Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.863
Filtrar
1.
Front Public Health ; 12: 1348416, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737866

RESUMEN

Background: The prevalence of mental health issues has been gradually increasing among college students in recent years. Improvements in mental health can be achieved through changes in daily behavior and the use of psychological counseling. This study aims to investigate the relationship between health-promoting behaviors and negative emotions among college freshmen as they enter the university. It also examines the impact of various sub-dimensions of health-promoting behaviors and other factors on the negative emotions (stress, anxiety, and depression) experienced by college freshmen. Methods: Using the Negative Emotion and Health-Promoting Behavior scales, a 7-month longitudinal study was conducted on 4,252 college freshmen, with collection of data at two time points (T1: November 12, 2021; T2: June 17, 2022). Out of this longitudinal study, 3,632 valid samples were obtained. This research aimed to explore the association and impact between negative emotions and the level of health-promoting behaviors among college students during their time at the university. Results: ① There were significant differences in the levels of health-promoting behaviors and negative emotions over the course of 7 months (P < 0.05). Health-promoting behaviors were found to have a significant negative correlation with negative emotions (P < 0.05). ② Negative emotions at T1 significantly negatively predicted health-promoting behaviors at T2 (ß = -0.11, P < 0.01), while health-promoting behaviors at T1 significantly negatively predicted negative emotions at T2 (ß = -0.12, P < 0.001). ③ Stress management (ß = -0.104, P < 0.05; ß = -0.087, P < 0.05), self-actualization (ß = -0.282, P < 0.01; ß = -0.260, P < 0.05), health responsibility (ß = -0.057, P < 0.05; ß = -0.088, P < 0.05), and interpersonal relations (ß = 0.068, P < 0.01; ß = 0.138, P < 0.05) were important components in improving stress and anxiety. Self-actualization (ß = -0.437, P < 0.001), exercise (ß = 0.048, P < 0.001), nutrition (ß = 0.044, P < 0.001), and interpersonal relations (ß = 0.065, P < 0.001) were important components in improving depression. ④ Gender, place of household registration, and whether the individual is the only child were significant factors affecting negative emotions in college freshmen. Conclusion: The level of health-promoting behaviors is an important indicator for assessing the negative emotional states of college freshmen. Enhancing health-promoting behaviors across various dimensions can help alleviate different types of negative emotions. Gender, place of household registration, and being the only child are significant factors that influence negative emotions.


Asunto(s)
Emociones , Conductas Relacionadas con la Salud , Promoción de la Salud , Estudiantes , Humanos , Masculino , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Femenino , Universidades , Estudios Longitudinales , Adulto Joven , Adolescente , Ansiedad/psicología , Encuestas y Cuestionarios , Depresión/psicología , Estrés Psicológico/psicología , Adulto
2.
Front Med (Lausanne) ; 11: 1329538, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38741763

RESUMEN

Objective: To explore the effect of applying the online to offline teaching mode in the training of non-anesthesiology residents in department of anesthesiology. Trial design: The randomized controlled trial was performed on non-anesthesiology residents from Affiliated Jiangning Hospital of Nanjing Medical University. Methods: All selected residents were randomly divided into the traditional teaching group (Group T) and the online to offline teaching group (Group O) by the random number table method. Traditional teaching mode was used in Group T, while the online to offline teaching mode was used in Group O. The training period lasted for two months. At the end of the training, theoretical and clinical skills were assessed for all residents, and students' satisfaction scores on teaching were investigated from the aspects of teaching mode, stimulating learning interest, improving learning process and teaching satisfaction. The teaching efficiency was compared and analyzed in the two groups. Results: In total, 39 cases in Group O and 38 cases in Group T were included in the statistical analysis. Compared with Group T, theory test scores, clinical skills test scores, and overall scores improved significantly in Group O (82.2 ± 8.1 vs. 91.3 ± 7.6; 85.1 ± 4.7 vs. 93.3 ± 5.4 and 83.4 ± 6.4 vs. 92.1 ± 6.7, respectively, p < 0.01). Compared with Group T, scores on teaching mode, stimulating learning interest, improving learning process and teaching satisfaction were higher in Group O (81.1 ± 6.9 vs. 93.7 ± 5.2; 83.6 ± 5.8 vs. 91.6 ± 6.4; 82.4 ± 5.3 vs. 90.9 ± 4.8 and 82.1 ± 5.9 vs. 92.1 ± 5.5, respectively, p < 0.01). Conclusion: The online to offline teaching mode can improve the level of professional theory and clinical skill operation, and teaching satisfaction of the non-anesthesiology residents in department of anesthesiology, thus improving the teaching effectiveness.

3.
Zool Res ; 45(3): 679-690, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38766749

RESUMEN

General anesthesia is widely applied in clinical practice. However, the precise mechanism of loss of consciousness induced by general anesthetics remains unknown. Here, we measured the dynamics of five neurotransmitters, including γ-aminobutyric acid, glutamate, norepinephrine, acetylcholine, and dopamine, in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective. Results revealed that the concentrations of γ-aminobutyric acid, glutamate, norepinephrine, and acetylcholine increased in the cortex during propofol-induced loss of consciousness. Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia. Notably, the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness. Furthermore, the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups. These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.


Asunto(s)
Anestésicos por Inhalación , Ratones Endogámicos C57BL , Neurotransmisores , Propofol , Sevoflurano , Sevoflurano/farmacología , Animales , Propofol/farmacología , Neurotransmisores/metabolismo , Ratones , Anestésicos por Inhalación/farmacología , Anestésicos Intravenosos/farmacología , Masculino , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo
4.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38731861

RESUMEN

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block tumor cell migration during clinical treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a better candidate for inhibiting NCAM polysialylation when compared with CMP and low-molecular-weight heparin (LMWH), which were determined based on our NMR studies. Furthermore, neutrophil extracellular traps (NETs) represent the most dramatic stage in the cell death process, and the release of NETs is related to the pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. In this study, the molecular mechanisms involved in the inhibition of NET release using LFcinB11 as an inhibitor were also determined. Based on these results, LFcinB11 is proposed as being a bifunctional inhibitor for inhibiting both NCAM polysialylation and the release of NETs.


Asunto(s)
Trampas Extracelulares , Lactoferrina , Moléculas de Adhesión de Célula Nerviosa , Ácidos Siálicos , Lactoferrina/farmacología , Lactoferrina/metabolismo , Humanos , Trampas Extracelulares/metabolismo , Trampas Extracelulares/efectos de los fármacos , Moléculas de Adhesión de Célula Nerviosa/metabolismo , Ácidos Siálicos/metabolismo , Neutrófilos/metabolismo , Neutrófilos/efectos de los fármacos , Heparina de Bajo-Peso-Molecular/farmacología
5.
Nat Commun ; 15(1): 4347, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773146

RESUMEN

Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients' blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.


Asunto(s)
Desmetilasa de ARN, Homólogo 5 de AlkB , Astrocitos , Trastorno Depresivo Mayor , Ratones Noqueados , Animales , Astrocitos/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/genética , Ratones , Humanos , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/patología , Masculino , Femenino , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Neuronas/metabolismo , Estrés Psicológico/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Transportador 2 de Aminoácidos Excitadores/metabolismo , Transportador 2 de Aminoácidos Excitadores/genética , Conducta Animal , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Depresión/metabolismo , Depresión/genética , Adulto , Transmisión Sináptica , Persona de Mediana Edad
6.
Small ; : e2402841, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693072

RESUMEN

Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO2/EPM) is designed and fabricated with porous structures and 3D VO2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO2/EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO2. Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO2/EPM before and after the phase transition. Moreover, the application of VO2/EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices.

8.
BMC Oral Health ; 24(1): 582, 2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38764019

RESUMEN

BACKGROUND: The operation accuracy and efficiency of dynamic navigated endodontic surgery were evaluated through in vitro experiments. This study provides a reference for future clinical application of dynamic navigation systems in endodontic surgery. MATERIALS AND METHODS: 3D-printed maxillary anterior teeth were used in the preparation of models for endodontic surgery. Endodontic surgery was performed with and without dynamic navigation by an operator who was proficient in dynamic navigation technology but had no experience in endodontic surgery. Optical scanning data were applied to evaluate the length and angle deviations of root-end resection. And the operation time was recorded. T tests were used to analyze the effect of dynamic navigation technology on the accuracy and duration of endodontic surgery. RESULTS: With dynamic navigation, the root-end resection length deviation was 0.46 ± 0.06 mm, the angle deviation was 2.45 ± 0.96°, and the operation time was 187 ± 22.97 s. Without dynamic navigation, the root-end resection length deviation was 1.20 ± 0.92 mm, the angle deviation was 16.20 ± 9.59°, and the operation time was 247 ± 61.47 s. Less deviation was achieved and less operation time was spent with than without dynamic navigation (P < 0.01). CONCLUSION: The application of a dynamic navigation system in endodontic surgery can improve the accuracy and efficiency significantly for operators without surgical experience and reduce the operation time.


Asunto(s)
Impresión Tridimensional , Humanos , Proyectos Piloto , Técnicas In Vitro , Cirugía Asistida por Computador/métodos , Apicectomía/métodos , Tempo Operativo , Sistemas de Navegación Quirúrgica
9.
Radiology ; 311(1): e230459, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38563669

RESUMEN

Background Microwave ablation (MWA) is currently under preliminary investigation for the treatment of multifocal papillary thyroid carcinoma (PTC) and has shown promising treatment efficacy. Compared with surgical resection (SR), MWA is minimally invasive and could preserve thyroid function. However, a comparative analysis between MWA and SR is warranted to draw definitive conclusions. Purpose To compare MWA and SR for preoperative US-detected T1N0M0 multifocal PTC in terms of overall and 1-, 3-, and 5-year progression-free survival rates and complication rates. Materials and Methods In this retrospective study, 775 patients with preoperative US-detected T1N0M0 multifocal PTC treated with MWA or SR across 10 centers between May 2015 and December 2021 were included. Propensity score matching (PSM) was performed for patients in the MWA and SR groups, followed by comparisons between the two groups. The primary outcomes were overall and 1-, 3-, and 5-year progression-free survival (PFS) rates and complication rates. Results After PSM, 229 patients (median age, 44 years [IQR 36.5-50.5 years]; 179 female) in the MWA group and 453 patients (median age, 45 years [IQR 37-53 years]; 367 female) in the SR group were observed for a median of 20 months (range, 12-74 months) and 26 months (range, 12-64 months), respectively. MWA resulted in less blood loss, shorter incision length, and shorter procedure and hospitalization durations (all P < .001). There was no evidence of differences in overall and 1-, 3-, or 5-year PFS rates (all P > .05) between MWA and SR (5-year rate, 77.2% vs 83.1%; P = .36) groups. Permanent hoarseness (2.2%, P = .05) and hypoparathyroidism (4.0%, P = .005) were encountered only in the SR group. Conclusion There was no evidence of a significant difference in PFS rates between MWA and SR for US-detected multifocal T1N0M0 PTC, and MWA resulted in fewer complications. Therefore, MWA is a feasible option for selected patients with multifocal T1N0M0 PTC. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Georgiades in this issue.


Asunto(s)
Microondas , Neoplasias de la Tiroides , Humanos , Femenino , Adulto , Persona de Mediana Edad , Microondas/uso terapéutico , Estudios Retrospectivos , Cáncer Papilar Tiroideo/diagnóstico por imagen , Cáncer Papilar Tiroideo/cirugía , Hospitalización , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía
10.
Comput Biol Chem ; 110: 108060, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38579550

RESUMEN

Developing new drugs is an expensive, time-consuming process that frequently involves safety concerns. By discovering novel uses for previously verified drugs, drug repurposing helps to bypass the time-consuming and costly process of drug development. As the largest family of proteins targeted by verified drugs, G protein-coupled receptors (GPCR) are vital to efficiently repurpose drugs by inferring their associations with drugs. Drug repurposing may be sped up by computational models that predict the strength of novel drug-GPCR pairs interaction. To this end, a number of models have been put forth. In existing methods, however, drug structure, drug-drug interactions, GPCR sequence, and subfamily information couldn't simultaneously be taken into account to detect novel drugs-GPCR relationships. In this study, based on a multi-graph convolutional network, an end-to-end deep model was developed to efficiently and precisely discover latent drug-GPCR relationships by combining data from multi-sources. We demonstrated that our model, based on multi-graph convolutional networks, outperformed rival deep learning techniques as well as non-deep learning models in terms of inferring drug-GPCR relationships. Our results indicated that integrating data from multi-sources can lead to further advancement.

11.
Invest Ophthalmol Vis Sci ; 65(4): 1, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38558095

RESUMEN

Purpose: The purpose of this study is to report five novel FZD4 mutations identified in familial exudative vitreoretinopathy (FEVR) and to analyze and summarize the pathogenic mechanisms of 34 of 96 reported missense mutations in FZD4. Methods: Five probands diagnosed with FEVR and their family members were enrolled in the study. Ocular examinations and targeted gene panel sequencing were conducted on all participants. Plasmids, each carrying 29 previously reported FZD4 missense mutations and five novel mutations, were constructed based on the selection of mutations from each domain of FZD4. These plasmids were used to investigate the effects of mutations on protein expression levels, Norrin/ß-catenin activation capacity, membrane localization, norrin binding ability, and DVL2 recruitment ability in HEK293T, HEK293STF, and HeLa cells. Results: All five novel mutations (S91F, V103E, C145S, E160K, C377F) responsible for FEVR were found to compromise Norrin/ß-catenin activation of FZD4 protein. After reviewing a total of 34 reported missense mutations, we categorized all mutations based on their functional changes: signal peptide mutations, cysteine mutations affecting disulfide bonds, extracellular domain mutations influencing norrin binding, transmembrane domain (TM) 1 and TM7 mutations impacting membrane localization, and intracellular domain mutations affecting DVL2 recruitment. Conclusions: We expanded the spectrum of FZD4 mutations relevant to FEVR and experimentally demonstrated that missense mutations in FZD4 can be classified into five categories based on different functional changes.


Asunto(s)
Enfermedades de la Retina , beta Catenina , Humanos , Vitreorretinopatías Exudativas Familiares , beta Catenina/metabolismo , Enfermedades de la Retina/patología , Células HEK293 , Células HeLa , Receptores Frizzled/genética , Mutación , Linaje , Análisis Mutacional de ADN , Tetraspaninas/genética
12.
Artículo en Inglés | MEDLINE | ID: mdl-38641937

RESUMEN

BACKGROUND: Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake. METHODS: An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0 g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30 g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition. RESULTS: In this trial, 97 out of 100 randomized participants (mean age: 64.65 ± 4.84 years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3 months of intervention, significant improvements in waist circumference (83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 cm, P for trend = 0.046), 6-min walking distance (525.65 ± 58.46 vs. 534.47 ± 51.87 vs. 552.02 ± 57.66 m, P for trend = 0.001), five-time sit-to-stand time (7.63 ± 1.63 vs. 6.81 ± 1.8 vs. 6.4 ± 1.42 s, P for trend <0.001), grip strength (26.74 ± 6.54 vs. 27.53 ± 6.99 vs. 28.52 ± 7.09 kg, P for trend <0.001), and MNA score (26.8 ± 2.14 vs. 27.73 ± 1.74 vs. 27.55 ± 1.72, P for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32 ± 49.84 vs. 101.36 ± 42.58 vs. 93.43 ± 41.49 mg/dL, P for trend = 0.023), increased HDL-C (60.04 ± 16.21 vs. 60 ± 17.37 vs. 62.55 ± 18.27 mg/dL, P for trend = 0.02), and DHEA-S levels (97.11 ± 54.39 vs. 103.39 ± 56.75 vs. 106.83 ± 60.56 µg/dL, P for trend = 0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88 ± 5811.68 vs. 11508.97 ± 7151.08 vs. 11220.80 ± 7190.71 pg/mL, P for trend = 0.016) in controls. The intervention group showed greater improvements in 6 min walking distance (ß = 0.71, 95% CI: 6.88 to 40.79, P = 0.006), five-time sit-to-stand test (ß = -0.87, 95% CI: -1.59 to -0.15, P = 0.017), MNA score (ß = 0.96, 95% CI: 0.20 to 1.71, P = 0.013), serum triglycerides (ß = -15.01, 95% CI: -27.83 to -2.20, P = 0.022), LDL-C (ß = -9.23, 95% CI: -16.98 to -1.47, P = 0.020), and DHEA-S levels (ß = 9.98, 95% CI: 0.45 to 19.51, P = 0.04) than controls. CONCLUSIONS: Protein-enriched soup with weekly exercise over 12 weeks significantly improved physical performance, lipid profile, and DHEA-S levels among middle-aged and older adults with inadequate protein intake, while studies assessing long-term benefits of the intervention are needed.

13.
Mol Med ; 30(1): 50, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622518

RESUMEN

BACKGROUND: Colorectal cancer standed as a global health challenge, ranking third in cancer incidence and second in cancer-related deaths worldwide. A deeper understanding of the intricate mechanisms driving colorectal cancer development was pressing need. STK16 had garnered attention in recent researches, while its involvement in cancer had been minimally explored. c-MYC had emerged as a key player in cancer biology. Due to its complex structure, multifunctionality, and intricate interactions, directly inhibiting the activity of c-MYC proves to be challenging. Hence, current research was directing efforts towards modulating c-MYC expression levels. METHODS: Immunoblot, Immunohistochemistry and immunoprecipitation assays were conducted to assess the indicated protein expression levels. RT-PCR was performed to detect the corresponding mRNA expression levels. The proliferation, migration, invasion, and colony formation abilities of the specified cancer cells were investigated using CCK8 assays, Brdu assays, transwell assays, and colony formation assays, respectively. Cellular and animal experiments were performed to investigate the correlation between STK16 signaling and c-MYC signaling. RESULTS: STK16 plays a positive regulatory role in the progression of colorectal cancer. Delving into the molecular mechanisms, we unveiled that STK16 phosphorylated c-MYC at serine 452, a pivotal event hindering the ubiquitin-proteasome pathway degradation of c-MYC. Importantly, colorectal cancer proliferation mediated by STK16 was found to be dependent on the phosphorylation of c-MYC at S452. Furthermore, the researchers demonstrated that STK16 knockout or pharmacological inhibition significantly curtailed colorectal cancer proliferation and c-MYC expression in in vivo animal models. CONCLUSION: We discovered that STK16 phosphorylates c-MYC at serine 452, hindering its degradation via the ubiquitin-proteasome pathway. STK16 inhibition, either genetically or pharmacologically, effectively curtails cancer growth and c-MYC expression in vivo. These findings highlight STK16 as a potential therapeutic target for colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , Transducción de Señal , Animales , Humanos , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Fosforilación , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Serina/metabolismo , Ubiquitinas/genética
14.
Artículo en Inglés | MEDLINE | ID: mdl-38607707

RESUMEN

Inferring potential drug indications plays a vital role in the drug discovery process. It can be time-consuming and costly to discover novel drug indications through biological experiments. Recently, graph learning-based methods have gained popularity for this task. These methods typically treat the prediction task as a binary classification problem, focusing on modeling associations between drugs and diseases within a graph. However, labeled data for drug indication prediction is often limited and expensive to acquire. Contrastive learning addresses this challenge by aligning similar drug-disease pairs and separating dissimilar pairs in the embedding space. Thus, we developed a model called DrIGCL for drug indication prediction, which utilizes graph convolutional networks and contrastive learning. DrIGCL incorporates drug structure, disease comorbidities, and known drug indications to extract representations of drugs and diseases. By combining contrastive and classification losses, DrIGCL predicts drug indications effectively. In multiple runs of hold-out validation experiments, DrIGCL consistently outperformed existing computational methods for drug indication prediction, particularly in terms of top-k. Furthermore, our ablation study has demonstrated a significant improvement in the predictive capabilities of our model when utilizing contrastive learning. Finally, we validated the practical usefulness of DrIGCL by examining the predicted novel indications of Aspirin. The prediction model's code is available at https://github.com/yuxunluo9/DrIGCL.

15.
Integr Comp Biol ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38599626

RESUMEN

How animal embryos determine their early cell fates is an important question in developmental biology. In various model animals asymmetrically localized maternal transcripts play important roles in axial patterning and cell fate specification. Cephalochordates (amphioxus), which have three living genera (Asymmetron, Epigonichthys, Branchiostoma), are an early branching chordate lineage and thus occupy a key phylogenetic position for understanding the evolution of chordate developmental mechanisms. It has been shown that in the zygote of Brachiostoma amphioxus, which possess bilateral gonads flanking both sides of their trunk region, maternal transcripts of germline determinants form a compact granule. During early embryogenesis this granule is inherited by a single blastomere that subsequently gives rise to a cluster of cells displaying typical characteristics of primordial germ cells (PGC). These PGCs then come to lie in the tailbud region and proliferate during posterior elongation of the larva to join in the gonad anlagen at the ventral tip of the developing myomeres in amphioxus larvae. However, in Asymmetron and Epigonichthys amphioxus, whose gonads are present only on the right side of their body, nothing is known about their PGC development or the cellular/morphogenetic processes resulting in the asymmetric distribution of gonads. Using conserved germline determinants as markers, we show that similarly to Brachiostoma amphioxus, Asymmetron also employ a preformation mechanism to specify their PGCs, suggesting that this mechanism represents an ancient trait dating back to the common ancestor of Cephalochordates. Surprisingly, we found that Asymmetron PGCs are initially deposited on both sides of the body during early larval development; however, the left side PGCs cease to exist in young juveniles, suggesting that PGCs are eliminated from the left body side during larval development or following metamorphosis. This is reminiscent of the PGC development in the sea urchin embryo, and we discuss the implications of this observation for the evolution of developmental mechanisms.

16.
Medicine (Baltimore) ; 103(14): e37686, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38579054

RESUMEN

BACKGROUND: Electroacupuncture (EA) is a promising rehabilitation treatment for upper-limb motor recovery in stroke patients. However, the neurophysiological mechanisms underlying its clinical efficacy remain unclear. This study aimed to explore the immediate modulatory effects of EA on brain network functional connectivity and topological properties. METHODS: The randomized, single-blinded, self-controlled two-period crossover trial was conducted among 52 patients with subacute subcortical stroke. These patients were randomly allocated to receive either EA as the initial intervention or sham electroacupuncture (SEA) as the initial intervention. After a washout period of 24 hours, participants underwent the alternate intervention (SEA or EA). Resting state electroencephalography signals were recorded synchronously throughout both phases of the intervention. The functional connectivity (FC) of the parietofrontal network and small-world (SW) property indices of the whole-brain network were compared across the entire course of the two interventions. RESULTS: The results demonstrated that EA significantly altered ipsilesional parietofrontal network connectivity in the alpha and beta bands (alpha: F = 5.05, P = .011; beta: F = 3.295, P = .047), whereas no significant changes were observed in the SEA group. When comparing between groups, EA significantly downregulated ipsilesional parietofrontal network connectivity in both the alpha and beta bands during stimulation (alpha: t = -1.998, P = .049; beta: t = -2.342, P = .022). Significant differences were also observed in the main effects of time and the group × time interaction for the SW index (time: F = 5.516, P = .026; group × time: F = 6.892, P = .01). In terms of between-group comparisons, the EA group exhibited a significantly higher SW index than the SEA group at the post-stimulation stage (t = 2.379, P = .018). CONCLUSION: These findings suggest that EA downregulates ipsilesional parietofrontal network connectivity and enhances SW properties, providing a potential neurophysiological mechanism for facilitating motor performance in stroke patients.


Asunto(s)
Electroacupuntura , Accidente Cerebrovascular , Humanos , Electroacupuntura/métodos , Estudios Cruzados , Accidente Cerebrovascular/terapia , Encéfalo , Electroencefalografía
17.
Sci Adv ; 10(17): eadm7737, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669331

RESUMEN

Flat membranes ubiquitously transform into mysterious complex shapes in nature and artificial worlds. Behind the complexity, clear determinative deformation modes have been continuously found to serve as basic application rules but remain unfulfilled. Here, we decipher two elemental deformation modes of thin membranes, spontaneous scrolling and folding as passing through shrinking channels. We validate that these two modes rule the deformation of membranes of a wide thickness range from micrometer to atomic scale. Their occurrence and the determinative fold number quantitatively correlate with the Föppl-von Kármán number and shrinkage ratio. The unveiled determinative deformation modes can guide fabricating foldable designer microrobots and delicate structures of two-dimensional sheets and provide another mechanical principle beyond genetic determinism in biological morphogens.

18.
Medicine (Baltimore) ; 103(17): e37101, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669387

RESUMEN

This study aimed to investigate the relationship between endoscopic gastroesophageal valve grading and mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave index (PSPWI) in patients with gastroesophageal reflux disease (GERD). A total of 120 patients diagnosed with GERD disease were included in the study. According to the classification of endoscopic gastroesophageal valves, the patients were divided into 5 groups, group 1 as baseline group, and Group 2-4 as Hill grade I-IV. Basic information about the patients was collected, including age and gender. The mean nocturnal baseline impedance and creep wave index induced by swallowing after rumination were measured by high resolution creep measurement technique. Through statistical analysis, the relationship between valve classification and observation index was discussed. In terms of MNBI, impedance values gradually decreased with increasing valve classification. The average impedance of the Grade 1 group was 23.5 mm Hg/cm2, while the average impedance of the Grade 5 group was 15.2 mm Hg/cm2. This reduction showed a significant decreasing trend (P < .001). In addition, in terms of the peristaltic wave index caused by swallowing after regurgitation, the peristaltic wave index gradually increased with the increase of valve classification. The mean index in the Grade 1 group was 1.8 beats/min, while the mean index in the Grade 5 group was 3.6 beats/min. This increase showed a significant positive relationship (P < .001). Endoscopic gastroesophageal valve grading was significantly correlated with MNBI and PSPWI in patients with GERD. These observations can serve as useful tools for assessing the severity of GERD and monitoring disease progression.


Asunto(s)
Deglución , Impedancia Eléctrica , Reflujo Gastroesofágico , Peristaltismo , Humanos , Reflujo Gastroesofágico/fisiopatología , Reflujo Gastroesofágico/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Peristaltismo/fisiología , Deglución/fisiología , Adulto , Anciano , Unión Esofagogástrica/fisiopatología , Índice de Severidad de la Enfermedad
19.
J Magn Reson Imaging ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38682602

RESUMEN

BACKGROUND: Metabolic syndrome (MetS) is associated with worse prognosis in patients with myocardial infarction (MI). However, it is unclear how MetS in MI patients is associated with left atrial (LA) and left ventricular (LV) deformation. PURPOSE: To determine the effect of MetS on LA and LV deformation and atrioventricular interactions in MI patients. STUDY TYPE: Retrospective. POPULATION: One hundred eighty-one MI patients (73 MetS+ and 108 MetS-), 107 age- and sex-matched controls (49 MetS+ and 58 MetS-). FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession (SSFP)/segmented phase-sensitive inversion recovery SSFP sequence. ASSESSMENT: LA strain and strain rates (reservoir, conduit, and active), left atrioventricular coupling index (LACI), and LV geometry and radial, circumferential and longitudinal global peak strains (PS) were compared among groups. STATISTICAL TESTS: Two-way analysis of variance, Spearman and Pearson's correlation coefficients, and multivariable linear regression analysis. P value <0.05 indicated statistical significance. RESULTS: Compared with controls, the MI patients with or without MetS showed impaired LA function (reservoir, conduit, and active) and LV deformation (radial, circumferential, and longitudinal PS) and higher LACI. The MetS+ group had lower LA reservoir and conduit function and LV deformation than MetS- group. The MetS-MI interaction was not statistically significant. Furthermore, multivariable linear regression showed that MetS was independently associated with LA and LV deformation (ß = -0.181 to -0.209) in MI patients; LA function was independently associated with LV circumferential PS (ß = 0.230 to 0.394) and longitudinal PS (ß = 0.189 to 0.420), and LA passive strain and strain rate were negatively associated with LV mass (ß = -0.178 and -0.298). DATA CONCLUSION: MetS may be associated with the LA and LV dysfunction in MI patients. Impaired LV deformation and LV hypertrophy are independently associated with LA dysfunction in MI patients, and the MI patients have higher LACI than controls, suggesting atrioventricular interaction alterations. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: 3.

20.
Food Funct ; 15(8): 4627-4641, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38592736

RESUMEN

Diet-induced thermogenesis (DIT) is crucial for maintaining body weight homeostasis, and the role of dietary fatty acids in modulating DIT is essential. However, the underlying mechanism of fatty acid regulated diet-induced thermogenesis remains elusive. Utilizing the diet- and genetic ablation-induced obese mice models, we found that the C16 unsaturated fatty acids, trans-palmitoleic acid (TPA) and cis-palmitoleic acid (CPA), significantly increased the energy expenditure by promoting the thermogenesis of brown adipose tissues and the production of beige cells in white adipose. As a result, there is a significant reduction in the occurrence of obesity, associated hepatic steatosis and hyperglycemia. Notably, TPA exhibited more potent effects on promoting DIT and alleviating obesity than CPA did. Using inhibitor and gene deletion mice models, we unveiled that TPA acted as a signaling molecule to play a biological function, which could be sensed by the hypothalamic FFAR1 to activate the sympathetic nervous system in promoting adipose tissue thermogenesis. Together, these results demonstrate the underlying mechanism of free fatty acids associated-DIT and will provide fresh insights into the roles of trans-fatty acids in the development of obesity.


Asunto(s)
Ácidos Grasos Monoinsaturados , Hipotálamo , Ratones Endogámicos C57BL , Obesidad , Receptores Acoplados a Proteínas G , Transducción de Señal , Termogénesis , Animales , Termogénesis/efectos de los fármacos , Ratones , Obesidad/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Ácidos Grasos Monoinsaturados/farmacología , Hipotálamo/metabolismo , Hipotálamo/efectos de los fármacos , Masculino , Transducción de Señal/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Dieta Alta en Grasa
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...