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1.
Nature ; 578(7794): 251-255, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32015545

RESUMO

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.
Mol Cell Proteomics ; : 100840, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39278598

RESUMO

Analysis of large-scale data-independent acquisition mass spectrometry (DIA-MS) metaproteomics data remains a computational challenge. Here, we present a computational pipeline called metaExpertPro for metaproteomics data analysis. This pipeline encompasses spectral library generation using data-dependent acquisition MS (DDA-MS), protein identification and quantification using DIA-MS, functional and taxonomic annotation, as well as quantitative matrix generation for both microbiota and hosts. By integrating FragPipe and DIA-NN, metaExpertPro offers compatibility with both Orbitrap and timsTOF MS instruments. To evaluate the depth and accuracy of identification and quantification, we conducted extensive assessments using human fecal samples and benchmark tests. Performance tests conducted on human fecal samples indicated that metaExpertPro quantified an average of 45,000 peptides in a 60-minute diaPASEF injection. Notably, metaExpertPro outperformed three existing software tools by characterizing a higher number of peptides and proteins. Importantly, metaExpertPro maintained a low factual false discovery rate (FDR) of approximately 5% for protein groups across four benchmark tests. Applying a filter of five peptides per genus, metaExpertPro achieved relatively high accuracy (F-score = 0.67-0.90) in genus diversity and showed a high correlation (rSpearman = 0.73-0.82) between the measured and true genus relative abundance in benchmark tests. Additionally, the quantitative results at the protein, taxonomy, and function levels exhibited high reproducibility and consistency across the commonly adopted public human gut microbial protein databases IGC and UHGP. In a metaproteomic analysis of dyslipidemia (DLP) patients, metaExpertPro revealed characteristic alterations in microbial functions and potential interactions between the microbiota and the host.

3.
Proc Natl Acad Sci U S A ; 120(52): e2307477120, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38134195

RESUMO

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.

4.
Hepatology ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39094016

RESUMO

BACKGROUND AND AIMS: The EAT-Lancet Commission devised a globally sustainable dietary pattern to jointly promote human health and sustainability. However, the extent to which this diet supports metabolic dysfunction-associated steatotic liver disease (MASLD) has not yet been assessed. This study aimed to investigate the association between the EAT-Lancet diet and the risk of MASLD and its severity. APPROACH AND RESULTS: This prospective multicohort study included 15,263 adults from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort, 1137 adults from the Guangzhou Nutrition and Health Study (GNHS) cohort, and 175,078 adults from the UK Biobank. In addition, 228 Chinese adults from the Prospective Epidemic Research Specifically of Non-alcoholic Steatohepatitis (PERSONS) with biopsy-proven MASLD were included. An EAT-Lancet diet index was created to reflect adherence to the EAT-Lancet reference diet. The TCLSIH cohort recorded 3010 MASLD cases during 53,575 person-years of follow-up, the GNHS cohort documented 624 MASLD cases during 6454 person-years of follow-up, and the UK Biobank developed 1350 MASLD cases during 1,745,432 person-years of follow-up. In multivariable models, participants in the highest tertiles of the EAT-Lancet diet index had a lower risk of MASLD compared with those in the lowest tertiles (TCLSIH: HR = 0.87, 95% CI: 0.78, 0.96; GNHS: HR = 0.79, 95% CI: 0.64, 0.98; UK Biobank: HR = 0.73, 95% CI: 0.63, 0.85). Moreover, liver-controlled attenuation parameter decreased with increasing the diet index in individuals with biopsy-proven MASLD (ß = -5.895; 95% CI: -10.014, -1.775). CONCLUSIONS: Adherence to the EAT-Lancet reference diet was inversely associated with the risk of MASLD as well as its severity.

5.
BMC Med ; 22(1): 104, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454425

RESUMO

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.


Assuntos
Microbioma Gastrointestinal , Microbiota , Hepatopatia Gordurosa não Alcoólica , Pessoa de Meia-Idade , Humanos , Animais , Camundongos , Idoso , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fígado/metabolismo , Vida Independente
6.
Cardiovasc Diabetol ; 23(1): 322, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39217368

RESUMO

BACKGROUND: Continuous glucose monitoring (CGM) devices provide detailed information on daily glucose control and glycemic variability. Yet limited population-based studies have explored the association between CGM metrics and fatty liver. We aimed to investigate the associations of CGM metrics with the degree of hepatic steatosis. METHODS: This cross-sectional study included 1180 participants from the Guangzhou Nutrition and Health Study. CGM metrics, covering mean glucose level, glycemic variability, and in-range measures, were separately processed for all-day, nighttime, and daytime periods. Hepatic steatosis degree (healthy: n = 698; mild steatosis: n = 242; moderate/severe steatosis: n = 240) was determined by magnetic resonance imaging proton density fat fraction. Multivariate ordinal logistic regression models were conducted to estimate the associations between CGM metrics and steatosis degree. Machine learning models were employed to evaluate the predictive performance of CGM metrics for steatosis degree. RESULTS: Mean blood glucose, coefficient of variation (CV) of glucose, mean amplitude of glucose excursions (MAGE), and mean of daily differences (MODD) were positively associated with steatosis degree, with corresponding odds ratios (ORs) and 95% confidence intervals (CIs) of 1.35 (1.17, 1.56), 1.21 (1.06, 1.39), 1.37 (1.19, 1.57), and 1.35 (1.17, 1.56) during all-day period. Notably, lower daytime time in range (TIR) and higher nighttime TIR were associated with higher steatosis degree, with ORs (95% CIs) of 0.83 (0.73, 0.95) and 1.16 (1.00, 1.33), respectively. For moderate/severe steatosis (vs. healthy) prediction, the average area under the receiver operating characteristic curves were higher for the nighttime (0.69) and daytime (0.66) metrics than that of all-day metrics (0.63, P < 0.001 for all comparisons). The model combining both nighttime and daytime metrics achieved the highest predictive capacity (0.73), with nighttime MODD emerging as the most important predictor. CONCLUSIONS: Higher CGM-derived mean glucose and glycemic variability were linked with higher steatosis degree. CGM-derived metrics during nighttime and daytime provided distinct and complementary insights into hepatic steatosis.


Assuntos
Biomarcadores , Automonitorização da Glicemia , Glicemia , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Humanos , Estudos Transversais , Masculino , Pessoa de Meia-Idade , Feminino , Glicemia/metabolismo , China/epidemiologia , Idoso , Fatores de Tempo , Automonitorização da Glicemia/instrumentação , Biomarcadores/sangue , Fatores de Risco , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Fatores Etários , Medição de Risco , Aprendizado de Máquina , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/epidemiologia , Monitoramento Contínuo da Glicose , População do Leste Asiático
7.
J Nutr ; 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39128547

RESUMO

BACKGROUND: Prior research has highlighted inverse associations between concentrations of circulating very long-chain saturated fatty acids (VLCSFAs) and coronary artery disease (CAD). However, the intricate links involving VLCSFAs, gut microbiota, and bile acids remain underexplored. OBJECTIVES: This study examined the association of erythrocyte VLCSFAs with CHD incidence, focusing on the mediating role of gut microbiota and fecal bile acids. METHODS: This 10-y prospective study included 2383 participants without CHD at baseline. Erythrocyte VLCSFAs [arachidic acid (C20:0), behenic acid (C22:0), and lignoceric acid (C24:0)] were measured using gas chromatography at baseline, and 274 CHD incidents were documented in triennial follow-ups. Gut microbiota in 1744 participants and fecal bile acid metabolites in 945 participants were analyzed using 16S ribosomal ribonucleic acid sequencing and ultra-performance liquid chromatography-tandem mass spectrometry at middle-term. RESULTS: The multivariable-adjusted hazard ratios (95% confidence interval) for CHD incidence in highest compared with lowest quartiles were 0.87 (0.61, 1.25) for C20:0, 0.63 (0.42, 0.96) for C22:0, 0.59 (0.41, 0.85) for C24:0, and 0.57 (0.39, 0.83) for total VLCSFAs. Participants with higher total VLCSFA concentrations exhibited increased abundances of Holdemanella, Coriobacteriales Incertae Sedis spp., Ruminococcaceae UCG-005 and UCG-010, and Lachnospiraceae ND3007 group. These 5 genera generated overlapping differential microbial scores (ODMSs) that accounted for 11.52% of the total VLCSFAs-CHD association (Pmediation = 0.018). Bile acids tauro_α_ and tauro_ß_muricholic acid were inversely associated with ODMS and positively associated with incident CHD. Opposite associations were found for glycolithocholic acid and glycodeoxycholic acid. Mediation analyses indicated that glycolithocholic acid, glycodeoxycholic acid, and tauro_α_ and tauro_ß_muricholic acid explained 56.40%, 35.19%, and 26.17% of the ODMS-CHD association, respectively (Pmediation = 0.002, 0.008, and 0.020). CONCLUSIONS: Elevated erythrocyte VLCSFAs are inversely associated with CHD risk in the Chinese population, with gut microbiota and fecal bile acid profiles potentially mediating this association. The identified microbiota and bile acid metabolites may serve as potential intervention targets in future studies. This trial was registered at www. CLINICALTRIALS: gov as NCT03179657.

8.
Liver Int ; 44(9): 2424-2433, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38847512

RESUMO

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.


Assuntos
Ceruloplasmina , ATPases Transportadoras de Cobre , Degeneração Hepatolenticular , Penicilamina , Humanos , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/tratamento farmacológico , Degeneração Hepatolenticular/sangue , Degeneração Hepatolenticular/terapia , Feminino , Masculino , Pré-Escolar , Ceruloplasmina/análise , Ceruloplasmina/metabolismo , ATPases Transportadoras de Cobre/genética , Penicilamina/uso terapêutico , Prognóstico , Alanina Transaminase/sangue , Criança , Cobre/sangue , Fatores de Risco , Falha de Tratamento , Diagnóstico Precoce , Progressão da Doença , Estimativa de Kaplan-Meier , Lactente , Quelantes/uso terapêutico
9.
Eur Radiol ; 34(1): 182-192, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37566270

RESUMO

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.


Assuntos
Neoplasias da Mama , Neoplasias , Humanos , Feminino , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Mama/diagnóstico por imagem , Mama/patologia , Tempo , Neoplasias/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Meios de Contraste
10.
Nutr J ; 23(1): 70, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982486

RESUMO

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.


Assuntos
Distribuição da Gordura Corporal , Metilaminas , Humanos , Metilaminas/sangue , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , Idoso , Distribuição da Gordura Corporal/métodos , Adulto , Absorciometria de Fóton/métodos , Composição Corporal , Estudos de Coortes , China
11.
J Nanobiotechnology ; 22(1): 525, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39217329

RESUMO

The complex anatomy and biology of craniofacial bones pose difficulties in their effective and precise reconstruction. Injectable hydrogels (IHs) with water-swollen networks are emerging as a shape-adaptive alternative for noninvasively rebuilding craniofacial bones. The advent of versatile nanomaterials (NMs) customizes IHs with strengthened mechanical properties and therapeutically favorable performance, presenting excellent contenders over traditional substitutes. Structurally, NM-reinforced IHs are energy dissipative and covalently crosslinked, providing the mechanics necessary to support craniofacial structures and physiological functions. Biofunctionally, incorporating unique NMs into IH expands a plethora of biological activities, including immunomodulatory, osteogenic, angiogenic, and antibacterial effects, further favoring controllable dynamic tissue regeneration. Mechanistically, NM-engineered IHs optimize the physical traits to direct cell responses, regulate intracellular signaling pathways, and control the release of biomolecules, collectively bestowing structure-induced features and multifunctionality. By encompassing state-of-the-art advances in NM-integrated IHs, this review offers a foundation for future clinical translation of craniofacial bone reconstruction.


Assuntos
Regeneração Óssea , Ossos Faciais , Hidrogéis , Nanoestruturas , Engenharia Tecidual , Hidrogéis/química , Humanos , Nanoestruturas/química , Animais , Regeneração Óssea/efeitos dos fármacos , Engenharia Tecidual/métodos , Crânio/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Materiais Biocompatíveis/química , Alicerces Teciduais/química
12.
J Math Biol ; 89(4): 39, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39249563

RESUMO

To explore the influence of state changes on brucellosis, a stochastic brucellosis model with semi-Markovian switchings and diffusion is proposed in this paper. When there is no switching, we introduce a critical value R s and obtain the exponential stability in mean square when R s < 1 by using the stochastic Lyapunov function method. Sudden climate changes can drive changes in transmission rate of brucellosis, which can be modelled by a semi-Markov process. We study the influence of stationary distribution of semi-Markov process on extinction of brucellosis in switching environment including both stable states, during which brucellosis dies out, and unstable states, during which brucellosis persists. The results show that increasing the frequencies and average dwell times in stable states to certain extent can ensure the extinction of brucellosis. Finally, numerical simulations are given to illustrate the analytical results. We also suggest that herdsmen should reduce the densities of animal habitation to decrease the contact rate, increase slaughter rate of animals and apply disinfection measures to kill brucella.


Assuntos
Brucelose , Simulação por Computador , Cadeias de Markov , Conceitos Matemáticos , Modelos Biológicos , Processos Estocásticos , Brucelose/transmissão , Brucelose/epidemiologia , Brucelose/microbiologia , Animais , Humanos , Modelos Epidemiológicos , Brucella/patogenicidade , Mudança Climática
13.
J Math Biol ; 89(1): 6, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38762831

RESUMO

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.


Assuntos
Simulação por Computador , Infecções por HIV , Evasão da Resposta Imune , Conceitos Matemáticos , Modelos Biológicos , Linfócitos T Citotóxicos , Carga Viral , Humanos , Infecções por HIV/imunologia , Infecções por HIV/virologia , Infecções por HIV/tratamento farmacológico , Linfócitos T Citotóxicos/imunologia , Evasão da Resposta Imune/imunologia , Coinfecção/imunologia , Coinfecção/virologia , HIV-1/imunologia , HIV-1/genética , Número Básico de Reprodução/estatística & dados numéricos , Modelos Imunológicos , Mutação
14.
Sensors (Basel) ; 24(17)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39275557

RESUMO

This study introduces RTEEMF (Real-Time Evaluation Electromagnetic Field)-PhoneAnts, a novel Deep Learning (DL) framework for the efficient evaluation of mobile phone antenna performance, addressing the time-consuming nature of traditional full-wave numerical simulations. The DL model, built on convolutional neural networks, uses the Near-field Electromagnetic Field (NEMF) distribution of a mobile phone antenna in free space to predict the Effective Isotropic Radiated Power (EIRP), Total Radiated Power (TRP), and Specific Absorption Rate (SAR) across various configurations. By converting antenna features and internal mobile phone components into near-field EMF distributions within a Huygens' box, the model simplifies its input. A dataset of 7000 mobile phone models was used for training and evaluation. The model's accuracy is validated using the Wilcoxon Signed Rank Test (WSR) for SAR and TRP, and the Feature Selection Validation Method (FSV) for EIRP. The proposed model achieves remarkable computational efficiency, approximately 2000-fold faster than full-wave simulations, and demonstrates generalization capabilities for different antenna types, various frequencies, and antenna positions. This makes it a valuable tool for practical research and development (R&D), offering a promising alternative to traditional electromagnetic field simulations. The study is publicly available on GitHub for further development and customization. Engineers can customize the model using their own datasets.

15.
Molecules ; 29(17)2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39274997

RESUMO

By using a scaffold hopping/ring equivalent and intermediate derivatization strategies, a series of compounds of 2,5-diphenyl-1,3-oxazoline with substituent changes at the 5-phenyl position were prepared, and their acaricidal activity was studied. However, the synthesized 2,5-diphenyl-1,3-oxazolines showed lower activity against mite eggs and larvae compared to the 2,4-diphenyl-1,3-oxazolines with the same substituents. We speculate that there is a significant difference in the spatial extension direction of the substituents between the two skeletons of compounds, resulting in differences in their ability to bind to the potential target chitin synthase 1. This work is helpful in inferring the internal structure of chitin synthase binding pockets.


Assuntos
Acaricidas , Oxazóis , Acaricidas/química , Acaricidas/farmacologia , Acaricidas/síntese química , Animais , Oxazóis/química , Oxazóis/síntese química , Oxazóis/farmacologia , Desenho de Fármacos , Relação Estrutura-Atividade , Ácaros/efeitos dos fármacos , Estrutura Molecular , Larva/efeitos dos fármacos , Quitina Sintase/antagonistas & inibidores , Quitina Sintase/metabolismo
16.
Psychogeriatrics ; 24(5): 1051-1064, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38987229

RESUMO

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.


Assuntos
Doença de Alzheimer , Cognição , Estimulação Transcraniana por Corrente Contínua , Humanos , Doença de Alzheimer/terapia , Doença de Alzheimer/psicologia , Estimulação Transcraniana por Corrente Contínua/métodos , Cognição/fisiologia , Atenção , Idoso , Função Executiva/fisiologia , Memória/fisiologia , Resultado do Tratamento , Masculino
17.
Hum Brain Mapp ; 44(13): 4710-4721, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37376719

RESUMO

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.


Assuntos
Regulação Emocional , Humanos , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Emoções/fisiologia , Estimulação Magnética Transcraniana , Córtex Cerebral
18.
BMC Med ; 21(1): 414, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37907866

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Efeitos Tardios da Exposição Pré-Natal , Inanição , Adulto , Humanos , Pessoa de Meia-Idade , China , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , População do Leste Asiático , Fome Epidêmica , Microbiota , Inanição/complicações , Adolescente , Adulto Jovem , Idoso , Idoso de 80 Anos ou mais
19.
J Intern Med ; 293(3): 340-353, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36433820

RESUMO

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.


Assuntos
Dieta , Hepatopatia Gordurosa não Alcoólica , Animais , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Estudos Prospectivos , Carne , Aves Domésticas , Proteínas de Plantas , Fatores de Risco
20.
J Transl Med ; 21(1): 101, 2023 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-36759852

RESUMO

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.


Assuntos
MicroRNAs , Técnicas de Movimentação Dentária , Remodelação Óssea/fisiologia , Ligamento Periodontal , Periodonto , MicroRNAs/genética
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