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Irritable bowel syndrome with diarrhea (IBS-D) is a common and chronic gastrointestinal disorder that is characterized by abdominal discomfort and occasional diarrhea. The pathogenesis of IBS-D is thought to be related to a combination of factors, including psychological stress, abnormal muscle contractions, and inflammation and disorder of the gut microbiome. However, there is still a lack of comprehensive analysis of the logical regulatory correlation among these factors. In this study, we found that stress induced hyperproduction of xanthine and altered the abundance and metabolic characteristics of Lactobacillus murinus in the gut. Lactobacillus murinus-derived spermidine suppressed the basal expression of type I interferon (IFN)-α in plasmacytoid dendritic cells by inhibiting the K63-linked polyubiquitination of TRAF3. The reduction in IFN-α unrestricted the contractile function of colonic smooth muscle cells, resulting in an increase in bowel movement. Our findings provided a theoretical basis for the pathological mechanism of, and new drug targets for, stress-exposed IBS-D.
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BACKGROUND: Hypokalemia has been associated with an increased risk of peritoneal dialysis (PD)-associated peritonitis. However, hypokalemia is commonly associated with malnutrition, inflammation, and severe coexisting comorbidities, which thus are suspected of being potential confounders. This study was aimed at testing whether hypokalemia was independently associated with the occurrence and prognosis of PD-associated peritonitis. METHODS: A national-level dataset from the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study was used to explore the independent association of serum potassium with PD-associated peritonitis. Unmatched and propensity score-adjusted multivariate competing risk models, as well as univariate competing risk models following 1:1 propensity score matching, were conducted to balance potential biases between patients with and without hypokalemia. The association between potassium levels prior to peritonitis and treatment failure due to peritonitis was also investigated. RESULTS: During a median follow-up of 25.7 months in 7220 PD patients, there was a higher incidence of peritonitis in patients with serum potassium below 4.0 mmol/L compared to those with higher serum levels (677 [0.114/patient-year] vs. 914 [0.096/patient-year], P = 0.001). After adjusting for demographics, laboratory tests, residual renal function, and medication use, baseline potassium levels below 4.0 mmol/L were not linked to an increased risk of peritonitis, with a hazard ratio of 0.983 (95% CI 0.855-1.130, P = 0.810). This result remained consistent in both the propensity score adjusted multivariate competing risk regression (HR = 0.974, 95% CI 0.829-1.145, P = 0.750) and the univariate competing risk regression after 1:1 propensity score matching (Fine-Gray test, P = 0.218). The results were similar when analyzing patients with serum potassium level above or below 3.5 mmol/L. Lastly, hypokalemia before the occurrence of peritonitis was not independently associated with treatment failure. CONCLUSION: Hypokalemia was not found to be an independent risk factor for PD-associated peritonitis or treatment failure of peritonitis in China.
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Alzheimer's disease (AD) is a common neurodegenerative disease with the main manifestations of progressive cognitive dysfunction,behavioral disorders,and gradual decline of living ability.The etiology of AD is complex,and the pathogenesis of this disease remains controversial.Calcium signaling plays an important role in regulating neuronal activities,including neurotransmitter release,synaptic plasticity,memory storage,and neuronal apoptosis.Increasing studies have shown that neuronal calcium dyshomeostasis is a major pathological factor in the occurrence and development of AD.This article reviews the role and research progress in intracellular calcium dyshomeostasis in AD,including the relationship between calcium homeostasis and amyloid ß,the role of calcium/calmodulin-dependent protein kinases in tau phosphorylation,calcium signaling pathways,the relationship between calcium homeostasis and mitochondrial function,autophagy,and neuroinflammation.
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Doença de Alzheimer , Cálcio , Homeostase , Doença de Alzheimer/metabolismo , Humanos , Cálcio/metabolismo , Peptídeos beta-Amiloides/metabolismo , Sinalização do Cálcio/fisiologia , Mitocôndrias/metabolismo , Proteínas tau/metabolismo , Autofagia/fisiologia , Animais , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Neurônios/metabolismo , FosforilaçãoRESUMO
OBJECTIVE: To determine the percentile reference values and reference curves of total body fat percentage in children and adolescents by sex and age, and to evaluate the reliability of different anthropometric indicators in screening for obesity in children and adolescents in order to explore the validity and practicality of a large-scale screening tool for childhood obesity and its desirable thresholds. METHODS: A total of 5983 children and adolescents aged 6-18 years from six primary and secondary schools were selected by stratified randomised cluster sampling in Hangzhou City in 2023, and their weight, height, waist and hip circumferences were measured, and the children's total body fat content was measured using the bioelectrical resistance-antibody composition analyser. A generalised additive model(GAMLSS) was used to construct a percentile reference curve for children's body fat percentage, and the performance of each anthropometric measure in correctly classifying children and adolescents as obese was assessed using receiver operating characteristic(ROC) curves. RESULTS: Over the period 6-18 years, body fat percentage in girls tended to increase with age from year to year, whereas in boys it tended to increase and then decrease. Fat mass index was the main factor contributing to the difference in BMI at the same age and sex(the optimal cutoff values were 26.82 and 24.52, with AUC values of 0.988 and 0.992, respectively), and the contribution of fat mass index was greater in those with a higher BMI. BMI, which had the largest area under the curve for both boys and girls, was the best indicator for assessing obesity in children and adolescents; the waist-to-height ratio(WHtR), with small variability and equally large area under curve values(0.980 for boys and 0.970 for girls), could simultaneously meet the requirements of accuracy and practicality for obesity assessment in mass screening of children and adolescents. CONCLUSION: This study establish the percentile reference value and reference curve of body fat percentage of children and adolescents aged 6-18 years in Hangzhou based on bioelectrical impedance method, and found that WHtR is a simple, effective and practical screening tool for childhood obesity with low variability, which can provide a reference basis for evaluating growth and development and identifying obesity in children aged 6-18 years in this region.
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Índice de Massa Corporal , Humanos , Adolescente , Criança , Masculino , Feminino , China , Valores de Referência , Obesidade Infantil/diagnóstico , Programas de Rastreamento/métodos , Antropometria/métodos , Peso Corporal , Tecido AdiposoRESUMO
BACKGROUND: There are few studies on the safety of sub-maximal exercise testing of aerobic exercise in apparently healthy Chinese populations. The purpose of this study was to explore the frequency of exercise electrocardiography (ECG) abnormalities and the corresponding exercise intensities, as well as the associated influencing factors, during a symptom-limited stepwise incremental cardiopulmonary exercise test (CPET) in an apparently healthy Chinese population. METHODS: A cross-sectional study was done in four communities, one urban and one rural in the North (Beijing) and in the South (Hezhou, Guangxi) of China from 1 January 2017 to 31 December 2018, respectively. Total of 1642 participants was recruited, 918 were eligible and completed demographic indicators, routine blood indicators, physical activity status, symptom-limited CPET and exercise ECG were included in the analysis. RESULTS: Of the exercise ECG outcomes, 10 (1.1%) were positive and occurred at exercise intensities ≥ 62.50% heart rate reserve (HRR); 44 (4.8%) were equivocal and 864 (94.1%) were normal. Individuals with Cardiovascular Disease Risk Factor (CVDRF) = 3-4 were 2.6 times more likely to have a equivocal and abnormal exercise ECG than those with CVDRF = 0-2. Exercise ECGs of individuals with CVDRF = 5-7 were 5.4 times more likely to be positive and abnormal than exercise ECGs of individuals with CVDRF = 0-2. CONCLUSIONS: The exercise intensity of 62.5% HRR can be used as a safe upper limit for safe participation in exercise in apparently healthy Chinese population; the greater the number of CVDRFs, the greater the likelihood of cardiovascular risk during exercise.
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Doenças Cardiovasculares , Eletrocardiografia , Teste de Esforço , Exercício Físico , Fatores de Risco de Doenças Cardíacas , Humanos , Estudos Transversais , Masculino , Feminino , China/epidemiologia , Adulto , Pessoa de Meia-Idade , Exercício Físico/fisiologia , Doenças Cardiovasculares/epidemiologia , População do Leste AsiáticoRESUMO
Excessive crowding in the visual periphery has been demonstrated in children with developmental dyslexia (DD). However, less is known about crowding in the fovea, even though foveal crowding is at least equally important, as reading is mostly accomplished through foveal vision. Here we used a special set of digit stimuli (Pelli fonts) to measure foveal crowding in DD and DD + ADHD children, and compared it to that in TD (typically developing) and ADHD children. We also used the Chinese reading acuity charts (C-READ) to assess the maximum reading speed and reading acuity, along with tests to evaluate cognitive attributes including phonological awareness, rapid automatized naming, morphological awareness, and orthographic knowledge. The results indicate significantly stronger foveal crowding in the DD and DD + ADHD groups, as well as in the ADHD group, than in the TD group. Furthermore, the DD and DD + ADHD groups exhibited poorer maximum reading speed and reading acuity compared to the ADHD and TD groups. Within the two DD groups, the slower maximum reading speed and higher reading acuity can be predicted by stronger foveal crowding. In addition, the DD and DD + ADHD groups performed the worst in four cognitive skills, with the DD group showing negative correlations between foveal crowding and performances across all these skills. Our findings thus move beyond previously well-documented peripheral crowding in dyslexia, and the easy administration of the Pelli-font-based crowding test may be useful for early diagnosis of developmental dyslexia in young children.
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High-performance circularly polarized luminescent (CPL) materials have received wide attention recently by virtue of broad application in circularly polarized light-emitting diodes, 3D display, and encryption. Reaching both high luminescence efficiency and strong luminescence dissymmetry factor (glum) is still a challenging goal that requires continuous efforts. Herein, we performed a systematic theoretical investigation on the chiroptical properties of helical cylindrical molecules (-)-[4]cyclo-2,6-anthracene [(-)-[4]CA2,6] and (P)-[4]cyclo-2,8-chrysenylene [(P)-[4]CC2,8], and found that the unique and symmetric cylindrical structure could make the transition dipole moment components offset along the cylindrical surface but concentrated along the vertical central axis. This structural superiority contributes the collinear electric and magnetic transition dipole moment vectors and thus the large glum. Based on the results of decomposed transition dipole moment vectors to individual atoms, an effective strategy to enhance the glum through introducing intramolecular short-range charge transfer by embedding B,N atoms is proposed. The decreased electric transition dipole moment and well-kept magnetic transition dipole moment enable the glum of B,N-embedded designed molecules (-)-[4]CA2,6-4BN and (P)-[4]CC2,8-4BN up to -0.31 and -0.56, respectively. This molecular-insight investigation deepens the understanding of the structure-property relationship and provides efficient guidance for improving glum of CPL materials.
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OBJECTIVE: Lower limb discrepancy (LLD) was frequently observed in patients with idiopathic scoliosis (IS), potentially associated with etiopathogenesis. Although sole lifts had been proposed as a conservative treatment for IS, evidence supporting their efficacy was limited. This study aimed to assess the effects of sole lift intervention on pediatric patients with mild IS, specifically focusing on thoracolumbar/lumbar (TL/L) curvature. METHODS: Twenty patients, with an average age of 12.3 ± 3.1 years and presenting mild TL/L curve (15.6° ± 6.2°), were selected from a pool of 267 pediatric IS patients in the outpatient of our spine center from February 2023 to August 2023. Inclusion criteria comprised a main TL/L curve ranging between 10° and 40°, the lower limb positioned at the convexity of the main curve, and LLD of less than 2 cm; individuals requiring bracing or surgical intervention were excluded. Custom sole lifts were used to address the shorter lower limb with the objective of leveling the pelvis. Radiographic evaluations were conducted both before and after intervention using standing full spine posteroanterior radiographs and full leg length radiographs. Statistical analysis was undertaken to evaluate curve correction and its associations with other influencing factors. RESULTS: The mean structural and functional LLD were 7.1 ± 4.5 mm and 7.1 ± 4.1 mm, respectively. Among the 20 patients, four exhibited structural LLD greater than 10 mm. The average follow-up duration was 6.4 ± 1.9 months (range: 3-8 months). Following sole lift intervention (7.0 ± 3.0 mm), a significant reduction was observed in the TL/L curve compared to the pre-sole lifting measurements (15.6° ± 6.2° vs. 12.1° ± 7.2°, p < 0.001), as well as a notable decrease in the thoracic curve (12.2° ± 4.0° vs. 8.6° ± 6.3°, p = 0.064). Nine patients experienced a significant curve reduction of ≥5°, while eight showed a reduction between 0° and 5°; however, two patients exhibited no change in curve magnitude. Furthermore, the correction rate of the TL/L curve correlated significantly with functional LLD (r = -0.484, p = 0.030) and pelvic obliquity (r = -0.556, p = 0.011), highlighting the active pelvic compensation in maintaining balance between the spine and lower limbs. Conversely, no significant correlation was observed between curve correction and structural LLD (p > 0.05). Additionally, even after adjusting for other influencing factors, the TL/L Cobb angle remained significantly different between pre- and post-sole lifting (p = 0.037). CONCLUSION: This study confirmed the effectiveness of sole lift intervention in correcting TL/L and thoracic curves among the mild IS children with a main TL/L curve, providing a supplementary conservative treatment option for patients with the lower limb at the convexity of the main curve. Moreover, our findings underscored the active compensation of the lower limbs and the pelvis in the etiopathogenesis of IS, highlighting the importance of considering their influence in treatment strategies.
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Integration of spirocycles with buckybowls is a promising strategy to construct three-dimensional (3D) curved π-systems and to endow distinctive physicochemical features arising from buckybowls. Herein, a series of carbon-bridged spiro-type heterosumanenes (spiro-HSEs) were synthesized by combining 9,9'-spirobifluorene and dichalcogenasumanenes (DCSs). It is found that spiro-conjugation plays an important role in the geometric and electronic structures of spiro-HSEs. The bowl depth of DCSs moiety becomes larger in the spiro-HSEs. Owing to the Jahn-Teller (J-T) effect, two DCSs segments of spiro-HSEs have different bowl depths accompanied with the unequal distribution of charge in radical cation state. Taking advantage of the typical reactions of DCSs, selective transformations of spiro-HSEs have been adopted in accordance to the nature of chalcogen atoms (S, Se, Te) to bestow the value-added functionalities. The emissive property is enhanced by converting the thiophene rings of S-doped spiro-HSE into thiophene S,S-dioxides. A chiroptical polycycle could be produced by ring-opening of the edge benzene of Se-doped spiro-HSE. The covalent adduct of Te-doped spiro-HSE with Br2 forms non-centrosymmetric halogen-bonded networks, resulting in the high performance second-order nonlinear optics (NLO).
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Non-benzenoid polycyclic aromatic hydrocarbons (PAHs) have received considerable attention owing to their distinctive optical and electrical properties. Nevertheless, the synthesis and optoelectronic application of non-benzenoid PAHs remain challenging. Herein, we present a facile synthesis of linear non-benzenoid PAH with an armchair edge, diACh, by fusing chrysene with two azulene units. We systematically investigated the optical and electrical properties, which were also compared to its isomers, including benzenoid and non-benzenoid zigzag edge isomers. diACh exhibits global aromaticity, good planarity, and suitable highest occupied molecular orbital/lowest unoccupied molecular orbital energy levels. The protonation of diACh in solution successively forms a stable tropylium cation and dication. Moreover, the neutral, cationic, and dicationic states of diACh can be transformed with remarkable reversibility during the protonation-deprotonation process, as confirmed by ultraviolet-visible absorptions, fluorescence spectra, 1H nuclear magnetic resonance, and theoretical calculations. Additionally, we fabricate p-type organic field-effect transistor (OFET) devices based on diACh with hole mobility up to 0.026 cm2 V-1 s-1, and we further develop OFET-based acid vapor sensors with good sensitivity, recyclability, and selectivity. These findings underscore the unique properties of linear non-benzenoid PAHs with an armchair edge engendered by the fusion of azulene with the acene backbone, showcasing prospective applications in organic optoelectronics.
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Doping polycyclic aromatic hydrocarbons with heteroatoms enables manipulation of their electronic structures. Herein, the structures and properties of phosphorus (P) doped heterosumanenes (HSEs) are regulated by varying the valence states of P-dopant. The phosphine sulfide (PV) and chalcogens (S, Se, Te) co-doped HSEs (1-3) are reduced to trivalent phosphorus (PIII) doped analogues 4-6. Then, the PIII-dopants on 4-6 are converted to phosphonium salts (R4P+), giving 7-9. The valence states of P-dopant show great influence on molecular geometries and electronic structures. Taking P and S co-doped HSEs as example, bowl-depths increase in the order of 1 (PV) < 7 (R4P+) < 4 (PIII), and the HOMO energy levels and HOMO-LUMO gaps increase to be 7 < 1 < 4. Consistent with the theoretical calculation, the first oxidation potentials decrease and the absorption/emission bands show blue shift from 7 to 1 to 4. The transformation of PV to PIII leads to large variations on the coordination with Ag+, owing to the alteration of coordination site from P=S to PIII. The phosphonium salts show ring-opening of phosphole rings under electrochemical reduction. It is found that chalcogen atoms play pivotal roles on coordination patterns of coordination complexes and the conversion rates of ring-opening reactions.
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Mechanochemistry studies the effect of mechanical force on chemical bonds, bringing opportunities for synthesizing alloys, ceramics, organics, polymers, and biomaterials. A vital issue of applying macro-scale mechanical force to manipulate crystal structures is finding ways to precisely adjust the force directions to break micro-scale target chemical bonds. Inspired by a common technique of driving a wedge into the wood to make wood chopping much easier, a wedging strategy of splitting three-dimensional structured crystalline frameworks and then converting them to nanosheets was proposed, where specific molecules were wedged into crystalline frameworks to drive the directional transmission of mechanical force to break chemical bonds. As a result, various crystalline framework nanosheets including metal-organic framework nanosheets, covalent organic framework nanosheets, and coordination polymer nanosheets were fabricated. This wedging crystal strategy exhibits advantages of operability, flexibility and designability, and furthermore, it is expected to expand mechanochemistry applications in material preparation.
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This paper presents the design of a Lyapunov matrix-based adaptive resilient controller for unmanned marine vehicles (UMVs) under state-dependent sensor attacks, input-dependent thruster attacks, and time delays. Different from the thruster attack model that depends on state information, the thruster attack model studied in this paper is related to control input, that is, the input-dependent thruster attacks. This implies that the designed correction signal is also affected by the attacks. To mitigate the impact of the considered sensor attacks and thruster attacks on UMVs, an adaptive mechanism is employed to estimate the attack factors. Furthermore, a Lyapunov matrix-based complete-type Lyapunov-Krasovskii functional (LKF) is introduced, in which more comprehensive time delay information are considered. Based on this, linear matrix inequality (LMI) method and Jensen's inequality are used to obtain sufficient conditions for the existence of the controller. The proposed controller guarantees that the state errors of UMVs converge asymptotically to zero with the adaptive H∞ performance index no larger than γ0. Finally, the efficacy of the proposed approach is verified by simulation results.
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Vaccines and first-generation antiviral therapeutics have provided important protection against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a need for additional therapeutic options that provide enhanced efficacy and protection against potential viral resistance. The SARS-CoV-2 papain-like protease (PLpro) is one of the two essential cysteine proteases involved in viral replication. While inhibitors of the SARS-CoV-2 main protease have demonstrated clinical efficacy, known PLpro inhibitors have, to date, lacked the inhibitory potency and requisite pharmacokinetics to demonstrate that targeting PLpro translates to in vivo efficacy in a preclinical setting. Here, we report the machine learning-driven discovery of potent, selective, and orally available SARS-CoV-2 PLpro inhibitors, with lead compound PF-07957472 (4) providing robust efficacy in a mouse-adapted model of COVID-19 infection.
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Antivirais , Tratamento Farmacológico da COVID-19 , Proteases Semelhantes à Papaína de Coronavírus , Modelos Animais de Doenças , SARS-CoV-2 , Animais , Camundongos , SARS-CoV-2/efeitos dos fármacos , Antivirais/farmacologia , Antivirais/química , Antivirais/farmacocinética , Antivirais/uso terapêutico , Proteases Semelhantes à Papaína de Coronavírus/antagonistas & inibidores , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , Humanos , COVID-19/virologia , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/uso terapêutico , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , Aprendizado de Máquina , Feminino , Replicação Viral/efeitos dos fármacosRESUMO
The untranslated regions (UTRs) within plant mRNAs play crucial roles in regulating gene expression and the functionality of post-translationally modified proteins by various mechanisms. These regions are vital for plants' ability to sense to multiple developmental and environmental stimuli. In this study, we conducted a genome-wide analysis of UTRs and UTR-containing genes in maize (Zea mays). Using the ZmLAZ1 family as a case study, we demonstrated that the length of 5' UTRs could influence gene expression levels by employing GUS reporter gene assays. Although maize and arabidopsis (Arabidopsis thaliana), as well as rice (Oryza sativa), have distinct functional categories of UTR-containing genes, we observed a similar lengthwise distribution of UTRs and a recurring appearance of certain gene ontology (GO) terms between maize and rice. These suggest a potentially conserved mechanism within the Poaceae species. Furthermore, the analysis of cis-acting elements in these 5' UTRs of the ZmLAZ1 gene family further supports the hypothesis that UTRs confer functional specificity to genes in a length-dependent manner. Our findings offer novel insights into the role of UTRs in maize, contributing to the broader understanding of gene expression regulation in plants.
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Regiões 5' não Traduzidas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Zea mays , Zea mays/genética , Zea mays/metabolismo , Regiões 5' não Traduzidas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oryza/genética , Oryza/metabolismo , Família Multigênica , Arabidopsis/genéticaRESUMO
High Fischer ratio oligopeptides derived from Antarctic krill (HFOPs-AK) were screened, and their hepatoprotective effects and potential mechanisms were investigated. Herein, HFOPs-AK, with a Fischer ratio of 29 g/g (40.22 mol/mol) (MW < 1000 Da), were prepared via two-step enzymatic hydrolysis using chymotrypsin and flavourzyme and aromatic amino acid removal. Seventy-eight characteristic peptides were identified from HFOPs-AK through UHPLC-Q/TOF, with peptides containing Leu, Val, or Ile accounting for 79%. High hepatoprotective peptides were purified using GFC and RP-HPLC and identified as SDELGW and LLGWDDM. Furthermore, a murine model of acute liver injury induced by alcohol was successfully established. It was demonstrated that the oral administration of HFOPs-AK (800 mg per kg bw per d) remarkably increased the contents of ADH and ALDH compared with the model group, reaching 3.40 and 5.10 U mg-1 prot, respectively. Further, it was revealed that HFOPs-AK could effectively mitigate hepatic oxidative stress by increasing the levels of GSH-Px (p < 0.01) and decreasing the level of MDA (p < 0.05). Additionally, HFOPs-AK (800 mg per kg bw per d) attenuated liver inflammation by down-regulating the mRNA levels of TNF-α, IL-1ß, and IL-6 by 40.45%, 38.48%, and 35.83%, respectively. Therefore, HFOPs-AK may have the potential as a new nutritional supplement for the treatment of alcoholic liver injury.
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Euphausiacea , Fígado , Oligopeptídeos , Estresse Oxidativo , Animais , Euphausiacea/química , Camundongos , Oligopeptídeos/farmacologia , Oligopeptídeos/química , Masculino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/prevenção & controle , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Regiões AntárticasRESUMO
The stability and nutritional integrity of emulsions are susceptible to various factors including thermal treatment, solid-liquid ratio, and sterilization. In this study, the physicochemical stability and immunomodulatory activities of an oil-in-water emulsion containing immune peptides (TUFSE) were assessed through particle size, zeta potential, related cytokines, and so on. When the temperature was 70°C and a solid-liquid ratio of 1:4, the emulsion revealed stability at high-pressure homogenization, with the small particle size. The loss rates of vitamins were 8.57%-62.26% in 6 months at 25°C. After treatment with cyclophosphamide (CTX), lymphocyte proliferation activity in TUFSE-H group increased (p < 0.05), and immune globulin levels were notably elevated (p < 0.05) in TUFSE groups compared to model group. It confirms the parameters of the emulsion, suggesting its ability to be prepared with minimal vitamin loss while simultaneously improving the disease status in CTX-treated tumor-bearing mice. It shows potential as an immune-enhancing supplement with significant potential value. PRACTICAL APPLICATION: This study validated the parameters of the oil-in-water emulsion and showed that it can be stably prepared with minor vitamin loss while simultaneously improving the disease status in CTX-treated tumor-bearing mice. TUFSE-H group exhibited a notable increase in lymphocytes proliferation activity, whereas serum cytokines and immune globulin levels were elevated compared to MC group, indicating its potential as an immune-enhancing supplement with substantial value.
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Emulsões , Tamanho da Partícula , Animais , Camundongos , Ciclofosfamida/farmacologia , Agentes de Imunomodulação/farmacologia , Citocinas/metabolismo , Água/química , Proliferação de Células/efeitos dos fármacos , Masculino , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Óleos/química , Óleos/farmacologia , Estabilidade de Medicamentos , Linhagem Celular Tumoral , Vitaminas/farmacologia , FemininoRESUMO
Objectives: To evaluate the efficacy of peri-trigger female reproductive hormones (FRHs) in the prediction of oocyte maturation in normal ovarian reserve patients during the in vitro fertilization-embryo transfer (IVF-ET) procedure. Materials and Methods: A hospital database was used to extract data on IVF-ET cases from January 2020 to September 2021. The levels of female reproductive hormones, including estradiol (E2), luteinizing hormone (LH), progesterone (P), and follicle-stimulating hormone (FSH), were initially evaluated at baseline, the day of the trigger, the day after the trigger, and the day of oocyte retrieval. The relative change in E2, LH, P, FSH between time point 1 (the day of trigger and baseline) and time point 2 (the day after the trigger and day on the trigger) was defined as E2_RoV1/2, LH_RoV1/2, P_RoV1/2, and FSH_RoV1/2, respectively. Univariable and multivariable regression were performed to screen the peri-trigger FRHs for the prediction of oocyte maturation. Results: A total of 118 patients were enrolled in our study. Univariable analysis revealed significant associations between E2_RoV1 and the rate of MII oocytes in the GnRH-agonist protocol group (p < 0.05), but not in the GnRH-antagonist protocol group. Conversely, P_RoV2 emerged as a potential predictor for the rate of MII oocytes in both protocol groups (p < 0.05). Multivariable analysis confirmed the significance of P_RoV2 in predicting oocyte maturation rate in both groups (p < 0.05), while the association of E2_RoV1 was not significant in either group. However, within the subgroup of high P_RoV2 in the GnRH-agonist protocol group, association was not observed to be significant. The C-index was 0.83 (95% CI [0.73-0.92]) for the GnRH-agonist protocol group and 0.77 (95% CI [0.63-0.90]) for the GnRH-antagonist protocol group. The ROC curve analysis further supported the satisfactory performance of the models, with area under the curve (AUC) values of 0.79 for the GnRH-agonist protocol group and 0.81 for the GnRH-antagonist protocol group. Conclusions: P_RoV2 showed significant predictive value for oocyte maturation in both GnRH-agonist and GnRH-antagonist protocol groups, which enhances the understanding of evaluating oocyte maturation and inform individualized treatment protocols in controlled ovarian hyperstimulation during IVF-ET for normal ovarian reserve patients.
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Transferência Embrionária , Estradiol , Fertilização in vitro , Hormônio Foliculoestimulante , Hormônio Luteinizante , Reserva Ovariana , Indução da Ovulação , Progesterona , Humanos , Feminino , Adulto , Estudos Retrospectivos , Fertilização in vitro/métodos , Reserva Ovariana/efeitos dos fármacos , Reserva Ovariana/fisiologia , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Transferência Embrionária/métodos , Progesterona/sangue , Indução da Ovulação/métodos , Oócitos/efeitos dos fármacos , Oócitos/crescimento & desenvolvimento , Gravidez , Oogênese/efeitos dos fármacos , Oogênese/fisiologia , Recuperação de Oócitos/métodosRESUMO
BACKGROUND AND OBJECTIVE: Diabetic foot (DF) complications often lead to severe vascular issues. This study investigated the effectiveness of enhanced external counterpulsation (EECP) and its derived innovative compression strategies in addressing poor perfusion in DF. Although developing non-invasive and efficient treatment methods for DF is critical, the hemodynamic alterations during EECP remain underexplored despite promising outcomes in microcirculation. This research sought to address this gap by developing a patient-specific 0D-1D model based on clinical ultrasound data to identify potentially superior compression strategies that could substantially enhance blood flow in patients with DF complications. METHODS: Data were gathered from 10 patients with DF utilizing ultrasound for blood flow rate and computed tomography angiography (CTA) to identify lower limb conditions. Clinical measurements during standard EECP, with varying cuff pressures, facilitated the creation of a patient-specific 0D-1D model through a two-step parameter estimation process. The accuracy of this model was verified via comparison with the clinical measurements. Four compression strategies were proposed and rigorously evaluated using this model: EECP-Simp-I (removing hip cuffs), EECP-Simp-II (further removing the cuffs around the lower leg), EECP-Impr-I (removing all cuffs around the affected side), and EECP-Impr-II (building a loop circulation from the healthy side to the affected side). RESULTS: The predicted results under the rest and standard EECP states were generally closely aligned with clinical measurements. The patient-specific 0D-1D model demonstrated that EECP-Simp-I and EECP-Impr-I contributed similar enhancement to perfusion in the dorsal artery (DA) and were comparable to standard EECP, while EECP-Simp-II had the least effect and EECP-Impr-II displayed the most significant enhancement. Pressure at the aortic root (AO) remained consistent across strategies. CONCLUSIONS: EECP-Simp-I is recommended for patients with DF, emphasizing device simplification. However, EECP-Simp-II is discouraged as it significantly diminished blood perfusion in this study, except in cases of limb fragility. EECP-Impr-II showed superior enhancement of blood perfusion in DA to all other strategies but required a more complex EECP device. Despite increased AO pressure in all the proposed compression strategies, safety could be guaranteed as the pressue remained within a safe range.