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1.
Environ Sci Technol ; 58(41): 18284-18294, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39364784

RESUMO

Biomass burning organic aerosol (BBOA), containing brown carbon chromophores, plays a critical role in atmospheric chemistry and climate forcing. However, the effects of evaporation on BBOA volatility and viscosity under different environmental conditions remain poorly understood. This study focuses on the molecular characterization of laboratory-generated BBOA proxies from wood pyrolysis emissions. The initial mixture, "pyrolysis oil (PO1)", was progressively evaporated to produce more concentrated mixtures (PO1.33, PO2, and PO3) with volume reduction factors of 1.33, 2, and 3, respectively. Chemical speciation and volatility were investigated using temperature-programmed desorption combined with direct analysis in real-time ionization and high-resolution mass spectrometry (TPD-DART-HRMS). This novel approach quantified saturation vapor pressures and enthalpies of individual species, enabling the construction of volatility basis set distributions and the quantification of gas-particle partitioning. Viscosity estimates, validated by poke-flow experiments, showed a significant increase with evaporation, slowing particle-phase diffusion and extending equilibration times. These findings suggest that highly viscous tar ball particles in aged biomass burning emissions form as semivolatile components evaporate. The study highlights the importance of evaporation processes in shaping BBOA properties, underscoring the need to incorporate these factors into atmospheric models for better predictions of BBOA aging and its environmental impact.


Assuntos
Aerossóis , Carbono , Carbono/química , Viscosidade , Atmosfera/química , Biomassa , Gases
2.
Biostatistics ; 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39412139

RESUMO

Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed iterative Sure Independence Screening (iSIS) in two subsamples to exclude the non-mediators, followed by ordinary least squares regressions for the variance estimation. We then constructed confidence intervals based on the newly derived closed-form asymptotic distribution of the R2 measure. Extensive simulation studies demonstrated that this proposed procedure is much more computationally efficient than the resampling-based method, with comparable coverage probability. Furthermore, when applied to the Framingham Heart Study, the proposed method replicated the established finding of gene expression mediating age-related variation in systolic blood pressure and identified the role of gene expression profiles in the relationship between sex and high-density lipoprotein cholesterol level. The proposed estimation procedure is implemented in R package CFR2M.

3.
Foods ; 13(19)2024 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-39410211

RESUMO

Rheum tanguticum is one of the primary rhubarb species used for food and medicinal purposes, and it has recently been gaining more attention and recognition. This research represents the first attempt to use stable isotopes and elemental analysis via IRMS to identify the geographical origin of Rheum tanguticum. A grand total of 190 rhubarb samples were gathered from 38 locations spread throughout the provinces of Gansu, Sichuan, and Qinghai in China. The carbon content showed a decreasing trend in the order of Qinghai, followed by Sichuan, and then Gansu. Nitrogen content was notably higher, with Qinghai and Sichuan displaying similar levels, while Gansu had the lowest nitrogen levels. Significant differences were noted in the δ13C (-28.9 to -26.5‱), δ15N (2.6 to 5.6‱), δ2H (-120.0 to -89.3‱), and δ18O (16.0‱ to 18.8‱) isotopes among the various rhubarb cultivation areas. A significant negative correlation was found between %C and both longitude and humidity. Additionally, δ13C and δ15N isotopes were negatively correlated with longitude, and δ15N showed a negative correlation with humidity as well. δ2H and δ18O isotopes exhibited a strong positive correlation with latitude, while significant negative correlations were observed between δ2H and δ18O isotopes and temperature, precipitation, and humidity. The LDA, PLS-DA, and k-NN models all exhibited strong classification performance in both the training and validation sets, achieving accuracy rates between 82.1% and 91.7%. The combination of stable isotopes, elemental analysis, and chemometrics provides a reliable and efficient discriminant model for accurately determining the geographical origin of R. tanguticum in different regions. In the future, the approach will aid in identifying the geographical origin and efficacy of rhubarb in other studies.

4.
Front Public Health ; 12: 1377070, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39403442

RESUMO

Background: Prenatal drug use may cause toxicity to bone health in newborns. We aimed to examine whether birth outcomes mediate the association between medication use and neonatal metabolic bone disease (MBD). Methods: A prospective cohort of 10,801 pregnant women (17-49 years) and their infants followed at a single center from 1 January 2012 to 31 December 2021 were included. Based on four single drugs, comprehensive medication use was determined and categorized into three groups using latent-class analysis: group 1 included antibiotics and furosemide or less than two drugs except for MgSO4; group 2 included MgSO4 without antibiotics or furosemide; and group 3 encompassed dexamethasone and antibiotics. Mediation analysis was conducted to assess the mediating effects of prematurity, low birth weight (LBW), and small for gestational age (SGA). Results: There were 138 (1.3%) infants with MBD; 2,701 (25%) were born preterm, 1717 (15.9%) had LBW, and 303 (2.8%) were SGA. Pregnant women in groups 2 and 3 were 2.52 to 14.66 times more likely to deliver an infant with MBD than those in group 1. Only LBW showed a significant mediating effect on the association between comprehensive medication use and MBD, with a mediation proportion of 51.8% (45.0-64.1%, p < 0.001). Conclusion: Comprehensive medication use during pregnancy was associated with an increased risk of neonatal MBD, largely mediated by LBW. Early antepartum monitoring and prevention targeting adverse birth outcomes are necessary to mitigate the risk of MBD.


Assuntos
Doenças Ósseas Metabólicas , Resultado da Gravidez , Humanos , Feminino , Gravidez , Estudos Prospectivos , Adulto , Recém-Nascido , China/epidemiologia , Adolescente , Doenças Ósseas Metabólicas/induzido quimicamente , Pessoa de Meia-Idade , Adulto Jovem , Complicações na Gravidez/tratamento farmacológico , Recém-Nascido de Baixo Peso , Recém-Nascido Pequeno para a Idade Gestacional , Nascimento Prematuro/epidemiologia , População do Leste Asiático
5.
Brain Behav ; 14(10): e70102, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39415635

RESUMO

BACKGROUND: Tremor-dominant (TD) and nontremor-dominant (NTD) Parkinson's disease (PD) showed different responses to rehabilitation. However, the neural mechanism behind this remains unclear. METHODS: This cohort study explores changes in motor function, brain activation, and functional connectivity following 2 weeks of rehabilitation in TD-PD and NTD-PD patients, respectively. A total of 11 TD-PD patients, 24 NTD-PD patients, and 21 age-matched healthy controls (HCs) were included. At baseline, all participants underwent functional magnetic resonance imaging (fMRI) while performing the foot tapping task. Motor symptoms, gait, balance, and task-based fMRI were then evaluated in patients before and after rehabilitation. RESULTS: Compared to HCs, TD-PD patients showed increased activity in the left inferior frontal gyrus and the right insula, and NTD-PD patients showed increased activations in the left postcentral gyrus and decreased within-cerebellar connectivity at baseline. Rehabilitation improved motor function in PD patients regardless of motor subtype. TD-PD patients showed increased recruitments of the sensorimotor cortex and the bilateral thalamus after rehabilitation, and NTD-PD patients showed increased cerebellar activation and within-cerebellar connectivity that was associated with better motor performance. CONCLUSIONS: This study demonstrated that rehabilitation-induced brain functional reorganization varied by motor subtypes in PD, which may have important implications for making individualized rehabilitation programs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ChiCTR1900020771.


Assuntos
Imageamento por Ressonância Magnética , Doença de Parkinson , Tremor , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Cerebelo/fisiopatologia , Cerebelo/diagnóstico por imagem , Estudos de Coortes , Reabilitação Neurológica/métodos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/reabilitação , Córtex Sensório-Motor/fisiopatologia , Córtex Sensório-Motor/diagnóstico por imagem , Tálamo/fisiopatologia , Tálamo/diagnóstico por imagem , Tremor/fisiopatologia , Tremor/diagnóstico por imagem , Tremor/reabilitação , Estudos de Casos e Controles
6.
Neurosci Bull ; 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39470972

RESUMO

The ability to localize sound sources rapidly allows human beings to efficiently understand the surrounding environment. Previous studies have suggested that there is an auditory "where" pathway in the cortex for processing sound locations. The neural activation in regions along this pathway encodes sound locations by opponent hemifield coding, in which each unilateral region is activated by sounds coming from the contralateral hemifield. However, it is still unclear how these regions interact with each other to form a unified representation of the auditory space. In the present study, we investigated whether functional connectivity in the auditory "where" pathway encoded sound locations during passive listening. Participants underwent functional magnetic resonance imaging while passively listening to sounds from five distinct horizontal locations (-90°, -45°, 0°, 45°, 90°). We were able to decode sound locations from the functional connectivity patterns of the "where" pathway. Furthermore, we found that such neural representation of sound locations was primarily based on the coding of sound lateralization angles to the frontal midline. In addition, whole-brain analysis indicated that functional connectivity between occipital regions and the primary auditory cortex also encoded sound locations by lateralization angles. Overall, our results reveal a lateralization-angle-based representation of sound locations encoded by functional connectivity patterns, which could add on the activation-based opponent hemifield coding to provide a more precise representation of the auditory space.

7.
EMBO J ; 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39433900

RESUMO

Lgr5+ intestinal stem cells (ISCs) are crucial for the intestinal epithelium renewal and regeneration after injury. However, the mechanism underlying the interplay between Wnt and BMP signaling in this process is not fully understood. Here we report that Bcl11b, which is downregulated by BMP signaling, enhances Wnt signaling to maintain Lgr5+ ISCs and thus promotes the regeneration of the intestinal epithelium upon injury. Loss of Bcl11b function leads to a significant decrease of Lgr5+ ISCs in both intestinal crypts and cultured organoids. Mechanistically, BMP suppresses the expression of Bcl11b, which can positively regulate Wnt target genes by inhibiting the function of the Nucleosome Remodeling and Deacetylase (NuRD) complex and facilitating the ß-catenin-TCF4 interaction. Bcl11b can also promote intestinal epithelium repair after injuries elicited by both irradiation and DSS-induced inflammation. Furthermore, Bcl11b deletion prevents proliferation and tumorigenesis of colorectal cancer cells. Together, our findings suggest that BMP suppresses Wnt signaling via Bcl11b regulation, thus balancing homeostasis and regeneration in the intestinal epithelium.

8.
PeerJ Comput Sci ; 10: e2252, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39314736

RESUMO

The world faces the ongoing challenge of terrorism and extremism, which threaten the stability of nations, the security of their citizens, and the integrity of political, economic, and social systems. Given the complexity and multifaceted nature of this phenomenon, combating it requires a collective effort, with tailored methods to address its various aspects. Identifying the terrorist organization responsible for an attack is a critical step in combating terrorism. Historical data plays a pivotal role in this process, providing insights that can inform prevention and response strategies. With advancements in technology and artificial intelligence (AI), particularly in military applications, there is growing interest in utilizing these developments to enhance national and regional security against terrorism. Central to this effort are terrorism databases, which serve as rich resources for data on armed organizations, extremist entities, and terrorist incidents. The Global Terrorism Database (GTD) stands out as one of the most widely used and accessible resources for researchers. Recent progress in machine learning (ML), deep learning (DL), and natural language processing (NLP) offers promising avenues for improving the identification and classification of terrorist organizations. This study introduces a framework designed to classify and predict terrorist groups using bidirectional recurrent units and self-attention mechanisms, referred to as BiGRU-SA. This approach utilizes the comprehensive data in the GTD by integrating textual features extracted by DistilBERT with features that show a high correlation with terrorist organizations. Additionally, the Synthetic Minority Over-sampling Technique with Tomek links (SMOTE-T) was employed to address data imbalance and enhance the robustness of our predictions. The BiGRU-SA model captures temporal dependencies and contextual information within the data. By processing data sequences in both forward and reverse directions, BiGRU-SA offers a comprehensive view of the temporal dynamics, significantly enhancing classification accuracy. To evaluate the effectiveness of our framework, we compared ten models, including six traditional ML models and four DL algorithms. The proposed BiGRU-SA framework demonstrated outstanding performance in classifying 36 terrorist organizations responsible for terrorist attacks, achieving an accuracy of 98.68%, precision of 96.06%, sensitivity of 96.83%, specificity of 99.50%, and a Matthews correlation coefficient of 97.50%. Compared to state-of-the-art methods, the proposed model outperformed others, confirming its effectiveness and accuracy in the classification and prediction of terrorist organizations.

9.
Genet Sel Evol ; 56(1): 68, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350051

RESUMO

BACKGROUND: Insect-based food and feed are increasingly attracting attention. As a domesticated insect, the silkworm (Bombyx mori) has a highly nutritious pupa that can be easily raised in large quantities through large-scale farming, making it a highly promising source of food. The ratio of pupa to cocoon (RPC) refers to the proportion of the weight of the cocoon that is attributed to pupae, and is of significant value for edible utilization, as a higher RPC means a higher ratio of conversion of mulberry leaves to pupa. In silkworm production, there is a trade-off between RPC and cocoon shell ratiao(CSR), which refers the ratio of silk protein to the entire cocoon, during metamorphosis process. Understanding the genetic basis of this balance is crucial for breeding edible strains with a high RPC and further advancing its use as feed. RESULTS: Using QTL-seq, we identified a quantitative trait locus (QTL) for the balance between RPC and CSR that is located on chromosome 11 and covers a 9,773,115-bp region. This locus is an artificial selection hot spot that contains ten non-overlapping genomic regions under selection that were involved in the domestication and genetic breeding processes. These regions include 17 genes, nine of which are highly expressed in the silk gland, which is a vital component in the trade-off between RPC and CSR. These genes are annotate with function related with epigenetic modifications and the regulation of DNA replication et al. We identified one and two single nucleotide polymorphisms (SNPs) in the exons of teh KWMTBOMO06541 and KWMTBOMO06485 genes that result in amino acid changes in the protein domains. These SNPs have been strongly selected for during the domestication process. The KWMTBOMO06485 gene encodes the Bombyx mori (Bm) tRNA methyltransferase (BmDnmt2) and its knockout results in a significant change in the trade-off between CSR and RPC in both sexes. CONCLUSIONS: Taken together, our results contribute to a better understanding of the genetic basis of RPC and CSR. The identified QTL and genes that affect RPC can be used for marker-assisted and genomic selection of silkworm strains with a high RPC. This will further enhance the production efficiency of silkworms and of closely-related insects for edible and feed purposes.


Assuntos
Bombyx , Larva , Pupa , Locos de Características Quantitativas , Seda , Animais , Bombyx/genética , Bombyx/metabolismo , Pupa/genética , Pupa/metabolismo , Larva/genética , Larva/metabolismo , Seda/genética , Seda/biossíntese , Polimorfismo de Nucleotídeo Único , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo
10.
Sci Rep ; 14(1): 22573, 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39343825

RESUMO

In this paper, a flexural Mikaelian lens in thin plate is designed by using conformation transformation. The propagation characteristics of flexural waves in the lens are investigated through rays trajectory equation, simulation analyses, and experimental tests, confirming the self-focusing properties of the Mikaelian lens. Additionally, the study explores the Talbot effect for flexural waves, revealing through simulation studies that the Talbot effect within the Mikaelian lens exhibits nearly diffraction-free properties. Building on the non-diffractive nature of the Talbot effect within the Mikaelian lens, we explore the potential for encoding flexural waves using active interference sources. The simulation and experiment results demonstrate the good performance of the designed active encoding system. This work opens up new avenues for the encoding of flexural waves, presenting promising implications for applications in communication such as structural health monitoring, wireless communication in solid media and data transmission in robotics and other areas related to flexural wave technology.

11.
Alzheimers Res Ther ; 16(1): 203, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39267112

RESUMO

BACKGROUND: The mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer's Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity. METHODS: This is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography-functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization. RESULTS: A total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus. CONCLUSION: Effects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03920826; Registration Date: 2019-04-19.


Assuntos
Doença de Alzheimer , Eletroencefalografia , Hipocampo , Imageamento por Ressonância Magnética , Estimulação Transcraniana por Corrente Contínua , Humanos , Doença de Alzheimer/terapia , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/diagnóstico por imagem , Masculino , Feminino , Estimulação Transcraniana por Corrente Contínua/métodos , Idoso , Método Duplo-Cego , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Eletroencefalografia/métodos , Resultado do Tratamento , Pessoa de Meia-Idade , Ritmo Gama/fisiologia , Testes Neuropsicológicos , Cognição/fisiologia
12.
Food Chem ; 463(Pt 4): 141424, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39348765

RESUMO

Medicinal food homologous (MFH) substances not only provide nutrition but also serve as a traditional means to overcome many health issues. Authentication of these products verifies their efficacity and assures consumers of a genuine product. In this review paper, we focus the determination of MFH authenticity including geographical identification and adulteration detection using mass spectrometry (liquid and gas chromatography) based metabolites and inorganic constituents (muti-elements and stable isotopes). The application of these techniques to determine product identification characteristics combined with chemometrics are discussed, along with the limitations of these techniques. Multi-elements, stable isotopes, and metabolite analysis are shown to provide an effective combination of techniques to resolve the origin of various MFH products. Most organic compounds from MFH products are identified using chromatographic separation techniques (HPLC, GC) combined with different detection methods. Chemometric analysis of organic and inorganic fingerprints offers a robust method to detect and classify mislabeled and suspected fraudulent samples of different MFH products.

13.
Front Nutr ; 11: 1450265, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246393

RESUMO

Introduction: The aim of this study is to investigate the impact of vitamin D supplementation on the muscle strength of the elderly. Methods: This retrospective, propensity score-matched study included 160 middle-aged and elderly individuals from a community in Beijing, China. The control group (n=110) received health education and lifestyle guidance, while the intervention group (n=50) was given oral vitamin D supplementation in addition to health education and lifestyle guidance. All participants underwent laboratory tests, muscle function, and physical function at baseline and follow-up. Results: In the propensity score-matched cohort of 41 patients per group, the levels of serum calcium and 25-hydroxyvitamin D in both groups were improved significantly by the end of the study (p<0.05), with the intervention group showing a more significant improvement. The muscle strength of the left lower limb in the intervention group significantly increased after the intervention (p<0.05). The results also showed that the grip strength and pinch strength of the patients in both groups increased after the intervention, and the difference between the two groups was statistically significant (p<0.05). Discussion: The findings of this study suggest that vitamin D supplementation, in conjunction with lifestyle guidance and health education, is beneficial for enhancing the upper and lower limb strength of patients.

14.
Asia Pac J Clin Nutr ; 33(4): 569-580, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39209367

RESUMO

BACKGROUND AND OBJECTIVES: Malnutrition is associated with a higher risk of osteoporosis. We aim to assess the relationship between serum albumin with geriatric nutritional risk index and osteopenia in Chinese elderly men. METHODS AND STUDY DESIGN: This is a nested case-control study from a prospective cohort enrolled 1109 individuals who were followed for seven years. Demographic data, medical history, signs and symptoms, and laboratory parameters were collected and analysed. Nutritional status and Geriatric Nutritional Risk Index (GNRI) were assessed. The nutrition-related indexes predictive value for osteopenia development was analyzed through multivariate Cox regression analysis and by creating a receiver operating characteristic curve (ROC), calculating the area under the curve (AUC). Kaplan-Meier (K-M) method was further used to find the nutritional status level in the elderly men. RESULTS: The ALB and GNRI correlated with the risk of osteopenia in Chinese elderly men. After adjusting for all covariates, people with higher ALB level (HR: 0.821; 95% CI: 0.790-0.852) and higher GNRI score (HR: 0.889; 95% CI: 0.869-0.908) had a smaller risk of osteopenia. ROC analysis showed that the AUC for ALB was 0.729 (p<0.05) and for the GNRI score was 0.731 (p<0.05). K-M curve indicated a significant difference in ALB level (p<0.001) and GNRI score (p<0.001) in the respective subgroups. CONCLUSIONS: This study found that lower ALB level and lower GNRI score are associated with a higher prevalence of osteopenia among elderly men in China.


Assuntos
Doenças Ósseas Metabólicas , Estado Nutricional , Albumina Sérica , Humanos , Masculino , Idoso , Estudos de Casos e Controles , Doenças Ósseas Metabólicas/epidemiologia , Albumina Sérica/análise , China/epidemiologia , Fatores de Risco , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos , Estudos Prospectivos , Avaliação Nutricional , Idoso de 80 Anos ou mais , Desnutrição/epidemiologia , População do Leste Asiático
15.
Food Chem ; 461: 140859, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39163723

RESUMO

Seasonings such as naturally fermented soy sauce without added monosodium glutamate (MSG), are currently a growth market in China. However, fraudulent and mislabeled zero-added MSG soy sauce may cause a risk of excessive MSG intake, increasing food safety issues for consumers. This study investigates stable carbon and nitrogen isotopes and 16 amino acids in typical Chinese in-market soy sauces and uses a similarity method to establish criteria to authenticate MSG addition claims. Results reveal most zero-added MSG soy sauces had lower δ13C values (-25.2 ‰ to -17.7 ‰) and glutamic acid concentrations (8.97 mg mL-1 to 34.76 mg mL-1), and higher δ15N values (-0.27 ‰ +0.95 ‰) and other amino acid concentrations than added-MSG labeled samples. A combined approach, using isotopes, amino acids, similarity coefficients and uncertainty values, was evaluated to rapidly and accurately identify zero-added MSG soy sauces from MSG containing counterparts.


Assuntos
Aminoácidos , Isótopos de Carbono , Glutamato de Sódio , Alimentos de Soja , Alimentos de Soja/análise , Aminoácidos/análise , Aminoácidos/química , Glutamato de Sódio/química , Glutamato de Sódio/análise , Isótopos de Carbono/análise , Isótopos de Nitrogênio/análise , China , Glycine max/química , Aditivos Alimentares/análise
16.
Nat Commun ; 15(1): 6894, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134521

RESUMO

SARS-CoV-2 has the capacity to evolve mutations that escape vaccine- and infection-acquired immunity and antiviral drugs. A variant-agnostic therapeutic agent that protects against severe disease without putting selective pressure on the virus would thus be a valuable biomedical tool that would maintain its efficacy despite the ongoing emergence of new variants. Here, we challenge male rhesus macaques with SARS-CoV-2 Delta-the most pathogenic variant in a highly susceptible animal model. At the time of challenge, we also treat the macaques with aerosolized RBD-62, a protein developed through multiple rounds of in vitro evolution of SARS-CoV-2 RBD to acquire 1000-fold enhanced ACE2 binding affinity. RBD-62 treatment equivalently suppresses virus replication in both upper and lower airways, a phenomenon not previously observed with clinically approved vaccines. Importantly, RBD-62 does not block the development of virus-specific T- and B-cell responses and does not elicit anti-drug immunity. These data provide proof-of-concept that RBD-62 can prevent severe disease from a highly virulent variant.


Assuntos
Enzima de Conversão de Angiotensina 2 , Antivirais , COVID-19 , SARS-CoV-2 , Replicação Viral , Animais , Humanos , Masculino , Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Antivirais/farmacologia , Chlorocebus aethiops , COVID-19/virologia , COVID-19/imunologia , COVID-19/prevenção & controle , Tratamento Farmacológico da COVID-19 , Modelos Animais de Doenças , Macaca mulatta , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero , Replicação Viral/efeitos dos fármacos
17.
Exp Gerontol ; 195: 112538, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39116956

RESUMO

Amyotrophic lateral sclerosis as a fatal neurodegenerative disease currently lacks effective therapeutic agents. Thus, finding new therapeutic targets to drive disease treatment is necessary. In this study, we utilized brain and plasma proteins as genetic instruments obtained from genome-wide association studies to conduct a Mendelian randomization analysis to identify potential drug targets for amyotrophic lateral sclerosis. Additionally, we validated our results externally using other datasets. We also used Bayesian co-localization analysis and phenotype scanning. Furthermore, we constructed a protein-protein interaction network to elucidate potential correlations between the identified proteins and existing targets. Mendelian randomization analysis indicated that elevated levels of ANO5 (OR = 1.30; 95 % CI, 1.14-1.49; P = 1.52E-04), SCFD1 (OR = 3.82; 95 % CI, 2.39-6.10; P = 2.19E-08), and SIGLEC9 (OR = 1.05; 95% CI, 1.03-1.07; P = 4.71E-05) are associated with an increased risk of amyotrophic lateral sclerosis, with external validation supporting these findings. Co-localization analysis confirmed that ANO5, SCFD1, and SIGLEC9 (coloc.abf-PPH4 = 0.848, 0.984, and 0.945, respectively) shared the same variant with amyotrophic lateral sclerosis, further substantiating potential role of these proteins as a therapeutic target. There are interactive relationships between the potential proteins and existing targets of amyotrophic lateral sclerosis. Our findings suggested that elevated levels of ANO5, SCFD1, and SIGLEC9 are connected with an increased risk of amyotrophic lateral sclerosis and might be promising therapeutic targets. However, further exploration is necessary to fully understand the underlying mechanisms involved.


Assuntos
Esclerose Lateral Amiotrófica , Encéfalo , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Mapas de Interação de Proteínas , Proteômica , Humanos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/tratamento farmacológico , Proteômica/métodos , Encéfalo/metabolismo , Anoctaminas/genética , Teorema de Bayes , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/metabolismo , Predisposição Genética para Doença
18.
Int J Biol Sci ; 20(9): 3480-3496, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993560

RESUMO

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver-related morbidity and mortality. Though high fructose intake is acknowledged as a metabolic hazard, its role in the etiology of MASLD requires further clarification. Here, we demonstrated that high dietary fructose drives MASLD development and promotes MASLD progression in mice, and identified Usp2 as a fructose-responsive gene in the liver. Elevated USP2 levels were detected in the hepatocytes of MASLD mice; a similar increase was observed following fructose exposure in primary hepatocytes and mouse AML12 cells. Notably, hepatocytes overexpressing USP2 presented with exaggerated lipid accumulation and metabolic inflammation when exposed to fructose. Conversely, USP2 knockdown mitigated these fructose-induced changes. Furthermore, USP2 was found to activate the C/EBPα/11ß-HSD1 signaling, which further impacted the equilibrium of cortisol and cortisone in the circulation of mice. Collectively, our findings revealed the role of dietary fructose in MASLD pathogenesis and identified the USP2-mediated C/EBPα/ 11ß-HSD1 signaling as a potential target for the management of MASLD.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1 , Frutose , Ubiquitina Tiolesterase , Animais , Camundongos , Frutose/efeitos adversos , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética , Masculino , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , Camundongos Endogâmicos C57BL , Transdução de Sinais , Fígado Gorduroso/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Endopeptidases/metabolismo
20.
Sensors (Basel) ; 24(14)2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39065841

RESUMO

Unmanned Aerial Vehicles (UAVs) have emerged as efficient tools in disaster-stricken areas, facilitating efficient data dissemination for post-disaster rescue operations. However, the limited onboard energy of UAVs imposes significant constraints on their operational lifespan, thereby presenting substantial challenges for efficient data dissemination. Therefore, this work investigates a data dissemination scheme to enhance the UAVs' bandwidth efficiency in multi-UAV-enabled Internet of Vehicles, thereby reducing UAVs' energy consumption and improving overall system performance when UAVs hover along designated flight trajectories for data dissemination. Specifically, first, we present a software-defined network-based framework for data dissemination in multi-UAV-enabled IoV. According to this framework, we formulate a problem called C2BS (Coding-based Cooperative Broadcast Scheduling) that focuses on optimizing the UAVs' bandwidth efficiency by leveraging the combined benefits of coding and caching. Furthermore, we demonstrate the NP-hardness of the C2BS problem by employing a polynomial time reduction technique on the simultaneous matrix completion problem. Then, inspired by the benefits offered by genetic algorithms, we propose a novel approach called the Genetic algorithm-based Cooperative Scheduling (GCS) algorithm to address the C2BS problem. This approach encompasses a coding scheme for representing individuals, a fitness function for assessing individuals, operators (i.e., crossover and mutation) for generating offspring, a local search technique to enhance search performance, and a repair operator employed to rectify infeasible solutions. Additionally, we present an analysis of the time complexity for the GCS algorithm. Finally, we present a simulation model to evaluate the performance. Experimental findings provide evidence of the excellence of the proposed scheme.

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