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PURPOSE: Lycium barbarum polysaccharides (LBPs) have been proven to protect the eyes by inhibiting apoptosis. This study was designed to investigate the effect of LBPs on DNA damage and oxidative stress induced by ultraviolet B (UVB) radiation in human corneal epithelial cells (HCECs). METHODS: HCECs were divided into a control group, UVB group and UVB + LBP group and treated with varying concentrations of LBP (0, 0.05, 0.1, 0.2, 0.4, 0.8, 1.6 and 3.2 mg/mL). Then, the effects of LBP on the viability and apoptosis of HCECs were detected via MTT assay and flow cytometry. Additionally, the contents of superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) in the cells of each group were measured to evaluate the level of oxidative stress. RESULTS: LBP at a concentration of 0.4 mg/mL showed the best effect on promoting the viability and inhibiting the apoptosis of HCECs. Compared with the control group, the UVB and UVB + LBP groups exhibited significantly decreased levels of cell viability and SOD and notably increased apoptosis, MDA, ROS, tail DNA percentage, olive tail moment, p-CHK2, and gamma histone (γH2AX). In contrast to the UVB group, the UVB + LBP group presented notably upregulated levels of cell viability and SOD and downregulated apoptosis, MDA, ROS, tail DNA percentage, olive tail moment, p-CHK2, and γH2AX. CONCLUSIONS: The optimal concentration of LBP to promote the viability and reduce the apoptosis of HCECs is 0.4 mg/mL. Moreover, LBP can alleviate DNA damage and oxidative stress induced by UVB in HCECs.
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Apoptose , Sobrevivência Celular , Dano ao DNA , Epitélio Corneano , Estresse Oxidativo , Espécies Reativas de Oxigênio , Raios Ultravioleta , Estresse Oxidativo/efeitos dos fármacos , Humanos , Raios Ultravioleta/efeitos adversos , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/efeitos da radiação , Epitélio Corneano/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Citometria de Fluxo , Medicamentos de Ervas Chinesas/farmacologia , Células Cultivadas , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismo , Western BlottingRESUMO
Diabetic wound healing is a complex physiological process often hindered by the underlying metabolic dysfunctions associated with diabetes. Despite existing treatments, there remains a critical need to explore innovative therapeutic strategies to improve patient outcomes. This article comprehensively examines the roles of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating key phases of the wound healing process: inflammation, angiogenesis, re-epithelialization, and tissue remodeling. Through a deep review of current literature, we discuss recent discoveries of ncRNAs that have been shown to either promote or impair the wound healing process in diabetic wound healing, which were not covered in earlier reviews. This review highlights the specific mechanisms by which these ncRNAs impact cellular behaviors and pathways critical to each healing stage. Our findings indicate that understanding these recently identified ncRNAs provides new insights into their potential roles in diabetic wound healing, thereby contributing valuable knowledge for future research directions in this field.
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RNA não Traduzido , Cicatrização , Humanos , Cicatrização/genética , RNA não Traduzido/genética , Animais , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Circular/genética , Complicações do Diabetes/genética , Complicações do Diabetes/metabolismoRESUMO
Alcohol use disorder (AUD) is a profound psychiatric condition marked by disrupted connectivity among distributed brain regions, indicating impaired functional integration. Previous connectome studies utilizing functional magnetic resonance imaging (fMRI) have predominantly focused on undirected functional connectivity, while the specific alterations in directed effective connectivity (EC) associated with AUD remain unclear. To address this issue, this study utilized multivariate pattern analysis (MVPA) and spectral dynamic causal modeling (DCM). We recruited 32 abstinent men with AUD and 30 healthy controls (HCs) men, and collected their resting-state fMRI data. A regional homogeneity (ReHo)-based MVPA method was employed to classify AUD and HC groups, as well as predict the severity of addiction in AUD individuals. The most informative brain regions identified by the MVPA were further investigated using spectral DCM. Our results indicated that the ReHo-based support vector classification (SVC) exhibits the highest accuracy in distinguishing individuals with AUD from HCs (classification accuracy: 98.57%). Additionally, our results demonstrated that ReHo-based support vector regression (SVR) could be utilized to predict the addiction severity (alcohol use disorders identification test, AUDIT, R2 = 0.38; Michigan alcoholism screening test, MAST, R2 = 0.29) of patients with AUD. The most informative brain regions for the prediction include left pre-SMA, right dACC, right LOFC, right putamen, and right NACC. These findings were validated in an independent data set (35 patients with AUD and 36 HCs, Classification accuracy: 91.67%; AUDIT, R2 = 0.17; MAST, R2 = 0.20). The results of spectral DCM analysis indicated that individuals with AUD exhibited decreased EC from the left pre-SMA to the right putamen, from the right dACC to the right putamen, and from the right LOFC to the right NACC compared to HCs. Moreover, the EC strength from the right NACC to left pre-SMA and from the right dACC to right putamen mediated the relationship between addiction severity (MAST scores) and behavioral measures (impulsive and compulsive scores). These findings provide crucial evidence for the underlying mechanism of impaired self-control, risk assessment, and impulsive and compulsive alcohol consumption in individuals with AUD, providing novel causal insights into both diagnosis and treatment.
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Alcoolismo , Lobo Frontal , Imageamento por Ressonância Magnética , Humanos , Masculino , Alcoolismo/fisiopatologia , Alcoolismo/diagnóstico por imagem , Adulto , Lobo Frontal/fisiopatologia , Lobo Frontal/diagnóstico por imagem , Conectoma , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/fisiopatologia , Estudos de Casos e Controles , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Adulto JovemRESUMO
Studies have revealed that somatization symptoms are associated with emotional memory in adolescents with depressive disorders. This study investigated somatization symptoms and emotional memory among adolescents with depressive disorders using low-frequency amplitude fluctuations (ALFF). Participants were categorized into the somatization symptoms (FSS) group, non-FSS group and healthy control group (HC). The correctness of negative picture re-recognition was higher in the FFS and HC group than in the non-FSS group. The right superior occipital gyrus and right inferior temporal gyrus were significantly larger in the FSS group than those in the non-FSS and HC groups. Additionally, the ALFF in the superior occipital and inferior temporal gyrus were positively correlated with CSI score. Furthermore, the ALFF values in the temporal region positively correlated with correct negative image re-recognition. The negative image re-recognition rate was positively correlated with the ALFF in the left and right middle occipital gyri. These findings indicated that somatization symptoms in adolescent depression are associated with the superior occipital gyrus and inferior temporal gyrus. Notably, somatization symptoms play a role in memory bias within depressive disorders, with middle occipital and inferior temporal gyri potentially serving as significant brain regions.
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Emoções , Imageamento por Ressonância Magnética , Transtornos Somatoformes , Humanos , Adolescente , Feminino , Transtornos Somatoformes/fisiopatologia , Transtornos Somatoformes/psicologia , Transtornos Somatoformes/diagnóstico por imagem , Masculino , Emoções/fisiologia , Memória/fisiologia , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Depressão/fisiopatologia , Depressão/psicologia , Transtorno Depressivo/fisiopatologia , Transtorno Depressivo/psicologia , Transtorno Depressivo/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologiaRESUMO
OBJECTIVES: To establish a rapid, accurate, and sensitive multiplex PCR detection method for the simultaneous identification of the six common edible meats (beef, lamp, chicken, pork, goose, duck), and to evaluate its application value in meat adulteration identification. METHODS: Based on complete mitochondrial genomic sequences of six species in the GenBank database, DNA sequences (cattleï¼16S rRNA; sheepï¼COX-1; chickensï¼Cytb; pigï¼COX-1; gooseï¼NADH2; duckï¼16S rRNA) with intra-species conservation and inter-species specificity were screened, and species-specific primers were designed to construct a multiplex PCR detection system that can simultaneously detect the meat of six common species. The species specificity, sensitivity and reproducibility of the system were studied, and the simulated mixture sample detection was performed. RESULTS: This study successfully constructed a multiplex PCR detection system that can detect the meats of six common species simultaneously. The system was not effective in DNA amplification of non-target species. When the DNA template sizes were 0.062 5-2 ng/µL, the amplified products of all six species could be detected. The duck component was still detected when the mixing ratio of duck and beef was as low as 0.5%. CONCLUSIONS: This study constructs and establishes a multiplex PCR detection system with strong specificity, high sensitivity, and good reproducibility. It can accurately identify the components of animal origin in common edible meats and provide a simple and practical method for identifying adulteration of common edible meats and meat products in China.
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Galinhas , Primers do DNA , Patos , Gansos , Carne , Reação em Cadeia da Polimerase Multiplex , Sensibilidade e Especificidade , Especificidade da Espécie , Animais , Reação em Cadeia da Polimerase Multiplex/métodos , Patos/genética , Reprodutibilidade dos Testes , Carne/análise , Ovinos , Suínos , Bovinos , RNA Ribossômico 16S/genética , Contaminação de Alimentos/análiseRESUMO
To investigate the effect of miR-3571 on traumatic brain injury (TBI) via the regulation of neuronal apoptosis through F-box-only protein 31/phosphoinositide 3-kinase/protein kinase B (Fbxo31/PI3K/AKT). We established TBI rat and cell models. Hematoxylinâeosin (HE) and Nissl staining were used to observe brain injury and the number of Nissl bodies, respectively. Cell proliferation and apoptosis were assessed by 5-ethynyl-2'-deoxyuridine (EdU), terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and flow cytometry. Gene and protein expression was measured via reverse transcription quantitative polymerase chain reaction (RTâqPCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). In this study, miR-3571 was highly expressed in TBI models. Inhibition of miR-3571 expression can suppress autophagy, reduce the expression of proinflammatory cytokines, and reduce neuronal apoptosis, thus alleviating the pathological conditions of tissue congestion, edema and structural damage after TBI. These experiments demonstrated that miR-3571 could target and regulate the level of Fbxo31. Knockdown of Fbxo31 weakened the remission effect of the miR-3571 inhibitor on TBI and promoted neurological damage; moreover, overexpression of Fbxo31 enhanced the protective effect on neural function, whereas the PI3K/AKT pathway inhibitor LY294002 increased the damage caused by miR-3571 on neural function and weakened the protective effect of Fbxo31. In conclusion, miR-3571 regulates the PI3K/AKT signaling pathway by reducing Fbxo31 expression, promotes neuronal apoptosis and exacerbates TBI.
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The recently discovered complete ammonia oxidation (comammox Nitrospira) containing clade A and clade B has further complemented our understanding of nitrification process. Nevertheless, understanding the community feature of comammox Nitrospira clades A and B and their relative contribution to nitrification in paddy rhizosphere are still in its infancy. In this study, we assessed the community diversity and structure of comammox Nitrospira clades A and B in paddy rhizosphere and bulk soils under thirty years of different fertilization strategies, i.e., non-fertilization control (CK), chemical fertilizers application (NPK), and NPK plus swine manure (NPKM), respectively. NPKM significantly increased the a-diversity (Chao1 and Shannon indices) of comammox Nitrospira clade A and altered the community structure (P < 0.05) but had little effect on clade B. A two-way analysis of variance (ANOVA) showed that the effect of long-term fertilization on soil comammox Nitrospira community and nitrification potential rate (PNR) was much greater than that of rhizosphere. Compared with NPK, soil PNR was greatly increased by 51.0% under the NPKM treatment in the rhizosphere (P < 0.05). Phylogenetic analysis showed that NPKM improved the relative abundances of sub-clade A.2.1 and sub-clade A.3.2 of the comammox clade A community, with an average increase of 212.2 and 210.4% in both rhizosphere and bulk soils relative to the NPK treatment. Soil organic matter, NH4+-N, and pH were significant soil drivers of comammox Nitrospira clades A and B community. Furthermore, linear regression and structural equation modeling clearly showed that comammox Nitrospira clade A a-diversity were significantly associated with soil PNR (P < 0.05). Our results suggest (i) that comammox Nitrospira clade A are sensitive to the organic fertilization; and (ii) that comammox Nitrospira clade A contribute more to nitrification than clade B under the long-term organic fertilized paddy soil.
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Fertilizantes , Nitrificação , Rizosfera , Microbiologia do Solo , Solo , Fertilizantes/análise , China , Solo/química , Filogenia , Amônia/metabolismo , OryzaRESUMO
BACKGROUND: By comprehensively analyzing the blood flow parameters of the umbilical and middle cerebral arteries, doctors can more accurately identify fetal intrauterine distress, as well as assess its severity, so that timely interventions can be implemented to safeguard the health and safety of the fetus. AIM: To identify the relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine distress. METHODS: Clinical data of pregnant women admitted between January 2021 and January 2023 were collected and divided into the observation and control groups (n = 50 each), according to the presence or absence of intrauterine distress. The ultrasound hemodynamic parameters of the uterine artery (UtA), fetal middle cerebral artery (MCA), and umbilical artery (UmA) were compared with neonatal outcomes and occurrence of intrauterine distress in the two groups. RESULTS: Comparison of ultrasonic hemodynamic parameters, resistance index (RI), pulsatility index (PI), and systolic maximal blood flow velocity of UmA compared to diastolic blood flow velocity (S/D), revealed higher values of fetal MCA, PI, and S/D of UmA in pregnant women with UtA compared to controls (P < 0.05), while there was no difference between the two groups in terms of RI (P < 0.05) The incidence of a neonatal Apgar score of 8-10 points was lower in the observation group (66.7%) than in the control group (90.0%), and neonatal weight (2675.5 ± 27.6 g) was lower than in the control group (3117.5 ± 31.2 g). Further, cesarean section rate was higher in the observation group (70.0%) than in the control group (11.7%), and preterm labor rate was higher in the observation group (40.0%) than in the control group (10.0%). The incidence of fetal distress, neonatal growth restriction and neonatal asphyxia were also higher in the observation group (all P < 0.05). CONCLUSION: Fetal MCA, UmA, and maternal UtA hemodynamic abnormalities all develop in pregnant women with intrauterine distress during late pregnancy, which suggests that clinical attention should be paid to them, and monitoring should be strengthened to provide guidance for clinical intervention.
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INTRODUCTION: Despite the extensive neurological symptoms induced by COVID-19 and the identification of SARS-CoV-2 in post-mortem brain samples from COVID-19 patients months after death, the precise mechanisms of SARS-CoV-2 invasion into the central nervous system remain unclear due to the lack of research models. METHODS: We collected glioma tissue samples from glioma patients who had a recent history of COVID-19 and examined the presence of the SARS-CoV-2 spike protein. Subsequently, spatial transcriptomic analyses were conducted on normal brain tissues, glioma tissues, and glioma tissues from glioma patients with recent COVID-19 history. Additionally, single-cell sequencing data from both glioma tissues and glioma organoids were collected and analyzed. Glioma organoids were utilized to evaluate the efficacy of potential COVID-19 blocking agents. RESULTS: Glioma tissues from glioma patients with recent COVID-19 history exhibited the presence of the SARS-CoV-2 spike protein. Differences between glioma tissues from glioma patients who had a recent history of COVID-19 and healthy brain tissues primarily manifested in neuronal cells. Notably, neuronal cells within glioma tissues of COVID-19 history demonstrated heightened susceptibility to Alzheimer's disease, depression, and synaptic dysfunction, indicative of neuronal aberrations. Expressions of SARS-CoV-2 entry factors were confirmed in both glioma tissues and glioma organoids. Moreover, glioma organoids were susceptible to pseudo-SARS-CoV-2 infection and the infections could be partly blocked by the potential COVID-19 drugs. CONCLUSIONS: Gliomas had inherent traits that render them susceptible to SARS-CoV-2 infection, leading to their representability of COVID-19 neurological symptoms. This established a biological foundation for the rationality and feasibility of utilization of glioma organoids as research and blocking drug testing model in SARS-CoV-2 infection within the central nervous system.
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Neoplasias Encefálicas , COVID-19 , Glioma , Organoides , SARS-CoV-2 , Humanos , Glioma/patologia , Glioma/virologia , COVID-19/complicações , COVID-19/patologia , Organoides/virologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/virologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Encéfalo/patologia , Encéfalo/virologia , Encéfalo/metabolismoRESUMO
PURPOSE: Women with gestational diabetes mellitus (GDM) or obesity are vulnerable to impaired gestational cardiovascular health (CVH) and cardiovascular disease (CVD) in the future. It is unclear if prenatal vitamin D supplementation improves gestational CVH, especially in women at high risk for developing CVD. Our goal was to find out if vitamin D supplementation could protect against gestational CVH, including the women with GDM or obesity. DESIGN: We randomly assigned women with a serum 25(OH)D concentration < 75 nmol/L to receive 1600 IU/d (intervention group) or 400 IU/d (control group) of vitamin D3 for two months at 24-28 weeks' gestation. The primary outcome was gestational CVH marks (lipids, inflammatory cytokines, endothelial function). RESULTS: There were 1537 participants divided into the intervention (N = 766) and control groups (N = 771). No baseline differences existed among study groups in CVH markers. At the two-month visit, the intervention group's HDL-C levels (2.01 ± 0.39 VS 1.96 ± 0.39 mmol/L) were significantly higher than those of the control group, while the hs-CRP levels were significantly lower (3.28 ± 2.02 VS 3.64 ± 2.42 mg/L). Subgroup analysis found that HDL-C, TC, hs-CRP, E-Selectin, and SBP were improved in the intervention group among women with GDM or overweight/obesity, and the improvement was not found in women without GDM or overweight/obesity. Vitamin D supplementation significantly decreased the mean triglyceride-glucose index at the two-month visit in women with GDM. CONCLUSIONS: Vitamin D supplementation at mid-gestation might optimize the gestational CVH status for pregnant women, particularly the women with GDM or obesity, which is advantageous for later-life primary prevention of CVD. CLINICAL TRIAL REGISTRATION: The Chinese Clinical Trial Registry (ChiCTR2100051914, 10/9/2021, Prospective registered, https://www.chictr.org.cn/showproj.aspx?proj=134700 ).
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Diabetes Gestacional , Suplementos Nutricionais , Obesidade , Vitamina D , Humanos , Feminino , Gravidez , Diabetes Gestacional/sangue , Adulto , Vitamina D/sangue , Vitamina D/administração & dosagem , Obesidade/sangue , Obesidade/complicações , Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/prevenção & controle , Biomarcadores/sangue , Complicações na Gravidez/sangueRESUMO
The current diagnosis of diabetic retinopathy is based on fundus images and clinical experience. However, considering the ineffectiveness and non-portability of medical devices, we aimed to develop a diagnostic model for diabetic retinopathy based on glucose series data from the wearable continuous glucose monitoring system. Therefore, this study developed a novel method, i.e., double deep latent autoencoder, for exploring glycemic variability influence from multi-day glucose data for diabetic retinopathy. Specifically, the model proposed in this research could encode continuous glucose sensor data with non-continuous and variable length via the integration of a data reorganization module and a novel encoding module with fragmented-missing-wise objective function. Additionally, the model implements a double deep autoencoder, which integrated convolutional neural network, long short-term memory, to jointly capturing the inter-day and intra-day glucose latent features from glucose series. The effectiveness of the proposed model is evaluated through a cross-validation method to clinical datasets of 765 type 2 diabetes patients. The proposed method achieves the highest accuracy value (0.89), precision value (0.88), and F1 score (0.73). The results suggest that our model can be used to remotely diagnose and screen for diabetic retinopathy by learning potential features of glucose series data collected by wearable continuous glucose monitoring systems.
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Glicemia , Retinopatia Diabética , Redes Neurais de Computação , Humanos , Retinopatia Diabética/diagnóstico , Glicemia/análise , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Automonitorização da Glicemia/métodos , Automonitorização da Glicemia/instrumentação , Dispositivos Eletrônicos Vestíveis , Aprendizado Profundo , Masculino , Feminino , AlgoritmosRESUMO
Background: The impact of the COVID-19 pandemic on mental health among healthcare workers has been widely reported during the initial and ongoing phases of the COVID-19 pandemic. Yet, little remains known about the mental health status of primary healthcare workers in China during the post-pandemic era. Methods: A cross-sectional study was conducted between March 1, 2023, and May 31, 2023 in Anhui China. A total of 13,530 primary healthcare workers were recruited. Multiple logistic regression was used to identify potential factors associated with the incidence of depression and anxiety among primary healthcare workers. Results: The prevalence of depression and anxiety among primary healthcare workers was 50.7 and 26.4%, respectively. Multiple logistic regression revealed that female gender (OR = 1.345, 95%CI = 1.222-1.479), being divorced or widowed (OR = 1.432, 95%CI = 1.128-1.817), being a nurse (OR = 1.250, 95%CI = 1.126-1.388), and working more than 8 h per day (OR = 1.710, 95%CI = 1.583-1.846) were significantly associated with depression. A higher risk of anxiety among primary healthcare workers was associated with female gender (OR = 1.338, 95%CI = 1.198-1.494), being divorced or widowed (OR = 1.373, 95%CI = 1.056-1.770), being a nurse (OR = 1.139, 95%CI = 1.013-1.282), and working more than 8 h per day (OR = 1.638, 95%CI = 1.497-1.794). Better monthly income, more than 21 years of working experience and without experience of workplace violence were protective factors against depression and anxiety during the post-pandemic era. Conclusion: Depressive symptoms are more common among primary healthcare workers in China during the post-pandemic era. Female gender, being divorced or widowed, being a nurse, working years, working seniority, monthly income, and experience of workplace violence were identified as associated factors. Targeted intervention is needed when developing strategies to reduce depression and improve primary healthcare workers' wellness and mental health.
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Ansiedade , COVID-19 , Depressão , Pessoal de Saúde , Atenção Primária à Saúde , Humanos , Feminino , China/epidemiologia , Masculino , Estudos Transversais , Adulto , COVID-19/epidemiologia , COVID-19/psicologia , Pessoal de Saúde/estatística & dados numéricos , Pessoal de Saúde/psicologia , Depressão/epidemiologia , Atenção Primária à Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Ansiedade/epidemiologia , Prevalência , Saúde Mental/estatística & dados numéricos , Fatores de Risco , PandemiasRESUMO
Epidermal growth factor receptor (EGFR) plays a pivotal role in the initiation and progression of gliomas. In particular, in glioblastoma, EGFR amplification emerges as a catalyst for invasion, proliferation, and resistance to radiotherapy and chemotherapy. Current approaches are not capable of providing rapid diagnostic results of molecular pathology. In this study, we propose a terahertz spectroscopic approach for predicting the EGFR amplification status of gliomas for the first time. A machine learning model was constructed using the terahertz response of the measured glioma tissues, including the absorption coefficient, refractive index, and dielectric loss tangent. The novelty of our model is the integration of three classical base classifiers, i.e., support vector machine, random forest, and extreme gradient boosting. The ensemble learning method combines the advantages of various base classifiers, this model has more generalization ability. The effectiveness of the proposed method was validated by applying an individual test set. The optimal performance of the integrated algorithm was verified with an area under the curve (AUC) maximum of 85.8 %. This signifies a significant stride toward more effective and rapid diagnostic tools for guiding postoperative therapy in gliomas.
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Receptores ErbB , Glioma , Espectroscopia Terahertz , Humanos , Glioma/genética , Glioma/patologia , Glioma/diagnóstico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Espectroscopia Terahertz/métodos , Aprendizado de Máquina , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Amplificação de Genes , Algoritmos , Máquina de Vetores de SuporteRESUMO
Ferrocene, ruthenium(II) and iridium(III) organometallic complexes, potential substitutes for platinum-based drugs, have shown good application prospects in the field of cancer therapy. Therefore, in this paper, six ferrocene-modified half-sandwich ruthenium(II) and iridium(III) propionylhydrazone complexes were prepared, and the anticancer potential was evaluated and compared with cisplatin. These complexes showed potential in-vitro anti-proliferative activity against A549 cancer cells, especially for Ir-based complexes, and showing favorable synergistic anticancer effect. Meanwhile, these complexes showed little cytotoxicity and effective anti-migration activity. Ir3, the most active complex (ferrocene-appended iridium(III) complex), could accumulate in the intracellular mitochondria, disturb the cell cycle (S-phase), induce the accumulation of reactive oxygen species, and eventually cause the apoptosis of A549 cells. Then, the design of these complexes provides a good structural basis for the multi-active nonplatinum organometallic anticancer complexes.
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Antineoplásicos , Apoptose , Complexos de Coordenação , Compostos Ferrosos , Hidrazonas , Irídio , Metalocenos , Rutênio , Humanos , Compostos Ferrosos/química , Compostos Ferrosos/farmacologia , Irídio/química , Irídio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Metalocenos/química , Metalocenos/farmacologia , Rutênio/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Hidrazonas/química , Hidrazonas/farmacologia , Hidrazonas/síntese química , Células A549 , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células/efeitos dos fármacosRESUMO
Considerable attention has been devoted to the exploration of organometallic iridium(III) (IrIII) complexes for their potential as metallic anticancer drugs. In this study, twelve half-sandwich IrIII imidazole-phenanthroline/phenanthrene complexes were prepared and characterized. Complexes exhibited promising in-vitro anti-proliferative activity, and some are obviously superior to cisplatin towards A549 cells. These complexes possessed suitable fluorescence, and a non-energy-dependent uptake pathway was identified, subsequently leading to their accumulation in the lysosome and the lysosomal damage. Additionally, complexes could inhibit the cell cycle (G1-phase) and catalyze intracellular NADH oxidation, thus substantiating the elevation of intracellular reactive oxygen species (ROS) level, which confirming the oxidative mechanism. Western blotting further confirmed that complexes could induce A549 cell apoptosis through the lysosomal-mitochondrial anticancer pathway, which was inconsistent with cisplatin. In summary, these complexes offer fresh concepts for the development of organometallic nonplatinum anticancer drugs.
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Antineoplásicos , Apoptose , Complexos de Coordenação , Imidazóis , Irídio , Fenantrolinas , Humanos , Irídio/química , Irídio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Fenantrolinas/química , Fenantrolinas/farmacologia , Imidazóis/química , Imidazóis/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Apoptose/efeitos dos fármacos , Células A549 , Espécies Reativas de Oxigênio/metabolismo , Fenantrenos/química , Fenantrenos/farmacologia , Proliferação de Células/efeitos dos fármacos , Lisossomos/metabolismo , Lisossomos/efeitos dos fármacosRESUMO
Fine-grained representation is fundamental to species classification based on deep learning, and in this context, cross-modal contrastive learning is an effective method. The diversity of species coupled with the inherent contextual ambiguity of natural language poses a primary challenge in the cross-modal representation alignment of conservation area image data. Integrating cross-modal retrieval tasks with generation tasks contributes to cross-modal representation alignment based on contextual understanding. However, during the contrastive learning process, apart from learning the differences in the data itself, a pair of encoders inevitably learns the differences caused by encoder fluctuations. The latter leads to convergence shortcuts, resulting in poor representation quality and an inaccurate reflection of the similarity relationships between samples in the original dataset within the shared space of features. To achieve fine-grained cross-modal representation alignment, we first propose a residual attention network to enhance consistency during momentum updates in cross-modal encoders. Building upon this, we propose momentum encoding from a multi-task perspective as a bridge for cross-modal information, effectively improving cross-modal mutual information, representation quality, and optimizing the distribution of feature points within the cross-modal shared semantic space. By acquiring momentum encoding queues for cross-modal semantic understanding through multi-tasking, we align ambiguous natural language representations around the invariant image features of factual information, alleviating contextual ambiguity and enhancing model robustness. Experimental validation shows that our proposed multi-task perspective of cross-modal momentum encoders outperforms similar models on standardized image classification tasks and image-text cross-modal retrieval tasks on public datasets by up to 8% on the leaderboard, demonstrating the effectiveness of the proposed method. Qualitative experiments on our self-built conservation area image-text paired dataset show that our proposed method accurately performs cross-modal retrieval and generation tasks among 8142 species, proving its effectiveness on fine-grained cross-modal image-text conservation area image datasets.
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Gas drainage with bedding boreholes is an efficient method for preventing gas and achieving coal and gas comining in underground mining engineering. An underground pressurized drilling method is proposed to maintain the borehole stability. However, the presence of natural fractures in coal seams poses challenges during pressurized drilling. Therefore, it is crucial to establish a low-leadage degradable drilling fluid system that minimizes coal seam damage. In this study, a degradable drilling fluid system was developed based on the characteristics of coal seams. The performance and influencing factors of the drilling fluid and the degrading capability of cellulase were examined. Moreover, the damage of the drilling fluid on fractured coal seams was investigated using core flow test methods. The results showed that additives significantly improved the rheology, filtration, and inhibition of the drilling fluid. The drilling fluid system exhibited excellent stability, rheological properties, low filtration, and sealing performance in coal seam environments. However, drilling fluid invasion and mud cake blockage negatively affected gas flow in fractured coal seams, and a higher content of filtrate reducer hindered the recovery of the gas flow rate. Cellulase was used to degrade polymers and alleviate the challenge of mud cake removal after drilling. Research on the influencing factors of cellulase indicates that the degradation efficiency of cellulase enzymes is influenced by the temperature, pH, salinity, and solid-phase content. For polluted coal samples, the gas flow rate significantly recovered after treatment with a cellulase solution. This study provides insights into a degradable drilling fluid system that can enhance underground pressurized drilling methods and minimize reservoir damage.
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Objectives: To study the socio-demographic characteristics and the prevalence of depression, anxiety, and stress among clinical therapists in China during the early Coronavirus disease 2019 (COVID-19) pandemic and to identify associated factors. Method: This cross-sectional study was part of a multicenter, nationally representative survey conducted through WeChat from January 2021 to March 2021. Data, including socio-demographics, health-related behaviors, and information on whether they participated in the frontline work of treating COVID-19, were collected anonymously. Respondents also completed the Depression Anxiety Stress Scales-21 (DASS-21). Results: In total, 396 clinical therapists in the selected hospitals completed the questionnaires, with a response rate of 89.0%. Respondents were predominantly female (77.3%). About 6.6% of the participants were current tobacco users, and 20.7% had participated in the frontline work of treating COVID-19. Overall, 22.0%, 17.9%, and 8.8% of participants were classified as having clinically meaningful depression, anxiety, and stress, respectively, based on DASS-21 scores. Multiple logistic regression in Model 1 and Model 2 showed that depression, anxiety, and stress were associated with regular physical activity and frequent insomnia (all, p < 0.05). In anxiety model 2, the associated factors for anxiety during the pandemic were identified as education (master's degree or more, OR=0.520; 95% CI=0.283-0.955), marital status (single, OR=2.064; 95% CI=1.022-4.168), tobacco use (OR=4.265; 95% CI=1.352-13.454), regular physical activity (OR=0.357; 95% CI=0.192-0.663), frequent insomnia (OR=6.298; 95% CI =2.522-15.729), and participation in the frontline work of treating COVID-19 (OR=3.179; 95% CI=1.697-5.954). The COVID-19 epidemic did not significantly increase the depression and stress levels among clinical therapists, but it did significantly increase anxiety levels. Conclusion: During the COVID-19 pandemic, depression, anxiety and stress were relatively common among clinical therapists in China. Regular physical activity and good sleep were important protective factors against emotional problems. Therefore, encouraging regular physical activity and actively addressing clinical therapists' sleep problems is beneficial to improving the ability to cope with negative emotions. The COVID-19 epidemic significantly increased anxiety, and awareness and interventions should be recommended to reduce anxiety among clinical therapists during the COVID-19 pandemic.
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AIM: The wealth of data generated by continuous glucose monitoring (CGM) provides new opportunities for revealing heterogeneities in patients with type 2 diabetes mellitus (T2DM). We aimed to develop a method using CGM data to discover T2DM subtypes and investigate their relationship with clinical phenotypes and microvascular complications. METHODS: The data from 3119 patients with T2DM who wore blinded CGM at an academic medical centre was collected, and a glucose symbolic pattern (GSP) metric was created that combined knowledge-based temporal abstraction with numerical vectorization. The k-means clustering was applied to GSP to obtain subgroups of patients with T2DM. Clinical characteristics and the presence of diabetic retinopathy and albuminuria were compared among the subgroups. The findings were validated in an independent population comprising 773 patients with T2DM. RESULTS: By using GSP, four subgroups were identified with distinct features in CGM profiles and parameters. Moreover, the clustered subgroups differed significantly in clinical phenotypes, including indices of pancreatic ß-cell function and insulin resistance (all p < .001). After adjusting for confounders, group C (the most insulin resistant) had a significantly higher risk of albuminuria (odds ratio = 1.24, 95% confidence interval: 1.03-1.39) relative to group D, which had the best glucose control. These findings were confirmed in the validation set. CONCLUSION: Subtyping patients with T2DM using CGM data may help identify high-risk patients for microvascular complications and provide insights into the underlying pathophysiology. This method may help refine clinically meaningful stratification of patients with T2DM and inform personalized diabetes care.
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Albuminúria , Diabetes Mellitus Tipo 2 , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Albuminúria/sangue , Glicemia/análise , Monitoramento Contínuo da Glicose , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Retinopatia Diabética/sangue , Retinopatia Diabética/etiologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Resistência à InsulinaRESUMO
AIM: To investigate the association between mental health symptoms, alcohol use, and alcohol misuse among psychiatrists in China during the early stage of the COVID-19 pandemic. METHODS: We conducted an online survey to collect data regarding mental health symptoms and alcohol use among psychiatrists in early 2020. The Depression Anxiety Stress Scale-Chinese Version (DASS-21) was used to assess depression, anxiety, and stress symptoms, and the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) was used to assess alcohol use. RESULTS: In total, 3774 psychiatrists completed the survey. AUDIT-C scores were positively correlated with DASS total and depression, anxiety, and stress subscales (total: r = 0.015, depression: r = 0.121, anxiety: r = 0.103, and stress: r = 0.096, all p < 0.05). Alcohol misuse was associated with male sex (OR = 4.754), cigarette smoking (OR = 2.441), administrative position (OR = 1.811), depression (OR = 1.489), and stress (OR = 1.504). Those who reported increased alcohol use during the pandemic were more likely to be male (OR = 2.174), endorse anxiety symptoms (OR = 2.386), or increased stress (OR = 2.402). CONCLUSIONS: Mental health symptoms were common among psychiatrists during the COVID-19 pandemic. Depression and stress symptoms were significantly associated with alcohol misuse. Anxiety and stress symptoms were associated with reported increases in alcohol use. Though a causal relationship cannot be inferred, our findings suggest that strategies promoting healthcare professionals' mental well-being should include alcohol use.