismo , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas de Ligação a RNA/genética , Células Th1/metabolismo
10.
Biochem Biophys Res Commun ; 611: 31-37, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35477090

RESUMO

Previous studies demonstrated that arginine biosynthesis was frequently impaired in acute liver injury. However, the underlying mechanisms remain elusive. In this study, we found that Argininosuccinate synthetase 1 (ASS1), a rate-limiting enzyme in arginine metabolism, was downregulated in the TAA-induced liver injury model. Single-cell RNA-seq data found that ASS1 was highly enriched in the hepatocytes. The reduction of ASS1 was attributed to the decreased expression of Farnesoid X receptor (FXR), which is a bile acid-activated nuclear hormone receptor with high expression in the liver. Subsequent studies demonstrated that activation of FXR by its agonist obeticholic acid (OCA) directly promoted ASS1 transcription and enhanced arginine synthesis, leading to the alleviation of TAA-mediated liver injury. Further experiments found that OCA, ASS1, and arginine supplement can rescue TAA-mediated hepatocytes apoptosis by decreasing the protein levels of Cyto C, PARP, and Caspase 3. Taken together, our study illustrated a protective role of the FXR/ASS1 axis in TAA-induced liver injury by targeting arginine metabolism, which might shed light on the development of novel therapeutic approaches for acute liver injury.


Assuntos
Arginina , Argininossuccinato Sintase , Doença Hepática Crônica Induzida por Substâncias e Drogas , Receptores Citoplasmáticos e Nucleares , Animais , Arginina/metabolismo , Argininossuccinato Sintase/genética , Argininossuccinato Sintase/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Fígado/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo
11.
Hum Brain Mapp ; 43(7): 2121-2133, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35165964

RESUMO

This study sought to identify a reference tissue-based quantification approach for improving the statistical power in detecting changes in brain glucose metabolism, amyloid, and tau deposition in Alzheimer's disease studies. A total of 794, 906, and 903 scans were included for 18 F-FDG, 18 F-florbetapir, and 18 F-flortaucipir, respectively. Positron emission tomography (PET) and T1-weighted images of participants were collected from the Alzheimer's disease Neuroimaging Initiative database, followed by partial volume correction. The standardized uptake value ratios (SUVRs) calculated from the cerebellum gray matter, centrum semiovale, and pons were evaluated at both region of interest (ROI) and voxelwise levels. The statistical power of reference tissues in detecting longitudinal SUVR changes was assessed via paired t-test. In cross-sectional analysis, the impact of reference tissue-based SUVR differences between cognitively normal and cognitively impaired groups was evaluated by effect sizes Cohen's d and two sample t-test adjusted by age, sex, and education levels. The average ROI t values of pons were 86.62 and 38.40% higher than that of centrum semiovale and cerebellum gray matter in detecting glucose metabolism decreases, while the centrum semiovale reference tissue-based SUVR provided higher t values for the detection of amyloid and tau deposition increases. The three reference tissues generated comparable d images for 18 F-FDG, 18 F-florbetapir, and 18 F-flortaucipir and comparable t maps for 18 F-florbetapir and 18 F-flortaucipir, but pons-based t map showed superior performance in 18 F-FDG. In conclusion, the tracer-specific reference tissue improved the detection of 18 F-FDG, 18 F-florbetapir, and 18 F-flortaucipir PET SUVR changes, which helps the early diagnosis, monitoring of disease progression, and therapeutic response in Alzheimer's disease.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Compostos de Anilina , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Carbolinas , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Estudos Transversais , Etilenoglicóis , Fluordesoxiglucose F18/metabolismo , Glucose/metabolismo , Humanos , Tomografia por Emissão de Pósitrons/métodos
12.
Front Neurol ; 12: 735033, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34938255

RESUMO

Background and Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy caused by mutations in the NOTCH3 gene is a hereditary cerebral small vessel disease, manifesting with stroke, cognitive impairment, and mood disturbances. Functional or structural changes in the default mode network (DMN), which plays important role in cognitive and mental maintenance, have been found in several neurological and mental diseases. However, it remains unclear whether DMN is altered in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods: Multimodal imaging methods, including MRI and positron emission tomography (PET), were applied to evaluate the functional, structural, and metabolic characteristics of DMN in 25 patients with CADASIL and 42 healthy controls. Results: Compared with controls, patients with CADASIL had decreased nodal efficiency and degree centrality of the dorsal medial pre-frontal cortex and hippocampal formation within DMN. Structural MRI and diffusion tensor imaging (DTI) showed decreased gray matter volume and fiber tracks presented in the bilateral hippocampal formation. Meanwhile, PET imaging showed decreased metabolism within the whole DMN in CADASIL. Furthermore, correlation analyses showed that these nodal characteristics, gray matter volume, and metabolic signals of DMN were related to cognitive scores in CADASIL. Conclusions: Our results suggested that altered network characteristics of DMN might play important roles in cognitive deficits of CADASIL.

13.
Mol Ther Nucleic Acids ; 26: 1351-1363, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34853732

RESUMO

Aberrant expression of long non-coding RNAs (lncRNAs) has been reported in multiple cancers. However, the underlying mechanisms mediated by super-enhancers remain elusive. Here we sought to define the role of a novel lncRNA termed lncRNA-DAW in tumorigenesis. Our results revealed that lncRNA-DAW was driven by a liver-specific super-enhancer and transcriptionally activated by HNF4G, leading to frequent elevation in hepatocellular carcinoma (HCC) specimens. Ectopic expression of lncRNA-DAW promoted both in vivo and in vitro tumor growth. By using RNA sequencing, Wnt2 was screened out as a downstream effector of lncRNA-DAW. We next found that lncRNA-DAW physically interacted with EZH2, a negative regulator of Wnt2. This interplay subsequently potentiated CDK1-EZH2 interaction, leading to the phosphorylation and ubiquitination of EZH2. The lncRNA-DAW-mediated EZH2 degradation facilitated the de-repression of Wnt2 transcription, which eventually activated the Wnt/ß-catenin pathway. Furthermore, we verified that Wnt2 potentiated in vitro and in vivo cancer cell growth by activating the Wnt/ß-catenin pathway. Finally, Wnt2 amplification was confirmed as a common event in liver cancer, and the expression of lncRNA-DAW was positively correlated with Wnt2 in HCC specimens. Collectively, we are the first to identify lncRNA-DAW as a novel candidate oncogene in liver cancer, and this lncRNA may serve as a novel clinical diagnosis biomarker for liver cancer.

14.
Front Cell Dev Biol ; 9: 762669, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722547

RESUMO

Proper development of mammalian skeletal muscle relies on precise gene expression regulation. Our previous studies revealed that muscle development is regulated by both mRNA and long non-coding RNAs (lncRNAs). Accumulating evidence has demonstrated that N6-methyladenosine (m6A) plays important roles in various biological processes, making it essential to profile m6A modification on a transcriptome-wide scale in developing muscle. Patterns of m6A methylation in lncRNAs in developing muscle have not been uncovered. Here, we reveal differentially expressed lncRNAs and report temporal m6A methylation patterns in lncRNAs expressed in mouse myoblasts and myotubes by RNA-seq and methylated RNA immunoprecipitation (MeRIP) sequencing. Many lncRNAs exhibit temporal differential expression, and m6A-lncRNAs harbor the consensus m6A motif "DRACH" along lncRNA transcripts. Interestingly, we found that m6A methylation levels of lncRNAs are positively correlated with the transcript abundance of lncRNAs. Overexpression or knockdown of m6A methyltransferase METTL3 alters the expression levels of these lncRNAs. Furthermore, we highlight that the function of m6A genic lncRNAs might correlate to their nearby mRNAs. Our work reveals a fundamental expression reference of m6A-mediated epitranscriptomic modifications in lncRNAs that are temporally expressed in developing muscle.

15.
Liver Res ; 5(4): 209-216, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34603826

RESUMO

BACKGROUND AND AIM: Coronavirus disease 2019 (COVID-19) is a life-threatening disease that predominantly causes respiratory failure. The impact of COVID-19 on other organs remains elusive. Herein, we aimed to investigate the effects of COVID-19 on the hepatobiliary system. METHODS: In the current study, we obtained the clinical records and laboratory results from 66 laboratory-confirmed patients with COVID-19 at the Wuhan Tongji Hospital between 10 February 2020 and 28 February 2020. The detailed clinical features and laboratory findings were collected for analysis. Bioinformatics analysis was conducted to evaluate the correlation between gamma-glutamyl transferase (GGT) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry receptor angiotensin-converting enzyme 2 (ACE2). RESULTS: In this cohort, 30 (51.7%) patients had abnormal liver function on admission, which was associated with disease severity and enriched in the male and diabetic patients. The elevated levels of direct bilirubin (P = 0.029) and GGT (P = 0.004) were common in patients with severe pneumonia when compared with those with mild pneumonia. In addition, elevated levels of GGT (P = 0.003) and aspartate aminotransferase (AST) (P = 0.007) were positively associated with longer hospital stay. The expression of ACE2 was closely associated with GGT in various human tissues because they shared the common transcriptional regulator hepatic nuclear factor-1ß (HNF1B). CONCLUSIONS: Increased GGT levels were common in severe cases and elevated GGT levels were positively associated with prolonged hospital stay and disease severity. Due to the consistent expression with ACE2, GGT is a potent biomarker indicating the susceptibility of SARS-CoV-2 infection.

16.
Chem Commun (Camb) ; 56(67): 9640-9643, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32692320

RESUMO

A well-formulated electrolyte is proposed based on a fluorinated carboxylate ester solvent, which shows a wide electrochemical window (0-4.73 V, vs. Li+/Li), low solvation energy (10.05 kJ mol-1) and ability to maintain a liquid state at temperatures as low as -120 °C. This electrolyte produced batteries with superior electrochemical performance at low temperatures relative to carbonate-based electrolytes.

17.
Adv Sci (Weinh) ; 7(14): 2000196, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32714749

RESUMO

Conventional intercalation compounds for lithium-ion batteries (LIBs) suffer from rapid capacity fading and are even unable to charge-discharge with temperature decline, owing to the sluggish kinetics and solvation/desolvation process. In this work, a high-performance rechargeable battery at ultralow temperature is developed by employing a nanosized Ni-based Prussian blue (NiHCF) cathode. The battery delivers a high capacity retention of 89% (low temperature of -50 °C) and 82% (ultralow temperature of -70 °C) compared with that at +25 °C. Various characterizations and electrochemical investigations, including operando Fourier transform infrared spectra, in situ X-ray diffraction, cyclic voltammetry response, and galvanostatic intermittent titration technique are carried out to detect the structural stability and electrochemical behavior at different temperatures. It turns out that the pseudocapacitive behavior drives the desolvation process at the interface, while fast diffusion in the bulk electrode accelerates the movement of Li+ from the interface to the bulk materials. The unique synergistic features of intercalation pseudocapacitance at the electrolyte/electrode interface and high diffusion coefficient in the bulk electrode enables the NiHCF cathode with excellent low temperature performance. These findings offer a new direction for the design of LIBs operated at low temperature.

18.
iScience ; 23(5): 101071, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32361271

RESUMO

Garnet-based bulk-type all-ceramic lithium battery (ACLB) is considered to be highly safe, but its electrochemical performance is severely hindered by the huge cathode/electrolyte interfacial resistance. Here, we demonstrate an in situ coated Li2.985B0.005OCl as sintering solder, which is uniformly coated on both LiCoO2 and Li7La3Zr2O12. With the low melting point (267°C) and high ionic conductivity (6.8 × 10-5 S cm-1), the Li2.985B0.005OCl solder not only restricts La/Co interdiffusion, but also provides fast Li+ transportation in the cathode. A low cathode/electrolyte interfacial resistance (386 Ω cm2) is realized owing to the densification of the ACLB by hot-press sintering. The strain/stress of the LiCoO2 is also released by the small elasticity modulus of Li2.985B0.005OCl, leading to a superior cycling stability. The study sheds light on the design of advanced garnet-based bulk-type ACLB by exploring proper solders with higher ionic conductivity, lower melting point, and smaller elasticity modulus.

19.
J Affect Disord ; 266: 243-251, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32056884

RESUMO

BACKGROUND: Subthreshold depression (StD) is a prevalent condition that may increase the risk of incident major depressive disorder (MDD). However, the relationship between StD and MDD remains unclear. METHODS: A total of 153 adult subjects, including 53 drug-naive MDD, 50 StD and 50 healthy control (HC) subjects, underwent a T1-weighted magnetic resonance imaging scan, and the gray matter volume (GMV) alterations among the three groups were quantitatively analyzed using voxel-based morphometry (VBM). Then, to capture the whole-brain connectivity characteristics, we constructed morphological brain networks (MBN) based on the similarity among brain regions of individual VBM images and compared the network connection strengths among the three groups. RESULTS: The StD and MDD subjects had similar patterns of GMV reductions in the orbitofrontal cortex and left temporal gyrus, although the magnitude of the reductions was smaller in StD subjects. Moreover, a total of 21 morphological connections were significantly different among the three groups. For the majority of the different connections (15/21), the connection strength of the StD group took an intermediate position between that of the MDD and HC groups. LIMITATIONS: There is still a lack of a consistent definition of StD, and the age range of the subjects in this study was wide. Meanwhile the mechanisms and biological significance of the MBN remains to be clarified. CONCLUSIONS: These results may support the hypothesis that depression is better expressed as a spectrum and that StD exists on a spectrum with MDD.


Assuntos
Transtorno Depressivo Maior , Adulto , Encéfalo/diagnóstico por imagem , Estudos de Casos e Controles , Depressão , Transtorno Depressivo Maior/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética
20.
Angew Chem Int Ed Engl ; 59(13): 5346-5349, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-31965702

RESUMO

Applying interlayers is the main strategy to address the large area specific resistance (ASR) of Li/garnet interface. However, studies on eliminating the Li2 CO3 and LiOH interfacial lithiophobic contaminants are still insufficient. Here, thermal-decomposition vapor deposition (TVD) of a carbon modification layer on Li6.75 La3 Zr1.75 Ta0.25 O12 (LLZTO) provides a contaminant-free surface. Owing to the protection of the carbon layer, the air stability of LLZTO is also improved. Moreover, owing to the amorphous structure of the low graphitized carbon (LGC), instant lithiation is achieved, and the ASR of the Li/LLZTO interface is reduced to 9â€…Ω cm2 . Lithium volatilization and Zr4+ reduction are also controllable during TVD. Compared with its high graphitized carbon counterpart (HGC), the LGC-modified Li/LLZTO interface displays a higher critical current density of 1.2 mA cm-2 , as well as moderate Li plating and stripping, which provides enhanced polarization voltage stability.

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