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Regulatory processes at the RNA transcript level play a crucial role in generating transcriptome diversity and proteome composition in human cells, impacting both physiological and pathological states. This study introduces FLIBase (www.FLIBase.org), a specialized database that focuses on annotating full-length isoforms using long-read sequencing techniques. We collected and integrated long-read (351 samples) and short-read (12 469 samples) RNA sequencing data from diverse normal and cancerous human tissues and cells. The current version of FLIBase comprises a total of 983 789 full-length spliced isoforms, identified through long-read sequences and verified using short-read exon-exon splice junctions. Of these, 188 248 isoforms have been annotated, while 795 541 isoforms remain unannotated. By overcoming the limitations of short-read RNA sequencing methods, FLIBase provides an accurate and comprehensive representation of full-length transcripts. These comprehensive annotations empower researchers to undertake various downstream analyses and investigations. Importantly, FLIBase exhibits a significant advantage in identifying a substantial number of previously unannotated isoforms and tumor-specific RNA transcripts. These tumor-specific RNA transcripts have the potential to serve as a source of immunogenic recurrent neoantigens. This remarkable discovery holds tremendous promise for advancing the development of tailored RNA-based diagnostic and therapeutic strategies for various types of human cancer.
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Processamento Alternativo , Bases de Dados Genéticas , Neoplasias , Humanos , Neoplasias/genética , Isoformas de Proteínas/genética , RNA , Análise de Sequência de RNA/métodos , TranscriptomaRESUMO
Early-onset Schizophrenia (EOS) is a profoundly progressive psychiatric disorder characterized by both positive and negative symptoms, whose pathogenesis is influenced by genes, environment and brain structure development. In this study, the MIND (Morphometric Inverse Divergence) network was employed to explore the relationship between morphological similarity and specific transcriptional expression patterns in EOS patients. This study involved a cohort of 187 participants aged between 7 and 17 years, consisting of 97 EOS patients and 90 healthy controls (HC). Multiple morphological features were used to construct the MIND network for all participants. Furthermore, we explored the associations between MIND network and brain-wide gene expression in EOS patients through partial least squares (PLS) regression, shared genetic predispositions with other psychiatric disorders, functional enrichment of PLS weighted genes, as well as transcriptional signature assessment of cell types, cortical layers, and developmental stages. The MIND showed similarity differences in the orbitofrontal cortex, pericalcarine cortex, lingual gyrus, and multiple networks in EOS patients compared to HC. Moreover, our exploration revealed a significant overlap of PLS2 weighted genes linking to EOS-related MIND differences and the dysregulated genes reported in other psychiatric diseases. Interestingly, genes correlated with MIND changes (PLS2-) exhibited a significant enrichment not only in metabolism-related pathways, but also in specific astrocytes, cortical layers (specifically layer I and III), and posterior developmental stages (late infancy to young adulthood stages). However, PLS2+ genes were primarily enriched in synapses signaling-related pathways and early developmental stages (from early-mid fetal to neonatal early infancy) but not in special cell types or layers. These findings provide a novel perspective on the intricate relationship between macroscopic morphometric structural abnormalities and microscopic transcriptional patterns during the onset and progression of EOS.
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Esquizofrenia , Recém-Nascido , Humanos , Adulto Jovem , Adulto , Criança , Adolescente , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Imageamento por Ressonância Magnética , Encéfalo , Córtex Pré-Frontal , Lobo OccipitalRESUMO
Skeletal muscle is striated muscle that moves autonomously and is innervated by peripheral nerves. Peripheral nerve injury is very common in clinical treatment. However, the commonly used treatment methods often focus on the regeneration of the injured nerve but overlook the pathological changes in the injured skeletal muscle. Acupuncture, as the main treatment for denervated skeletal muscle atrophy, is used extensively in clinical practice. In the present study, a mouse model of lower limb sciatic nerve detachment was constructed and treated with electroacupuncture Stomach 36 to observe the atrophy of lower limb skeletal muscle and changes in skeletal muscle fibre types before and after electroacupuncture Stomach 36 treatment. Mice with skeletal muscle denervation showed a decrease in the proportion of IIa muscle fibres and an increase in the proportion of IIb muscle fibres, after electroacupuncture Stomach 36. The changes were reversed by specific activators of p38 MAPK, which increased IIa myofibre ratio. The results suggest that electroacupuncture Stomach 36 can reverse the change of muscle fibre type from IIb to IIa after denervation of skeletal muscle by inhibiting p38 MAPK. The results provide an important theoretical basis for the treatment of clinical peripheral nerve injury diseases with electroacupuncture, in addition to novel insights that could facilitate the study of pathological changes of denervated skeletal muscle.
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Eletroacupuntura , Traumatismos dos Nervos Periféricos , Ratos , Camundongos , Animais , Ratos Sprague-Dawley , Traumatismos dos Nervos Periféricos/terapia , Fibras Musculares Esqueléticas , Músculo Esquelético , Nervo Isquiático/lesões , Atrofia Muscular/terapia , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
BACKGROUND: Early-onset schizophrenia (EOS) is a type of schizophrenia (SCZ) with an age of onset of < 18 years. An abnormal inflammatory immune system may be involved in the occurrence and development of SCZ. We aimed to identify the immune characteristic genes and cells involved in EOS and to further explore the pathogenesis of EOS from the perspective of immunology. METHODS: We obtained microarray data from a whole-genome mRNA expression in peripheral blood mononuclear cells (PBMCs); 19 patients with EOS (age range: 14.79 ± 1.90) and 18 healthy controls (HC) (age range: 15.67 ± 2.40) were involved. We screened for differentially expressed genes (DEGs) using the Limma software package and modular genes using weighted gene co-expression network analysis (WGCNA). In addition, to identify immune characteristic genes and cells, we performed enrichment analysis, immune infiltration analysis, and receiver operating characteristic (ROC) curve analysis; we also used a random forest (RF), a support vector machine (SVM), and the LASSO-Cox algorithm. RESULTS: We selected the following immune characteristic genes: CCL8, PSMD1, AVPR1B and SEMG1. We employed a RF, a SVM, and the LASSO-Cox algorithm. We identified the following immune characteristic cells: activated mast cells, CD4+ memory resting T cells, resting mast cells, neutrophils and CD4+ memory activated T cells. In addition, the AUC values of the immune characteristic genes and cells were all > 0.7. CONCLUSION: Our results indicate that immune system function is altered in SCZ. In addition, CCL8, PSMD1, AVPR1B and SEMG1 may regulate peripheral immune cells in EOS. Further, immune characteristic genes and cells are expected to be diagnostic markers and therapeutic targets of SCZ.
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Leucócitos Mononucleares , Esquizofrenia , Humanos , Esquizofrenia/imunologia , Esquizofrenia/genética , Masculino , Feminino , Adolescente , Leucócitos Mononucleares/imunologia , Perfilação da Expressão Gênica , Idade de Início , Redes Reguladoras de Genes , Quimiocina CCL8/genética , Sistema Imunitário , Curva ROC , Máquina de Vetores de SuporteRESUMO
INTRODUCTION: Epithelial barrier disruption is the initial cause of various diseases. We previously reported that acupoint catgut embedding (AE) improves tight junction proteins (TJs) in rats with allergic rhinitis. However, whether AE improves the epithelial barrier in local allergic rhinitis (LAR) remains unknown. METHODS: A total of 36 Sprague Dawley (SD) male rats aged 5-7 weeks were divided into 6 groups with 6 rats each: control group, LAR model group, false acupoint embedding + LAR group, acupoint embedding + LAR group, capsaicin + LAR group, and tunicamycin + acupoint embedding + LAR group. Behavioral observation, ELISA to detect inflammatory factors in nasal lavage fluid and serum IgE, nasal mucosal permeability test, hematoxylin-eosin staining, PCR to detect Substance P (SP), Western blot, and immunofluorescence to detect endoplasmic reticulum stress (ERS) index and TJs were used to investigate the mechanism of AE in LAR. RESULTS: AE improved the symptoms and pathological features of nasal mucosa of LAR rats, reduced the inflammatory factors (IL4, IL5, IL13) of nasal lavage fluid, and showed no significant change in serum IgE levels in all groups. In addition, AE decreased the expression of SP in nasal mucosa of LAR rats, inhibited ERS, increased the expression of tight junction protein, reduced the permeability of nasal mucosa, and improved the function of nasal mucosal barrier. CONCLUSION: This study confirms that AE can improve the nasal mucosal barrier function of LAR by reducing the expression of SP, inhibiting ERS and increasing the expression of TJs, thus enhancing the nasal mucosal barrier function.
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Pontos de Acupuntura , Mucosa Nasal , Ratos Sprague-Dawley , Rinite Alérgica , Animais , Mucosa Nasal/imunologia , Mucosa Nasal/patologia , Mucosa Nasal/metabolismo , Rinite Alérgica/imunologia , Rinite Alérgica/terapia , Ratos , Masculino , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático , Substância P/metabolismo , Terapia por Acupuntura/métodos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Junções Íntimas/metabolismo , Citocinas/metabolismo , Proteínas de Junções Íntimas/metabolismo , PermeabilidadeRESUMO
OBJECTIVE: Hydrogen sulfide (H2S) is associated with depressive-like behavior in rodents. We undertook cross-sectional and longitudinal analyses of plasma levels of H2S and its substrate homocysteine (Hcy) in depression and assessed the association of both parameters with psychopathology and cognitive function. METHODS: Forty-one patients suffering from depression (PSDs) and 48 healthy volunteers were recruited. PSDs were treated for 8 weeks. Analyzable data were collected from all participants for assessment of their psychopathology and cognitive function. Plasma was collected for determination of levels of H2S and Hcy, and data were correlated to determine their potential as plasma biomarkers. RESULTS: Cross-sectional analyses revealed PSDs to have a low plasma H2S level and high Hcy level. Longitudinal analyses revealed that 8 weeks of treatment reversed the changes in plasma levels of H2S and Hcy in PSDs. Plasma levels of H2S and Hcy were associated with psychopathology and cognitive function in depression. The area under the receiver operating characteristic curve (AUC) for a combination of plasma levels of H2S and Hcy and expression of the TNF gene (i.e., H2S-Hcy-TNF) was 0.848 for diagnosing depression and 0.977 for predicting the efficacy of antidepressant agents. CONCLUSION: Plasma levels of H2S and Hcy reflect changes in psychopathology and cognitive function in depression and H2S-Hcy-TNF has the potential to diagnose depression and predict the efficacy of antidepressant medications.
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Sulfeto de Hidrogênio , Humanos , Sulfeto de Hidrogênio/metabolismo , Estudos Transversais , HomocisteínaRESUMO
OBJECTIVES: Insomnia has been the subject of much systematic research because it is a risk factor for a variety of diseases. There is some evidence that gamma sensory stimulation therapy has also been demonstrated to improve sleep quality for people with Alzheimer's disease. However, it is unclear whether this method is effective for treating insomnia. The principal objective of this project was to investigate the efficacy and safety of gamma sensory flicker in improving the sleep quality of insomnia patients. METHODS: Thirty-seven participants with insomnia were recruited for this prospective observational study. For a duration of 8 weeks, participants were exposed to flicker stimulation through a light and sound device. RESULTS: During the main phase of the study, adherence rates averaged 92.21%. Additionally, no severe adverse events were reported for flicker treatment. Analysis of sleep diaries indicated that 40 Hz flickers can enhance sleep quality by reducing sleep onset latencies, and arousals, and increasing total sleep duration. CONCLUSIONS: Gamma sensory flicker improves sleep quality in people suffering from insomnia.
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The sirtuin family, a group of NAD+-dependent class 3 histone deacetylases (HDACs), was extensively studied initially as a group of longevity genes that are activated in caloric restriction and act in concert with nicotinamide adenine dinucleotides to extend the lifespan. Subsequent studies have found that sirtuins are involved in various physiological processes, including cell proliferation, apoptosis, cell cycle progression, and insulin signaling, and they have been extensively studied as cancer genes. In recent years, it has been found that caloric restriction increases ovarian reserves, suggesting that sirtuins may play a regulatory role in reproductive capacity, and interest in the sirtuin family has continued to increase. The purpose of this paper is to summarize the existing studies and analyze the role and mechanism of SIRT1, a member of the sirtuin family, in regulating ovarian function. Research and review on the positive regulation of SIRT1 in ovarian function and its therapeutic effect on PCOS syndrome.
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BACKGROUND: This study aimed to investigate the neuroanatomical subtypes among early-onset schizophrenia (EOS) patients by exploring the association between structural alterations and molecular mechanisms using a combined analysis of morphometric similarity network (MSN) changes and specific transcriptional expression patterns. METHODS: We recruited 206 subjects aged 7 to 17 years, including 100 EOS patients and 106 healthy controls (HC). Heterogeneity through discriminant analysis (HYDRA) was used to identify the EOS subtypes within the MSN strength. The differences in morphometric similarity between each EOS subtype and HC were compared. Furthermore, we examined the link between morphometric changes and brain-wide gene expression in different EOS subtypes using partial least squares regression (PLS) weight mapping, evaluated genetic commonalities with psychiatric disorders, identified functional enrichments of PLS-weighted genes, and assessed cellular transcriptional signatures. RESULTS: Two distinct MSN-based EOS subtypes were identified, each exhibiting different abnormal MSN strength and cognitive functions compared to HC. The PLS1 score mapping demonstrated anterior-posterior gradients of gene expression in EOS1, whereas inverse distributions were observed in EOS2 cohorts. Genetic commonalities were identified in autistic disorder and adult schizophrenia with EOS1 and inflammatory bowel diseases with EOS2 cohorts. The EOS1 PLS1- genes (Z < -5) were significantly enriched in synaptic signaling-related functions, whereas EOS2 demonstrated enrichments in virtual infection-related pathways. Furthermore, the majority of observed associations with EOS1-specific MSN strength differences contributed to specific transcriptional changes in astrocytes and neurons. CONCLUSIONS: The findings of this study provide a comprehensive analysis of neuroanatomical subtypes in EOS, shedding light on the intricate relationships between macrostructural and molecular aspects of the EOS disease.
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Esquizofrenia , Adulto , Humanos , Esquizofrenia/genética , Encéfalo , Cognição , Imageamento por Ressonância MagnéticaRESUMO
Marine lectins are a group of proteins that possess specific carbohydrate recognition and binding domains. They exhibit various activities, including antimicrobial, antitumor, antiviral, and immunomodulatory effects. In this study, a novel galectin-binding lectin gene named PFL-96 (GenBank: OQ561753.1) was cloned from Pinctada fucata. The PFL-96 gene has an open reading frame of 324 base pairs (bp) and encodes a protein comprising 107 amino acids. The protein has a molecular weight of 11.95 kDa and an isoelectric point of 9.27. It contains an N-terminal signal peptide and a galactose-binding lectin domain. The sequence identity to lectin proteins from fish, echinoderms, coelenterates, and shellfish ranges from 31.90 to 40.00 %. In the phylogenetic analysis, it was found that the PFL-96 protein is closely related to the lectin from Pteria penguin. The PFL-96 recombinant protein exhibited coagulation activity on 2 % rabbit red blood cells at a concentration of ≥8 µg/mL. Additionally, it showed significant hemolytic activity at a concentration of ≥32 µg/mL. The PFL-96 recombinant protein exhibited significant antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Candida albicans, and Vibrio alginolyticus, with minimum inhibitory concentrations (MIC) of 4, 8, 16, and 16 µg/mL, respectively. The minimum bactericidal concentrations (MBC) were determined to be 8, 16, 32, and 32 µg/mL, respectively. Furthermore, the PFL-96 recombinant protein exhibited inhibitory effects on the proliferation of Hela tumor cells, HepG2 tumor cells, and C666-1 tumor cells, with IC50 values of 7.962, 8.007, and 9.502 µg/mL, respectively. These findings suggest that the recombinant protein PFL-96 exhibits significant bioactivity in vitro, contributing to a better understanding of the active compounds found in P. fucata. The present study establishes a fundamental basis for further investigation into the mechanism of action and structural optimization of the recombinant protein PFL-96. The aim is to develop potential candidates for antibacterial and anti-tumor agents.
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Pinctada , Animais , Coelhos , Pinctada/metabolismo , Sequência de Aminoácidos , Filogenia , Clonagem Molecular , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/metabolismo , Galectinas/genética , Galectinas/metabolismo , Antibacterianos/metabolismoRESUMO
BACKGROUND: The exosomal lncRNA-miRNA-mRNA networks in first episode schizophrenia (FOS) have not reported yet. This study examined the lncRNA, miRNA and mRNA expression level in exosome derived from first episode schizophrenia (FOS) patients, and explored the the potential of exosomes as biomarkers for schizophrenia. METHODS: We recruited 10 FOS patients and healthy controls (HCs) respectively, examined the lncRNA, miRNA and mRNA expression level of plasma exosome by high throughput sequencing, constructed lncRNA-miRNA-mRNA network, and performed correlation analysis, GO and KEGG pathway analysis, PPI network construction and ROC analysis. RESULTS: There were 746 differently expressed lncRNA, 22 differently expressed miRNA, and 2637 differently expressed mRNA in plasma exosome in FOS compared with HCs. Then we constructed ceRNA network consisting of 8 down-regulated lncRNA, 7 up-regulated miRNA and 65 down-regulated mRNA, and 1 up-regulated lncRNA, 1 down-regulated miRNA and 4 up-regulated mRNA. The expression level of 1 lncRNA and 7 mRNA in exosomal network were correlated with PANSS score. GO and KEGG pathway analysis showed that 4 up-regulated mRNAs were enriched in neuropsychiatric system function. Down-regulated mRNA EZH2 and SIRT1 were identified as hub gene. Finally, we detected the ROC curve of ENSG00000251562, miR-26a-5p, EZH2, miR-22-3p, SIRT1, ENSG00000251562-miR-26a-5p-EZH2, ENSG00000251562-miR-22-3p-SIRT1, and found that the AUC of ceRNA network was higher than lncRNA, miRNA and mRNA alone. CONCLUSION: We constructed the lncRNA-miRNA-mRNA network in exosome derived from FOS plasma, and found that lncRNA-miRNA-mRNA network has potential as biomarkers for FOS.
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Exossomos , MicroRNAs , RNA Longo não Codificante , Esquizofrenia , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genética , Sirtuína 1 , Exossomos/genética , Esquizofrenia/diagnóstico , Esquizofrenia/genética , RNA Mensageiro/genéticaRESUMO
BACKGROUND: Glucolipid metabolism plays an important role in the occurrence and development of diabetes mellitus. However, there is limited research on the characteristics of glucolipid metabolism and complications in different subgroups of newly diagnosed diabetes. This study aimed to investigate the characteristics of glucolipid metabolism and complications in novel cluster-based diabetes subgroups and explore the contributions of different glucolipid metabolism indicators to the occurrence of complications and pancreatic function. METHODS: This retrospective study included 547 newly diagnosed type 2 diabetes patients. Age, body mass index (BMI), glycated hemoglobin (HbA1C), homeostasis model assessment-2 beta-cell function (HOMA2-ß), and homeostasis model assessment-2 insulin resistance (HOMA2-IR) were used as clustering variables. The participants were divided into 4 groups by k-means cluster analysis. The characteristics of glucolipid indicators and complications in each subgroup were analyzed. Regression analyses were used to evaluate the impact of glucolipid metabolism indicators on complications and pancreatic function. RESULTS: Total cholesterol (TC), triglycerides (TG), triglyceride glucose index (TyG), HbA1C, fasting plasma glucose (FPG), and 2-h postprandial plasma glucose (2hPG) were higher in the severe insulin-resistant diabetes (SIRD) and severe insulin-deficient diabetes (SIDD) groups. Fasting insulin (FINS), fasting C-peptide (FCP), 2-h postprandial insulin (2hINS), 2-h postprandial C-peptide (2hCP), and the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) were higher in mild obesity-related diabetes (MOD) and SIRD. 2hCP, FCP, and FINS were positively correlated with HOMA2-ß, while FPG, TyG, HbA1C, and TG were negatively correlated with HOMA2-ß. FINS, FPG, FCP, and HbA1C were positively correlated with HOMA2-IR, while high-density lipoprotein (HDL) was negatively correlated with HOMA2-IR. FINS (odds ratio (OR),1.043;95% confidence interval (CI) 1.006 ~ 1.081), FCP (OR,2.881;95%CI 2.041 ~ 4.066), and TyG (OR,1.649;95%CI 1.292 ~ 2.104) contributed to increase the risk of nonalcoholic fatty liver disease (NAFLD); 2hINS (OR,1.015;95%CI 1.008 ~ 1.022) contributed to increase the risk of atherosclerotic cardiovascular disease (ASCVD); FCP (OR,1.297;95%CI 1.027 ~ 1.637) significantly increased the risk of chronic kidney disease (CKD). CONCLUSIONS: There were differences in the characteristics of glucolipid metabolism as well as complications among different subgroups of newly diagnosed type 2 diabetes. 2hCP, FCP, FINS, FPG, TyG, HbA1C, HDL and TG influenced the function of insulin. FINS, TyG, 2hINS, and FCP were associated with ASCVD, NAFLD, and CKD in newly diagnosed T2DM patients.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Insuficiência Renal Crônica , Humanos , Estudos Retrospectivos , Glicemia/metabolismo , Peptídeo C , Resistência à Insulina/fisiologia , Insulina , Triglicerídeos , Lipoproteínas HDL , HDL-ColesterolRESUMO
Desertification and microplastic pollution are major environmental issues that impact the function of the ecosystem and human well-being of drylands. Land desertification may influence soil microplastics' abundance, transport, and distribution, but their distribution in the dryland deserts of Central Asia's Amu Darya-Aral Sea basin is unknown. Here, we investigated the abundance and distribution of microplastics in dryland desert soils from the Amu Darya River to the Aral Sea basin in Central Asia at a spatial scale of 1000 km and soil depths ranging from 0 to 50 cm. Microplastics were found in soils from all sample locations, with abundances ranging from 182 to 17841 items kg-1 and a median of 3369. Twenty-four polymers were identified, with polyurethane (PU, 37.3%), silicone resin (SR, 17.0%), and chlorinated polyethylene (CPE, 9.8%) accounting for 64.1% of all polymer types. The abundance of microplastics was significantly higher in deep (20-50 cm) soils than in surface (0-5, 5-20 cm) soils. The main morphological characteristics of the observed microplastics were small size (20-50 µm) and irregular particles with no round edges (mean eccentricity 0.65). The abundance was significantly and positively related to soil EC and TP. According to the findings, desertification processes increase the abundance of microplastic particles in soils and promote migration to deeper soil layers. Human activities, mainly grazing, may be the region's primary cause of desertification and microplastic pollution. Our findings provide new information on the diffusion of microplastics in drylands during desertification; these findings are critical for understanding and promoting dryland plastic pollution prevention and control.
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Microplásticos , Poluentes Químicos da Água , Humanos , Solo , Plásticos , Ecossistema , Conservação dos Recursos Naturais , Monitoramento Ambiental , Ásia , Poluentes Químicos da Água/análise , ChinaRESUMO
Sea-level rise is one of the most critical challenges facing coastal ecosystems under climate change. Observations of elevated tree mortality in global coastal forests are increasing, but important knowledge gaps persist concerning the mechanism of salinity stress-induced nonhalophytic tree mortality. We monitored progressive mortality and associated gas exchange and hydraulic shifts in Sitka-spruce (Picea sitchensis) trees located within a salinity gradient under an ecosystem-scale change of seawater exposure in Washington State, USA. Percentage of live foliated crown (PLFC) decreased and tree mortality increased with increasing soil salinity during the study period. A strong reduction in gas exchange and xylem hydraulic conductivity (Ks) occurred during tree death, with an increase in the percentage loss of conductivity (PLC) and turgor loss point (πtlp). Hydraulic and osmotic shifts reflected that hydraulic function declined from seawater exposure, and dying trees were unable to support osmotic adjustment. Constrained gas exchange was strongly related to hydraulic damage at both stem and leaf levels. Significant correlations between foliar sodium (Na+) concentration and gas exchange and key hydraulic parameters (Ks, PLC, and πtlp) suggest that cellular injury related to the toxic effects of ion accumulation impacted the physiology of these dying trees. This study provides evidence of toxic effects on the cellular function that manifests in all aspects of plant functioning, leading to unfavourable osmotic and hydraulic conditions.
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Mudança Climática , Picea/fisiologia , Estresse Salino , Água do Mar/efeitos adversos , Árvores/fisiologia , Xilema/efeitos dos fármacos , Washington , Xilema/fisiologiaRESUMO
BACKGROUND AND PURPOSE: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is characterized by a range of cognitive impairments, especially in executive function. Our study aims to identify the abnormal regional homogeneity (ReHo) in anti-NMDAR encephalitis patients and its relationship with the executive function. METHODS: Forty patients and 42 healthy volunteers undertook an Attention Network Test and a resting-state functional magnetic resonance imaging scan. ReHo analysis was performed to investigate the neuronal activity synchronization in all subjects. Based on ReHo analysis, a multivariate pattern analysis (MVPA) was carried out to identify the brain regions that differed the most between the two groups. RESULTS: Compared to controls, the patients had higher executive control scores (p < 0.05). The patients presented reduced ReHo values in the bilateral posterior cerebellar lobe, anterior cerebellar lobe, midbrain, bilateral caudate nucleus, right superior frontal gyrus, right middle temporal gyrus, bilateral inferior parietal lobule and the left middle frontal gyrus. The ReHo values of the bilateral inferior parietal lobule in patients were found to be negatively associated with executive control scores. The classification of patients and controls using MVPA had an accuracy of 76.83%, a sensitivity of 82.50%, a specificity of 71.43% and the area under the curve was 0.83. CONCLUSIONS: Our study provides evidence of abnormal cerebral function in anti-NMDAR encephalitis patients, which may contribute to unveiling the neuropathological mechanisms of anti-NMDAR encephalitis and their influences on executive dysfunction. The MVPA classifier, based on ReHo, is helpful in identifying anti-NMDAR encephalitis patients from healthy controls.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Disfunção Cognitiva , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico por imagem , Encéfalo/patologia , Mapeamento Encefálico/métodos , Disfunção Cognitiva/complicações , Disfunção Cognitiva/etiologia , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Curcumin is a polyphenol plant-derived compound with anti-inflammatory, antioxidant stress, and anticancer properties that make it have the potential to treat cancer cachexia. However, the role of it in breast cancer cachexia remains unclear. METHODS: The 4T1 cells were subcutaneously injected into BALB/c mice to induce breast cancer cachexia. After tumor formation, the animals were divided into groups and given curcumin or saline interventions. The therapeutic effect of curcumin on breast cancer cachexia was characterized by tumor growth, changes in body mass and gastrocnemius mass, muscle function test, histopathology, and serum nutrition indexes. Mitochondrial function in muscle tissue was observed by transmission electron microscopy and ATP detection, muscle inflammatory factors were detected by ELISA, muscle differential metabolites were detected by 1HNMR metabolomics, and the muscle tissue ubiquitination levels and NF-KB expression were also analyzed by RT-qPCR and Western blot. RESULTS: Dynamic in vivo bioluminescence imaging find that curcumin inhibited the growth of tumor in triple-negative breast cancer- (TNBC-) bearing mice, slowed down the loss of body weight and gastrocnemius weight, corrected the mitochondrial dysfunction and malnutrition status, and also significantly improved skeletal muscle function. ELISA analysis found that the level of inflammatory factors in muscle tissue was reduced. 1HNMR metabolomics analysis suggested that curcumin could regulate energy metabolism pathways. RT-qPCR and Western blot analysis found that the expression of myogenic factor myogenin was increased and the expression of myodegradation factor myostatin was decreased in the gastrocnemius; the level of ubiquitination and activation of the NF-κB pathway were also declined. CONCLUSIONS: Curcumin reduces ubiquitination, inflammation in skeletal muscle by regulating the NF-KB/UPS axis and improves muscle malignant metabolic phenotype and mitochondrial dysfunction, to alleviate muscle atrophy and loss of function in mice with breast cancer cachexia.
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Curcumina , Neoplasias de Mama Triplo Negativas , Animais , Caquexia/tratamento farmacológico , Curcumina/farmacologia , Curcumina/uso terapêutico , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Músculo Esquelético/metabolismo , Atrofia Muscular/patologia , NF-kappa B/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismoRESUMO
Background: Allergic rhinitis (AR) is a common chronic inflammatory disease with bothersome symptoms. However, the effect of air pollution on the prevalence of AR in children is controversial. Objective: This study aimed to investigate the association between air pollution and the prevalence of AR in Chinese children. Methods: This study, in China, included 160,356 students ages 0-18 years who completed a questionnaire about the accuracy of the International Study of Asthma and Allergies in Childhood (ISAAC). The effect of different air pollutants on the prevalence rate were evaluated by meta-analysis. Also, it evaluated the effect of different air pollutants on the prevalence rate. Results: The differences in the effects of sulfur dioxide (SO2) exposure (combined odds ratio [ORcombined] 1.03 [95% confidence interval {CI}, 1.01-1.05]; p = 0.010) and nitrogen dioxide (NO2) exposure (ORcombined 1.11 [95% CI, 1.05-1.18]; p = 0.0006) on the risk of childhood AR was statistically significant. The effect of particulate matter with aerodynamic diameter of <10 µm (PM10) exposure on the risk of childhood AR was statistically significant (ORcombined 1.02 [95% CI, 1.01-1.03]; p < 0.001), the effect of particulate matter with aerodynamic diameter of <2.5 µm (PM2.5) exposure on the risk of childhood AR was statistically significant (ORcombined 1.15 [95% CI, 1.03-1.29]; p = 0.02), and the effect of ozone exposure on the risk of childhood AR was not statistically significant (ORcombined 0.98 [95% CI, 0.67-1.41]; p = 0.13). Conclusion: NO2, SO2, PM2.5, and PM10 were associated with the prevalence of AR in Chinese children. PM2.5 had the highest correlation with AR prevalence.
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Poluentes Atmosféricos , Poluição do Ar , Rinite Alérgica , Adolescente , Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Criança , Pré-Escolar , China/epidemiologia , Exposição Ambiental/efeitos adversos , Humanos , Lactente , Recém-Nascido , Dióxido de Nitrogênio/análise , Material Particulado/efeitos adversos , Prevalência , Rinite Alérgica/epidemiologia , Rinite Alérgica/etiologia , Dióxido de Enxofre/efeitos adversos , Dióxido de Enxofre/análiseRESUMO
Mammalian adipose tissue can be divided into white and brown adipose tissue based on its colour, location, and cellular structure. Certain conditions, such as sympathetic nerve excitement, can induce the white adipose adipocytes into a new type of adipocytes, known as beige adipocytes. The process, leading to the conversion of white adipocytes into beige adipocytes, is called white fat browning. The dynamic balance between white and beige adipocytes is closely related to the body's metabolic homeostasis. Studying the signal transduction pathways of the white fat browning might provide novel ideas for the treatment of obesity and alleviation of obesity-related glucose and lipid metabolism disorders. This article aimed to provide an overview of recent advances in understanding white fat browning and the role of BAT in lipid metabolism.
Assuntos
Metabolismo dos Lipídeos , Termogênese , Adipócitos Brancos/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Metabolismo Energético , Humanos , Mamíferos , Obesidade/metabolismo , Termogênese/fisiologiaRESUMO
Long-chain noncoding RNAs (lncRNAs) are RNAs that do not code for proteins, widely present in eukaryotes. They regulate gene expression at multiple levels through different mechanisms at epigenetic, transcription, translation, and the maturation of mRNA transcripts or regulation of the chromatin structure, and compete with microRNAs for binding to endogenous RNA. Adipose tissue is a large and endocrine-rich functional tissue in mammals. Excessive accumulation of white adipose tissue in mammals can cause metabolic diseases. However, unlike white fat, brown and beige fats release energy as heat. In recent years, many lncRNAs associated with adipogenesis have been reported. The molecular mechanisms of how lncRNAs regulate adipogenesis are continually investigated. In this review, we discuss the classification of lncRNAs according to their transcriptional location. lncRNAs that participate in the adipogenesis of white or brown fats are also discussed. The function of lncRNAs as decoy molecules and RNA double-stranded complexes, among other functions, is also discussed.
Assuntos
Adipogenia , RNA Longo não Codificante , Adipócitos/metabolismo , Adipócitos Marrons/metabolismo , Adipogenia/genética , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Mamíferos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Carbon (C) and nitrogen (N) cycles of terrestrial ecosystems play key roles in global climate change and ecosystem sustainability. In recent decades, climate change has threatened the nutrient balance of dryland ecosystems. However, its impact on soil organic carbon (SOC) and soil total nitrogen (STN) in drylands of China are still unclear. In this study, the structural equation model (SEM) was used to explain the relationship between environmental variables used by the best model and SOC or STN. Then Adaptive Boosting Regressor (AdaBoost), Gradient Boosting Regression (GBRT), Extreme gradient boosting Regression (XGBoost) and Random Forest Regression (RF) were used to establish the prediction model of SOC and STN based on soil samples along with environmental variables. The performance of these models was assessed based on a 10-fold cross-validation method using three statistical indicators. Finally, we predicted the SOC and STN of soil samples from 2000 to 2019 based on the best model. Overall, the RF model performed better at predicting SOC and STN in drylands than the other three prediction models (AdaBoost, GBRT, XGBoost). Climate factors were the main factors affecting SOC and STN in the study area. In the Alashan, a dryland in northern China, the precipitation in the growing season increased from 2000 to 2019, at a rate of 12.9 mm/decade. During the same period, the annual sunshine duration significantly decreased by 66 h/decade. Along with interannual hydrothermal variability, SOC showed a fluctuating upward trend at a rate of 0.04 g/kg/decade, while STN exhibited a fluctuating downward trend at 0.003 g/kg/decade from 2000 to 2019. Due to the effects of climate change, dryland were considered as potential sites for carbon sequestration. However, due to the annual hydrothermal variance causing dynamic annual changes, it was deemed unstable. Moreover, it would cause STN loss, which might reduce soil fertility. More attention should be paid to STN monitoring in dryland in the future.