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1.
Nature ; 578(7794): 251-255, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32015545

RESUMEN

Solid-state lithium metal batteries require accommodation of electrochemically generated mechanical stress inside the lithium: this stress can be1,2 up to 1 gigapascal for an overpotential of 135 millivolts. Maintaining the mechanical and electrochemical stability of the solid structure despite physical contact with moving corrosive lithium metal is a demanding requirement. Using in situ transmission electron microscopy, we investigated the deposition and stripping of metallic lithium or sodium held within a large number of parallel hollow tubules made of a mixed ionic-electronic conductor (MIEC). Here we show that these alkali metals-as single crystals-can grow out of and retract inside the tubules via mainly diffusional Coble creep along the MIEC/metal phase boundary. Unlike solid electrolytes, many MIECs are electrochemically stable in contact with lithium (that is, there is a direct tie-line to metallic lithium on the equilibrium phase diagram), so this Coble creep mechanism can effectively relieve stress, maintain electronic and ionic contacts, eliminate solid-electrolyte interphase debris, and allow the reversible deposition/stripping of lithium across a distance of 10 micrometres for 100 cycles. A centimetre-wide full cell-consisting of approximately 1010 MIEC cylinders/solid electrolyte/LiFePO4-shows a high capacity of about 164 milliampere hours per gram of LiFePO4, and almost no degradation for over 50 cycles, starting with a 1× excess of Li. Modelling shows that the design is insensitive to MIEC material choice with channels about 100 nanometres wide and 10-100 micrometres deep. The behaviour of lithium metal within the MIEC channels suggests that the chemical and mechanical stability issues with the metal-electrolyte interface in solid-state lithium metal batteries can be overcome using this architecture.

2.
Proc Natl Acad Sci U S A ; 120(52): e2307477120, 2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38134195

RESUMEN

Potassium-ion batteries (PIBs) have attracted ever-increasing interest due to the abundant potassium resources and low cost, which are considered a sustainable energy storage technology. However, the graphite anodes employed in PIBs suffer from low capacity and sluggish reaction kinetics caused by the large radius of potassium ions. Herein, we report nitrogen-doped, defect-rich hollow carbon nanospheres with contact curved interfaces (CCIs) on carbon nanotubes (CNTs), namely CCI-CNS/CNT, to boost both electron transfer and potassium-ion adsorption. Density functional theory calculations validate that engineering CCIs significantly augments the electronic state near the Fermi level, thus promoting electron transfer. In addition, the CCIs exhibit a pronounced affinity for potassium ions, promoting their adsorption and subsequently benefiting potassium storage. As a result, the rationally designed CCI-CNS/CNT anode shows remarkable cyclic stability and rate capability. This work provides a strategy for enhancing the potassium storage performance of carbonaceous materials through CCI engineering, which can be further extended to other battery systems.

3.
BMC Med ; 22(1): 104, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38454425

RESUMEN

BACKGROUND: The specific microbiota and associated metabolites linked to non-alcoholic fatty liver disease (NAFLD) are still controversial. Thus, we aimed to understand how the core gut microbiota and metabolites impact NAFLD. METHODS: The data for the discovery cohort were collected from the Guangzhou Nutrition and Health Study (GNHS) follow-up conducted between 2014 and 2018. We collected 272 metadata points from 1546 individuals. The metadata were input into four interpretable machine learning models to identify important gut microbiota associated with NAFLD. These models were subsequently applied to two validation cohorts [the internal validation cohort (n = 377), and the prospective validation cohort (n = 749)] to assess generalizability. We constructed an individual microbiome risk score (MRS) based on the identified gut microbiota and conducted animal faecal microbiome transplantation experiment using faecal samples from individuals with different levels of MRS to determine the relationship between MRS and NAFLD. Additionally, we conducted targeted metabolomic sequencing of faecal samples to analyse potential metabolites. RESULTS: Among the four machine learning models used, the lightGBM algorithm achieved the best performance. A total of 12 taxa-related features of the microbiota were selected by the lightGBM algorithm and further used to calculate the MRS. Increased MRS was positively associated with the presence of NAFLD, with odds ratio (OR) of 1.86 (1.72, 2.02) per 1-unit increase in MRS. An elevated abundance of the faecal microbiota (f__veillonellaceae) was associated with increased NAFLD risk, whereas f__rikenellaceae, f__barnesiellaceae, and s__adolescentis were associated with a decreased presence of NAFLD. Higher levels of specific gut microbiota-derived metabolites of bile acids (taurocholic acid) might be positively associated with both a higher MRS and NAFLD risk. FMT in mice further confirmed a causal association between a higher MRS and the development of NAFLD. CONCLUSIONS: We confirmed that an alteration in the composition of the core gut microbiota might be biologically relevant to NAFLD development. Our work demonstrated the role of the microbiota in the development of NAFLD.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Enfermedad del Hígado Graso no Alcohólico , Persona de Mediana Edad , Humanos , Animales , Ratones , Anciano , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Hígado/metabolismo , Vida Independiente
4.
Liver Int ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847512

RESUMEN

BACKGROUND AND AIMS: Few studies have focused on the outcomes of Wilson's disease (WD) diagnosed before age of 5 years. This study aimed to summarize the clinical features of early diagnosed WD and analyse treatment outcomes and the risk factors associated with treatment failure. METHODS: A total of 139 children confirmed with WD before 5 years were enrolled in this study. Only patients with follow-up over 1 year were analysed with Kaplan-Meier survival analysis. The composite outcomes included death, progression to liver failure or acute hepatitis, development of renal or neurological symptoms and persistent elevation of alanine aminotransferase (ALT). The treatment failure was defined as occurrence of at least one of above outcomes. RESULTS: Among 139 WD patients at diagnosis, two (1.4%) WD patients presented with symptomatic liver disease, whereas 137 (98.6%) were phenotypically asymptomatic, including 135 with elevated ALT and 2 with normal liver function. Median serum ceruloplasmin (Cp) was 3.1 mg/dL, and urinary copper excretion was 87.4 µg/24-h. There were 71 variants identified in the the copper-transporting ATPase beta gene, and 29 were loss of function (LOF). 51 patients with LOF variant were younger at diagnosis and had lower Cp than 88 patients without LOF. Among 93 patients with over 1 year of follow-up, 19 (20.4%) received zinc monotherapy, and 74 (79.6%) received a zinc/D-penicillamine combination therapy. 14 (15.1%) patients underwent treatment failure, and its occurrence was associated with poor compliance (p < .01). CONCLUSIONS: Cp is a reliable biomarker for early diagnosis, and zinc monotherapy is an effective treatment for WD during early childhood. Good treatment compliance is critical to achieve a favourable outcome.

5.
Eur Radiol ; 34(1): 182-192, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37566270

RESUMEN

OBJECTIVES: To propose a novel model-free data-driven approach based on the voxel-wise mapping of DCE-MRI time-intensity-curve (TIC) profiles for quantifying and visualizing hemodynamic heterogeneity and to validate its potential clinical applications. MATERIALS AND METHODS: From December 2018 to July 2022, 259 patients with 325 pathologically confirmed breast lesions who underwent breast DCE-MRI were retrospectively enrolled. Based on the manually segmented breast lesions, the TIC of each voxel within the 3D whole lesion was classified into 19 subtypes based on wash-in rate (nonenhanced, slow, medium, and fast), wash-out enhancement (persistent, plateau, and decline), and wash-out stability (steady and unsteady), and the composition ratio of these 19 subtypes for each lesion was calculated as a new feature set (type-19). The three-type TIC classification, semiquantitative parameters, and type-19 features were used to build machine learning models for identifying lesion malignancy and classifying histologic grades, proliferation status, and molecular subtypes. RESULTS: The type-19 feature-based model significantly outperformed models based on the three-type TIC method and semiquantitative parameters both in distinguishing lesion malignancy (respectively; AUC = 0.875 vs. 0.831, p = 0.01 and 0.875vs. 0.804, p = 0.03), predicting tumor proliferation status (AUC = 0.890 vs. 0.548, p = 0.006 and 0.890 vs. 0.596, p = 0.020), but not in predicting histologic grades (p = 0.820 and 0.970). CONCLUSION: In addition to conventional methods, the proposed computational approach provides a novel, model-free, data-driven approach to quantify and visualize hemodynamic heterogeneity. CLINICAL RELEVANCE STATEMENT: Voxel-wise intra-lesion mapping of TIC profiles allows for visualization of hemodynamic heterogeneity and its composition ratio for differentiation of malignant and benign breast lesions. KEY POINTS: • Voxel-wise TIC profiles were mapped, and their composition ratio was compared between various breast lesions. • The model based on the composition ratio of voxel-wise TIC profiles significantly outperformed the three-type TIC classification model and the semiquantitative parameters model in lesion malignancy differentiation and tumor proliferation status prediction in breast lesions. • This novel, data-driven approach allows the intuitive visualization and quantification of the hemodynamic heterogeneity of breast lesions.


Asunto(s)
Neoplasias de la Mama , Neoplasias , Humanos , Femenino , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Mama/diagnóstico por imagen , Mama/patología , Tiempo , Neoplasias/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Medios de Contraste
6.
Nutr J ; 23(1): 70, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982486

RESUMEN

BACKGROUND: Trimethylamine-N-oxide (TMAO) is linked with obesity, while limited evidence on its relationship with body fat distribution. Herein, we investigated the associations between serum TMAO and longitudinal change of fat distribution in this prospective cohort study. METHODS: Data of 1964 participants (40-75y old) from Guangzhou Nutrition and Health Study (GNHS) during 2008-2014 was analyzed. Serum TMAO concentration was quantified by HPLC-MS/MS at baseline. The body composition was assessed by dual-energy X-ray absorptiometry at each 3-y follow-up. Fat distribution parameters were fat-to-lean mass ratio (FLR) and trunk-to-leg fat ratio (TLR). Fat distribution changes were derived from the coefficient of linear regression between their parameters and follow-up duration. RESULTS: After an average of 6.2-y follow-up, analysis of covariance (ANCOVA) and linear regression displayed women with higher serum TMAO level had greater increments in trunk FLR (mean ± SD: 1.47 ± 4.39, P-trend = 0.006) and TLR (mean ± SD: 0.06 ± 0.24, P-trend = 0.011). Meanwhile, for women in the highest TMAO tertile, linear mixed-effects model (LMEM) analysis demonstrated the annual estimated increments (95% CI) were 0.03 (95% CI: 0.003 - 0.06, P = 0.032) in trunk FLR and 1.28 (95% CI: -0.17 - 2.73, P = 0.083) in TLR, respectively. In men, there were no similar significant observations. Sensitivity analysis yielded consistent results. CONCLUSION: Serum TMAO displayed a more profound correlation with increment of FLR and TLR in middle-aged and older community-dwelling women in current study. More and further studies are still warranted in the future. TRIAL REGISTRATION: NCT03179657.


Asunto(s)
Distribución de la Grasa Corporal , Metilaminas , Humanos , Metilaminas/sangre , Femenino , Persona de Mediana Edad , Masculino , Estudios Prospectivos , Anciano , Distribución de la Grasa Corporal/métodos , Adulto , Absorciometría de Fotón/métodos , Composición Corporal , Estudios de Cohortes , China
7.
J Math Biol ; 89(1): 6, 2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38762831

RESUMEN

Multiple infections enable the recombination of different strains, which may contribute to viral diversity. How multiple infections affect the competition dynamics between the two types of strains, the wild and the immune escape mutant, remains poorly understood. This study develops a novel mathematical model that includes the two strains, two modes of viral infection, and multiple infections. For the representative double-infection case, the reproductive numbers are derived and global stabilities of equilibria are obtained via the Lyapunov direct method and theory of limiting systems. Numerical simulations indicate similar viral dynamics regardless of multiplicities of infections though the competition between the two strains would be the fiercest in the case of quadruple infections. Through sensitivity analysis, we evaluate the effect of parameters on the set-point viral loads in the presence and absence of multiple infections. The model with multiple infections predict that there exists a threshold for cytotoxic T lymphocytes (CTLs) to minimize the overall viral load. Weak or strong CTLs immune response can result in high overall viral load. If the strength of CTLs maintains at an intermediate level, the fitness cost of the mutant is likely to have a significant impact on the evolutionary dynamics of mutant viruses. We further investigate how multiple infections alter the viral dynamics during the combination antiretroviral therapy (cART). The results show that viral loads may be underestimated during cART if multiple-infection is not taken into account.


Asunto(s)
Simulación por Computador , Infecciones por VIH , Evasión Inmune , Conceptos Matemáticos , Modelos Biológicos , Linfocitos T Citotóxicos , Carga Viral , Humanos , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Infecciones por VIH/tratamiento farmacológico , Linfocitos T Citotóxicos/inmunología , Evasión Inmune/inmunología , Coinfección/inmunología , Coinfección/virología , VIH-1/inmunología , VIH-1/genética , Número Básico de Reproducción/estadística & datos numéricos , Modelos Inmunológicos , Mutación
8.
Psychogeriatrics ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987229

RESUMEN

BACKGROUND: Numerous studies have investigated the potential effects of transcranial direct current stimulation (tDCS) on improving symptoms related to Alzheimer's disease (AD). However, these studies have produced inconsistent results, leading to a need for further investigation. METHODS: A comprehensive search was conducted, including articles published from the initial availability date to 5 April 2024. The extracted study data were analyzed using STATA 12.0 software. The standard mean difference (SMD) and a 95% confidence interval (CI) were calculated to assess the effects of tDCS. RESULTS: A total of 18 studies assessing the effects of tDCS on AD were included in the study. The study revealed that tDCS has an immediate positive impact on general cognitive, executive, language, and visuospatial function. However, the study did not observe any other significant effect of tDCS treatment on improvements in brain function, including long-term effects on general cognitive, attention, language, and memory function, as well as immediate effects on attention and memory function. CONCLUSIONS: In conclusion, the study suggests that tDCS may be a promising intervention for improving the cognitive function of patients with AD. However, given the complex and multifactorial nature of AD, further well-designed studies with larger sample sizes are necessary to clarify the effectiveness of tDCS and determine the optimal combination of tDCS parameters.

9.
Hum Brain Mapp ; 44(13): 4710-4721, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37376719

RESUMEN

The right ventrolateral prefrontal cortex (rVLPFC) is highly engaged in emotion regulation of social pain. However, there is still lack of both inhibition and excitement evidence to prove the causal relationship between this brain region and voluntary emotion regulation. This study used high-frequency (10 Hz) and low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) to separately activate or inhibit the rVLPFC in two groups of participants. We recorded participants' emotion ratings as well as their social attitude and prosocial behaviors following emotion regulation. Also, we used eye tracker to record the changes of pupil diameter to measure emotional feelings objectively. A total of 108 healthy participants were randomly assigned to the activated, inhibitory or sham rTMS groups. They were required to accomplish three sequential tasks: the emotion regulation (cognitive reappraisal) task, the favorability rating task, and the donation task. Results show that the rVLPFC-inhibitory group reported more negative emotions and showed larger pupil diameter while the rVLPFC-activated group showed less negative emotions and reduced pupil diameter during emotion regulation (both compared with the sham rTMS group). In addition, the activated group gave more positive social evaluation to peers and donated more money to a public welfare activity than the rVLPFC-inhibitory group, among which the change of social attitude was mediated by regulated emotion. Taken together, these findings reveal that the rVLPFC plays a causal role in voluntary emotion regulation of social pain and can be a potential brain target in treating deficits of emotion regulation in psychiatric disorders.


Asunto(s)
Regulación Emocional , Humanos , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Emociones/fisiología , Estimulación Magnética Transcraneal , Corteza Cerebral
10.
BMC Med ; 21(1): 414, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37907866

RESUMEN

BACKGROUND: The early life stage is critical for the gut microbiota establishment and development. We aimed to investigate the lifelong impact of famine exposure during early life on the adult gut microbial ecosystem and examine the association of famine-induced disturbance in gut microbiota with type 2 diabetes. METHODS: We profiled the gut microbial composition among 11,513 adults (18-97 years) from three independent cohorts and examined the association of famine exposure during early life with alterations of adult gut microbial diversity and composition. We performed co-abundance network analyses to identify keystone taxa in the three cohorts and constructed an index with the shared keystone taxa across the three cohorts. Among each cohort, we used linear regression to examine the association of famine exposure during early life with the keystone taxa index and assessed the correlation between the keystone taxa index and type 2 diabetes using logistic regression adjusted for potential confounders. We combined the effect estimates from the three cohorts using random-effects meta-analysis. RESULTS: Compared with the no-exposed control group (born during 1962-1964), participants who were exposed to the famine during the first 1000 days of life (born in 1959) had consistently lower gut microbial alpha diversity and alterations in the gut microbial community during adulthood across the three cohorts. Compared with the no-exposed control group, participants who were exposed to famine during the first 1000 days of life were associated with consistently lower levels of keystone taxa index in the three cohorts (pooled beta - 0.29, 95% CI - 0.43, - 0.15). Per 1-standard deviation increment in the keystone taxa index was associated with a 13% lower risk of type 2 diabetes (pooled odds ratio 0.87, 95% CI 0.80, 0.93), with consistent results across three individual cohorts. CONCLUSIONS: These findings reveal a potential role of the gut microbiota in the developmental origins of health and disease (DOHaD) hypothesis, deepening our understanding about the etiology of type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Efectos Tardíos de la Exposición Prenatal , Inanición , Adulto , Humanos , Persona de Mediana Edad , China , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Pueblos del Este de Asia , Hambruna , Microbiota , Inanición/complicaciones , Adolescente , Adulto Joven , Anciano , Anciano de 80 o más Años
11.
J Intern Med ; 293(3): 340-353, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36433820

RESUMEN

BACKGROUND: Emerging evidence suggests that animal protein foods may increase the risk of nonalcoholic fatty liver disease (NAFLD). We therefore examined the NAFLD risk reduction related to substituting plant protein foods for animal protein foods. METHODS: The cohort in North China included 14,541 participants from the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) study, and the cohort in South China included 1297 participants from the Guangzhou Nutrition and Health Study (GNHS). Dietary intake was assessed using validated food frequency questionnaires. NAFLD was ascertained by abdominal ultrasound. The Cox model was used to fit the substitution analysis. RESULTS: In the TCLSIH cohort, when replacing one type of animal protein food (eggs, processed meat, unprocessed red meat, poultry, and fish) with an equivalent serving of plant protein foods (nuts, legumes, and whole grains), the replacement of animal protein foods with whole grains showed the strongest benefit; substituting one serving per day of whole grains for an equal amount of eggs (hazard ratio [HR] = 0.89; 95% confidence interval [CI]: 0.79, 1.00), processed meat (HR = 0.76; 95% CI: 0.64, 0.91), unprocessed red meat (HR = 0.90; 95% CI: 0.81, 1.00), poultry (HR = 0.81; 95% CI: 0.72, 0.92), or fish (HR = 0.87; 95% CI: 0.78, 0.97) was associated with a lower risk of NAFLD. In both the TCLSIH and GNHS cohorts, replacing poultry with fish, nuts, legumes, or whole grains was associated with a lower risk of NAFLD. When different numbers of protein foods were simultaneously replaced, the risk reduction of NAFLD was stronger. CONCLUSIONS: Our findings suggest that replacing animal protein foods with plant protein foods is related to a significant reduction in NAFLD risk.


Asunto(s)
Dieta , Enfermedad del Hígado Graso no Alcohólico , Animales , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/etiología , Estudios Prospectivos , Carne , Aves de Corral , Proteínas de Plantas , Factores de Riesgo
12.
J Transl Med ; 21(1): 101, 2023 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-36759852

RESUMEN

Orthodontic tooth movement (OTM) is biologically based on the spatiotemporal remodeling process in periodontium, the mechanisms of which remain obscure. Noncoding RNAs (ncRNAs), especially microRNAs and long noncoding RNAs, play a pivotal role in maintaining periodontal homeostasis at the transcriptional, post-transcriptional, and epigenetic levels. Under force stimuli, mechanosensitive ncRNAs with altered expression levels transduce mechanical load to modulate intracellular genes. These ncRNAs regulate the biomechanical responses of periodontium in the catabolic, anabolic, and coupling phases throughout OTM. To achieve this, down or upregulated ncRNAs actively participate in cell proliferation, differentiation, autophagy, inflammatory, immune, and neurovascular responses. This review highlights the regulatory mechanism of fine-tuning ncRNAs in periodontium remodeling during OTM, laying the foundation for safe, precise, and personalized orthodontic treatment.


Asunto(s)
MicroARNs , Técnicas de Movimiento Dental , Remodelación Ósea/fisiología , Ligamento Periodontal , Periodoncio , MicroARNs/genética
13.
Environ Sci Technol ; 57(1): 428-439, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36546883

RESUMEN

To gather enough energy to respond to harmful stimuli, most immune cells quickly shift their metabolic profile. This process of immunometabolism plays a critical role in the regulation of immune cell function. Triclosan, a synthetic antibacterial component present in a wide range of consumer items, has been shown to cause immunotoxicity in a number of organisms. However, it is unclear whether and how triclosan impacts immunometabolism. Here, human macrophages were used as model cells to explore the modulatory effect of triclosan on immunometabolism. Untargeted metabolomics using integrated liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) revealed that triclosan changed the global metabolic profile of macrophages. Furthermore, Seahorse energy analysis and 13C isotope-based metabolic flux analysis revealed that triclosan decreased mitochondrial respiratory activity and promoted a metabolic transition from oxidative phosphorylation to glycolysis. Triclosan also polarizes macrophages to the proinflammatory M1 phenotype and activates the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing receptor 3 (NLRP3) inflammasome, which is consistent with triclosan-induced metabolic phenotypic modifications. Collectively, these findings showed that triclosan exposure at micromolar concentrations caused metabolic reprogramming in macrophages, which triggered an inflammatory response. These findings are important for understanding the immunotoxicity caused by triclosan, which is necessary for determining the risk posed by triclosan in the environment.


Asunto(s)
Inflamasomas , Triclosán , Humanos , Inflamasomas/metabolismo , Inflamasomas/farmacología , Triclosán/toxicidad , Macrófagos/metabolismo , Antibacterianos/farmacología , Metabolómica
14.
J Epidemiol ; 2023 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-37813622

RESUMEN

BACKGROUND: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration. METHODS: The population-based sample of adults in Guangzhou, China (baseline: 40-83 years old; n = 5118) was followed up about every 3 years. All will be tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-d real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome. RESULTS: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5118 participants aged 40-83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3628 (71%) completed at least one on-site follow-up with a median duration of 9.48 years. CONCLUSION: The cohort will provide data that have been influential in establishing the role of nutrition in metabolic diseases with multi-omics.

15.
J Math Biol ; 86(5): 80, 2023 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-37093296

RESUMEN

In this paper, we first formulate a system of ODEs-PDE to model diseases with latency-age and differential infectivity. Then, based on the ways how latent individuals leave the latent stage, one ODE and two DDE models are derived. We only focus on the global stability of the models. All the models have some similarities in the existence of equilibria. Each model has a threshold dynamics for global stability, which is completely characterized by the basic reproduction number. The approach is the Lyapunov direct method. We propose an idea on constructing Lyapunov functionals for the two DDE and the original ODEs-PDE models. During verifying the negative (semi-)definiteness of derivatives of the Lyapunov functionals along solutions, a novel positive definite function and a new inequality are used. The idea here is also helpful in applying the Lyapunov direct method to prove the global stability of some epidemic models with age structure or delays.


Asunto(s)
Epidemias , Modelos Biológicos , Humanos , Número Básico de Reproducción
16.
Proc Natl Acad Sci U S A ; 117(1): 573-583, 2020 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-31852820

RESUMEN

Fuchs endothelial corneal dystrophy (FECD) is a leading cause of corneal endothelial (CE) degeneration resulting in impaired visual acuity. It is a genetically complex and age-related disorder, with higher incidence in females. In this study, we established a nongenetic FECD animal model based on the physiologic outcome of CE susceptibility to oxidative stress by demonstrating that corneal exposure to ultraviolet A (UVA) recapitulates the morphological and molecular changes of FECD. Targeted irradiation of mouse corneas with UVA induced reactive oxygen species (ROS) production in the aqueous humor, and caused greater CE cell loss, including loss of ZO-1 junctional contacts and corneal edema, in female than male mice, characteristic of late-onset FECD. UVA irradiation caused greater mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage in female mice, indicative of the sex-driven differential response of the CE to UVA, thus accounting for more severe phenotype in females. The sex-dependent effect of UVA was driven by the activation of estrogen-metabolizing enzyme CYP1B1 and formation of reactive estrogen metabolites and estrogen-DNA adducts in female but not male mice. Supplementation of N-acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS), diminished the morphological and molecular changes induced by UVA in vivo. This study investigates the molecular mechanisms of environmental factors in FECD pathogenesis and demonstrates a strong link between UVA-induced estrogen metabolism and increased susceptibility of females for FECD development.


Asunto(s)
Citocromo P-450 CYP1B1/metabolismo , Aductos de ADN/efectos de la radiación , Daño del ADN/efectos de la radiación , Estrógenos/metabolismo , Distrofia Endotelial de Fuchs/etiología , Rayos Ultravioleta/efectos adversos , Acetilcisteína/administración & dosificación , Animales , Humor Acuoso/efectos de los fármacos , Humor Acuoso/metabolismo , Humor Acuoso/efectos de la radiación , Aductos de ADN/metabolismo , Daño del ADN/efectos de los fármacos , ADN Mitocondrial/metabolismo , ADN Mitocondrial/efectos de la radiación , Modelos Animales de Enfermedad , Endotelio Corneal/efectos de los fármacos , Endotelio Corneal/patología , Endotelio Corneal/efectos de la radiación , Femenino , Depuradores de Radicales Libres/administración & dosificación , Distrofia Endotelial de Fuchs/diagnóstico , Distrofia Endotelial de Fuchs/tratamiento farmacológico , Distrofia Endotelial de Fuchs/patología , Humanos , Masculino , Ratones , Estrés Oxidativo/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Índice de Severidad de la Enfermedad
17.
Chaos ; 33(7)2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37463094

RESUMEN

In this paper, a reaction-diffusion-chemotaxis HIV-1 model with a cytotoxic T lymphocyte (CTL) immune response and general sensitivity is investigated. We first prove the global classical solvability and L∞-boundedness for the considered model in a bounded domain with arbitrary spatial dimensions, which extends the previous existing results. Then, we apply the global existence result to the case with a linear proliferation immune response and an incidence rate. We study the spatiotemporal dynamics about the three types of spatially homogeneous steady states: infection-free steady state S0, CTL-inactivated infection steady state S1, and CTL-activated infection steady state S∗. Our analyses indicate that S0 is globally asymptotically stable if the basic reproduction number R0 is less than 1; if R0 is between 1 and a threshold, then S1 is globally asymptotically stable. However, if R0 is larger than the threshold, then the chemoattraction and chemorepulsion can destabilize S∗, and thus, a spatiotemporal pattern forms as the chemotactic sensitivity crosses certain critical values. We obtain two kinds of important patterns, which are induced by chemotaxis: stationary Turing pattern and irregular oscillatory pattern. We also find that different chemotactic response functions can affect system's dynamics. Based on some empirical parameter values, numerical simulations are given to illustrate the effectiveness of the theoretical predications.


Asunto(s)
VIH-1 , Linfocitos T Citotóxicos , Simulación por Computador , Quimiotaxis , Inmunidad , Modelos Biológicos
18.
Phytother Res ; 37(2): 672-678, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36205605

RESUMEN

The aim of the study was to testify the association of dietary resveratrol (RSV) intakes with hip fracture risk in Chinese elderly. This was a 1:1 age- and gender- matched case-control study. Eligible cases were newly diagnosed patients of hip fracture. Dietary assessment was made by a 79-item validated food frequency questionnaire. Habitual RSV intakes were estimated as the sum of trans- and cis- isomers of resveratrol and piceid according to the available database. Multivariable conditional logistic regression was applied to examine the relationship of dietary RSV and RSV-rich foods with hip fracture risk. A total of 1,070 pairs of hip fracture incident cases and controls were recruited and 1,065 were included for analysis. Compared with the lowest group, total RSV in the highest quartile group had significantly reduced hip fracture risk by 66.3% (OR: 0.337, 0.222 ~ 0.571, ptrend < 0.001). Similar findings were observed for cis- and trans-RSV, cis- and trans-Piceid, as well as RSV-rich foods (grapes, apples and nuts) respectively. Subgroup analysis suggested more evident findings among female and less obese participants. Our findings demonstrated that higher habitual RSV intakes and RSV-rich foods, even in a relatively low amount, were associated with reduced risk of hip fracture in Chinese elderly.


Asunto(s)
Pueblos del Este de Asia , Fracturas de Cadera , Humanos , Femenino , Anciano , Resveratrol , Estudios de Casos y Controles , Riesgo , Fracturas de Cadera/epidemiología , Fracturas de Cadera/prevención & control , Factores de Riesgo
19.
Sensors (Basel) ; 23(9)2023 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-37177600

RESUMEN

The present work developed an electrochemical genosensor for the detection of virulence outer membrane protein A (ompA, tDNA) gene of Cronobacter sakazakii (C. sakazakii) by exploiting the excellent glucose-oxidase-mimicking activity of copper Metal-organic frameworks (Cu-MOF) doped with gold nanoparticle (AuNPs). The signal nanotags of signal probes (sDNA) that biofunctionalized AuNPs@Cu-MOF (sDNA-AuNPs@Cu-MOF) were designed using an Au-S bond. The biosensor was prepared by immobilization capture probes (cDNA) onto an electrodeposited AuNPs-modified glassy carbon electrode (GCE). AuNPs@Cu-MOF was introduced onto the surface of the GCE via a hybridization reaction between cDNA and tDNA, as well as tDNA and sDNA. Due to the enhanced oxidase-mimicking activity of AuNPs@Cu-MOF to glucose, the biosensor gave a linear range of 1.0 × 10-15 to 1.0 × 10-9 mol L-1 to tDNA with a detection limit (LOD) of 0.42 fmol L-1 under optimized conditions using differential pulse voltammetry measurement (DPV). It can be applied in the direct detection of ompA gene segments in total DNA extracts from C. sakazakii with a broad linear range of 5.4-5.4 × 105 CFU mL-1 and a LOD of 0.35 CFU mL-1. The biosensor showed good selectivity, fabricating reproducibility and storage stability, and can be used for the detection of ompA gene segments in real samples with recovery between 87.5% and 107.3%.


Asunto(s)
Técnicas Biosensibles , Cronobacter sakazakii , Nanopartículas del Metal , Estructuras Metalorgánicas , Estructuras Metalorgánicas/química , Oro/química , Cobre/química , ADN Complementario , Glucosa Oxidasa , Reproducibilidad de los Resultados , Límite de Detección , Nanopartículas del Metal/química , Carbono/química , Glucosa , Técnicas Electroquímicas , Electrodos
20.
J Prosthet Dent ; 130(3): 381.e1-381.e7, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37482533

RESUMEN

STATEMENT OF PROBLEM: Altering the internal design of 3-dimensionally (3D) printed dental casts may help to reduce material and time consumption. However, it remains unclear whether such changes would compromise the accuracy of the casts. Further research is also needed to determine the optimal internal design that would maximize printing accuracy. PURPOSE: The purpose of this in vitro study was to evaluate the impact of internal design on the accuracy (trueness and precision) of 3D printed dental casts fabricated by stereolithography (SLA) and digital light processing (DLP) technology. MATERIAL AND METHODS: A reference digital cast was obtained by scanning a maxillary typodont with an intraoral scanner to create 4 types of internal designs, including hollow interior with perforated base (HWB), hollow interior without base (HB), all solid (S), and internal support structure with perforated base (SWB). Digital casts with different internal designs were printed by two 3D printers with different technologies (SLA and DLP). The printed casts were scanned by a desktop scanner to obtain standard tessellation language (STL) format research digital casts. All reference and research digital casts were imported into a software program for comparison and analysis of accuracy. Differences between the reference and research digital casts were quantitatively indicated by the root mean square (RMS) value. The Kruskal-Wallis 1-way ANOVA was used to test significant differences between the different internal design types and the Mann-Whitney U test was used to test significant differences between the two 3D printers (α=.05). RESULTS: The Kruskal-Wallis 1-way ANOVA revealed significant differences in the trueness and precision of different internal design types (all P<.001) for casts printed by both 3D printers. The trueness and precision were significantly worse for the HB design than for the other design types for casts printed by both 3D printers (all P<.05). Regardless of the design type, the trueness was significantly better for casts printed by the SLA-based printer than for casts printed by the DLP-based printer (all P<.05). The precision was significantly worse for casts printed by the SLA-based printer than for casts printed by the DLP-based printer (all P<.05). CONCLUSIONS: The internal design may affect the accuracy of 3D printing. The base is necessary to ensure the accuracy of 3D printed dental casts, whereas the internal support structure did not affect the accuracy of 3D printed dental casts. An all-solid design led to higher precision, but not higher trueness. Dental casts printed with SLA technology have higher trueness and lower precision than those printed with DLP technology.


Asunto(s)
Diseño Asistido por Computadora , Estereolitografía , Modelos Dentales , Impresión Tridimensional , Maxilar
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