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1.
Front Psychol ; 15: 1331691, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38445063

RESUMO

Background: As the main driver of talent cultivation in colleges and universities, the learning and development level of college students is a core indicator of the quality of talent cultivation. The current status of college students' learning has always been a heavily researched topic. However, there is a lack of academic research on the potential mechanisms of self-control about how it affects college students' learning engagement. This study explored the relationship between college students' self-control and learning engagement and the potential mechanisms underlying this relationship with reference to a large sample. Methods: A total of 765 college students from Guangxi, China, completed the self-control scale, the resilience scale, the positive emotions scale, and the learning engagement scale. SPSS 26.0 was used to conduct common method bias tests, descriptive statistics, correlation tests, and regression analyses. Structural equation modeling was constructed using AMOS 26.0, and mediation effects were tested. Results: This article mainly used questionnaires to collect data and, on this basis, examined the relationship between self-control, resilience, positive emotions, and the learning engagement of college students. The results showed that (1) self-control positively affected college students' learning engagement; (2) resilience partially mediated the relationship between self-control and college students' learning engagement; (3) positive emotions partially mediated the relationship between self-control and college students' learning engagement; and (4) resilience and positive emotions played a chain-mediating role between self-control and college students' learning engagement. Conclusion: The present study identifies the potential mechanism underlying the association between the self-control and learning engagement of college students. The results of this study have practical implications for enhancing the learning engagement of Chinese college students by increasing their psychological resources and improving the teaching of university teachers.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38448769

RESUMO

Drinking water is vital for human health and life, but detecting multiple contaminants in it is challenging. Traditional testing methods are both time-consuming and labor-intensive, lacking the ability to capture abrupt changes in water quality over brief intervals. This paper proposes a direct analysis and rapid detection method of three indicators of arsenic, cadmium, and selenium in complex drinking water systems by combining a novel long-path spectral imager with machine learning models. Our technique can obtain multiple parameters in about 1 s. The experiment involved setting up samples from various drinking water backgrounds and mixed groups, totaling 9360 injections. A raw visible light source ranging from 380 to 780 nm was utilized, uniformly dispersing light into the sample cell through a filter. The residual beam was captured by a high-definition camera, forming a distinctive spectrum. Three deep learning models-ResNet-50, SqueezeNet V1.1, and GoogLeNet Inception V1-were employed. Datasets were divided into training, validation, and test sets in a 6:2:2 ratio, and prediction performance across different datasets was assessed using the coefficient of determination and root mean square error. The experimental results show that a well-trained machine learning model can extract a lot of feature image information and quickly predict multi-dimensional drinking water indicators with almost no preprocessing. The model's prediction performance is stable under different background drinking water systems. The method is accurate, efficient, and real-time and can be widely used in actual water supply systems. This study can improve the efficiency of water quality monitoring and treatment in water supply systems, and the method's potential for environmental monitoring, food safety, industrial testing, and other fields can be further explored in the future.

3.
Int J Neural Syst ; 34(5): 2450022, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38487872

RESUMO

Deep convolutional neural networks have shown advanced performance in accurately segmenting images. In this paper, an SNP-like convolutional neuron structure is introduced, abstracted from the nonlinear mechanism in nonlinear spiking neural P (NSNP) systems. Then, a U-shaped convolutional neural network named SNP-like parallel-convolutional network, or SPC-Net, is constructed for segmentation tasks. The dual-convolution concatenate (DCC) and dual-convolution addition (DCA) network blocks are designed, respectively, in the encoder and decoder stages. The two blocks employ parallel convolution with different kernel sizes to improve feature representation ability and make full use of spatial detail information. Meanwhile, different feature fusion strategies are used to fuse their features to achieve feature complementarity and augmentation. Furthermore, a dual-scale pooling (DSP) module in the bottleneck is designed to improve the feature extraction capability, which can extract multi-scale contextual information and reduce information loss while extracting salient features. The SPC-Net is applied in medical image segmentation tasks and is compared with several recent segmentation methods on the GlaS and CRAG datasets. The proposed SPC-Net achieves 90.77% DICE coefficient, 83.76% IoU score and 83.93% F1 score, 86.33% ObjDice coefficient, 135.60 Obj-Hausdorff distance, respectively. The experimental results show that the proposed model can achieve good segmentation performance.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação
4.
Head Neck ; 46(5): 1009-1019, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38441255

RESUMO

OBJECTIVE: To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the "low-risk" classification for tailored treatment strategies. METHODS: This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis. RESULTS: Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule-capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility. CONCLUSION: This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of "low-risk" categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Esvaziamento Cervical , Tireoidectomia , Metástase Linfática/patologia , Estudos Retrospectivos , Linfonodos/patologia , Fatores de Risco
5.
bioRxiv ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38464211

RESUMO

Introduction: Dibutyl phthalate (DBP), a phthalate congener, is widely utilized in consumer products and medication coatings. Women of reproductive age have a significant burden of DBP exposure through consumer products, occupational exposure, and medication. Prenatal DBP exposure is associated with adverse pregnancy/fetal outcomes and cardiovascular diseases in the offspring. However, the mechanisms underlying DBP exposure-associated adverse pregnancy outcomes are unclear. We hypothesize that prenatal exposure to environmentally relevant low dosage DBP adversely affects fetal-placental vascular function and development during pregnancy. Methods: Adult female CD-1 mice (8-10wks) were orally treated with vehicle (control) or with environmentally relevant DBP dosages (100, 10, and 0.1 µg/kg/day; DBP100, DBP10, DBP0.1) daily from 30 days before pregnancy through gestational day (GD) 18.5. Dam body mass composition (fat/lean mass) was measured non-invasively using the echo-magnetic resonance imaging system. Placental lipid disposition was examined using Oil Red O staining. Results: DBP100 and 10 dose dependently increased weight of non-pregnant female mice, while DBP0.1 did not affect their weight. DBP0.1 exposure also did not affect the maternal weight gain pattern and body fat % during pregnancy. However, DBP0.1 exposure significantly increased the placental weight and decreased the fetal/placental weight ratio (indicative of decreased placental efficiency) at GD18.5. We further observed that while DBP0.1 did not affect lipid disposition in maternal decidual, it significantly decreased lipid disposition in fetal labyrinth of female, but not male placentas. Conclusions: Prenatal DBP exposure to environmentally relevant low-dosage adversely impacts the fetal-placental efficiency and lipid disposition in a fetal sex specific manner.

6.
BMC Cancer ; 24(1): 164, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38302968

RESUMO

BACKGROUND: For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers. METHODS: Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (< 12 LNs), poorly differentiated histology, perineural invasion (PNI), lymphatic vascular invasion (LVI), or elevated preoperative carcinoembryonic antigen (CEA). The low-risk group did not have any risk factors above. Factors associated with disease-free survival (DFS) were included in univariate and multivariate Cox analyses. RESULTS: We collected a total of 262 consecutive patients with stage II dMMR colon cancer. 179 patients (68.3%) have at least one high-risk factor. With a median follow-up of 50.1 months, the low-risk group was associated with a tended to have a better 3-year DFS than the high-risk group (96.4% vs 89.4%; P = 0.056). Both elevated preoperative CEA (HR 2.93; 95% CI 1.26-6.82; P = 0.013) and pT4 disease (HR 2.58; 95% CI 1.06-6.25; P = 0.037) were independent risk factors of recurrence. Then, the 3-year DFS was 92.6% for the surgery alone group and 88.1% for the adjuvant chemotherapy group (HR 1.64; 95% CI 0.67-4.02; P = 0.280). Furthermore, no survival benefit from oxaliplatin-based adjuvant chemotherapy was observed in the high-risk group and in the subgroups with pT4 disease or < 12 LNs. CONCLUSIONS: These data suggests that not all high-risk factors have a similar impact on stage II dMMR colon cancers. Elevated preoperative CEA and pT4 tumor stage are associated with increased recurrence risk. However, oxaliplatin-based adjuvant chemotherapy shows no survival benefits in stage II dMMR colon cancers, either with or without high-risk factors.


Assuntos
Neoplasias Encefálicas , Neoplasias do Colo , Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA , Síndromes Neoplásicas Hereditárias , Humanos , Estudos Retrospectivos , Oxaliplatina/uso terapêutico , Estadiamento de Neoplasias , Antígeno Carcinoembrionário , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/cirurgia , Prognóstico , Quimioterapia Adjuvante
7.
Asia Pac Psychiatry ; 16(1): e12552, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38348641

RESUMO

BACKGROUND: Major depressive disorder (MDD) is one of the global burdens of disease, and its pathogenesis remains unclear. An increasing amount of research indicates that ghrelin regulates mood in patients with MDD. Still, current results are inconsistent, and the mechanisms underlying how ghrelin modulates depressive symptoms are inconclusive, especially in first-episode drug-naïve MDD patients. Therefore, this study aims to investigate the relationship and potential mechanism between ghrelin and first-episode drug-naïve MDD. METHODS: Ninety first-episode drug-naïve MDD patients and 65 healthy controls (HCs) were included. Hamilton Depression Scale (HAMD-17) as a measure of depressive symptoms. Plasma levels of ghrelin and hypothalamic-pituitary-adrenal axis (HPA-axis) hormones were measured in all participants. RESULTS: Compared to HCs, the ghrelin levels were higher in the MDD (p < .001) and still showed significance after covarying for sex, age, and Body Mass Index (BMI). Ghrelin was positively related to corticotropin-releasing-hormone (CRH) levels (r = .867, p < .001), adrenocorticotropic hormone (ACTH) levels (r = .830, p < .001), and cortisol levels (r = .902, p < .001) in partial correlation analysis. In addition, there was a positive correlation between HAMD total score and ghrelin levels (r = .240, p = .026). Other than that, the HAMD total score also had a positive correlation with the CRH (r = .333, p = .002) and cortisol (r = .307, p = .004) levels. Further mediation analysis demonstrated that the relationship between ghrelin and HAMD total score was mediated by CRH (ab-path; ß = .4457, 95% CI = 0.0780-1.0253, c-path; ß = .2447, p = .0260, c'-path; ß = -.2009, p = .3427). CONCLUSIONS: These findings revealed that plasma ghrelin provides a pivotal link to depressive symptoms in first-episode drug-naive MDD patients. CRH mediated the relationship between ghrelin and HAMD total score. It might provide new insights into understanding the pathogenesis of MDD, contributing to intervention and treatment from this approach.


Assuntos
Transtorno Depressivo Maior , Humanos , Depressão , Sistema Hipotálamo-Hipofisário , Hidrocortisona , Grelina , Sistema Hipófise-Suprarrenal
8.
Front Endocrinol (Lausanne) ; 15: 1337322, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38362277

RESUMO

Background: Robotic assistance in thyroidectomy is a developing field that promises enhanced surgical precision and improved patient outcomes. This study investigates the impact of the da Vinci Surgical System on operative efficiency, learning curve, and postoperative outcomes in thyroid surgery. Methods: We conducted a retrospective cohort study of 104 patients who underwent robotic thyroidectomy between March 2018 and January 2022. We evaluated the learning curve using the Cumulative Sum (CUSUM) analysis and analyzed operative times, complication rates, and postoperative recovery metrics. Results: The cohort had a mean age of 36 years, predominantly female (68.3%). The average body mass index (BMI) was within the normal range. A significant reduction in operative times was observed as the series progressed, with no permanent hypoparathyroidism or recurrent laryngeal nerve injuries reported. The learning curve plateaued after the 37th case. Postoperative recovery was consistent, with no significant difference in hospital stay duration. Complications were minimal, with a noted decrease in transient vocal cord palsy as experience with the robotic system increased. Conclusion: Robotic thyroidectomy using the da Vinci system has demonstrated a significant improvement in operative efficiency without compromising safety. The learning curve is steep but manageable, and once overcome, it leads to improved surgical outcomes and high patient satisfaction. Further research with larger datasets and longer follow-up is necessary to establish the long-term benefits of robotic thyroidectomy.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Glândula Tireoide , Humanos , Feminino , Adulto , Masculino , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia
10.
Nat Commun ; 15(1): 499, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216551

RESUMO

Mutant KRAS (KRASMUT) is often exploited by cancers to shape tumor immunity, but the underlying mechanisms are not fully understood. Here we report that tumor-specific cytotoxic T lymphocytes (CTLs) from KRASMUT cancers are sensitive to activation-induced cell death (AICD). circATXN7, an NF-κB-interacting circular RNA, governs T cell sensitivity to AICD by inactivating NF-κB. Mechanistically, histone lactylation derived from KRASMUT tumor cell-produced lactic acid directly activates transcription of circATXN7, which binds to NF-κB p65 subunit and masks the p65 nuclear localization signal motif, thereby sequestering it in the cytoplasm. Clinically, circATXN7 upregulation in tumor-specific CTLs correlates with adverse clinical outcomes and immunotherapeutic resistance. Genetic ablation of circAtxn7 in CD8+ T cells leads to mutant-selective tumor inhibition, while also increases anti-PD1 efficacy in multiple tumor models in female mice. Furthermore, targeting circATXN7 in adoptively transferred tumor-reactive CTLs improves their antitumor activities. These findings provide insight into how lymphocyte-expressed circRNAs contribute to T-cell fate decisions and anticancer immunotherapies.


Assuntos
Neoplasias , Proteínas Proto-Oncogênicas p21(ras) , RNA Circular , Evasão Tumoral , Animais , Feminino , Camundongos , Linfócitos T CD8-Positivos , Morte Celular/genética , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , RNA Circular/genética , Evasão Tumoral/genética , Humanos
11.
Orthop Surg ; 16(2): 412-419, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38169155

RESUMO

OBJECTIVES: The collapse of femoral head is a serious symptom of osteonecrosis of the femoral head (ONFH), resulting in hip pain and deformity. However, it is hardly possible to reestablish the femoral head nonoperatively once the collapse happens. Predicting femoral head collapse is of great value for the prognosis of ONFH. This study aimed to develop a new method to quantify the preserved thickness of femoral head and to assess its diagnostic contribution in predicting femoral head collapse on plain radiographs. METHODS: This was a single-center retrospective study. A total of 101 hips (85 patients) with ARCO stage II from January 2008 to December 2016 were included in this study. The preserved thickness was measured on standard anteroposterior (AP) and frog-leg (FL) radiographs. The anteroposterior view's preserved thickness ratio (APTR) and the frog-leg view's preserved thickness ratio (FPTR) were calculated to show the preserved thickness ratio of the femoral head anteriorly and laterally. Univariate and multivariate logistic regression was performed to determine the risk factors for collapse. Sensitivity, specificity, and cut-off values for APTR and FPTR were determined by the receiver operating characteristic (ROC) curve analysis. Kaplan-Meier (K-M) analysis was applied to determine femoral head survival in ONFH patients. RESULTS: The mean age of the 27 females and 58 males was 38.93 years old. The mean follow-up time was 74.62 (36-124) months in the non-collapse group and 18.66 (3-82) months in the collapse group. Femoral head collapse was observed in 62 hips during the follow-up period. Logistic regression analysis and ROC results showed that APTR <24.79% and FPTR <10.62% were significantly correlated with femoral head collapse. The Kaplan-Meier survival curve suggested that the overall survival rate of APTR ≥24.79% was 68.2% at 5 and 10 years and FPTR ≥10.62% was 71.63% at 5 and 10 years. At the last follow-up, 26 hips had collapse on the anterior side of the femoral head, 12 hips occurred on the lateral side, and 24 hips happened to collapse on both anterior and lateral sides. CONCLUSION: Femoral head collapse predominantly occurred anteriorly rather than laterally in ONFH patients. The measurements of APTR and FPTR have noticeable implications for the prediction of femoral head collapse, and contribute to the selection of treatment options for ONFH patients with types B and C1 according to the JIC classification.


Assuntos
Necrose da Cabeça do Fêmur , Masculino , Feminino , Humanos , Adulto , Necrose da Cabeça do Fêmur/cirurgia , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/cirurgia , Estudos Retrospectivos , Prognóstico , Quadril
12.
Tissue Eng Part A ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38183628

RESUMO

Fractures occur commonly with multiple injuries, and their incidence has increased in recent years. Trace amounts of cobalt are necessary for many living organisms as it stimulates hematopoiesis and improves bone health. However, cobalt is also toxic, as it might cause allergic reactions and tissue destruction. These factors limit the application of cobalt in some medical fields. We studied the tea polysaccode-cobalt complex (TPS-Co) prepared from Qingzhuan Dark Tea polysaccharides. We used 6-week-old Sprague-Dawley rats to establish a femoral fracture model and evaluated the effects of CoCl2 and TPS-Co on the healing of femoral fractures. In this study, treatment with TPS-Co for the same content of cobalt intake decreased the side effects associated with CoCl2 treatment and accelerated the healing of femoral fractures in rats. This treatment method promoted angiogenesis by upregulating the expression of vascular endothelial growth factor and hypoxia-inducible factor. Bone formation was promoted via the upregulation of the expression of bone morphogenetic protein 2 and serum bone alkaline phosphatase. TPS-Co was found to actively regulate bone and vascular systems, resulting in significant bone regeneration effects. Therefore, the Qingzhuan Dark Tea polysaccharide cobalt complex might be used as an additive or drug to promote fracture healing, and thus, it might have a huge market value.

13.
Angew Chem Int Ed Engl ; 63(1): e202316781, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37955211

RESUMO

Lithium-carbon dioxide (Li-CO2 ) battery technology presents a promising opportunity for carbon capture and energy storage. Despite tremendous efforts in Li-CO2 batteries, the complex electrode/electrolyte/CO2 triple-phase interfacial processes remain poorly understood, in particular at the nanoscale. Here, using in situ atomic force microscopy and laser confocal microscopy-differential interference contrast microscopy, we directly observed the CO2 conversion processes in Li-CO2 batteries at the nanoscale, and further revealed a laser-tuned reaction pathway based on the real-time observations. During discharge, a bi-component composite, Li2 CO3 /C, deposits as micron-sized clusters through a 3D progressive growth model, followed by a 3D decomposition pathway during the subsequent recharge. When the cell operates under laser (λ=405 nm) irradiation, densely packed Li2 CO3 /C flakes deposit rapidly during discharge. Upon the recharge, they predominantly decompose at the interfaces of the flake and electrode, detaching themselves from the electrode and causing irreversible capacity degradation. In situ Raman shows that the laser promotes the formation of poorly soluble intermediates, Li2 C2 O4 , which in turn affects growth/decomposition pathways of Li2 CO3 /C and the cell performance. Our findings provide mechanistic insights into interfacial evolution in Li-CO2 batteries and the laser-tuned CO2 conversion reactions, which can inspire strategies of monitoring and controlling the multistep and multiphase interfacial reactions in advanced electrochemical devices.

14.
Autophagy ; 20(1): 114-130, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37615625

RESUMO

Bevacizumab plays an important role in the first and second line treatment for metastatic colorectal cancer (CRC). And induction of hypoxia and the tumors response to it plays an important role in determining the efficacy of antiangiogenic therapy while the connection between them remains unclear. Here, we found that lactate accumulated in the tumor environment of CRC and acted as substrates for histone lactylation, and this process was further induced by cellular enhanced glycolysis in hypoxia. We determined that CRC patients resistant to bevacizumab treatment presented with elevated levels of histone lactylation and inhibition of histone lactylation efficiently suppressed CRC tumorigenesis, progression and survival in hypoxia. Histone lactylation promoted the transcription of RUBCNL/Pacer, facilitating autophagosome maturation through interacting with BECN1 (beclin 1) and mediating the recruitment and function of the class III phosphatidylinositol 3-kinase complex, which had a crucial role in hypoxic cancer cells proliferation and survival. Moreover, combining inhibition of histone lactylation and macroautophagy/autophagy with bevacizumab treatment demonstrated remarkable treatment efficacy in bevacizumab-resistance patients-derived pre-clinical models. These findings delivered a new exploration and important supplement of metabolic reprogramming-epigenetic regulation, and provided a new strategy for improving clinical efficacy of bevacizumab in CRC by inhibition of histone lactylation.Abbreviations: 2-DG: 2-deoxy-D-glucose; BECN1: beclin 1; CQ: chloroquine; CRC: colorectal cancer; DMOG: dimethyloxalylglycine; H3K18la: histone H3 lysine 18 lactylation; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; Nala: sodium lactate; PDO: patient-derived orgnoid; PDX: patient-derived xenograft; RUBCNL/Pacer: rubicon like autophagy enhancer; SQSTM1/p62: sequestosome 1.


Assuntos
Neoplasias Colorretais , Histonas , Humanos , Autofagia/fisiologia , Proteína Beclina-1/metabolismo , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Epigênese Genética , Histonas/metabolismo , Hipóxia , Ácido Láctico , Lisina/metabolismo
15.
J Neural Transm (Vienna) ; 131(1): 73-81, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37801108

RESUMO

Depressive symptoms are common in Parkinson's disease (PD). The relationships between autophagy and PD or depression have been documented. However, no studies explored the role of autophagy markers associated with depressive symptoms in PD. Our study aimed to investigate the relationships between autophagy markers, cognitive impairments and depressive symptoms in PD patients. A total of 163 PD patients aged 50-80 years were recruited. Plasma concentrations of autophagy markers (LC3-I, LC3-II and p62/SQSTM1) and glycolipid parameters were measured. Depressive symptoms, cognitive impairments, and motor function were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA), and the Movement Disorders Society Unified Parkinson's Rating Scale Part III (MDS-UPDRS-III), respectively. There were no significant differences between depressed and non-depressed PD patients for LC3-I, LC3-II, LC3-II/LC3-I and p62/SQSTM1. After controlling confounding variables, LC3-II/LC3-I showed an independent relationship with depressive symptoms in PD patients (Beta = 10.082, t = 2.483, p = 0.014). Moreover, in depressive PD patients, p62/SQSTM1 was associated with MoCA score (Beta = - 0.002, t = - 2.380, p = 0.020); Further, p62/SQSTM1 was related to naming ability; in addition, p62/SQSTM1 was independently associated with delayed recall (Beta = - 0.001, t = - 2.452, p = 0.017). LC3-II/LC3-I was related to depressive symptoms in PD patients. In depressive PD patients, p62/SQSTM1 was associated with cognitive function, especially naming ability and delayed recall.


Assuntos
Disfunção Cognitiva , Doença de Parkinson , Humanos , Depressão/etiologia , Proteína Sequestossoma-1 , Disfunção Cognitiva/complicações , Cognição , Autofagia
16.
Int Immunopharmacol ; 127: 111328, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38064810

RESUMO

Nicotinamide adenine dinucleotide (NAD+) is an essential element in cellular metabolism that regulates fundamental biological processes. Growing evidence suggests that a decline in NAD+ is a common pathological factor in various diseases and aging. However, its role in airway epithelial barrier function in response to asthma remains underexplored. The current study aims to explore the efficacy of restoring cellular NAD+ concentration through supplementation with the NAD+ precursor, nicotinamide mononucleotide (NMN), in the treatment of allergic asthma and to investigate the role of SIRT3 in mediating the effects of NAD+ precursors. In this research, NMN alleviated airway inflammation and reduced mucus secretion in house dust mite (HDM)-induced asthmatic mice. It also mitigated airway epithelial barrier disruption in HDM-induced asthma in vitro and in vivo. But inhibition of SIRT3 expression abolished the effects of NMN. Mechanistically, HDM induced SIRT3 SUMOylation and proteasomal degradation. Mutation of these two SIRT3 SUMO modification sites enhanced the stability of SIRT3. Additionally, SIRT3 was targeted by SENP1 which acted to de-conjugate SUMO. And down-regulation of SENP1 expression in HDM-induced models was reversed by NMN. Collectively, these findings suggest that NMN attenuates airway epithelial barrier dysfunction via inhibiting SIRT3 SUMOylation in asthma. Blockage of SIRT3 SUMOylation emerges as for the treatment of allergic asthma.


Assuntos
Asma , Sirtuína 3 , Camundongos , Animais , NAD/metabolismo , Mononucleotídeo de Nicotinamida/metabolismo , Sirtuína 3/genética , Sirtuína 3/metabolismo , Sumoilação , Pyroglyphidae
17.
Mol Cancer ; 22(1): 202, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38087322

RESUMO

BACKGROUND: Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Emerge evidence suggests that circular RNA (circRNA) is a pivotal player in cancer progression. However, its role in CRC liver metastasis remains largely unknown. METHODS: Circ-YAP expression was detected by qRT-PCR and in situ hybridization. The function of circ-YAP was tested by wound healing, transwell and CCK-8 assays. RNA immunoprecipitation, pull-down, luciferase reporter, chromatin immunoprecipitation assays were used to investigate the mechanism underlying circ-YAP promoting CRC liver metastasis. CRC liver metastasis animal model was established to assess the effect of circ-YAP in vivo. RESULTS: Circ-YAP was notably upregulated in CRC with liver metastasis, which was associated with dismal prognosis. Circ-YAP promoted CRC cell migration and invasion in vitro, and facilitated liver metastasis in patient-derived xenografts (PDX) models in vivo. Mechanistically, circ-YAP encoded a novel truncated protein containing 220 amino acids, termed as YAP-220aa, which competitively bound to LATS1, resulting in YAP dephosphorylation and nuclear translocation, thereby activating a cohort of metastasis-promoting genes. Importantly, N6-methyladenosine (m6A) modification orchestrated efficient initiation of circ-YAP translation, requiring m6A reader YTHDF3 and eIF4G2 translation initiation complex. Intriguingly, circ-YAP was transcriptionally enhanced by YAP/TEAD complex, thus forming a positive regulatory feed-forward loop. CONCLUSIONS: Our findings reveal a previously uncharacterized oncoprotein encoded by circ-YAP, implying a promising biomarker and therapeutic target for CRC patients with liver metastasis.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , MicroRNAs , Animais , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Retroalimentação , RNA/genética , Neoplasias Hepáticas/genética , Neoplasias Colorretais/patologia , Proliferação de Células/genética , MicroRNAs/genética , Regulação Neoplásica da Expressão Gênica
18.
Cancer Med ; 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38133437

RESUMO

BACKGROUND: To improve the early detection rate of multiple myeloma (MM), the M-protein screening system has been performed in the hospital population at Zhongshan Hospital Fudan University since 2014, with electrophoretic-based monoclonal immunoglobulin (M-protein) screening integrated into the blood biochemistry panel. This study updated 7-year follow-up findings of MM patients diagnosed by screening-driven and symptom-driven approaches. METHODS: The retrospective study compared the characteristics and outcomes of patients diagnosed through two patterns by reviewing the plasma cell disease database from January 2014 to October 2021. The screening-driven group included patients diagnosed through the screening system during workups of unrelated medical conditions or routine checkups. In contrast, patients who visited or were referred to the hematological department due to myeloma-related end-organ damage were categorized into the symptom-driven group. RESULTS: There were 3,110,218 serum protein electrophoresis (SPEP) tests performed during 7 years, with 1.95% (60,609) patients yielding positive SPEP results. Of 911 confirmed MM cases (excluding concurrent amyloidosis), 366 were assigned to the screening-driven group, while 545 were to the symptom-driven group. Compared to the symptom-driven group, the screening group had more IgG subtypes, earlier International Stage System stages, fewer disease-related symptoms, lower ECOG scores, less extramedullary disease, a lower percentage of bone marrow plasma cells, and a lower level of lactate dehydrogenase. Frontline response results of two groups were similar. Patients detected through screening had a significantly improved median progression-free survival (PFS) than the symptom-driven group (62.2 vs. 24.9 months, p < 0.001, HR: 2.12, 95% CIs: 1.69-2.65), with median follow-ups of 32.6 and 27.4 months. Furthermore, the median overall survival (OS) was significantly longer in patients of the screening group (not reached vs. 62.3 months, p < 0.001, HR: 2.49, 95% CIs: 1.81-3.41). After being adjusted for well-acknowledged myeloma prognostic factors, the screening-driven diagnostic pattern remained an independent prognostic factor indicating improved PFS and OS in MM patients. CONCLUSION: Routine M-protein screening for MM in the hospital population results in an earlier diagnosis and better patient outcomes.

19.
Cancer Med ; 12(24): 21651-21665, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37965778

RESUMO

OBJECTIVES: Intratumor heterogeneity (ITH) is an important factor for clinical outcomes in patients with multiple myeloma (MM). High ITH has been proven to be a key reason for tumor immune escape and treatment resistance. Neoantigens are thought to be associated with ITH, but the specific correlation and functional basis for this remains unclear. METHODS: We study this question through the whole-exome sequencing (WES) data from 43 high ITH newly diagnosed MM patients in our center. Mutant allele tumor heterogeneity (MATH) was conducted to quantify ITH. The cutoff value for high intratumor heterogeneity was determined by comparing MATH of different kinds of tumors. NeoPredPipe was performed to predict neoantigens and binding affinity. RESULTS: Compared to other tumors, MM has a relatively low tumor mutation burden but a high ITH. Patients with high MATH had significantly shorter progression-free survival times than those with low MATH (p = 0.001). In high ITH samples, there is a decrease in strong-binding neoantigens (p = 0.019). The loss of strong-binding neoantigens is a key factor for insensitivity to therapy (p = 0.015). Loss of heterozygosity in HLA was not observed. In addition, patients with fewer neoantigens loss had higher rates of disease remission (p = 0.047). CD8 + T cells (p = 0.012) and NK cells (p = 0.011) decreased significantly in patients with high neoantigens loss rate. A prediction model based on neoantigens was built to evaluate the strength of immune escape. CONCLUSION: The loss of strong-binding neoantigens explains why tumors with high ITH have a higher degree of immune escape and may be feasible for deciding the clinical treatment of MM.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/genética , Mutação , Antígenos de Neoplasias/genética , Linfócitos T CD8-Positivos
20.
Heliyon ; 9(11): e21986, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38027633

RESUMO

Introduction: Alexithymia and perceived stress have been recognized as risk factors for suicide in patients with major depressive disorder (MDD). However, few studies have been conducted to examine the relationship between these factors. Methods: A cross-sectional study was conducted on 105 MDD patients. Alexithymia was assessed by the 20-Item Toronto Alexithymia Scale (TAS), perceived stress was assessed by the Perceived Stress Scale (PSS), severity of depression was assessed by the 17-item Hamilton Depression Rating Scale (HAMD), and suicidal ideation was assessed by the self-report Beck Scale for Suicide Ideation (SSI). A sequential mediation model was established to test the mediating effects of perceived stress and severity of depression on the association between alexithymia and suicidal ideation. Results: 81 of the 105 participants (77.14 %) had suicidal ideation. Patients with suicidal ideation had greater difficulty in identifying feelings (DIF) (p = 0.046), higher severity of depression (p = 0.005) and perceived stress (p = 0.003). DIF subscale score of TAS was associated with perceived stress (r = 0.292, p = 0.003), severity of depression (r = 0.349, p < 0.001) and suicidal ideation (r = 0.229, p = 0.012). Sequential mediation model showed that perceived stress and severity of depression mediated the effect of DIF on suicidal ideation. Conclusions: This study suggests that perceived stress and severity of depression fully mediate the relationship between difficulty in identifying feelings and suicidal ideation in MDD patients.

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