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1.
J Affect Disord ; 356: 499-506, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38574869

RESUMEN

BACKGROUND: Suicide is one of the most lethal complications of late-life depression (LLD), and habenular dysfunction may be involved in depression-related suicidality and may serve as a potential target for alleviating suicidal ideation. This study aimed to investigate abnormal functional connectivity of the habenula in LLD patients with suicidal ideation. METHODS: One hundred twenty-seven patients with LLD (51 with suicidal ideation (LLD-S) and 76 without suicidal ideation (LLD-NS)) and 75 healthy controls (HCs) were recruited. The static functional connectivity (sFC) and dynamic functional connectivity (dFC) between the habenula and the whole brain were compared among the three groups, and correlation and moderation analyses were applied to investigate whether suicidal ideation moderated the relationships of habenular FC with depressive symptoms and cognitive impairment. RESULTS: The dFC between the right habenula and the left orbitofrontal cortex (OFC) increased in the following order: LLD-S > LLD-NS > control. No significant difference in the habenular sFC was found among the LLD-S, LLD-NS and control groups. The dFC between the right habenula and the left OFC was positively associated with global cognitive function and visuospatial skills, and the association between this dFC and visuospatial skills was moderated by suicidal ideation in patients with LLD. CONCLUSION: The increased variability in dFC between the right habenula and left OFC was more pronounced in the LLD-S group than in the LLD-NS group, and the association between habenular-OFC dFC and visuospatial skills was moderated by suicidal ideation in patients with LLD.


Asunto(s)
Habénula , Imagen por Resonancia Magnética , Ideación Suicida , Humanos , Habénula/fisiopatología , Femenino , Masculino , Anciano , Persona de Mediana Edad , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Depresión/fisiopatología , Depresión/psicología , Estudios de Casos y Controles , Trastorno Depresivo/fisiopatología , Trastorno Depresivo/psicología
2.
J Org Chem ; 89(5): 3279-3291, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38377542

RESUMEN

The construction of 3,4-dihydroquinolone derivatives has attracted a considerable amount of attention due to their extensive applications in medicinal chemistry. In this study, we present the Pd-catalyzed [4+2] cycloaddition of vinyl benzoxazinanones with α-alkylidene succinimides for the efficient synthesis of 3,4-dihydroquinolones. This approach presents numerous advantages, including the ready availability of starting materials, mild reaction conditions without the use of additional bases, and a wide range of substrates. In particular, all of the desired products can be easily afforded in high yields (≤99%) and excellent diastereoselectivities (>20:1). The practicality and reliability of this strategy were demonstrated by the successful scale-up synthesis and subsequent straightforward synthetic transformations.

3.
Brain Imaging Behav ; 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38349505

RESUMEN

Early onset depression (EOD) and late onset depression (LOD) are thought to have different pathogeneses, but lack of pathological evidence. In the current study we describe the dynamic rich-club properties of patients with EOD and LOD to address this question indirectly. We recruited 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. Memory, executive function and processing speed were measured, and resting-stage functional MRI was performed with all participants. We constructed a dynamic functional connectivity network and carried out rich-club and modularity analyses. Normalized mutual information (NMI) was applied to describe the variance in rich-club nodes distribution and partitioning. The NMI coefficient of rich club nodes distribution among the three groups was the lowest in the EOD patients (F = 4.298; P = 0.0151, FDR = 0.0231), which was positively correlated with rich-club connectivity (R = 0.886, P < 0.001) and negatively correlated with memory (R = -0.347, P = 0.038) in the EOD group. In the LOD patients, non-rich-club connectivity was positively correlated with memory (R = 0.353, P = 0.030 and R = 0.420, P = 0.009). Furthermore, local connectivity was positively correlated with processing speed in the LOD patients (R = 0.374, P = 0.021). The modular partition was different between the EOD patients and the HCs (P = 0.0013 < 0.05/3). The temporal instability of rich-club nodes was found in the EOD patients, but not the LOD patients, supporting the hypothesis that EOD and LOD result from different pathogenesis, and showing that the instability of the rich-club nodes across time might disrupt rich-club connectivity.

4.
ACS Appl Mater Interfaces ; 16(6): 7686-7699, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38289234

RESUMEN

The pathogenesis of ulcerative colitis (UC) is associated with the shedding of the gut mucus. Herein, inspired by the biological functions of mucus, growth factors-loaded in situ hydrogel (PHE-EK) was designed for UC treatment by integrating dihydrocaffeic acid-modified poloxamer as a thermosensitive material with hyaluronic acid (colitis-specific adhesive), epigallocatechin-3-gallate (antibacterial agent), and bioactive factors (KPV tripeptide and epidermal growth factor). PHE-EK presented good thermosensitive properties, as a flowable liquid at room temperature and gelled within 10 s when exposed to body temperature. PHE-EK hydrogel presented good mechanical strength with a strain of 77.8%. Moreover, PHE-EK hydrogel displayed antibacterial activity against Escherichia coli. Importantly, in vitro and in vivo adhesive tests showed that the PHE-EK hydrogel could specifically adhere to the inflamed colon via electrostatic interaction. When PHE-EK as a biomimetic mucus was rectally administrated to colitis rats, it effectively hindered the body weight loss, reduced the disease activity index and improved the colonic shorting. Moreover, the expression of pro-inflammatory cytokines (e.g., IL-1ß, IL-6, and TNF-α) at the laminae propria or epitheliums of the colon for colitis rats was substantially inhibited by PHE-EK. Besides, the colonic epitheliums were well rearranged, and the tight junction proteins (Zonula-1 and Claudin-5) between them were greatly upregulated after PHE-EK treatment. Collectively, PHE-EK might be a promising therapy for UC.


Asunto(s)
Colitis Ulcerosa , Colitis , Ratones , Ratas , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Hidrogeles/farmacología , Biomimética , Temperatura , Colitis/metabolismo , Moco/metabolismo , Modelos Animales de Enfermedad
5.
Comput Biol Med ; 170: 107917, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38228030

RESUMEN

In standard hospital blood tests, the traditional process requires doctors to manually isolate leukocytes from microscopic images of patients' blood using microscopes. These isolated leukocytes are then categorized via automatic leukocyte classifiers to determine the proportion and volume of different types of leukocytes present in the blood samples, aiding disease diagnosis. This methodology is not only time-consuming and labor-intensive, but it also has a high propensity for errors due to factors such as image quality and environmental conditions, which could potentially lead to incorrect subsequent classifications and misdiagnosis. Contemporary leukocyte detection methods exhibit limitations in dealing with images with fewer leukocyte features and the disparity in scale among different leukocytes, leading to unsatisfactory results in most instances. To address these issues, this paper proposes an innovative method of leukocyte detection: the Multi-level Feature Fusion and Deformable Self-attention DETR (MFDS-DETR). To tackle the issue of leukocyte scale disparity, we designed the High-level Screening-feature Fusion Pyramid (HS-FPN), enabling multi-level fusion. This model uses high-level features as weights to filter low-level feature information via a channel attention module and then merges the screened information with the high-level features, thus enhancing the model's feature expression capability. Further, we address the issue of leukocyte feature scarcity by incorporating a multi-scale deformable self-attention module in the encoder and using the self-attention and cross-deformable attention mechanisms in the decoder, which aids in the extraction of the global features of the leukocyte feature maps. The effectiveness, superiority, and generalizability of the proposed MFDS-DETR method are confirmed through comparisons with other cutting-edge leukocyte detection models using the private WBCDD, public LISC and BCCD datasets. Our source code and private WBCCD dataset are available at https://github.com/JustlfC03/MFDS-DETR.


Asunto(s)
Enfermedades Hematológicas , Trabajo de Parto , Piperazinas , Humanos , Embarazo , Femenino , Leucocitos , Hospitales
6.
CNS Neurosci Ther ; 30(4): e14490, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-37804094

RESUMEN

BACKGROUND: Functional abnormalities of the habenula in patients with depression have been demonstrated in an increasing number of studies, and the habenula is involved in cognitive processing. However, whether patients with late-life depression (LLD) exhibit disrupted habenular functional connectivity (FC) and whether habenular FC mediates the relationship between depressive symptoms and cognitive impairment remain unclear. METHODS: Overall, 127 patients with LLD and 75 healthy controls were recruited. The static and dynamic FC between the habenula and the whole brain was compared between LLD patients and healthy controls, and the relationships of habenular FC with depressive symptoms and cognitive impairment were explored by correlation and mediation analyses. RESULTS: Compared with the controls, patients with LLD exhibited decreased static FC between the right habenula and bilateral inferior frontal gyrus (IFG); there was no significant difference in dynamic FC of the habenula between the two groups. Additionally, the decreased static FC between the right habenula and IFG was associated with more severe depressive symptoms (especially psychomotor retardation) and cognitive impairment (language, memory, and visuospatial skills). Last, static FC between the right habenula and left IFG partially mediated the relationship between depressive symptoms (especially psychomotor retardation) and cognitive impairment (verbal fluency and working memory). CONCLUSIONS: Patients with LLD exhibited decreased static FC between the habenula and IFG but intact dynamic FC of the habenula. This decreased static FC mediated the relationship between depressive symptoms and cognitive impairment.


Asunto(s)
Disfunción Cognitiva , Habénula , Humanos , Memoria a Corto Plazo , Depresión , Disfunción Cognitiva/psicología , Lenguaje , Imagen por Resonancia Magnética
7.
Small ; 20(2): e2305379, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37658512

RESUMEN

The fabrication of perovskite light-emitting diodes (PeLEDs) with vacuum deposition shows great potential and commercial value in realizing large-area display panel manufacturing. However, the electroluminescence (EL) performance of vacuum-deposited PeLEDs still lags behind the counterparts fabricated by solution process, especially in the field of blue PeLEDs. Here, the fabrication of high-quality CsPbBr3- x Clx film through tri-source co-evaporation is reported to achieve high photoluminescence quantum yield (PLQY). Compared with the conventional traditional dual-source co-evaporation, the tri-source co-evaporation method allows for freely adjustable elemental ratios, enabling the introduction of the lattice-matched Cs4 Pb(Br/Cl)6 phase with the quantum-limited effect into the inorganic CsPb(Br/Cl)3 emitter. By adjusting the phase distribution, the surface defects of the emitter can be effectively reduced, leading to better blue emission and film quality. Further, the effects of Cs/Pb ratio and Br/Cl ratio on the PLQY and carrier recombination dynamics of perovskite films are investigated. By optimizing the deposition rate of each precursor source, spectrally stable blue PeLEDs are achieved with tunable emission ranging from 468 to 488 nm. Particularly, the PeLEDs with an EL peak at 488 nm show an external quantum efficiency (EQE) of 4.56%, which is the highest EQE value for mixed-halide PeLEDs fabricated by vacuum deposition.

9.
J Appl Microbiol ; 134(10)2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37858303

RESUMEN

AIMS: Extreme environment of microbial fermentation is the focus of research, which provides new thinking for the production and application of Monascus pigments (MPs). In this work, the high-sugar synergistic high-salt stress fermentation (HSSF) of MPs was investigated. METHODS AND RESULTS: The Monascus fungus grew well under HSSF conditions with 35 g L-1 NaCl and 150 g L-1 glucose, and the extracellular yellow pigment and intracellular orange pigment yield in HSSF was 98% and 43% higher than that in conventional fermentation, respectively. Moreover, the mycelial morphology was maintained in a better status with more branches and complete surface structure, indicating good biocatalytic activity for pigment synthesis. Four extracellular yellow pigments (Y1, Y2, Y3, and Y4) were transformed into each other, and ratio of the relative content of intracellular orange pigments to yellow pigments (O/Y) significantly (P < 0.05) changed. Moreover, the ratio of unsaturated fatty acids to saturated fatty acids (unsaturated/saturated) was significantly (P < 0.05) increased, indicating that the metabolism and secretion of intracellular and extracellular pigment might be regulated in HSSF. The pigment biosynthesis genes mppB, mppC, mppD, MpPKS5, and MpFasB2 were up-regulated, whereas the genes mppR1, mppR2, and mppE were down-regulated, suggesting that the gene expression to regulate pigment biosynthesis might be a dynamic change process in HSSF. CONCLUSIONS: The HSSF system of MPs is successfully performed to improve the pigment yields. Mycelial morphology is varied to enhanced pigment secretion, and gene expression is dynamically regulated to promote pigment accumulation in HSSF.


Asunto(s)
Monascus , Fermentación , Monascus/genética , Monascus/metabolismo , Pigmentos Biológicos/química , Estrés Salino , Expresión Génica , Azúcares/metabolismo
10.
Am J Obstet Gynecol MFM ; 5(12): 101176, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37813304

RESUMEN

BACKGROUND: Oxytocin is considered the drug of choice for the induction of labor, although the optimal protocol and infusion duration remain to be determined. OBJECTIVE: This study aimed to assess whether the duration of oxytocin infusion increases 24-hour delivery rates and affects the length of time-to-delivery and patient's experience. STUDY DESIGN: A randomized controlled trial was performed at a single tertiary medical center, between January 1, 2020 and June 30, 2022. Nulliparous patients with a singleton pregnancy at a vertex presentation and a Bishop score ≥6 were randomly assigned to receive either continuous (16 hours, with a 4 hours pause in between infusions) or intermittent (8 hours, with a 4 hours pause in between infusions) oxytocin infusion, until delivery. In both groups, infusion was halted when signs of maternal or fetal compromise were observed. Randomization was conducted with a computer randomization sequence generation program. The primary outcome was delivery within 24 hours from the first oxytocin infusion and the secondary outcome included time-to-delivery, mode of delivery, and additional maternal and neonatal outcomes. Seventy-two patients per group were randomized to reach 80% statistical power with a 20% difference in the primary outcome according to previous studies. RESULTS: A total of 153 patients were randomized, 72 to the continuous oxytocin infusion group and 81 to the intermittent infusion group. The total oxytocin infusion time was similar between the groups. Patients in the continuous arm were more likely to deliver within 24 hours from oxytocin initiation (79.73% vs 62.96%, P<.05), and had a shorter oxytocin-to-delivery time interval, compared with patients receiving intermittent treatment (9.3±3.7 hours vs 21±11.7 hours, P<.001). Furthermore, time from ruptured membranes to delivery was shorter (9.3±3.7 hours vs 21±11.7 hours; P<.0001) and chorioamnionitis was less frequent (9.46% vs 21%; P<.05) in the continuous compared with the intermittent arm. Cesarean delivery rate was 20% in both groups (P=.226). There was no difference in postpartum hemorrhage, or adverse neonatal outcomes between the groups. Patients receiving continuous oxytocin infusion were more satisfied with the birthing experience. CONCLUSION: Continuous infusion of oxytocin for labor induction in nulliparous patients with a favorable cervix may be superior to intermittent oxytocin infusion, because it shortens time-to-delivery, decreases chorioamnionitis rate, and improves maternal satisfaction, without affecting adverse maternal or neonatal outcomes.


Asunto(s)
Corioamnionitis , Oxitócicos , Femenino , Recién Nacido , Humanos , Embarazo , Oxitocina/efectos adversos , Oxitócicos/efectos adversos , Corioamnionitis/tratamiento farmacológico , Maduración Cervical , Trabajo de Parto Inducido/métodos
11.
Chem Commun (Camb) ; 59(81): 12140-12143, 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37740333

RESUMEN

Placing blocking layers between electrodes has shown paramount prospects in suppressing the shuttle effect of Li-S batteries, but the associated ionic transport would be a concurrent obstacle. Herein, we present a Li-based crystal composited with carbon (LiPN2@C) by a one-step annealing of Li+ absorbed melamine polyphosphate, which simultaneously achieves alleviated polysulfide-shuttling and facilitated Li+ transport. As a homologous crystal, LiPN2 with abundant lithiophilic sites makes Li+ transport more efficient and sustainable. With a LiPN2@C-modified separator, the Li2S cathode exhibits a much-lower activation potential of 2.4 V and a high-rate capacity of 519 mA h g-1 at 2C. Impressively, the battery delivers a capacity of 726 mA h g-1 at 0.5C with a low decay rate of 0.25% per cycle during 100 continuous cycles.

12.
FASEB J ; 37(10): e23206, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37718485

RESUMEN

There is a higher expression level of epidermal growth factor receptor (EGFR) in up to 90% of advanced head and neck squamous cell carcinoma (HNSCC) tissue than in normal surrounding tissues. However, the role of RNA-binding proteins (RBPs) in EGFR-associated metastasis of HNSCC remains unclear. In this study, we reveal that RBPs, specifically nucleolin (NCL) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1), correlated with the mesenchymal phenotype of HNSCC. The depletion of RBPs significantly attenuated EGF-induced HNSCC metastasis. Intriguingly, the EGF-induced EMT markers, such as fibronectin, were regulated by RBPs through the ERK and NF-κB pathway, followed by the enhancement of mRNA stability of fibronectin through the 5' untranslated region (5'-UTR) of the gene. The upregulation of fibronectin triggered the integrin signaling activation to enhance tumor cells' attachment to endothelial cells and increase endothelial permeability. In addition, the concurrence of EGFR and RBPs or EGFR and fibronectin was associated with overall survival and disease-free survival of HNSCC. The in vivo study showed that depletion of NCL, hnRNPA2B1, and fibronectin significantly inhibited EGF-promoted extravasation of tumor cells into lung tissues. The depletion of fibronectin or treatment with integrin inhibitors dramatically attenuated EGF-induced HNSCC metastatic nodules in the lung. Our data suggest that the RBPs/fibronectin axis is essential for EGF-induced tumor-endothelial cell interactions to enhance HNSCC cell metastasis.


Asunto(s)
Fibronectinas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Fibronectinas/genética , Células Endoteliales , Factor de Crecimiento Epidérmico , Receptores ErbB/genética , Regiones no Traducidas 5' , Integrinas , Neoplasias de Cabeza y Cuello/genética
13.
Theranostics ; 13(13): 4650-4666, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37649607

RESUMEN

Background: Multigene mutations in colorectal cancer (CRC), including KRAS, BRAF, and p53, afford high metastatic ability and resistance to EGFR-targeting therapy. Understanding the molecular mechanisms regulating anti-EGFR-resistant CRC metastasis can improve CRC therapy. This study aimed to investigate the effects of IL-8 and the activation of KRAS on reactive oxygen species (ROS) production and metastasis of hyperlipidemia-associated CRC harboring mutations of KRAS and p53. Methods: The cytokine array analysis determined the up-expression of secreted factors, including IL-8. The clinical relevance of the relationship between IL-8 and angiopoietin-like 4 (ANGPTL4) was examined in CRC patients from National Cheng Kung University Hospital and TCGA dataset. Expressions of IL-8, ANGPTL4, NADPH oxidase 4 (NOX4), and epithelial-mesenchymal transition (EMT) markers in free fatty acids (FFAs)-treated KRAS/p53 mutant CRC cells were determined. The hyperlipidemia-triggered metastatic ability of CRC cells under treatments of antioxidants, statin, and cetuximab or knockdown of IL-8, KRAS, and EGFR was evaluated in vitro and in vivo. In addition, the effects of antioxidants and depletion of IL-8 and KRAS on the correlation between ROS production and hyperlipidemia-promoted CRC metastasis were also clarified. Results: In this study, we found that free fatty acids promoted KRAS/p53-mutant but not single-mutant or non-mutant CRC cell metastasis. IL-8, the most abundant secreted factor in KRAS/p53-mutant cells, was correlated with the upregulation of NOX4 expression and ROS production under oleic acid (OA)-treated conditions. In addition, the metastasis of KRAS/p53-mutant CRC relies on the ANGPTL4/IL-8/NOX4 axis and the activation of KRAS. The antioxidants and inactivation of KRAS also inhibited OA-induced EMT and metastasis. Although KRAS mediated EGF- and OA-promoted CRC cell invasion, the inhibition of EGFR did not affect OA-induced ANGPTL4/IL-8/NOX4 axis and CRC metastasis. The high-fat diet mice fed with vitamin E and statin or in IL-8-depleted cells significantly inhibited tumor extravasation and metastatic lung growth of CRC. Conclusion: The antioxidants, statins, and targeting IL-8 may provide better outcomes for treating metastatic CRC that harbors multigene mutations and anti-EGFR resistance.


Asunto(s)
Neoplasias del Colon , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Animales , Ratones , Anticuerpos , Antioxidantes , Ácidos Grasos no Esterificados , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Interleucina-8 , Ácidos Oléicos , Proteínas Proto-Oncogénicas p21(ras)/genética , Especies Reactivas de Oxígeno , Proteína p53 Supresora de Tumor/genética , Humanos
14.
BMC Bioinformatics ; 24(1): 244, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37296383

RESUMEN

BACKGROUND: High throughput experiments in cancer and other areas of genomic research identify large numbers of sequence variants that need to be evaluated for phenotypic impact. While many tools exist to score the likely impact of single nucleotide polymorphisms (SNPs) based on sequence alone, the three-dimensional structural environment is essential for understanding the biological impact of a nonsynonymous mutation. RESULTS: We present a program, 3DVizSNP, that enables the rapid visualization of nonsynonymous missense mutations extracted from a variant caller format file using the web-based iCn3D visualization platform. The program, written in Python, leverages REST APIs and can be run locally without installing any other software or databases, or from a webserver hosted by the National Cancer Institute. It automatically selects the appropriate experimental structure from the Protein Data Bank, if available, or the predicted structure from the AlphaFold database, enabling users to rapidly screen SNPs based on their local structural environment. 3DVizSNP leverages iCn3D annotations and its structural analysis functions to assess changes in structural contacts associated with mutations. CONCLUSIONS: This tool enables researchers to efficiently make use of 3D structural information to prioritize mutations for further computational and experimental impact assessment. The program is available as a webserver at https://analysistools.cancer.gov/3dvizsnp or as a standalone python program at https://github.com/CBIIT-CGBB/3DVizSNP .


Asunto(s)
Biología Computacional , Mutación Missense , Biología Computacional/métodos , Genómica/métodos , Programas Informáticos , Mutación
15.
Am J Geriatr Psychiatry ; 31(11): 905-915, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37271652

RESUMEN

OBJECTIVE: The dorsal lateral prefrontal cortex (DLPFC) has been identified as a neuromodulation target for alleviating suicidal ideation. Dysfunctional DLPFC has been implicated in suicidality in depression. This study aimed to investigate the functional connectivity (FC) of the DLPFC in late-life depression (LLD) with suicidal ideation. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data from 32 LLD patients with suicidal ideation (LLD-S), 41 LLD patients without suicidal ideation (LLD-NS), and 54 healthy older adults (HOA) were analyzed using DLPFC seed-based FC analyses. Group differences in FC were examined, and machine learning was applied to explore the potential of DLPFC-FC for classifying LLD-S from LLD-NS. RESULTS: Abnormal DLPFC-FC patterns were observed in LLD-S, characterized by lower connectivity with the angular gyrus, precuneus, and superior frontal gyrus compared to LLD-NS and healthy controls. A classification model based on the identified DLPFC-FC achieved an accuracy of 75%. CONCLUSION: The lower FC of DLPFC networks may contribute to the neurobiological mechanism of suicidal ideation in late-life depression. These findings may facilitate suicide prevention for LLD by providing potential neuroimaging markers and network-based neuromodulation targets. However, further confirmation with larger sample sizes and experimental designs is warranted.

16.
J Alzheimers Dis ; 93(4): 1317-1327, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37182865

RESUMEN

BACKGROUND: Both late-life depression (LLD) and short sleep duration increase the risk of cognitive impairment. Increased insular resting-state functional connectivity (FC) has been reported in individuals with short sleep duration and dementia. OBJECTIVE: This study aimed to investigate whether short sleep duration is associated with impaired cognition and higher insular FC in patients with LLD. METHODS: This case- control study recruited 186 patients with LLD and 83 normal controls (NC), and comprehensive psychometric assessments, sleep duration reports and resting-state functional MRI scans (81 LLD patients and 54 NC) were conducted. RESULTS: Patients with LLD and short sleep duration (LLD-SS patients) exhibited more severe depressive symptoms and worse cognitive function than those with normal sleep duration (LLD-NS patients) and NC. LLD-SS patients exhibited higher FC between the bilateral insula and inferior frontal gyrus (IFG) pars triangularis than LLD-NS patients and NC, while LLD-NS patients exhibited lower FC than NC. Increased insular FC was correlated with short sleep duration, severe depressive symptoms, and slower information processing speeds. Furthermore, an additive effect was found between sleep duration and LLD on global cognition and insular FC. CONCLUSION: LLD-SS patients exhibited impaired cognition and increased insular FC. Abnormal FC in LLD-SS patients may be a therapeutic target for neuromodulation to improve sleep and cognitive performance and thus decrease the risk of dementia.


Asunto(s)
Disfunción Cognitiva , Demencia , Humanos , Depresión/diagnóstico por imagen , Duración del Sueño , Autoinforme , Imagen por Resonancia Magnética , Disfunción Cognitiva/diagnóstico por imagen , Sueño
17.
J Sep Sci ; 46(13): e2200987, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37029089

RESUMEN

Antioxidants and tyrosinase inhibitory components were successfully screened and separated from Rosa rugosa cv. 'Plena' by high-performance liquid chromatography microfractionation bioactive screening combined with several separation and purification methods. Ethyl acetate extract of Rosa rugosa cv. 'Plena' showed high antioxidant activity and tyrosinase inhibitory activity. High-speed countercurrent chromatography, silica gel column chromatography, and semi-preparative high-performance liquid chromatography were used for the preparative separation of four bioactive components from ethyl acetate extract. Two tyrosinase-inhibiting active substances, flavogallonic acid, and N1 -N5 -N10 -tri-4-p-coumaroylspermidine, were isolated from Rosa rugosa cv. 'Plena', and they showed great monophenolase inhibition activity (half-maximal inhibitory concentration: 664.60 and 23.77 µg/ml, respectively) and excellent diphenolase inhibition activity (half-maximal inhibitory concentration: 23 614.61 and 16.80 µg/ml, respectively). Meanwhile, gallic acid, flavogallonic acid, and ellagic acid were shown to have excellent 1,1-diphenyl-2-picryl-hydrazyl antioxidant activity (half maximal inhibitory concentration: 6.66, 20.17, and 13.45 µg/ml), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) antioxidant activity (half maximal inhibitory concentration: 3.53, 3.83, and 2.78 µg/ml). Molecular docking revealed that flavogallonic acid and N1 -N5 -N10 -tri-4-p-coumaroylspermidine had a strong binding affinity (-9.3 and -10 kcal/mol, respectively) to tyrosinase through hydrogen bonding and hydrophobic interactions.


Asunto(s)
Antioxidantes , Rosa , Monofenol Monooxigenasa/química , Monofenol Monooxigenasa/metabolismo , Rosa/química , Inhibidores Enzimáticos , Simulación del Acoplamiento Molecular , Extractos Vegetales/química
18.
Front Cell Dev Biol ; 11: 1080419, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36910147

RESUMEN

Introduction: Gestational vascular complications (GVCs), including gestational hypertension and preeclampsia, are leading causes of maternal morbidity and mortality. Elevated levels of extracellular vesicles (EVs), in GVC have been linked to vascular injury. This study aims to characterize placental and circulating EV miRNA in GVCs, and explores the involvement of EV-miRNA in GVC, and whether they may be used to distinguish between placental and maternal pathologies. Methods: Blood samples were obtained from 15 non-pregnant (NP), 18 healthy-pregnant (HP), and 23 women with GVC during the third trimester. Placental sections were obtained after caesarian section. Platelet-poor-plasma (PPP) and EV pellets were characterized: EV size/concentration, protein content and miRNA expression were measured by nanoparticle tracking analysis, western blot, nano-string technology and RT-PCR. The effects of EVs on trophoblasts and EC miRNA expression were evaluated. Results: Higher EVs concentrations were observed in HP-PPP and GVC-PPP (p < 0.0001) compared to the NP-PPP. The concentration of large EVs (>100 nm) was higher in PPP and EV pellets of HP and GVC compared to the NP group. EV pellets of pregnant women demonstrated lower expression of exosomal markers CD63/CD81 compared to NP-EVs. GVC-EVs expressed more human placental lactogen (hPL) hormone than HP-EVs, reflecting their placental origin. Screening of miRNAs in EV pellets and in PPP identified certain miRNAs that were highly expressed only in EVs pellets of the HP (13%) and GVC groups (15%), but not in the NP group. Differences were detected in the expression of hsa-miR-16-5p, hsa-miR-210, and hsa-miR-29b-3p. The expression of hsa-miR-16-5p and hsa-miR-210 was low in EV pellets obtained from NP, higher in HP-EVs, and significantly lower in GVC-EVs. Except for hsa-miR-29b-3p, which was upregulated in GVC, no significant differences were found in the levels of other miRNAs in placental sections. Exposure to GVC-EVs resulted in higher expression of hsa-miR-29b-3p compared to cells exposed to HP-EVs in villous trophoblasts, but not in EC. Conclusion: Expression of hsa-miR-16-5p and hsa-miR-210 reflects maternal pathophysiological status, while hsa-miR-29b-3p reflects placental status. These findings suggest that EV-miRNA are involved in GVC, and that they may be used to distinguish between pathologies of placental and maternal origins in preeclampsia.

19.
Plant Physiol Biochem ; 197: 107654, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36989984

RESUMEN

Polyamines (PAs), one of plant growth regulators, play an important role in the plant resistance to drought stress. However, the precise function of putrescine (Put) transformation to other forms of PAs is not clear in filling maize grain embryos. In this study, two maize (Zea mays L.) cultivars, Yedan No. 13 (drought-resistant) and Xundan No. 22 (drought-sensitive), were used as experimental materials. Maize was planted in big plastic basins during whole growth period, and from the 25th day after fertilization, the plants were treated with drought (-1.0 MPa), PAs and inhibitors for 12 d. The experiments were performed during three consecutive years. The changes in the levels of three main free PAs, Put, spermidine (Spd) and spermine (Spm), covalently conjugated PAs (perchloric acid-soluble), covalently bound PAs (perchloric acid-insoluble), the activities of arginine decarboxylase, S-adenosylmethionine decarboxylase, and transglutaminase were investigated in embryos of filling grains. During drought stress, free Put increased from 109 to 367 nmol g-1 FW and from 107 to 142 nmol g-1 FW in Xundan 22 and in Yedan 13, respectively. Meanwhile, free Spd, free Spm and bound Put increased 2.7, 3.0 and 4.2 times in Yedan 13, respectively, and they merely increased about 1.5 times in Xundan 22. These results suggested that free Spd/Spm and bound Put, which were transformed from free Put, were possibly involved in drought resistance. Exogenous Spd treatment enhanced the drought-induced increase in endogenous free Spd/Spm content in drought-sensitive Xundan 22, coupled with the increase in drought resistance, as judged by the decrease in ear leaf relative plasma membrane permeability and increases in ear leaf relative water content, 1000-grain weight and grain number per ear. The suggestion was further testified with methylglyoxal-bis guanylhydrazone and o-phenanthrolin treatments. Collectively, it could be inferred that transformation of free Put to free Spd/Spm and bound Put in filling grain embryos functioned in enhancing the resistance of maize plants to soil drought.


Asunto(s)
Poliaminas , Putrescina , Poliaminas/metabolismo , Putrescina/metabolismo , Zea mays/metabolismo , Sequías , Espermidina/farmacología , Espermina/metabolismo , Grano Comestible/metabolismo
20.
ACS Appl Mater Interfaces ; 15(12): 15768-15774, 2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-36924193

RESUMEN

Multisource coevaporation is such a promising method for the preparation of perovskite films. However, there is limited research about the effects of the buried interface on thermal-evaporated perovskite light-emitting diodes (PeLEDs). In this study, the effects of buried interfaces on thermal-evaporated all-inorganic perovskite films are systematically investigated. It is found that the low-surface-energy buried interface promotes the formation of columnar grain by suppressing heterogeneous nucleation, and functional groups on the high-surface-energy interface have a significant effect on the actual element ratio of the film. The substrate temperature can affect the nucleation and film-formation kinetics of the columnar grains. As a result of the synergistic strategy, a peak external quantum efficiency (EQE) of 8.6% is achieved in the green PeLEDs with a stable emission peak at 516 nm, which is among the best thermal-evaporated PeLEDs reported. This work provides an insight into the preparation of perovskites by thermal evaporation and builds the groundwork for future studies.

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