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During mammalian retinal development, the differentiation of multipotent progenitors depends on the coordinated action of a variety of intrinsic factors including non-coding RNAs (ncRNAs). To date, many small open reading frames have been identified in ncRNAs to encode micropeptides that function in diverse biological processes; however, it remains unclear whether they have a role in retinal development. Here we report that the 47-amino acid (AA) mitochondrial micropeptide Stmp1 encoded by the lncRNA 1810058I24Rik is involved in retinal differentiation. As the major protein product of 1810058I24Rik, Stmp1 promotes the differentiation of bipolar, amacrine and Müller cells as 1810058I24Rik does when overexpressed in neonatal murine retinas. Moreover, we have identified the 15-AA N-terminus of Stmp1 as its mitochondrion-targeting sequence as well as 5 conserved AA residues that affect protein stability and/or retinal cell differentiation. Together, our data reveal several novel characteristics of Stmp1 and uncover a role for Stmp1 in retinal cell differentiation perhaps through regulating mitochondrial function.
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Diferenciação Celular , Peptídeos e Proteínas de Sinalização Intracelular , Mitocôndrias , Proteínas Mitocondriais , Retina , Animais , Camundongos , Células Ependimogliais/citologia , Mitocôndrias/metabolismo , Neurônios/citologia , Retina/citologia , RNA não Traduzido/genética , Proteínas Mitocondriais/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologiaRESUMO
The TRPC family consists of multiple important cationic channels in mammals that participate in a variety of physiological and pathological processes. Our previous studies have shown that transforming growth factor-ß1 (TGF-ß1) increases the expression of TRPC6 in podocytes, but the roles of other members of the TRPC family in podocytes require further investigation. In this study, we investigated the effect of TGF-ß1 on the expression of the TRPC family and the role of the TRPC family in the changes of the intracellular Ca2+ concentration ([Ca2+]i) in podocytes induced by TGF-ß1. The model of podocyte injury was established by treatment with TGF-ß1 in immortalized glomerular podocytes (MPC5) in vitro. qRT-PCR and Western blot were used to detect the effect of TGF-ß1 on the mRNA and protein expression of each TRPC family member. After the expression of each TRPC family member was knocked down by a siRNA-based approach and blocked by SKF96365, respectively, free cytosolic Ca2+ was measured using the fluorescent Ca2+ indicator Fluo-3/AM, and the dynamic change of [Ca2+]i in podocytes was detected by a dynamic high-speed calcium imaging system. The results showed that TGF-ß1 increased the protein expression of TRPC1/3/6 in podocytes, but had no effects on the protein expression of TRPC4. The protein expression levels of TRPC5/7 were only affected by 4 ng/mL and 8 ng/mL TGF-ß1, respectively. TGF-ß1 increased TRPC1/3/6 mRNA levels in podocytes, however had no effects on TRPC4/5/7 mRNA. TGF-ß1 significantly increased [Ca2+]i in podocytes. Knockdown of TRPC1/4/5/7 in podocytes had no significant effect on the [Ca2+]i induced by TGF-ß1, but TRPC3/6 knockdown significantly decreased the [Ca2+]i. There was no significant difference in the [Ca2+]i between the TRPC6 siRNA-treated group and SKF96365-treated group, but the [Ca2+]i of the TRPC3 siRNA-treated group was significantly higher than that of SKF96365-treated group. These results demonstrate that TGF-ß1 increases the expression of the TRPC1/3/6 in podocytes. TGF-ß1 increases [Ca2+]i in podocytes, which is dependent on the TRPC3/6 expression. Our results also suggest that the effect of TRPC6 on [Ca2+]i in podocytes may be greater than that of TRPC3.
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Cálcio , Podócitos , Animais , Canal de Cátion TRPC6/genética , Canal de Cátion TRPC6/metabolismo , Cálcio/metabolismo , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismo , Podócitos/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , RNA Interferente Pequeno/metabolismo , RNA Mensageiro/metabolismo , Mamíferos/genética , Mamíferos/metabolismoRESUMO
BACKGROUND: The therapeutic effects of tacrolimus (TAC) versus cyclophosphamide (CTX) were not fully illustrated for patients with idiopathic membranous nephropathy (IMN). METHODS: The PubMed, EmBase, Cochrane library, and CNKI were systematically searched throughout March 2020 for randomized controlled trials evaluating the therapeutic effects of TAC versus CTX for IMN patients treated with steroids. The pooled relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS: Twelve trials recruited a total of 868 IMN patients were identified and contained in final meta-analysis. Patients in TAC group was associated with an increased incidence of overall remission (12 trials: 868 patients; RR: 1.21; 95% CI: 1.11-1.31; p < 0.001) and complete remission (12 trials: 868 patients; RR: 1.50; 95% CI: 1.25-1.80; p < 0.001). Moreover, we noted TAC therapy significantly reduced urinary protein excretion (9 trials: 567 patients; WMD: -1.06; 95%CI: -1.41 to -0.71; p < 0.001), and increased serum albumin (9 trials: 567 patients; WMD: 5.37; 95%CI: 2.97 to 7.77; p < 0.001) than CTX therapy. Furthermore, no significant difference between TAC and CTX for serum creatinine was detected (6 trials: 378 patients; WMD: 0.15; 95%CI: -3.46 to 3.75; p = 0.936). Finally, the risk of alopecia (p = 0.008), infection (p = 0.045), leukocytosis (p = 0.002), and elevated ALT/AST (p = 0.011) in TAC group was significantly lower than CTX group, whereas TAC was associated with an increased risk of tremor than CTX (p = 0.010). CONCLUSIONS: This study found IMN patients treated with TAC combined with steroids provides a better therapeutic effect and less adverse events than those treated with CTX combined with steroids, with moderate-certainty evidence.
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Ciclofosfamida/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Esteroides/uso terapêutico , Tacrolimo/uso terapêutico , Ciclofosfamida/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Esteroides/efeitos adversos , Tacrolimo/efeitos adversosRESUMO
The aberrant expression of sialylated glycans (SGs) is closely associated with the occurrence, progression, and metastasis of various cancers, and sialylated glycoproteins have been widely used as clinical biomarkers for cancers. However, the identification and comprehensive analysis of SGs are exceptionally complex, which urgently need an innovative and effective method of capturing SGs from biosamples prior to MS analysis. Here, we report that a novel dynamic covalent chemistry strategy based on Schiff base hydrolysis can be applied to the precise capture of SGs. The prepared glucopyranoside-Schiff base-modified silica gel displays extraordinary enrichment selectivity (even at a ratio of 1:5000 with interference), high adsorption capacity (120 mg·g-1), and satisfying enrichment recovery (95.5%) toward sialylated glycopeptides, contributing to a highly specific, efficient, mild, and reversible SG capturing approach that can remarkably promote the development of glycoproteomics and sialic acid sensing devices and can be considerably promising in cancer biomarker discovery. Meanwhile, the facile hydrolysis characteristic of our Schiff base material completely subverts conventional knowledge of enrichment materials, the chemical stability of which is usually regarded as a prerequisite. Importantly, we find an exciting story hidden behind the Schiff base hydrolysis reaction, which demonstrates the unique advantage of dynamic covalent chemistry in glycoproteomics and biomolecule sensing.
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OBJECTIVE: Abdominal aortic aneurysm (AAA) is an aneurysm-like dilated and highly fatal cardiovascular disease. CD8+ T cells have been shown to be critical for vascular pathological processes, but the contribution of these lymphocytes to vascular diseases remains elusive. METHODS AND RESULTS: Eight-week-old male wildtype (CD8+/+) and Cd8a knockout (CD8-/-) mice were used in a calcium chloride2 (CaCl2)-induced experimental AAA model. At 6âweeks after surgery, CD8+ T-cell deletion prevented the formation of AAA, accompanied by reductions of the levels of inflammatory (interferon-γ [IFN-γ], interleukin-1ß, monocyte chemoattractant protein-1, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, NOD-like receptor protein 3, caspase-1), oxidative stress [NADPH oxidase and gp91phox], and proteolysis (cathepsin S, cathepsin K, matrix metalloproteinase-2 [MMP-2] and MMP-9) proteins and/or genes in plasma and/or AAA tissues. Immunoreactivities of MMP-2 and MMP-9 were observed in macrophages. An injection of IFN-γ and adoptive transfer of CD8+ T cells of IFN-γ+/+ mice diminished CD8-/--mediated vasculoprotective actions in the AAA mice. In vitro, IFN-γ enhanced MMP-2 and MMP-9 gelatinolytic activities in macrophage and/or vascular smooth muscle cells. CONCLUSION: The vasculoprotective effects of CD8+ T-cell deletion in a mouse CaCl2-induced AAA model were likely attributable to, at least in part, the attenuation of IFN-γ-dependent inflammation action, oxidative stress production, and proteolysis, suggesting a novel therapeutic target for AAA formation by regulating CD8+ T-cell-derived IFN-γ secretion.
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Metabolic flux analysis was used to reveal the metabolic distributions in Gluconacetobacter xylinus (CGMCC no. 2955) cultured on different carbon sources. Compared with other sources, glucose, fructose, and glycerol could achieve much higher bacterial cellulose (BC) yields from G. xylinus (CGMCC no. 2955). The glycerol led to the highest BC production with a metabolic yield of 14.7 g/mol C, which was approximately 1.69-fold and 2.38-fold greater than that produced using fructose and glucose medium, respectively. The highest BC productivity from G. xylinus CGMCC 2955 was 5.97 g BC/L (dry weight) when using glycerol as the sole carbon source. Metabolic flux analysis for the central carbon metabolism revealed that about 47.96 % of glycerol was transformed into BC, while only 19.05 % of glucose and 24.78 % of fructose were transformed into BC. Instead, when glucose was used as the sole carbon source, 40.03 % of glucose was turned into the by-product gluconic acid. Compared with BC from glucose and fructose, BC from the glycerol medium showed the highest tensile strength at 83.5 MPa, with thinner fibers and lower porosity. As a main byproduct of biodiesel production, glycerol holds great potential to produce BC with superior mechanical and microstructural characteristics.
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Celulose/biossíntese , Gluconacetobacter xylinus/metabolismo , Celulose/química , Meios de Cultura/metabolismo , Frutose/metabolismo , Gluconacetobacter xylinus/química , Glucose/metabolismo , Glicerol/metabolismo , Análise do Fluxo MetabólicoRESUMO
BACKGROUND: Executive function (EF) deficit is considered to be a core cognitive deficit in ADHD. The current study combined functional near-infrared spectroscopy (fNIRS) and numerical switching tasks to investigate the cognitive flexibility of adult ADHD as an important part of EF. MATERIAL AND METHODS: The Wender Utah Rating Scale and the adult ADHD self-rating scale were respectively used to assess ADHD symptoms in childhood and adulthood. A 22 adults with ADHD and 24 healthy controls (HCs) participated in the large/small and odd/even switching tasks. RESULTS: Behavioral results were indicative of the ADHD switch costs being lower than the HCs. The fNIRS results also showed that ADHD's frontal eye field was over-activated both in magnitude and switched judgment tasks. The dorsolateral prefrontal cortex was also over-activated in magnitude judgment tasks. CONCLUSION: These results revealed that adults with ADHD's cognitive flexibility performed better than the HCs, which result is different from mainstream ideas that EF is a core deficit in ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Córtex Pré-Frontal , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Função Executiva/fisiologia , CogniçãoRESUMO
With the increasing development of science and technology, the Internet has become an essential part of people's daily lives providing great convenience. However, the Internet also leads to problematic Internet use (PIU) among adolescents, which has attracted increasing attention from the academic community. Peer victimization is a pervasive stressor among adolescents and has been proven to lead to a series of mental health challenges. Although the association between peer victimization and PIU has been well documented, the underlying mechanism remains unclear. This study aimed to understand how and when peer victimization increases the risk of PIU among adolescents. Building on Agnew's general strain theory, this study hypothesized that depression mediates the relationship between peer victimization and PIU and humor moderates the mediating model. To examine these hypotheses, 469 middle school students were recruited to complete a series of questionnaires on peer victimization, depression, humor, and PIU. The results showed that depression partially mediated the relationship between peer victimization and PIU. A moderated mediation analysis indicated that humor moderated the indirect pathway, consistent with the reverse stress-buffering model, the relationship between peer victimization and depression was stronger for adolescents with high humor. However, the relationship between depression and PIU was weaker in adolescents with high humor, which is in line with the stress-buffering model. These findings could be of significance in understanding the underlying mechanism of PIU associated with peer victimization and provide a new perspective for preventing PIU among adolescents, especially those experiencing peer victimization. The limitations and considerations for future research are discussed.
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Comportamento do Adolescente , Comportamento Aditivo , Vítimas de Crime , Humanos , Adolescente , Uso da Internet , Comportamento Aditivo/psicologia , Comportamento do Adolescente/psicologia , Inquéritos e Questionários , InternetRESUMO
As a common pathology of many ocular disorders such as diabetic retinopathy and glaucoma, retinal ischemia/reperfusion (IR) triggers inflammation and microglia activation that lead to irreversible retinal damage. The detailed molecular mechanism underlying retinal IR injury, however, remains poorly understood at present. Here we report the bioinformatic identification of a lncRNA 1810058I24Rik (181-Rik) that was shown to encode a mitochondrion-located micropeptide Stmp1. Its deficiency in mice protected retinal ganglion cells from retinal IR injury by attenuating the activation of microglia and the Nlrp3 inflammasome pathway. Moreover, its genetic knockout in mice or knockdown in primary microglia promoted mitochondrial fusion, impaired mitochondrial membrane potential, and reactive oxygen species (ROS) production, diminished aerobic glycolysis, and ameliorated inflammation. It appears that 181-Rik may trigger the Nlrp3 inflammasome activation by controlling mitochondrial functions through inhibiting expression of the metabolic sensor uncoupling protein 2 (Ucp2) and activating expression of the Ca2+ sensors S100a8/a9. Together, our findings shed new light on the molecular pathogenesis of retinal IR injury and may provide a fresh therapeutic target for IR-associated neurodegenerative diseases.
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RNA Longo não Codificante , Traumatismo por Reperfusão , Camundongos , Animais , Microglia/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , RNA Longo não Codificante/metabolismo , Doenças Neuroinflamatórias , Mitocôndrias/metabolismo , Inflamação/genética , Inflamação/metabolismo , Traumatismo por Reperfusão/metabolismo , Isquemia/metabolismo , MicropeptídeosRESUMO
B-cell activating factor receptor (BAFF-R) is a mature B-cell survival receptor, which is highly expressed in a wide variety of B-cell malignancies but with minimal expression in immature B cells. These properties make BAFF-R an attractive target for therapy of B-cell lymphomas. We generated a novel humanized anti BAFF-R monoclonal antibody (mAb) with high specificity and potent in vitro and in vivo activity against B-cell lymphomas and leukemias. The humanized variants of an original chimeric BAFF-R mAb retained BAFF-R binding affinity and antibody-dependent cellular cytotoxicity (ADCC) against a panel of human cell lines and primary lymphoma samples. Furthermore, 1 humanized BAFF-R mAb clone and its afucosylated version, glycoengineered to optimize the primary mechanism of action, prolonged survival of immunodeficient mice bearing human tumor cell lines or patient-derived lymphoma xenografts in 3 separate models, compared with controls. Finally, the tissue specificity of this humanized mAb was confirmed against a broad panel of normal human tissues. Taken together, we have identified a robust lead-candidate BAFF-R mAb for clinical development.
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Linfoma de Células B , Linfoma , Humanos , Camundongos , Animais , Anticorpos Monoclonais/uso terapêutico , Linfócitos B , Linfoma de Células B/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Linfoma/tratamento farmacológicoRESUMO
With the development of advanced technologies, many small open reading frames (sORFs) have been found to be translated into micropeptides. Interestingly, a considerable proportion of micropeptides are located in mitochondria, which are designated here as mitochondrion-located peptides (MLPs). These MLPs often contain a transmembrane domain and show a high degree of conservation across species. They usually act as co-factors of large proteins and play regulatory roles in mitochondria such as electron transport in the respiratory chain, reactive oxygen species (ROS) production, metabolic homeostasis, and so on. Deficiency of MLPs disturbs diverse physiological processes including immunity, differentiation, and metabolism both in vivo and in vitro. These findings reveal crucial functions for MLPs and provide fresh insights into diverse mitochondrion-associated biological processes and diseases.
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Mitocôndrias , Peptídeos , Fases de Leitura Aberta , Peptídeos/química , Mitocôndrias/metabolismoRESUMO
This study tested whether cognitive deficit in patients with adult attention deficit hyperactivity disorder (ADHD) is a working memory deficit or cognitive state disorder during the N-back task. Twenty-two adults with ADHD and twenty-four healthy controls participated in the N-back task. The functional near-infrared spectroscopy (fNIRS) was combined with three perspectives from behavioral and spatial and temporal activation characteristics of blood oxygen levels in the prefrontal cortex to examine the psychological and neuroprocessing characteristics of adult ADHD. Data were acquired using a block design during an N-back task with three memory loads. Visual stimuli were presented on a computer monitor. Behaviorally, response time and accuracy showed no significant differences between the two groups. Spatially, in the left orbitofrontal area and the left frontopolar area (Channels 4 and 11), adult ADHD had significantly higher activation levels of oxyHb in the 2-back task and lower activation levels of deoxyHb in the 3-back task than healthy controls (corrected p < 0.05). Therefore, Channel 4 in the 2-back condition and Channel 11 in the 3-back condition were used as the regions of interest (ROI). Temporally, adults with ADHD peaked earlier in the ROIs than healthy controls. Furthermore, working memory deficit was not found directly from the behavioral performance in adult ADHD. However, adult ADHD can be affected by memory load, task duration, and novelty stimulus. Our findings suggest that patients with adult ADHD have cognitive state disorder instead of working memory deficit.
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Transtorno do Deficit de Atenção com Hiperatividade , Memória de Curto Prazo , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Cognição , Humanos , Imageamento por Ressonância Magnética , Transtornos da Memória/etiologia , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodosRESUMO
Separation, purification, and identification of glycoproteins are essential for understanding their vital roles in biological and pathological processes. However, glycoproteins are difficult to be captured due to their low abundance, strong interference from non-glycosylated proteins. Here, we report a promising dipeptide-based saccharide recognition platform to selectively enrich two typical glycoproteins, named immunoglobin G (IgG) and horseradish peroxidase (HRP). Different from the conventional glycoprotein enrichment method based on boronic acid affinity or hydrophilic interaction with glycans, the present method was established based on affinity between Pro-Glu (PE) dipeptide and mannose, which is a key unit in the pentasaccharide core of the IgG and HRP glycans. The prepared PE homopolymer surface was proved to selectively bind IgG and HRP superior to that of bovine serum albumin (BSA). Benefiting from this feature, selective enrichment of IgG and HRP was achieved from a protein mixture containing 200-fold BSA interference by using polyPE@SiO2 under a dispersive solid-phase extraction (dSPE) mode. High adsorption capacity, controllable and selective adsorption behaviors, as well as satisfactory recovery demonstrated the high potential of the dipeptide-based polymeric material in IgG and HRP enrichment. This study might provide a new insight to solve the challenging problem of glycoprotein separation.
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Glicoproteínas , Dióxido de Silício , Dipeptídeos , Glicopeptídeos , Peroxidase do Rábano Silvestre , Imunoglobulina GRESUMO
To investigate the effects of father-child conflict and regulatory emotional self-efficacy (RESE) on Chinese adolescent depression, 654 middle-school students were measured. The results showed that: (1) Father-son conflict was significantly lower than father-daughter conflict, girls' depression was significantly higher than that of boys, and boys' RESE and self-efficacy in regulating negative emotions (NEG) were significantly higher than that for girls, but there was no significant difference between boys and girls in self-efficacy in expressing positive emotions (POS). (2) Father-child conflict was significantly positively associated with Chinese adolescent depression. Father-child conflict was negatively correlated with RESE, and its two dimensions. Both POS and NEG played a partial mediating role in the relationship between father-child conflict and adolescent depression. (3) Gender only regulated the relationship between NEG and adolescent depression. Compared to boys, girls are more affected by depression at the low level of NEG.
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Protein post-translational modification (PTM) is at the forefront of focus of proteomics research. It not only regulates protein folding, state, activity, localization, and protein interactions, but also helps scientists understand the biological processes of organisms more comprehensively, providing stronger support and basis for the prediction, diagnosis, and treatment of diseases. In living organisms, there are more than 300 types of PTMs of proteins and their modification processes are dynamic. At the same time, protein modifications do not exist in isolation. The occurrence of the same physiological or pathological process requires the joint action of various modified proteins, which affect and coordinate with each other. Owing to the low abundance of PTM products (e. g., phosphorylated peptides or glycopeptides) and the presence of strong background interference, it is difficult to analyze them directly through mass spectrometry. Therefore, the development efficient materials and techniques for the selective enrichment of PTM peptides is urgently needed. Conventional separation methods have partially solved the challenges involved in the enrichment of glycopeptides and phosphorylated peptides; however, there are some inevitable issues, such as the excessive binding force of metal ions (e. g., Fe3+and Ti4+) toward multiple phosphorylated peptides, resulting in difficulty in elution and identification through mass spectrometry. In addition, owing to the insufficient binding affinity of materials toward glycopeptides, most glycopeptides that have been identified at present are of the sialic acid type, and a large number of neutral glycans, for instance, O-link glycopeptides and high mannose-type glycans are difficult to enrich and identify.The emergence of smart polymers provides a new avenue for the development of PTM-enriched materials. Several studies have reported that smart polymers can reversibly change their structure and function through external physical, chemical, or biological stimulation, to achieve highly controllable adsorption and desorption of phosphorylated peptides and glycopeptides. Based on this strategy, a series of novel enrichment materials and methods have been developed, which have greatly attracted the interest of researchers. On the one hand, the response changes of smart polymers include the increase or decrease of hydrophobicity, the change of shape and morphology, the redistribution of surface charge, the exposure or hiding of affinity ligands, etc. Changes in these properties can be achieved by simply changing external conditions such as temperature, pH, solvent polarity, and biomolecules. These properties, in turn, enable the fine-tuning of the affinity between the target and the smart polymers. Furthermore, the affinity can provide an additional driving force, which can significantly improve biological separation.On the other hand, smart polymers provide a series of convenient and expandable platforms for integrating various functional modules, such as specific recognition components, which will facilitate the development of novel enrichment materials for protein methylation, acetylation, and ubiquitination. Smart polymer materials show great potential in the field of separation, which is promising for the analysis and research of protein PTMs. This review summarizes the research progress of smart polymer materials for the separation and enrichment of phosphorylated peptides and glycopeptides according to nearly 50 representative articles from the Web of Science in the past two decades.
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Glicopeptídeos , Materiais Inteligentes , Polímeros Responsivos a Estímulos , Glicopeptídeos/química , Materiais Inteligentes/química , Polímeros Responsivos a Estímulos/químicaRESUMO
MicroRNA-155 (miR-155) is associated with various diseases. However, the potential role of miR-155 in early glomerular disease (EGD) remains elusive. In the present study, the clinical significance of urinary miR-155 expression was explored in patients with EGD using receiver operating characteristic curve analysis. Conditionally immortalized mouse podocytes were cultured in vitro and treated with transforming growth factor-ß1 (TGF-ß1) at different concentrations and durations. The gene expression levels of mRNAs and miR-155 were detected using reverse transcription-quantitative PCR. Synaptopodin, CD2-associated protein (CD2AP), p38, and extracellular signal-regulated kinase (Erk) 1/2 expressions were detected using western blotting. Cell supernatants were collected for assaying tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations using enzyme-linked immunosorbent assay. The Pearson correlation analysis was used to analyze the correlation between miR-155 levels and TNF-α or IL-6. It was found that miR-155 levels in urine have high sensitivity and specificity in the diagnosis of EGD. Time- and dose-dependent TGF-ß1 treatments downregulated synaptopodin and CD2AP expression levels, and activated the p38 and Erk 1/2 pathway. However, these effects were attenuated by p38 and Erk 1/2 phosphorylation inhibitors. Additionally, TNF-α and IL-6 secretions were elevated, and their concentrations were positively correlated with the expression of miR-155 during podocyte injury. Thus, the present study indicated that miR-155 is a potential biomarker for the diagnosis of EGD, and its expression is associated with the release of pro-inflammatory cytokines and activation of mitogen-activated protein kinase (MAPK) pathway in TGF-ß1-induced podocyte injury. The present study suggests that the TGF-ß1/miR-155/MAPK axis is a novel target in the mechanism of EGD.
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Cellulose nanocrystals (CNCs) are powerful photonic building blocks for the fabrication of biosourced colored films. A combination of the advantages of self-assembled CNCs and multiple templating agents offers access to the development of novel physicochemical sensors, structural coatings, and optic devices. However, due to the inherent brittleness and water instability of CNC-derived materials, their further applications are widely questionable and restrictive. Here, a soft polymer of poly(vinyl alcohol) (PVA) was introduced into the rigid CNC system to balance molecular interactions, whereafter two hard/soft nanocomposites were fastened through a cross-linking reaction of glutaraldehyde (GA), resulting in a highly flexible, water-stable, and chiral nematic CNC composite film through an evaporation-induced self-assembly technique. For a 1.5 wt % GA-cross-linked 70 wt % CNC loading film, its treatment with harsh hydrophilic exposure (soaking in a strong acid, strong base, and seawater) and various organic solvents show exceptional solvent-resistant abilities. Furthermore, the film can even withstand a weight of 167 g cm-2 without failure, which is a highly stiff and durable character. Importantly, the film remains a highly ordered chiral nematic organization, being able to act as a highly transparent substrate for selective reflection of left-handed circularly polarized light, preparing fully covered and patterned full-color coatings on various substrates. Our work paves the way for applications in low-cost, durable, and photonic cellulosic coatings.
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PURPOSE: Bullying is a serious problem among adolescents. Many scholars have examined school bullying in recent years; however, there are many psychological and behavioral mechanisms for bully that still remain unclear. Based on the theory of self-worth orientation, this study examined the influence of academic achievement on bullying behavior among adolescents and explored the moderating effects of perceived social support and age cohort. METHODS: Participants were 3227 middle and high school students in the 7th through 12th grades in China. A self-report method was used to measure academic achievement, social support, bullying, and demographic variables. RESULTS: Moderation analyses indicated that the relationship between academic achievement and bullying behavior was moderated by the perceived social support of adolescents and their age cohort. Specifically, social support moderated the relationship between achievement and bullying behavior positively in the middle school group but negatively in the high school group. CONCLUSION: The results support the hypothesis of self-worth orientation theory and indicate that bullying intervention could be enhanced by addressing the relationships between academic achievement, social support, age cohort, and bullying.
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INTRODUCTION: To explore the moderating effect of physical activity and the mediating effect of depression on the relationship between marital satisfaction and adolescents' problematic internet use (PIU). METHODS: This study adopted a sample of 288 adolescents and their parents, and measured adolescents' depression, PIU, physical activity, and parents' marital satisfaction. RESULTS: These results showed that parental marital satisfaction negatively predicted adolescents' PIU. Adolescents' depression played a mediating role between parental marital satisfaction and adolescents' PIU. Further mediated moderation effect analysis showed that the interaction between marital satisfaction and adolescents' physical activity affected the PIU through adolescents' depression. Specifically, for individuals with lower physical activity, the marital satisfaction affected the PIU through adolescents' depression. However, for the group with higher physical activity, physical activity weakened the effects of marital satisfaction on adolescents' depression, and the mediating effect of depression did not reach a significant level. CONCLUSION: These results are of theoretical and practical significance in understanding and intervening to address adolescents' PIU.