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1.
Sci Rep ; 14(1): 8669, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622251

RESUMO

The factors influencing geogrid-soil interface characteristics are critical design parameters in some geotechnical designs. This study describes pull-out tests performed on gravelly soils commonly encountered in the Xinjiang region and reinforced with two types of geogrids. The factors affecting the geogrid-gravelly soil interface properties are investigated with different experimental loading methods (pull-out velocity, normal stress), geogrid types, and soil particle size distributions and water contents. The ultimate pull-out force increases with the normal stress and pull-out velocity. Furthermore, with increasing coarse particle content and water content, the ultimate pull-out force increases and then decreases sharply. Based on these research results, this paper provides reasonable parameters and recommendations for the design and pull-out testing of reinforced soil in engineering structures. In reinforced soil structure design, the grid depth should be increased appropriately, and the coarse particle content of the overlying soil should be between 30 and 40%. During construction, the gravelly soil should be compacted to the maximum compaction at the optimal water content, and the structure should have a reasonable waterproofing system. According to the calculation results of the interface strength parameters, the uniaxial geogrid-gravelly soil interface has a high cohesive force csg, which should not be ignored in reinforced soil structure design.

2.
Sci Rep ; 14(1): 8670, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622371

RESUMO

Hypoxic pulmonary hypertension (HPH) is a pulmonary vascular disease primarily characterized by progressive pulmonary vascular remodeling in a hypoxic environment, posing a significant clinical challenge. Leveraging data from the Gene Expression Omnibus (GEO) and human autophagy-specific databases, osteopontin (OPN) emerged as a differentially expressed gene, upregulated in cardiovascular diseases such as pulmonary arterial hypertension (PAH). Despite this association, the precise mechanism by which OPN regulates autophagy in HPH remains unclear, prompting the focus of this study. Through biosignature analysis, we observed significant alterations in the PI3K-AKT signaling pathway in PAH-associated autophagy. Subsequently, we utilized an animal model of OPNfl/fl-TAGLN-Cre mice and PASMCs with OPN shRNA to validate these findings. Our results revealed right ventricular hypertrophy and elevated mean pulmonary arterial pressure (mPAP) in hypoxic pulmonary hypertension model mice. Notably, these effects were attenuated in conditionally deleted OPN-knockout mice or OPN-silenced hypoxic PASMCs. Furthermore, hypoxic PASMCs with OPN shRNA exhibited increased autophagy compared to those in hypoxia alone. Consistent findings from in vivo and in vitro experiments indicated that OPN inhibition during hypoxia reduced PI3K expression while increasing LC3B and Beclin1 expression. Similarly, PASMCs exposed to hypoxia and PI3K inhibitors had higher expression levels of LC3B and Beclin1 and suppressed AKT expression. Based on these findings, our study suggests that OPNfl/fl-TAGLN-Cre effectively alleviates HPH, potentially through OPN-mediated inhibition of autophagy, thereby promoting PASMCs proliferation via the PI3K-AKT signaling pathway. Consequently, OPN emerges as a novel therapeutic target for HPH.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Camundongos , Humanos , Animais , Hipertensão Pulmonar/tratamento farmacológico , Osteopontina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Artéria Pulmonar/metabolismo , Hipóxia/complicações , Hipóxia/genética , Hipóxia/metabolismo , Hipertensão Arterial Pulmonar/metabolismo , RNA Interferente Pequeno/metabolismo , Autofagia/genética , Proliferação de Células , Miócitos de Músculo Liso/metabolismo , Remodelação Vascular
3.
Neurol Neuroimmunol Neuroinflamm ; 11(3): e200221, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38579189

RESUMO

BACKGROUND AND OBJECTIVES: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims to investigate the genetic basis of this disease in the Chinese Han population. METHODS: We performed a genome-wide association study and fine-mapping study within the major histocompatibility complex (MHC) region of 413 Chinese patients with anti-NMDAR encephalitis recruited from 6 large tertiary hospitals and 7,127 healthy controls. RESULTS: Our genome-wide association analysis identified a strong association at the IFIH1 locus on chromosome 2q24.2 (rs3747517, p = 1.06 × 10-8, OR = 1.55, 95% CI, 1.34-1.80), outside of the human leukocyte antigen (HLA) region. Furthermore, through a fine-mapping study of the MHC region, we discovered associations for 3 specific HLA class I and II alleles. Notably, HLA-DQB1*05:02 (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59) demonstrates the strongest association among classical HLA alleles, closely followed by HLA-A*11:01 (p = 4.36 × 10-7; OR, 1.52; 95% CI 1.29-1.79) and HLA-A*02:07 (p = 1.28 × 10-8; OR, 1.87; 95% CI 1.50-2.31). In addition, we uncovered 2 main HLA amino acid variation associated with anti-NMDAR encephalitis including HLA-DQß1-126H (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59), exhibiting a predisposing effect, and HLA-B-97R (p = 3.40 × 10-8; OR, 0.63; 95% CI 0.53-0.74), conferring a protective effect. Computational docking analysis suggested a close relationship between the NR1 subunit of NMDAR and DQB1*05:02. DISCUSSION: Our findings indicate that genetic variation in IFIH1, involved in the type I interferon signaling pathway and innate immunity, along with variations in the HLA class I and class II genes, has substantial implications for the susceptibility to anti-NMDAR encephalitis in the Chinese Han population.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Cadeias beta de HLA-DQ , Helicase IFIH1 Induzida por Interferon , Humanos , Encefalite Antirreceptor de N-Metil-D-Aspartato/genética , Estudo de Associação Genômica Ampla , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II/genética , Antígenos HLA-A/genética , Cadeias beta de HLA-DQ/genética , Helicase IFIH1 Induzida por Interferon/genética
4.
Med Biol Eng Comput ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38622437

RESUMO

Mandibular defect repair has always been a clinical challenge, facing technical bottleneck. The new materials directly affect technological breakthroughs in mandibular defect repair field. Our aim is to fabricate a scaffold of advanced biomaterials for repairing of small mandibular defect. Therefore, a novel dual-channel scaffold consisting of silk fibroin/collagen type-I/hydroxyapatite (SCH) and polycaprolactone/hydroxyapatite (PCL/HA) was fabricated by cryogenic 3D printing technology with double nozzles. The mechanical properties and behaviors of the dual-channel scaffold were investigated by performing uniaxial compression, creep, stress relaxation, and ratcheting experiments respectively. The experiments indicated that the dual-channel scaffold was typical non-linear viscoelastic consistent with cancellous tissue; the Young's modulus of this scaffold was 60.1 kPa. Finite element analysis (FEA) was employed performing a numerical simulation to evaluate the implantation effect in mandible. The stress distribution of the contact area between scaffold and defect was uniform, the maximum Mises stress of cortical bone and cancellous bone in defect area were 54.520 MPa and 3.196 MPa, and the maximum displacement of cortical bone and cancellous bone in defect area were 0.1575 mm and 0.1555 mm respectively, which distributed in the incisor region. The peak maximum Mises stress experienced by the implanted scaffold was 3.128 × 10-3 MPa, and the maximum displacement was 6.453 × 10-2 mm distributed near incisor area. The displacement distribution of the scaffold was consistent with that of cortical and cancellous bone. The scaffold recovered well when the force applied on it disappeared. Above all, the dual-channel scaffold had excellent bio-mechanical properties in implanting mandible, which provides a new idea for the reconstruction of irregular bone defects in the mandible and has good clinical development prospects.

5.
Regen Biomater ; 11: rbae031, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605850

RESUMO

The utilization of intracanal medicaments is an indispensable procedure in root-canal treatment. However, the conventional intracanal medicaments still need improvement regarding antimicrobial efficacy and ease of clinical operation. To address the above issues, OCT/PECT@OCT + ALK composite hydrogel characterized by programming sequential release of dual antimicrobial agents has been proposed. Thanks to the self-assemble ability of amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT), dual hydrophilic and hydrophobic antimicrobial agents could be easily encapsulated in the hydrogel system and tailored for sequential drug release for a better antibiofilm effect. The hydrophilic octenidine (Octenidine dihydrochloride, OCT-HCl) is encapsulated in the hydrophilic part of hydrogel for instantaneous elevating the drug concentration through bursting release, and the hydrophobic octenidine (Octenidine, OCT) is further loaded into the PECT nanoparticles to achieve a slower and sustained-release profile. Additionally, calcium hydroxide (Ca(OH)2) was incorporated into the system and evenly dispersed among PECT nanoparticles to create an alkaline (ALK) environment, synergistically enhancing the antibiofilm effect with higher efficiency and prolonged duration. The antibiofilm effect has been demonstrated in root-canal models and apical periodontitis rats, exhibiting superior performance compared to clinically used Ca(OH)2 paste. This study demonstrates that OCT/PECT@OCT + ALK composite thermosensitive hydrogel is a potential intracanal medicament with excellent antibiofilm effect and clinical operability.

6.
Early Hum Dev ; 192: 106007, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38608365

RESUMO

BACKGROUND: In recent years, China has adjusted its fertility policies to optimize the population structure by implementing the two-child and three-child policies. Some patients with systemic lupus erythematosus (SLE) are considering the possibility of having a second child. The issue is whether the offspring from the second childbirth will have favorable long-term developmental outcomes. OBJECTIVE: The research aims to investigate the long-term physical, neurological, and social-emotional development outcomes of children born to mothers with SLE at different parities. This study aims to offer valuable insights and references for SLE patients who are considering subsequent pregnancies and require information about potential developmental outcomes for their future children. METHODS: The study conducted a follow-up of children born to SLE mothers who were admitted to the obstetrics department between January 1, 2016, and September 30, 2021. The SLE patients were categorized into two groups based on their history of live delivery: the primiparity group and the multiparity group. The physical development status, including weight, height (length), and other relevant factors, was evaluated in both groups. The Ages and Stages Questionnaires, Third Edition (ASQ-3) was utilized to assess the neurological development in five domains, encompassing communication, gross motor, fine motor, problem solving and personal-social. Social-emotional development was assessed using the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE). The weight, height (length), body mass index, and ASQ-3 domain scores were standardized into Z-scores to enable comparison across various ages and genders. RESULTS: The study revealed that the weight Z-score and BMI Z-score of the children in the multiparity group were significantly higher compared to those in the primiparity group. However, there were no statistically significant differences in the proportions of overweight and obesity between the two groups. In terms of neurological developmental outcomes, the Z-scores of the communication and gross motor domains in the ASQ-3 assessment were significantly higher in the multiparity group compared to those in the primiparity group. The proportion of abnormal screening for social and emotional development in the children of the multiparity group was lower than that of the primiparity group, although this difference did not reach statistical significance. CONCLUSIONS: The long-term weight development, communication and gross motor development of children born to SLE patients in the multiparity group were better than those in the primiparity group. However, there was no significant difference in social-emotional development between the two groups.

7.
Heliyon ; 10(7): e29129, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601559

RESUMO

To better meet the emotional needs of older residents and to improve the design of age-friendly indoor interface forms, this study uses Kansei engineering as the theoretical basis for an exploration of the mapping relationship between emotional needs and interface forms. First, we collected spatial interface forms through in-home research, and using focus groups, we summarized and produced test samples for interface forms; at the same time, we screened out adjective word pairs that could fully represent the emotional needs of older people in the city of Jinan, drawing on expert interviews; then, we invited 500 older adults living in Jinan all year to evaluate each interface form using representative adjective word pairs as the emotional evaluation criteria, following the semantic differential method. Subsequently, the participants were invited to evaluate and score the interface form samples using representative adjective word pairs as the standard of emotional evaluation, employing the semantic differential method. Finally, the evaluation scores were input into SPSS software for the Kruskal-Wallis test to explore the relationships between various interface forms and emotional needs. The experimental results showed that the assessment scoring results for each interface form in each set of pairs of adjectives that differed significantly, where each interface had a clear emotional tendency. This study successfully established a mapping model for matching indoor interface forms with emotional needs in age-friendly housing in Jinan. These findings can provide a reference for future practice of designing residential indoor interface forms to match the emotional needs of older people in Jinan.

8.
Asian J Surg ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604847
10.
Adv Sci (Weinh) ; : e2400336, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605606

RESUMO

The practical application of aqueous Zn-ion batteries (AZIBs) is hindered by the crazy Zn dendrites growth and the H2O-induced side reactions, which rapidly consume the Zn anode and H2O molecules, especially under the lean electrolyte and Zn anode. Herein, a natural disaccharide, d-trehalose (DT), is exploited as a novel multifunctional co-solvent to address the above issues. Molecular dynamics simulations and spectral characterizations demonstrate that DT with abundant polar -OH groups can form strong interactions with Zn2+ ions and H2O molecules, and thus massively reconstruct the coordination structure of Zn2+ ions and the hydrogen bonding network of the electrolyte. Especially, the strong H-bonds between DT and H2O molecules can not only effectively suppress the H2O activity but also prevent the rearrangement of H2O molecules at low temperature. Consequently, the AZIBs using DT30 electrolyte can show high cycling stability even under lean electrolyte (E/C ratio = 2.95 µL mAh-1), low N/P ratio (3.4), and low temperature (-12 °C). As a proof-of-concept, a Zn||LiFePO4 pack with LiFePO4 loading as high as 506.49 mg can be achieved. Therefore, DT as an eco-friendly multifunctional co-solvent provides a sustainable and effective strategy for the practical application of AZIBs.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38607487

RESUMO

In building cooling, the demand for cooling surges during specific times, stressing air-conditioner operation, and additional cooling is often wasted during low-demand periods. Water-phase change material (W-PCM)-based thermal energy storage (TES) allows for load shifting and effective management of peak demand by storing cooling energy when the demand is low. This stored energy can be deployed during peak hours, decreasing energy usage and associated CO2 emissions. However, the use of W-PCMs was hindered by phase separation, slow energy transfer, and high supercooling degree (SCD). We synthesized coconut shell (CNS)-produced activated carbon (ACC) to use as a thermal enhancer in W-PCMs for the first time. First, ACC was synthesized from CNS via steam activation. Then, transmission electron microscopy was used to confirm the pore morphology of the CNS-ACC. The synthesis of the W-PCM with various weight percentages (0.1, 0.6, and 1.2) of CNS-ACC was accomplished in two steps. Zeta potential distribution analysis revealed that the W-PCM with CNS-ACC exhibited colloidal stability. Thermal conductivity (TC) and thermogram analyses revealed that a dose of 1.2 wt% CNS-ACC enhanced liquid and solid TC by 9% and 22%, respectively, despite a 6% and 8% decrease in specific heat and latent heat. More specifically, solidification assessment in a spherical enclosure revealed 100% suppression of SCD with 1.2 wt% CNS-ACC. As a result of this and the enhanced TC, the overall solidification process was accelerated, reducing the overall duration by 18.5%. Thus, the combination of CNS-derived ACC and W-PCM for TES in building cooling could reduce energy consumption and associated CO2 emissions.

12.
Poult Sci ; 103(6): 103705, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38598913

RESUMO

Compared to high-yield commercial laying hens, Chinese indigenous chicken breeds have poor egg laying capacity due to the lack of intensive selection. However, as these breeds have not undergone systematic selection, it is possible that there is a greater abundance of genetic variations related to egg laying traits. In this study, we assessed 5 egg number (EN) traits at different stages of the egg-laying period: EN1 (from the first egg to 23 wk), EN2 (from 23 to 35 wk), EN3 (from 35 to 48 wk), EN4 (from the first egg to 35 wk), and EN5 (from the first egg to 48 wk). To investigate the molecular mechanisms underlying egg number traits in a Chinese local chicken breed, we conducted a genome-wide association study (GWAS) using data from whole-genome sequencing (WGS) of 399 Laiwu Black chickens. We obtained a total of 3.01 Tb of raw data with an average depth of 7.07 × per individual. A total of 86 genome-wide suggestive or significant single-nucleotide polymorphisms (SNP) contained within a set of 45 corresponding candidate genes were identified and found to be associated with stages EN1-EN5. The genes vitellogenin 2 (VTG2), lipase maturation factor 1 (LMF1), calcium voltage-gated channel auxiliary subunit alpha2delta 3 (CACNA2D3), poly(A) binding protein cytoplasmic 1 (PABPC1), programmed cell death 11 (PDCD11) and family with sequence similarity 213 member A (FAM213A) can be considered as the candidate genes associated with egg number traits, due to their reported association with animal reproduction traits. Noteworthy, results suggests that VTG2 and PDCD11 are not only involved in the regulation of EN3, but also in the regulation of EN5, implies that VTG2 and PDCD11 have a significant influence on egg production traits. Our study offers valuable genomic insights into the molecular genetic mechanisms that govern egg number traits in a Chinese indigenous egg-laying chicken breed. These findings have the potential to enhance the egg-laying performance of chickens.

13.
medRxiv ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38585931

RESUMO

Background: Water, sanitation, hygiene (WSH), nutrition (N), and combined (N+WSH) interventions are often implemented by global health organizations, but WSH interventions may insufficiently reduce pathogen exposure, and nutrition interventions may be modified by environmental enteric dysfunction (EED), a condition of increased intestinal permeability and inflammation. This study investigated the heterogeneity of these treatments' effects based on individual pathogen and EED biomarker status with respect to child linear growth. Methods: We applied cross-validated targeted maximum likelihood estimation and super learner ensemble machine learning to assess the conditional treatment effects in subgroups defined by biomarker and pathogen status. We analyzed treatment (N+WSH, WSH, N, or control) randomly assigned in-utero, child pathogen and EED data at 14 months of age, and child LAZ at 28 months of age. We estimated the difference in mean child length for age Z-score (LAZ) under the treatment rule and the difference in stratified treatment effect (treatment effect difference) comparing children with high versus low pathogen/biomarker status while controlling for baseline covariates. Results: We analyzed data from 1,522 children, who had median LAZ of -1.56. We found that myeloperoxidase (N+WSH treatment effect difference 0.0007 LAZ, WSH treatment effect difference 0.1032 LAZ, N treatment effect difference 0.0037 LAZ) and Campylobacter infection (N+WSH treatment effect difference 0.0011 LAZ, WSH difference 0.0119 LAZ, N difference 0.0255 LAZ) were associated with greater effect of all interventions on growth. In other words, children with high myeloperoxidase or Campylobacter infection experienced a greater impact of the interventions on growth. We found that a treatment rule that assigned the N+WSH (LAZ difference 0.23, 95% CI (0.05, 0.41)) and WSH (LAZ difference 0.17, 95% CI (0.04, 0.30)) interventions based on EED biomarkers and pathogens increased predicted child growth compared to the randomly allocated intervention. Conclusions: These findings indicate that EED biomarker and pathogen status, particularly Campylobacter and myeloperoxidase (a measure of gut inflammation), may be related to impact of N+WSH, WSH, and N interventions on child linear growth.

14.
Front Plant Sci ; 15: 1335850, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38571709

RESUMO

Fungi play a pivotal role in fermentation processes, influencing the breakdown and transformation of metabolites. However, studies focusing on the effects of fungal-metabolite correlations on leaf fermentation quality enhancement are limited. This study investigated specific metabolites and fungi associated with high- and low-quality fermented plant leaves. Their changes were monitored over fermentation periods of 0, 8, 16, and 24 days. The results indicated that organoheterocyclic compounds, lipids, lipid-like molecules, organic nitrogen compounds, phenylpropanoids, and polyketides were predominant in high-quality samples. The fungi Saccharomyces (14.8%) and Thermoascus (4.6%) were predominantly found in these samples. These markers exhibited significant changes during the 24-day fermentation period. The critical influence of fungal community equilibrium was demonstrated by interspecies interactions (e.g., between Saccharomyces and Eurotium). A co-occurrence network analysis identified Saccharomyces as the primary contributor to high-quality samples. These markers collectively enhance the quality and sensory characteristics of the final product.

15.
Acta Pharm Sin B ; 14(4): 1592-1604, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572097

RESUMO

Organic anion-transporting polypeptides 1B1 (OATP1B1) plays a crucial role in the transport of statins. However, there are too few animal models related to OATP1B1, especially humanized animal models. In this study, the human SLCO1B1 cDNA was inserted into the second exon of the rat Slco1b2 gene using CRISPR/Cas9 technology. Pharmacokinetic characteristics of statins were conducted in wild-type (WT), humanized OATP1B1 (hOATP1B1), and OATP1B2 knockout (OATP1B2 KO) rats, respectively. The results showed that human OATP1B1 was successfully expressed in rat liver and exhibited transport function. Furthermore, the pharmacokinetic results revealed that OATP1B1 exhibited varying uptake levels of pivastatin, rosuvastatin, and fluvastatin, leading to different levels of exposure within the body. These results were consistent with those obtained from in vitro experiments using overexpressed cell lines. In conclusion, we established a novel humanized SLCO1B1 transgenic rat model to assess the role of human OATP1B1 in the uptake of different statins. The different uptake mediated by OATP1B1 may be an important reason for the different efficacy of statins. The hOATP1B1 rat is a promising model for improving the prediction of human drug transport.

16.
World Neurosurg ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38575061

RESUMO

BACKGROUND AND PURPOSE: Extensive research has confirmed the safety and effectiveness of flow diverters in the treatment of unruptured intracranial aneurysms. However, their use in cases of acute rupture remains a subject of debate. METHODS: This study was conducted as a single-center retrospective investigation from January 2018 to January 2022 and included patients with acutely ruptured intracranial aneurysms (within three days of rupture) who were treated using the Pipeline Embolization Device (PED) with adjunctive coil embolization. Patient demographics, operative procedures, and outcomes were analyzed. Antiplatelet therapy included intra-arterial tirofiban and postoperative dual therapy with clopidogrel and aspirin. RESULTS: A total of 21 patients (5 males, 16 females) diagnosed with acutely ruptured intracranial aneurysms were included in this study. The aneurysm types included 7 blood blister-like aneurysms (30.0%), 3 dissecting (14.3%), and 1 fusiform aneurysm (4.8%). Perioperative complications occurred in 2 patients (9.5%), and both cases involved thrombogenesis. Nineteen patients completed digital subtraction angiography during follow-up, with an average follow-up time of 8.7 months (5-18 months). Results showed a complete embolization rate of 94.7% (18/19), with a partial aneurysm still present in 1 patient. A total of 90.4% (19/21) of patients had a favorable prognosis (modified Rankin Scale score = 0-2). CONCLUSION: The PED with adjunctive coil embolization proved to be a viable option for managing acutely ruptured intracranial aneurysms, notwithstanding the potential for ischemic complications.

17.
Chem Biol Interact ; : 110952, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38570061

RESUMO

High throughput transcriptomics (HTTr) profiling has the potential to rapidly and comprehensively identify molecular targets of environmental chemicals that can be linked to adverse outcomes. We describe here the construction and characterization of a 50-gene expression biomarker designed to identify estrogen receptor (ER) active chemicals in HTTr datasets. Using microarray comparisons, the genes in the biomarker were identified as those that exhibited consistent directional changes when ER was activated (4 ER agonists; 4 ESR1 gene constitutively active mutants) and opposite directional changes when ER was suppressed (4 antagonist treatments; 4 ESR1 knockdown experiments). The biomarker was evaluated as a predictive tool using the Running Fisher algorithm by comparison to annotated gene expression microarray datasets including those evaluating the transcriptional effects of hormones and chemicals in MCF-7 cells. Depending on the reference dataset used, the biomarker had a predictive accuracy for activation of up to 96%. To demonstrate applicability for HTTr data analysis, the biomarker was used to identify ER activators in a set of 15 chemicals that are considered potential bisphenol A (BPA) alternatives examined at up to 10 concentrations in MCF-7 cells and analyzed by full-genome TempO-Seq. Using benchmark dose (BMD) modeling, the biomarker genes stratified the ER potency of BPA alternatives consistent with previous studies. These results demonstrate that the ER biomarker can be used to accurately identify ER activators in transcript profile data derived from MCF-7 cells.

18.
Opt Express ; 32(7): 11387-11394, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38570987

RESUMO

We reported an intra-cavity pumped Q-switched laser with dual-wavelength synchronous output at 2066.7 nm and 1940nm. Ho:YLF crystal was pumped by a self-Q-switched Tm:YAP laser, which was served as both a gain medium and a saturable absorber simultaneously. For Ho:YLF laser, under 11.4-W incident pump power, a stable pulse laser was achieved at 2066.7 nm with the highest peak power of 69.65 W and the pulse repetition rate of 42.14 kHz. Under the same incident pump power, the highest peak power and pulse repetition rate of Tm:YAP laser were 17.85 W and 50.82 kHz, corresponding to the central wavelength of 1940nm. These results suggested that Q-switching without additional absorber element were effective way to obtain high-efficiency and compact 2.1 µm pulsed laser.

19.
Int J Psychophysiol ; 199: 112341, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38580171

RESUMO

The ability to select task-relevant information and filter out task-irrelevant information is critical to our success in daily goal-directed behavior. Researchers call this ability filtering efficiency and divide it into three cognitive processing stages: detection of distractors, initiation of filtering, and unnecessary storage. Although researchers have conducted more studies on ERP components related to filtration efficiency, there are few studies related to neural oscillations. Alpha oscillation activity is related to the active processing of information and the suppression of distractors. In the current EEG study, we used the change detection task with distracted items to examine whether alpha activity during filtering initiation reflects reactive suppression of distractors by manipulating memory load levels and the presence or absence of distractors. Results showed that, the presence of the distractors caused an increase in the degree of desynchronization of the alpha oscillations, and in the subsequent time, the alpha activity level returned to a level consistent with the absence of interference conditions. Phase synchronization between frontal and posterior brain regions in the upper alpha oscillations found no effects associated with distractors. Based on these results, we believed that the alpha activity during the filtering initiation phase reflected the active processing of distractors, but this may also be due to lower perceptual load of the target items. In addition, we observed a dominance effect of the right hemisphere in both time-frequency results and connectivity results. We speculate that this effect is related to the activation of the right ventral frontoparietal network.

20.
Ecotoxicol Environ Saf ; 276: 116284, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581912

RESUMO

Fluorosis due to high fluoride levels in drinking water profoundly affects the development of human skeletal and dental structures. Sodium butyrate (NaB) has been found to regulate overall bone mass and prevent pathological bone loss. However, the mechanism of NaB action on fluorosis remains unclear. In this study, a rat model of fluorosis induced by 100 mg/L sodium fluoride was used to investigate the impact of NaB on bone homeostasis and serum metabolomics. It was found that NaB significantly reduced the levels of bone resorption markers CTX-Ⅰ and TRACP-5B in fluorosis rats. Moreover, NaB increased calcium and magnesium levels in bone, while decreasing phosphorus levels. In addition, NaB improved various bone microstructure parameters, including bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone separation (Tb. SP), and structural model index (SMI) in the femur. Notably, NaB intervention also enhanced the antioxidant capacity of plasma in fluorosis rats. Furthermore, a comprehensive analysis of serum metabolomics by LC-MS revealed a significant reversal trend of seven biomarkers after the intervention of NaB. Finally, pathway enrichment analysis based on differential metabolites indicated that NaB exerted protective effects on fluorosis by modulating arginine and proline metabolic pathways. These findings suggest that NaB has a beneficial effect on fluorosis and can regulate bone homeostasis by ameliorating metabolic disorders.

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