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1.
Plant Cell Physiol ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38578169

RESUMO

Due to their sessile lifestyle, plants need to optimize their growth in order to adapt to ever-changing environments. Plants receive stimuli from the environment and convert them into cellular responses. Brassinosteroids (BRs), as growth-promoting steroid hormones, play a significant role in the tradeoff between growth and environmental responses. Here, we provide a comprehensive summary for understanding the crosstalk between BR and various environmental stresses, including water availability, temperature fluctuations, salinization, nutrient deficiencies and diseases. We also highlight the bottlenecks that need to be addressed in future studies. Ultimately, we suppose to improve plant environmental adaptability and crop yield by excavating natural BR mutants or modifying BR signaling and its targets.

2.
Nano Lett ; 24(15): 4546-4553, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38588452

RESUMO

Organic materials have attracted extensive attention for potassium-ion batteries due to their flexible structure designability and environmental friendliness. However, organic materials generally suffer from unavoidable dissolution in aprotic electrolytes, causing an unsatisfactory electrochemical performance. Herein, we designed a weakly solvating electrolyte to boost the potassium storage performance of perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA). The electrolyte induces an in situ morphology evolution and achieves a nanowire structure. The weakly dissolving capability of ethylene glycol diethyl ether-based electrolyte and unique nanowire structure effectively avoid the dissolution of PTCDA. As a result, PTCDA shows excellent cycling stability (a capacity retention of 89.1% after 2000 cycles) and good rate performance (70.3 mAh g-1 at 50C). In addition, experimental detail discloses that the sulfonyl group plays a key role in inducing morphology evolution during the charge/discharge process. This work opens up new opportunities in electrolyte design for organic electrodes and illuminates further developments of potassium-ion batteries.

3.
Biomed Chromatogr ; : e5877, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618898

RESUMO

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs that can cause liver toxicity. The aim of this study was to integrate bioanalytical and population pharmacokinetic (PopPK) assay to rapidly screen and quantify the concentrations of NSAIDs in plasma and monitor clinical safety. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of acetaminophen (APAP), flurbiprofen (FLB), aspirin (ASP), and ibuprofen (IBP), four commonly used NSAIDs. The PopPK model of the signature toxicant was analyzed based on the published literature. The LC-MS/MS method was successfully validated and applied to determine NSAID concentrations in patient plasma samples. APAP, ASP, and IBP data were best fitted using a one-compartment model, and FLB data were best fitted using a two-compartment model. Bootstrapping and visual predictive checks suggested that a robust and reliable pharmacokinetic model was developed. A fast, simple, and sensitive LC-MS/MS method was developed and validated for determining APAP, FLB, ASP, and IBP in human plasma. Combined with the PopPK model, this method was applied to rapidly analyze the concentrations of NSAIDs in clinical samples from patients presenting to the emergency department with acute liver dysfunction and monitored NSAIDs clinical safety.

4.
Commun Biol ; 7(1): 490, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654111

RESUMO

Bile infarct is a pivotal characteristic of obstructive biliary disease, but its evolution during the disease progression remains unclear. Our objective, therefore, is to explore morphological alterations of the bile infarct in the disease course by means of multiscale X-ray phase-contrast CT. Bile duct ligation is performed in mice to mimic the obstructive biliary disease. Intact liver lobes of the mice are scanned by phase-contrast CT at various resolution scales. Phase-contrast CT clearly presents three-dimensional (3D) images of the bile infarcts down to the submicron level with good correlation with histological images. The CT data illustrates that the infarct first appears on day 1 post-BDL, while a microchannel between the infarct and hepatic sinusoids is identified, the number of which increases with the disease progression. A 3D model of hepatic acinus is proposed, in which the infarct starts around the portal veins (zone I) and gradually progresses towards the central veins (zone III) during the disease process. Multiscale phase-contrast CT offers the comprehensive analysis of the evolutionary features of the bile infarct in obstructive biliary disease. During the course of the disease, the bile infarcts develop infarct-sinusoidal microchannels and gradually occupy the whole liver, promoting the disease progression.


Assuntos
Tomografia Computadorizada por Raios X , Animais , Camundongos , Colestase/diagnóstico por imagem , Colestase/patologia , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/patologia , Progressão da Doença , Masculino , Fígado/diagnóstico por imagem , Fígado/patologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Imageamento Tridimensional/métodos , Infarto/diagnóstico por imagem , Infarto/patologia
5.
Front Endocrinol (Lausanne) ; 15: 1359407, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529396

RESUMO

Aims: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cetagliptin (CAS number:2243737-33-7) in Chinese patients with type 2 diabetes mellitus (T2DM). A population PK/PD model was developed to quantify the PK and PD characteristics of cetagliptin in patients. Materials and methods: 32 Chinese adults with T2DM were enrolled in this study. The subjects were randomly assigned to receive either cetagliptin (50 mg or 100 mg), placebo, or sitagliptin (100 mg) once daily for 14 days. Blood samples were collected for PK and PD analysis. Effects on glucose, insulin, C-peptide, and glucagon were evaluated following an oral glucose tolerance test (OGTT) (day15). Effects on HbA1c and glycated albumin (GA), and safety assessments were also conducted. Meanwhile, a population PK/PD model was developed by a sequential two-step analysis approach using Phoenix. Results: Following multiple oral doses, cetagliptin was rapidly absorbed and the mean half-life were 34.9-41.9 h. Steady-state conditions were achieved after 1 week of daily dosing and the accumulation was modest. The intensity and duration of DPP-4 inhibition induced by 50 mg cetagliptin were comparable with those induced by sitagliptin, and 100 mg cetagliptin showed a much longer sustained DPP-4 inhibition (≥80%) than sitagliptin. Compared with placebo group, plasma active GLP-1 AUEC0-24h increased by 2.20- and 3.36-fold in the 50 mg and 100 mg cetagliptin groups. A decrease of plasma glucose and increase of insulin and C-peptide were observed following OGTT in cetagliptin groups. Meanwhile, a tendency of reduced GA was observed, whereas no decreasing trend was observed in HbA1c. All adverse events related to cetagliptin and sitagliptin were assessed as mild. A population PK/PD model was successfully established. The two-compartment model and Sigmoid-Emax model could fit the observed data well. Total bilirubin (TBIL) was a covariate of volume of peripheral compartment distribution (V2), and V2 increased with the increase of TBIL. Conclusions: Cetagliptin was well tolerated, inhibited plasma DPP-4 activity, increased plasma active GLP-1 levels, and exhibited a certain trend of glucose-lowering effect in patients with T2DM. The established population PK/PD model adequately described the PK and PD characteristics of cetagliptin.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Adulto , Humanos , Hipoglicemiantes/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Hemoglobinas Glicadas , Peptídeo C , Glicemia , Fosfato de Sitagliptina/farmacologia , Fosfato de Sitagliptina/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon , Insulina/uso terapêutico
6.
Artigo em Inglês | MEDLINE | ID: mdl-38507161

RESUMO

Urbanizations and industrializations may accelerate the contamination and deterioration of groundwater quality. This study aimed to evaluate the quality and potential human health risks associated with shallow groundwater in Shenzhen, China, a city characterized by high levels of urbanization and industrialization. The hydrochemistry characteristics, water quality levels, and human health risks of main ions, nutrient elements, and metals in 220 samples collected from Maozhou River Basin (MRB) located in the northwest of Shenzhen were investigated. It showed that chemical constituents of the groundwater were further complicated by seawater intrusion and urbanization expansion. Water quality evaluated by fuzzy comprehensive method showed that 21.05% of samples distributed around reservoirs were classified into grade II or better. Nearly 79% of samples distributed in the densely populated urban land were classified into grade III or worse, indicating pollution from anthropogenic factors cannot be ignored. For the river tidal reach where river stage fluctuated about 0.5 to 1.5 m within a tidal cycle, the chemical composition of groundwater was influenced by frequent water exchange with the river. The carcinogenic and non-carcinogenic health risks for different age groups, from the high to the low, were children, adult women, adult men, adolescent women, and adolescent men, respectively. Approximately 39% of groundwater samples distributed around the densely populations area with health risk larger than 5 × 10-5 were unacceptable for children. This investigation would be helpful for improving groundwater management and as a practical reference for sustainable groundwater exploitation in the MRB.

7.
Mol Pharm ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551309

RESUMO

This study aims to explore and characterize the role of pediatric sedation via rectal route. A pediatric physiologically based pharmacokinetic-pharmacodynamic (PBPK/PD) model of midazolam gel was built and validated to support dose selection for pediatric clinical trials. Before developing the rectal PBPK model, an intravenous PBPK model was developed to determine drug disposition, specifically by describing the ontogeny model of the metabolic enzyme. Pediatric rectal absorption was developed based on the rectal PBPK model of adults. The improved Weibull function with permeability, surface area, and fluid volume parameters was used to extrapolate pediatric rectal absorption. A logistic regression model was used to characterize the relationship between the free concentrations of midazolam and the probability of sedation. All models successfully described the PK profiles with absolute average fold error (AAFE) < 2, especially our intravenous PBPK model that extended the predicted age to preterm. The simulation results of the PD model showed that when the free concentrations of midazolam ranged from 3.9 to 18.4 ng/mL, the probability of "Sedation" was greater than that of "Not-sedation" states. Combined with the rectal PBPK model, the recommended sedation doses were in the ranges of 0.44-2.08 mg/kg for children aged 2-3 years, 0.35-1.65 mg/kg for children aged 4-7 years, 0.24-1.27 mg/kg for children aged 8-12 years, and 0.20-1.10 mg/kg for adolescents aged 13-18 years. Overall, this model mechanistically quantified drug disposition and effect of midazolam gel in the pediatric population, accurately predicted the observed clinical data, and simulated the drug exposure for sedation that will inform dose selection for following pediatric clinical trials.

8.
Angew Chem Int Ed Engl ; : e202400406, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491786

RESUMO

Diluents have been extensively employed to overcome the disadvantages of high viscosity and sluggish kinetics of high-concentration electrolytes, but generally do not change the pristine solvation structure. Herein, a weakly coordinating diluent, hexafluoroisopropyl methyl ether (HFME), is applied to regulate the coordination of Na+ with diglyme and anion and form a diluent-participated solvate. This unique solvation structure promotes the accelerated decomposition of anions and diluents, with the construction of robust inorganic-rich electrode-electrolyte interphases. In addition, the introduction of HFME reduces the desolvation energy of Na+, improves ionic conductivity, strengthens the antioxidant, and enhances the safety of the electrolyte. As a result, the assembled Na||Na symmetric cell achieves a stable cycle of over 1800 h. The cell of Na||P'2-Na0.67MnO2 delivers a high capacity retention of 87.3 % with a high average Coulombic efficiency of 99.7 % after 350 cycles. This work provides valuable insights into solvation chemistry for advanced electrolyte engineering.

9.
Traffic Inj Prev ; 25(3): 454-462, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478461

RESUMO

OBJECTIVE: In vehicle frontal collisions, it is crucial that the lap belt is designed to engage with the anterior superior iliac spine (ASIS) of occupants for a reliable restraint. This study aims to understand the influence of different seated postures on the geometrical relationship of the seat belt and the pelvis for various occupants using 3D upright and supine computed tomography (CT) systems. METHODS: The 3D shapes of bones and soft tissues around the pelvis were acquired through a CT scan for 30 participants. They were seated in a rigid seat equipped with a lap belt simulating the front seat of a small car, and wore a lap belt in three seated postures: upright, slouched and reclined. Parameters related to the likelihood of submarining occurrences, such as belt-ASIS overlap (an index for assessing the potential engagement of the lap belt with the ASIS) and the belt-pelvis angle (the difference between the belt angle and the normal direction of the anterior edge of the ilium) were compared. RESULTS: It was observed that the pelvis angle tilted rearward as the hip point was positioned forward and seatback angle increased. This can be seen in the slouched and reclined posture. The belt-pelvis angle was comparable between the slouched and the reclined postures, and was closer to zero (indicating that the lap belt path is closer to perpendicular to the anterior edge of the ilium) compared to the upright posture. In contrast, the belt-ASIS overlap increased with an increasing flesh margin of the ASIS and shallower belt angle. This suggests that the belt-pelvis angle is influenced by the seated posture whereas the belt-ASIS overlap is dependent more on an individual's anthropometry. The plot of belt-pelvis angle and belt-ASIS overlap exhibited significant variability among participants. CONCLUSIONS: The belt-pelvis angle and the belt-ASIS overlap of individuals will provide valuable information for understanding the current belt-fit location and predicting submarining occurrences for individuals in various postures when designing restraint systems.


Assuntos
Acidentes de Trânsito , Cintos de Segurança , Humanos , Antropometria/métodos , Postura , Fenômenos Biomecânicos , Tomografia
10.
Tissue Cell ; 87: 102340, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447334

RESUMO

Chondrocytes undergo endoplasmic reticulum stress (ERS)-induced apoptosis under abnormal stimulation. However, the underlying molecular mechanism remains unclear. We investigated the regulatory effect of the PI3K/AKT signaling pathway on ERS and its effect on chondrocyte apoptosis. In addition, we established a unilateral anterior crossbite (UAC) model in rats to induce temporomandibular joint osteoarthritis (TMJOA). Chondrocytes were isolated from the temporomandibular joints and treated with lipopolysaccharide (LPS) in vitro. Protein expression of ERS and apoptosis markers (GRP78 and CASP12) was analyzed by immunohistochemistry and western blotting. The expression of GRP78, CASP12, p-PI3K, and p-AKT significantly increased in the UAC group. LY294002, a PI3K/AKT signaling pathway inhibitor, reduced the protein expression of GRP78, ATF4, CHOP, and CASP12, whereas 740 Y-P, an activation agent, elevated the expression of proteins GRP78, ATF4, CHOP, and CASP12. In the present study, UAC and LPS stimulation induced apoptosis of chondrocytes in the ERS pathway. Inhibition of the PI3K/AKT signaling pathway reduced ERS-induced chondrocyte apoptosis.


Assuntos
Condrócitos , Proteínas Proto-Oncogênicas c-akt , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Condrócitos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Chaperona BiP do Retículo Endoplasmático , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Transdução de Sinais , Estresse do Retículo Endoplasmático , Apoptose
11.
Chemosphere ; 352: 141377, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38346514

RESUMO

In recent years, emerging pollutants, including nonylphenol (NP) and nonylphenol ethoxylate (NPE), have become a prominent topic. These substances are also classified as persistent organic pollutants. NP significantly affects the hormone secretion of organisms and exhibits neurotoxicity, which can affect the human hippocampus. Therefore, various countries are paying increased attention to NP regulation. NPEs are precursors of NPs and are widely used in the manufacture of various detergents and lubricants. NPEs can easily decompose into NPs, which possess strong biological and environmental toxicity. This review primarily addresses the distribution, toxicity mechanisms and performance, degradation technologies, management policies, and green alternative reagents of NPs and NPEs. Traditional treatment measures have been unable to completely remove NP from wastewater. With the progressively tightening management and regulatory policies, identifying proficient and convenient treatment methods and a sustainable substitute reagent with comparable product effectiveness is crucial.


Assuntos
Fenóis , Poluentes Químicos da Água , Humanos , Fenóis/toxicidade , Etilenoglicóis/toxicidade , Águas Residuárias , Poluentes Químicos da Água/análise
12.
Plant J ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332528

RESUMO

Cannabis glandular trichomes (GTs) are economically and biotechnologically important structures that have a remarkable morphology and capacity to produce, store, and secrete diverse classes of secondary metabolites. However, our understanding of the developmental changes and the underlying molecular processes involved in cannabis GT development is limited. In this study, we developed Cannabis Glandular Trichome Detection Model (CGTDM), a deep learning-based model capable of differentiating and quantifying three types of cannabis GTs with a high degree of efficiency and accuracy. By profiling at eight different time points, we captured dynamic changes in gene expression, phenotypes, and metabolic processes associated with GT development. By integrating weighted gene co-expression network analysis with CGTDM measurements, we established correlations between phenotypic variations in GT traits and the global transcriptome profiles across the developmental gradient. Notably, we identified a module containing methyl jasmonate (MeJA)-responsive genes that significantly correlated with stalked GT density and cannabinoid content during development, suggesting the existence of a MeJA-mediated GT formation pathway. Our findings were further supported by the successful promotion of GT development in cannabis through exogenous MeJA treatment. Importantly, we have identified CsMYC4 as a key transcription factor that positively regulates GT formation via MeJA signaling in cannabis. These findings provide novel tools for GT detection and counting, as well as valuable information for understanding the molecular regulatory mechanism of GT formation, which has the potential to facilitate the molecular breeding, targeted engineering, informed harvest timing, and manipulation of cannabinoid production.

13.
Lasers Med Sci ; 39(1): 83, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38418639

RESUMO

PURPOSE: To evaluate the changes in macular structures following subthreshold micropulse laser (SHML) treatment for chronic central serous chorioretinopathy (cCSC). METHODS: Data of 33 eyes from 31 cCSC patients treated with SHML and followed up for at least 6 months has been included in this retrospective study. Main outcome measurements include resolution of subretinal fluid (SRF) and pigment epithelial detachment (PED), the recovery of ellipsoid zone (EZ) continuity, and the foveal outer nuclear layer (ONL) thickness along with its ratio. RESULTS: Mean observation period is 7.355 months (ranging from 6 to 24 months) and mean number of treatments administered is 1.839 (ranging from 1 to 5). 6 months after SHML treatment, there is a significant decrease in the area of SRF and PED (P < 0.001, P = 0.010, respectively). Additionally, the frequency of continuous EZ and the foveal ONL thickness reveal a significant increase (P<0.001, P = 0.005, respectively). The ratio of foveal ONL thickness is significantly higher after laser treatment, particularly in patients with a disease duration of ≤12 months (p = 0.022, P=0.036, respectively). CONCLUSION: SHML treatment proves to be effective in cCSC eyes, leading to satisfactory recovery of macular structures, especially the photoreceptor layer.


Assuntos
Coriorretinopatia Serosa Central , Terapia a Laser , Humanos , Coriorretinopatia Serosa Central/radioterapia , Coriorretinopatia Serosa Central/cirurgia , Estudos Retrospectivos , Angiofluoresceinografia , Acuidade Visual , Retina , Tomografia de Coerência Óptica , Doença Crônica
14.
Biomacromolecules ; 25(2): 1180-1190, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38240673

RESUMO

In recent years, the utilization of medical devices has gradually increased and implantation procedures have become common treatments. However, patients are susceptible to the risk of implant infections. This study utilized chemical grafting to immobilize polyethylenimine (QPEI) and hyaluronic acid (HA) on the surface of the mesh to improve biocompatibility while being able to achieve antifouling antimicrobial effects. From the in vitro testing, PP-PDA-Q-HA exhibited a high antibacterial ratio of 93% against S. aureus, 93% against E. coli, and 85% against C. albicans. In addition, after five rounds of antimicrobial testing, the coating continued to exhibit excellent antimicrobial properties; PP-PDA-Q-HA also inhibits the formation of bacterial biofilms. In addition, PP-PDA-Q-HA has good hemocompatibility and cytocompatibility. In vivo studies in animal implantation infection models also demonstrated the excellent antimicrobial properties of PP-PDA-Q-HA. Our study provides a promising strategy for the development of antimicrobial surface medical materials with excellent biocompatibility.


Assuntos
Anti-Infecciosos , Incrustação Biológica , Animais , Humanos , Staphylococcus aureus , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes , Anti-Infecciosos/farmacologia , Hérnia , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química , Propriedades de Superfície
15.
J Ginseng Res ; 48(1): 77-88, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38223829

RESUMO

Background: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied. Methods: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model. Results: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation. Conclusion: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.

16.
Bioorg Chem ; 144: 107131, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38271824

RESUMO

Ginsenoside 20 (R)-25-methoxy-dammarane-3 ß, twelve ß, 20 triol (AD-1) is a promising new drug for the treatment of prostate cancer, but its bioavailability is low. This study investigated the effects of the main metabolites PD and M6 of AD-1 on prostate cancer cell PC3. The in vitro experimental results showed that the IC50 values of PC3 cells treated with PD and M6 were 65.61 and 11.72, respectively. Both PD and M6 inhibited the migration of PC3 cells, and the cell cycle was blocked in the G1 phase. The apoptosis rates of cells following M6 treatment at concentrations of 7.5, 15, and 30 µM were 13.4 %, 17.5 %, and 41.4 %, respectively, which stimulated the expression of apoptosis protein and significantly increased intracellular ROS levels. In xenograft models, PD and M6 have been reported to significantly inhibit tumor growth. We used a genome-wide mRNA expression profile to study the effects of PD and M6 on gene expression in PC3 cancer cells. PD and M6 induced downregulation of HSP70 subtypes HSPA1A and HSPA1B. RT-PCR confirmed that the significant down-regulation of HSP70 subtype expressions was consistent with the results of Transcriptome analysis. Moreover, M6 significantly downregulated the expression of AR, which was further proved by Western blot analysis. In summary, our research findings provide a scientific basis for interpreting the significant activity of AD-1 in prostate cancer, and for the research and development of PD and M6 as novel HSP70 inhibitors.


Assuntos
Ginsenosídeos , Neoplasias da Próstata , Masculino , Humanos , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Proliferação de Células , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Ciclo Celular , Apoptose , Linhagem Celular Tumoral
17.
Brain Cogn ; 175: 106131, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219416

RESUMO

Variance characterizes the structure of the environment. This statistical concept plays a critical role in evaluating the reliability of evidence for human decision-making. The present study examined the involvement of subcortical structures in the processing of visual variance. To this end, we used a stereoscope to sequentially present two circle arrays in a dichoptic or monocular fashion while participants compared the perceived variance of the two arrays. In Experiment 1, two arrays were presented monocularly to the same eye, dichopticly to different eyes, or binocularly to both eyes. The variance judgment was less accurate in different-eye condition than the other conditions. In Experiment 2, the first circle array was split into a large-variance and a small-variance set, with either the large-variance or small-variance set preceding the presentation of the second circle array in the same eye. The variance of the first array was judged larger when the second array was preceded by the large-variance set in the same eye, showing that the perception of variance was modulated by the visual variance processed in the same eye. Taken together, these findings provide evidence for monocular processing of visual variance, suggesting that subcortical structures capture the statistical structure of the visual world.


Assuntos
Visão Monocular , Córtex Visual , Humanos , Reprodutibilidade dos Testes , Visão Binocular , Percepção Visual
18.
Traffic Inj Prev ; 25(2): 147-155, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38019483

RESUMO

OBJECTIVE: The engagement of the lap belt with the pelvis is critical for occupant safety during vehicle frontal crashes to prevent occupant submarining. This study aims to develop a predictive model for submarining risk based on anthropometric parameters and lap belt positioning using finite element (FE) analyses. METHODS: FE analyses were conducted using human body models representing various body shapes (a 50th percentile male, low and high BMI males, and a 5th percentile female) in three seated postures (standard, reclined, and slouched). The lap belt-ASIS overlap and the belt-pelvis angle were used as key parameters for predicting submarining risk. A logistic regression analysis was utilized to correlate submarining occurrence with the initial values of these two parameters at the beginning of impact. Subsequently, this submarining prediction model was applied to computer tomography (CT) measurements of human subjects in different seated postures (upright, reclined, and slouched), and submarining risks were calculated based on the developed model. RESULTS: FE simulations indicated that submarining was more likely to occur as the initial belt-pelvis angle approached zero and there was a smaller initial belt-ASIS overlap. The logistic regression analysis demonstrated that the initial belt-pelvis angle and belt-ASIS overlap were statistically significant for predicting submarining risk. The derived model effectively distinguished submarining occurrence based on the initial values of these two parameters. The application of the submarining model to CT measurements of human subjects showed that submarining risk was lower in the order of upright, slouched, and reclined postures. In the reclined posture, the high submarining risk was attributed to a small belt-ASIS overlap and a rearward-tilted pelvis angle; whereas in the slouched posture, the risk was mostly associated with a rearward-tilted pelvis angle. CONCLUSIONS: The submarining prediction model was developed based on the belt-pelvis angle and the belt-ASIS overlap. This predictive model may help to design restraint systems for various body types and seated postures of occupants.


Assuntos
Acidentes de Trânsito , Automóveis , Humanos , Masculino , Feminino , Cintos de Segurança , Antropometria/métodos , Pelve/diagnóstico por imagem , Fenômenos Biomecânicos
19.
Int Orthop ; 48(1): 183-191, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37726561

RESUMO

PURPOSE: MR arthrography (MRA) is the most accurate method for preoperatively diagnosing superior labrum anterior-posterior (SLAP) lesions, but diagnostic results can vary considerably due to factors such as experience. In this study, deep learning was used to facilitate the preliminary identification of SLAP lesions and compared with radiologists of different seniority. METHODS: MRA data from 636 patients were retrospectively collected, and all patients were classified as having/not having SLAP lesions according to shoulder arthroscopy. The SLAP-Net model was built and tested on 514 patients (dataset 1) and independently tested on data from two other MRI devices (122 patients, dataset 2). Manual diagnosis was performed by three radiologists with different seniority levels and compared with SLAP-Net outputs. Model performance was evaluated by the receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), etc. McNemar's test was used to compare performance among models and between radiologists' models. The intraclass correlation coefficient (ICC) was used to assess the radiologists' reliability. p < 0.05 was considered statistically significant. RESULTS: SLAP-Net had AUC = 0.98 and accuracy = 0.96 for classification in dataset 1 and AUC = 0.92 and accuracy = 0.85 in dataset 2. In dataset 1, SLAP-Net had diagnostic performance similar to that of senior radiologists (p = 0.055) but higher than that of early- and mid-career radiologists (p = 0.025 and 0.011). In dataset 2, SLAP-Net had similar diagnostic performance to radiologists of all three seniority levels (p = 0.468, 0.289, and 0.495, respectively). CONCLUSIONS: Deep learning can be used to identify SLAP lesions upon initial MR arthrography examination. SLAP-Net performs comparably to senior radiologists.


Assuntos
Aprendizado Profundo , Lesões do Ombro , Articulação do Ombro , Humanos , Ombro/diagnóstico por imagem , Artrografia/métodos , Lesões do Ombro/diagnóstico por imagem , Estudos Retrospectivos , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/patologia , Artroscopia , Sensibilidade e Especificidade
20.
J Phys Condens Matter ; 36(13)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38091623

RESUMO

With the discovery of two-dimensional (2D) ferroelectric materials such as CuInP2S6andα-In2Se3, the ferroelectric field effect transistors (Fe-FETs) based on these materials have entered a rapid-development period. The metal/semiconductor contact is an unavoidable topic in the construction of devices. In this paper, heterostructuresα-In2Se3/metals (Pd, Pt, Cu, Ag and Au) are discussed. According to different stacking types, the structures and energy of 160 heterostructures are calculated and compared. Whenα-In2Se3contacts with the Pd, Pt and Cu, theα-In2Se3may transforms intoß-In2Se3. This phenomenon has hardly been mentioned or analyzed in previous reports. Contacting with the Au and Ag, theα-In2Se3maintains the original structure. The internal physical mechanism of phase transition is explained from the binding energy and the charge transfer. The paper provides sufficient theoretical support for research and development of the Fe-FETs based onα-In2Se3.

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