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1.
Food Chem ; 462: 140963, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39208739

RESUMO

Different scented teas provide various choices for consumers from appearance, aroma, flavor and others. Aiming to define advantages and market positions of different scented teas and promote optimization of market structure, characteristics for scented tea favored by consumers and outstanding attributes of different scented teas should be clarified. Rose tea was taken as study object. Sensory evaluation and consumer acceptance were investigated. GC-MS and HPLC fingerprints were established. Physicochemical characteristics were determined. RGB integration analysis was inventively proposed for correlation analysis. The volatile compounds with spicy, green or herbal odor as camphene, ß-phenethyl acetate, eugenol, and physicochemical parameters as antioxidant capacity, reducing sugar content, pH showed positive correlation with popular sensory properties. Six models for consumer preference by objective description were built through GA-SVR (accuracy = 1), and APP was developed. The research mode of scented tea has been successfully established to study multiple subjective characteristics with measurable objective parameters.


Assuntos
Odorantes , Paladar , Odorantes/análise , Humanos , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/análise , Chá/química , Cromatografia Gasosa-Espectrometria de Massas , Comportamento do Consumidor , Antioxidantes/química , Antioxidantes/análise , Rosa/química , Cromatografia Líquida de Alta Pressão
2.
J Am Heart Assoc ; : e035341, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291508

RESUMO

BACKGROUND: We aimed to investigate the associations of long-term exposure to ambient formaldehyde with hypertension and angina pectoris symptoms in Chinese adults. METHODS AND RESULTS: Participants' information was obtained from the WHO SAGE (World Health Organization Study on Global Aging and Adult Health) study. The Cox proportional hazards regression model was applied to estimate the associations of formaldehyde with hypertension and angina pectoris symptoms. Mediating effect analysis was used to investigate the mediating effect of hypertension between formaldehyde exposure and angina pectoris symptoms. Long-term exposure to formaldehyde was positively associated with the risk of angina pectoris symptoms (hazard ratio [HR], 1.66 [95% CI, 1.29-2.13], per interquartile range [IQR], 3.33, 1015 molecules/cm2) and hypertension (HR, 1.17 [95% CI, 1.02-1.34], per IQR, 3.34, 1015 molecules/cm2). The associations between formaldehyde and angina pectoris symptoms were greater in participants aged ≥65 years (HR, 1.90 [95% CI, 1.29-2.80]) and in rural areas (HR, 2.71 [95% CI, 1.54-4.77]), whereas the associations of formaldehyde with hypertension were stronger in men (HR, 1.27 [95% CI, 1.02-1.58]), rural areas (HR, 1.22 [95% CI, 0.94-1.59]), and in ever smokers (HR, 1.33 [95% CI, 1.02-1.72]). The mediation effect analysis indicated that 18.44% (95% CI, 2.17-37.65) of the association between formaldehyde exposure and angina pectoris symptoms was mediated by hypertension. CONCLUSIONS: Long-term exposure to ambient formaldehyde was positively associated with hypertension and angina pectoris symptoms. The effects of formaldehyde may be modified by age, sex, urbanicity, and smoking status. Hypertension might play a mediating effect in formaldehyde-induced angina pectoris symptoms.

3.
Biomed Pharmacother ; 179: 117383, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39232383

RESUMO

Ischemic heart disease (IHD) is a significant global health concern, resulting in high rates of mortality and disability among patients. Although coronary blood flow reperfusion is a key treatment for IHD, it often leads to acute myocardial ischemia-reperfusion injury (IRI). Current intervention strategies have limitations in providing adequate protection for the ischemic myocardium. DJ-1, originally known as a Parkinson's disease related protein, is a highly conserved cytoprotective protein. It is involved in enhancing mitochondrial function, scavenging reactive oxygen species (ROS), regulating autophagy, inhibiting apoptosis, modulating anaerobic metabolism, and exerting anti-inflammatory effects. DJ-1 is also required for protective strategies, such as ischemic preconditioning, ischemic postconditioning, remote ischemic preconditioning and pharmacological conditioning. Therefore, DJ-1 emerges as a potential target for the treatment of myocardial IRI. Our comprehensive review delves into its protective mechanisms in myocardial IRI and the structural foundations underlying its functions.

4.
Microbiol Resour Announc ; : e0034024, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39248544

RESUMO

The draft genome sequence of Taiwanofungus gaoligongensis YAF008 was reported. The genome size of T. gaoligongensis YAF008 was 34.7M bp with 50.72% GC content. The genome resource will support future research into potential secondary metabolite diversity of this fungus.

5.
Ann Med ; 56(1): 2391536, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39149760

RESUMO

BACKGROUND: Submucosal fibrosis is associated with adverse events of endoscopic submucosal dissection (ESD). The present study mainly aimed to establish a predictive model for submucosal fibrosis in patients with early gastric cancer (EGC) undergoing ESD. METHODS: Eligible patients with EGC, identified at Qilu Hospital of Shandong University from April 2013 to December 2023, were retrospectively included and randomly split into a training set and a validation set in a 7:3 ratio. Logistic regression analyses were used to pinpoint the risk factors for submucosal fibrosis. A nomogram was developed and confirmed using receiver operating characteristic (ROC) curves, calibration plots, Hosmer-Lemeshow (H-L) tests, and decision curve analysis (DCA) curves. Besides, a predictive model for severe submucosal fibrosis was further conducted and tested. RESULTS: A total of 516 cases in the training group and 220 cases in the validation group were recruited. The nomogram for submucosal fibrosis contained the following items: tumour location (long axis), tumour location (short axis), ulceration, and biopsy pathology. ROC curves showed high efficiency with an area under the ROC of 0.819 in the training group, and 0.812 in the validation group. Calibration curves and H-L tests indicated good consistency. DCA proved the nomogram to be clinically beneficial. Furthermore, the four items were also applicable for a nomogram predicting severe fibrosis, and the model performed well. CONCLUSION: The predictive models, initially constructed in this study, were validated as convenient and feasible for endoscopists to predict submucosal fibrosis and severe fibrosis in patients with EGC undergoing ESD.


Assuntos
Ressecção Endoscópica de Mucosa , Fibrose , Mucosa Gástrica , Nomogramas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Masculino , Feminino , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Idoso , Centros de Atenção Terciária/estatística & dados numéricos , Curva ROC , Fatores de Risco
6.
PLoS One ; 19(8): e0302291, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39186727

RESUMO

PURPOSE: Sarcopenia is considered to be an important predictor of adverse outcomes following spinal surgery, but the specific relationship between the two is not clear. The purpose of this meta-analysis is to systematically review all relevant studies to evaluate the impact of sarcopenia on spinal surgery outcomes. METHODS: We systematically searched PubMed, Embase and the Cochrane Library for relevant articles published on or before January 9, 2023. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated in a random effects meta-analysis. The main outcome was the risk of adverse outcomes after spinal surgery, including adverse events and mortality. This systematic review and meta-analysis was conducted following the PRISMA guidelines to evaluate the impact of sarcopenia on spinal surgery outcomes. In addition, we also conducted a subgroup analysis and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results. RESULTS: Twenty-four cohort studies, with a total of 243,453 participants, met the inclusion criteria. The meta-analysis showed that sarcopenia was significantly associated with adverse events (OR 1.63, 95% CI 1.17-2.27, P < 0.001) but was no significantly associated with mortality (OR 1.17, 95% CI 0.93-1.46, P = 0.180), infection (OR 2.24, 95% CI 0.95-5.26, P < 0.001), 30-day reoperation (OR 1.47, 95% CI 0.92-2.36, P = 0.413), deep vein thrombosis (OR 1.78, 95% CI 0.69-4.61, P = 0.234), postoperative home discharge (OR 0.60, 95% CI 0.26-1.37, P = 0.002) and blood transfusion (OR 3.28, 95% CI 0.74-14.64, P = 0.015). CONCLUSION: The current meta-analysis showed that patients with sarcopenia have an increased risk of adverse events and mortality after spinal surgery. However, these results must be carefully interpreted because the number of studies included is small and the studies are significantly different. These findings may help to increase the clinicians' awareness of the risks concerning patients with sarcopenia to improve their prognosis.


Assuntos
Complicações Pós-Operatórias , Sarcopenia , Coluna Vertebral , Humanos , Sarcopenia/complicações , Sarcopenia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Coluna Vertebral/cirurgia , Incidência
7.
Biomed Pharmacother ; 179: 117371, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39216447

RESUMO

The continuous activation of macrophages play a critical role in the pathogenesis of cytokine storm (CS). Considering that CS results from the participation of multiple cytokines, the therapeutic effect of a single cytokine or its receptor-targeted blockade therapy remains uncertain. Melittin, which can systematically suppress the overexpression of proinflammatory mediators via inhibiting the mitogen-activated protein kinase and nuclear factor kappa-B pathways in activated macrophages, shows great potential in alleviating CS and acute inflammatory injury (AII). However, its clinical application is limited by its hemolytic activity, non-specific cytotoxicity and lack of targeting. In this study, a folic acid-modified and melittin stable-loaded solid lipid nanoparticle (Fa-MpG@LNP) with a core-shell structure was developed for CS control via targeted inhibition of the overproduction of proinflammatory mediators in activated macrophages with specific expression of folate receptor-ß. The resultant Fa-MpG@LNP showed ideal physicochemical properties and stability, low hemolytic activity and non-specific cytotoxicity, and it can specifically bind to lipopolysaccharide (LPS)-stimulated macrophages and effectively reduce the elevated levels of proinflammatory mediators. After intravenous administration, the Fa-MpG@LNP accumulated at inflamed tissue and significantly downregulate the overproduction of proinflammatory cytokines in tissue-infiltrated macrophages, resulting in a significant decrease of cytokine concentration in inflamed tissue and serum in LPS-induced acute pneumonia mice, and finally alleviate AII with undetectable toxic side effects. These results indicate the clinical application potential of Fa-MpG@LNP in alleviating CS and its related symptoms.

8.
Microbiol Resour Announc ; 13(9): e0024024, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39162487

RESUMO

The Amyloporia genus is an important Chinese medicinal fungus. Here, we present a draft genome sequence of Amyloporia xantha strain YAFMF0618. The genome resource will support subsequent research into the potential secondary metabolite diversity of A. xantha.

9.
Plant Physiol ; 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39217410

RESUMO

Arabidopsis (Arabidopsis thaliana) H+-ATPase1 (AHA1), a plasma membrane (PM)-localized H+-ATPase, plays a key role in plant alkali stress tolerance by pumping protons from the cytoplasm to the apoplast. However, its molecular dynamics are poorly understood. We report that many C2-domain ABA-related (CAR) protein family members interact with AHA1 in Arabidopsis. Single or double mutants of CAR1, CAR6, and CAR10 had no obvious phenotype of alkali stress tolerance, while their triple mutants showed significantly higher tolerance to this stress. The disruption of AHA1 largely compromised the increased alkali stress tolerance of the car1car6car10 mutant, revealing a key role of CARs in AHA1 regulation during the plant's response to a high alkali pH. Furthermore, variable angle total internal reflection fluorescence microscopy was used to observe AHA1-mGFP5 in intact Arabidopsis seedlings, revealing the presence of heterogeneous diffusion coefficients and oligomerization states in the AHA1 spots. In the aha1 complementation lines, alkali stress curtailed the residence time of AHA1 at the PM and increased the diffusion coefficient and particle velocity of AHA1. In contrast, the absence of CAR proteins decreased the restriction of the dynamic behavior of AHA1. Our results suggest that CARs play a negative role in plant alkali stress tolerance by interacting with AHA1 and provide a perspective to investigate the regulatory mechanism of PM H+-ATPase activity at the single-particle level.

10.
Sensors (Basel) ; 24(16)2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39204981

RESUMO

For the purpose of improving performance and reducing the fabrication difficulty of terahertz traveling wave tubes (TWTs), this paper proposes a novel single-section high-gain slow wave structure (SWS), which is named the symmetrical quasi-synchronous step-transition (SQSST) folded waveguide (FW). The SQSST-FW SWS has an artificially designed quasi-synchronous region (QSR) to suppress self-oscillations for sustaining a high gain in an untruncated circuit. Simultaneously, a symmetrical design can improve the efficiency performance to some extent. A prototype of the SQSST-FW SWS for 650 GHz TWTs is designed based on small-signal analysis and numerical simulation. The simulation results indicate that the maximum saturation gain of the designed 650 GHz SQSST-FW TWT is 39.1 dB in a 34.3 mm slow wave circuit, occurring at the 645 GHz point when a 25.4 kV 15 mA electron beam and a 0.43 mW sinusoidal input signal are applied. In addition, a maximum output power exceeding 4 W is observed at the 648 GHz point using the same beam with an increased input power of around 2.8 mW.

11.
Sci Total Environ ; 949: 174946, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39053531

RESUMO

Micro-nano plastics (MNPs) pollution is currently a hot topic of global concern. However, there is still a lack of reliable analytical methods for completely quantitative analysis of MNPs, especially nanoplastics. This study proposes meniscus self-assembly enrichment method, which deposits nanoplastics more uniformly in a specific area. The meniscus self-assembly method greatly overcomes the agglomeration or dispersion of nanoplastics caused by traditional enrichments, and facilitates particles counting. This study investigates the effect of key parameters (e.g. time and initial concentration) on meniscus self-assembly enrichment performance. Besides, due to the large size difference between MNPs, it leads to incomplete quantification analysis when MNPs are counted at the same scale. In response to this problem, this study proposes a one-stop method to count MNPs separately through filtering. The plastics (>1 µm) are collected on the filter paper, then plastics (<1 µm) in the filtrate are homogeneously enriched by meniscus self-assembly, and finally statistically counted by scanning electron microscopy (SEM). The migration of MNPs from take-out plastic containers are detected, with microplastics of 460.55 particles/mL and nanoplastics of 4196.61 particles/mL found. The method has the advantages of saving time and effort, economic efficiency and comprehensive statistics compared with the traditional method.

12.
Phys Rev Lett ; 132(25): 250204, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38996245

RESUMO

The Hamiltonian, which determines the evolution of a quantum system, is fundamental in quantum physics. Therefore, it is crucial to implement high-precision generation and measurement of the Hamiltonian in a practical quantum system. Here, we experimentally demonstrate ultrahigh-precision Hamiltonian parameter estimation with a significant quantum advantage in a superconducting circuit via sequential control. We first observe the commutation relation for noncommuting operations determined by the system Hamiltonian, both with and without adding quantum control, verifying the commuting property of controlled noncommuting operations. Based on this control-induced commuting property, we further demonstrate Hamiltonian parameter estimation for polar and azimuth angles in superconducting circuits, achieving ultrahigh metrological gains in measurement precision exceeding the standard quantum limit by up to 16.0 and 16.1 dB at N=100, respectively.

13.
Biol Trace Elem Res ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39069562

RESUMO

To investigate a cross-sectional association between blood metal mixture and myocardial enzyme profile, we quantified creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LD), α-hydroxybutyrate dehydrogenase (α-HBD), and aspartate transaminase (AST) levels among participants from the manganese-exposed workers healthy cohort (MEWHC) (n = 544). The levels of 22 metals in blood cells were determined using inductively coupled plasma mass spectrometry. The least absolute shrinkage and selection operator (LASSO) penalized regression model was utilized for screening metals. The exposure-response relationship between specific metal and myocardial enzyme profile was identified by general linear regression and restricted cubic spline analyses. The overall effect and interactions were evaluated using Bayesian kernel machine regression (BKMR). Manganese was linearly and positively associated with CK (Poverall = 0.019, Pnon-linearity = 0.307), dominating the positive overall effect of mixture exposure (manganese, arsenic, and rubidium) on CK level. Calcium and zinc were linearly and negatively associated with LD levels (Poverall < 0.05, Pnon-linearity > 0.05), and asserted dominance in the negative overall effect of metal mixtures (rubidium, molybdenum, zinc, nickel, cobalt, calcium, and magnesium) on LD level. Interestingly, we observed a U-shaped dose-response relationship of molybdenum with LD level (Poverall < 0.001, Pnon-linearity = 0.015), an interaction between age and calcium on LD level (Pinteration = 0.041), and an interaction between smoking and molybdenum on LD level (Pinteration = 0.035). Our study provides evidence that metal mixture exposure affects the myocardial enzyme profile. Additional investigation is required to confirm these associations, and to reveal the fundamental mechanisms involved.

14.
Methods Mol Biol ; 2837: 185-198, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39044085

RESUMO

Covalently closed circular DNA (cccDNA) exists as a stable episomal minichromosome in the nucleus of hepatocytes and is responsible for hepatitis B virus (HBV) persistence. We recently reported a technique involving recombinant cccDNA (rcccDNA) of HBV by site-specific DNA recombination. A floxed monomeric HBV genome was engineered into a precursor plasmid (prcccDNA) which was excised via Cre/loxP-mediated DNA recombination to form a 3.3-kb rcccDNA bearing a loxP-chimeric intron. The foreign sequence was efficiently removed during RNA splicing, rendering a functionally seamless insertion. We characterized rcccDNA formation, effective viral transcription, and replication induced by rcccDNA both in vitro and in vivo. Furthermore, we closely simulated chronic hepatitis by using a replication-defective recombinant adenoviral vector to deliver rcccDNA to the transgenic mice expressing Cre recombinase, which led to prominent HBV persistence. Here, we describe a detailed protocol about how to construct and evaluate Cre/loxP-based recombinant HBV cccDNA system both in vitro and in vivo.


Assuntos
DNA Circular , DNA Viral , Vírus da Hepatite B , Integrases , Recombinação Genética , Replicação Viral , DNA Circular/genética , Vírus da Hepatite B/genética , Animais , Integrases/genética , Integrases/metabolismo , Camundongos , DNA Viral/genética , Humanos , Vetores Genéticos/genética , Camundongos Transgênicos , Plasmídeos/genética , DNA Recombinante/genética
15.
Protein Pept Lett ; 31(5): 386-394, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38967080

RESUMO

BACKGROUND: Staphylococcus aureus is a common pathogen with strains that are resistant to existing antibiotics. MurJ from S. aureus (SaMurJ), an integral membrane protein functioning as Lipid II flippase, is a potential target for developing new antibacterial agents against this pathogen. Successful expression and purification of this protein shall be useful in the development of drugs against this target. OBJECTIVE: In this study, we demonstrated the optimized expression and purification procedures of SaMurJ, identified suitable detergent for extracting and solubilizing the protein, and examined the peptidisc system to generate a detergent-free environment. METHODS: SaMurJ fused with N-terminal ten-His tag was expressed without induction. Six detergents were selected for screening the most efficient candidate for extraction and solubilization of the protein. The thermostability of the detergent-solubilized protein was assessed by evaluated temperature incubation. Different ratios of peptidisc bi-helical peptide (NSPr) to SaMurJ were mixed and the on-bead peptidisc assembly method was applied. RESULTS: SaMurJ expressed in BL21(DE3) was confirmed by peptide fingerprinting, with a yield of 1 mg SaMurJ per liter culture. DDM was identified as the optimum detergent for solubilization and the nickel affinity column enabled SaMurJ purification with a purity of ~88%. However, NSPr could not stabilize SaMurJ. CONCLUSION: The expression and purification of SaMurJ were successful, with high purity and good yield. SaMurJ can be solubilized and stabilized by a DDM-containing buffer.


Assuntos
Proteínas de Bactérias , Staphylococcus aureus , Staphylococcus aureus/enzimologia , Staphylococcus aureus/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/isolamento & purificação , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/metabolismo , Detergentes/química , Escherichia coli/genética , Escherichia coli/metabolismo , Solubilidade , Expressão Gênica , Uridina Difosfato Ácido N-Acetilmurâmico/análogos & derivados
16.
Sensors (Basel) ; 24(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38931492

RESUMO

A staggered vane-shaped slot-line slow-wave structure (SV-SL SWS) for application in W-band traveling wave tubes (TWTs) is proposed in this article. In contrast to the conventional slot-line SWSs with dielectric substrates, the proposed SWS consists only of a thin metal sheet inscribed with periodic grooves and two half-metal enclosures, which means it can be easily manufactured and assembled and has the potential for mass production. This SWS not only solves the problem of the dielectric loading effect but also improves the heat dissipation capability of such structures. Meanwhile, the SWS design presented here covers a -15 dB S11 frequency range from 87.5 to 95 GHz. The 3-D simulation for a TWT based on the suggested SWS is also investigated. Under dual-electron injection conditions with a total voltage of 17.2 kV and a total current of 0.3 A, the maximum output power at 90 GHz is 200 W, with a 3 dB bandwidth up to 4 GHz. With a good potential for fabrication using microfabrication techniques, this structure can be a good candidate for millimeter-wave TWT applications.

17.
J Food Drug Anal ; 32(2): 213-226, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38934690

RESUMO

Citrus peels contain abundant polyphenols, particularly flavonoids, and have been shown to exert lipid accumulation decreasing ability. In this study, Citrus depressa peel applied to oven drying and extracted with ethanol extract as CDEE to analyze its flavonoids compositions and investigated its effects on a high-fat diet (HFD)-induced obese mice model. CDEE contained several flavonoids such as hesperidin, sinesentin, nobiletin, tangeretin, 5-demethylnobiletin, and 5-demethyltangeretin. The mice fed an HFD, and administration of 2% CDEE to could decrease weight gain, abdominal fat weight, inguinal fat weight, and the adipocyte size, and CDEE also reduced serum total cholesterol (TCHO), triacylglycerol (TG) compared with mice fed only on HFD. CDEE hindered lipid accumulation through a decreased fatty acid synthase (FAS) protein expression via upregulation of the protein expression of AMP-activated protein kinase α (AMPKα). Moreover, CDEE modulated gut microbiota that altered by HFD through an increased abundance of Lactobacillus reuteri compared with the HFD group. The results demonstrated that CDEE helps decrease lipid accumulation through the AMPK pathway, which also indicates a prebiotic-like effect on gut microbiota.


Assuntos
Citrus , Dieta Hiperlipídica , Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade , Extratos Vegetais , Prebióticos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Citrus/química , Masculino , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Prebióticos/administração & dosagem , Prebióticos/análise , Dieta Hiperlipídica/efeitos adversos , Humanos , Triglicerídeos/metabolismo , Triglicerídeos/sangue , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/metabolismo , Bactérias/efeitos dos fármacos
18.
Front Genet ; 15: 1413484, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38894722

RESUMO

Injuries to the spinal cord nervous system often result in permanent loss of sensory, motor, and autonomic functions. Accurately identifying the cellular state of spinal cord nerves is extremely important and could facilitate the development of new therapeutic and rehabilitative strategies. Existing experimental techniques for identifying the development of spinal cord nerves are both labor-intensive and costly. In this study, we developed a machine learning predictor, ScnML, for predicting subpopulations of spinal cord nerve cells as well as identifying marker genes. The prediction performance of ScnML was evaluated on the training dataset with an accuracy of 94.33%. Based on XGBoost, ScnML on the test dataset achieved 94.08% 94.24%, 94.26%, and 94.24% accuracies with precision, recall, and F1-measure scores, respectively. Importantly, ScnML identified new significant genes through model interpretation and biological landscape analysis. ScnML can be a powerful tool for predicting the status of spinal cord neuronal cells, revealing potential specific biomarkers quickly and efficiently, and providing crucial insights for precision medicine and rehabilitation recovery.

19.
Adv Drug Deliv Rev ; 211: 115364, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38936664

RESUMO

The challenges of drug development in pediatric, pregnant and geriatric populations are a worldwide concern shared by regulatory authorities, pharmaceutical companies, and healthcare professionals. Model-informed drug development (MIDD) can integrate and quantify real-world data of physiology, pharmacology, and disease processes by using modeling and simulation techniques to facilitate decision-making in drug development. In this article, we reviewed current MIDD policy updates, reflected on the integrity of physiological data used for MIDD and the effects of physiological changes on the drug PK, as well as summarized current MIDD strategies and applications, so as to present the state of the art of MIDD in pediatric, pregnant and geriatric populations. Some considerations are put forth for the future improvements of MIDD including refining regulatory considerations, improving the integrity of physiological data, applying the emerging technologies, and exploring the application of MIDD in new therapies like gene therapies for special populations.


Assuntos
Desenvolvimento de Medicamentos , Humanos , Desenvolvimento de Medicamentos/métodos , Gravidez , Feminino , Criança , Idoso , Modelos Biológicos
20.
Diabetol Metab Syndr ; 16(1): 136, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907296

RESUMO

BACKGROUND: The interplay between diabetes mellitus (DM), glycemic traits, and vascular and valvular calcifications is intricate and multifactorial. Exploring potential mediators may illuminate underlying pathways and identify novel therapeutic targets. METHODS: We utilized univariable and multivariable Mendelian randomization (MR) analyses to investigate associations and mediation effects. Additionally, the multivariable MR analyses incorporated cardiometabolic risk factors, allowing us to account for potential confounders. RESULTS: Type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) were positively associated with both coronary artery calcification (CAC) and calcific aortic valvular stenosis (CAVS). However, fasting glucose (FG) was only linked to CAVS and showed no association with CAC. Additionally, CAVS demonstrated a causal effect on FG. Calcium levels partially mediated the impact of T2DM on both types of calcifications. Specifically, serum calcium was positively associated with both CAC and CAVS. The mediation effects of calcium levels on the impact of T2DM on CAC and CAVS were 6.063% and 3.939%, respectively. The associations between T2DM and HbA1c with calcifications were influenced by body mass index (BMI) and smoking status. However, these associations were generally reduced after adjusting for hypertension. CONCLUSION: Our findings suggest a genetically supported causal relationship between DM, glycemic traits, and vascular and valvular calcifications, with serum calcium playing a critical mediating role.

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