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Developing ultrasensitive lateral flow immunoassays (LFIAs) has garnered significant attention in the field of point-of-care testing. In this study, a trimetallic dendritic nanozyme (Pd@Pt-Ru) was synthesized through Ru deposition on a Pd@Pt core and utilized to enhancing the sensitivity of LFIAs. Pd@Pt-Ru exhibited a Km value of 5.23 mM for detecting H2O2, which indicates an H2O2 affinity comparable with that of horseradish peroxidase. The Ru surface layer reduces the activation energy barrier, which increases the maximum reaction rate. As a proof of concept, the proposed Pd@Pt-Ru nanozyme was incorporated into LFIAs (A-Pd@Pt-Ru-LFIAs) for detecting human chorionic gonadotropin (hCG). Compared with conventional gold nanoparticle (AuNP)-LFIAs, A-Pd@Pt-Ru-LFIAs demonstrated 250-fold increased sensitivity, thereby enabling a visible detection limit as low as 0.1 IU/L. True positive and negative rates both reached 100%, which renders the proposed Pd@Pt-Ru nanozyme suitable for detecting hCG in clinical samples.
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Gonadotropina Coriônica , Peróxido de Hidrogênio , Limite de Detecção , Nanopartículas Metálicas , Paládio , Platina , Rutênio , Paládio/química , Platina/química , Imunoensaio/métodos , Humanos , Rutênio/química , Gonadotropina Coriônica/análise , Nanopartículas Metálicas/química , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/química , Ouro/química , Dendrímeros/química , Técnicas Biossensoriais/métodos , Peroxidase/química , CatáliseRESUMO
Molecular dynamics simulations were performed to investigate the fracture mechanism and mechanical response of Ni/Graphene nanocomposites under nanoindentation. The effects of size and location of defect pores were explored by examining the pore structure transition, microstructure transition, variation of HCP atomic fraction and dislocation density with indentation depth, load-displacement relationship, and stress distribution. It was found that when the long edges of the pore are located along the longer dimension, the pores are fractured by indentation forces from the short edges. The closer the pore is to the indent, the smaller loading force is required for the pores to reach its fracture limit. For the long edges located along the transverse direction, the maximum indentation depth increases with the distance of the pore away from the indenter. The density of HCP atoms and dislocations in the composite gradually increases with the indentation depth. To understand the physical mechanism of the fracture behavior, we also evaluated the stress distribution in graphene at the fracture point.
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OBJECTIVE: To evaluate the diagnostic values of serum platelet count (PC), mean platelet volume ratio (MPV), platelet count to mean platelet volume ratio (PVR), platelet to lymphocyte ratio (PLR), platelet to neutrophil ratio (PNR), PC/Albumin-globulin ratio (PC/AGR), and PC/C-reactive protein (PC/ CRP) in the diagnosis of periprosthetic joint infection (PJI). METHODS: The medical records were retrospectively analyzed of the 158 patients who had undergone hip or knee revisions from January 2018 to May 2022. Of them, 79 cases were diagnosed with PJI and 79 with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of CRP, the erythrocyte sedimentation rate (ESR), PC, MPV, PVR, PLR, PNR, PC/AGR, and PC/CRP in the 2 groups were recorded and analyzed. In addition, tests were performed according to different joint types. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator. The diagnostic value for each indicator was calculated according to the area under the curve (AUC). RESULTS: The PC, PVR, PLR and PC/AGR levels in the PJI group were significantly higher than those in the AL group, while PC/CRP levels were significantly lower (P < 0.001). The AUC for PC/CRP, and PC/AGR was 0.804 and 0.802, respectively, which were slightly lower than that of CRP (0.826) and ESR (0.846). ROC analysis for PC/CRP, and PC/AGR revealed a cut-off value of 37.80 and 160.63, respectively, which provided a sensitivity of 73.42% and 84.81% and a specificity of 75.95% and 65.82% for PJI. The area under the curve of PLR and PC was 0.738 and 0.702. The area under the curve values for PVR, PNR, and MPV were 0.672, 0.553, and 0.544, respectively. CONCLUSIONS: The results of this study suggest that PC, PLR, PC/CRP, and PC/AGR values do not offer significant advantages over ESR or CRP values when employed for the diagnosis of PJI. PVR, PNR, and MPV were not reliable in the diagnosis of PJI.
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Artrite Infecciosa , Artroplastia de Quadril , Infecções Relacionadas à Prótese , Humanos , Biomarcadores , Estudos Retrospectivos , Infecções Relacionadas à Prótese/cirurgia , Artroplastia de Quadril/efeitos adversos , Proteína C-Reativa/análise , Sensibilidade e Especificidade , Artrite Infecciosa/cirurgia , Sedimentação SanguíneaRESUMO
The CmXTH11 gene, a member of the XTH (xyloglucan endotransglycosylase/hydrolase) family, plays a crucial role in plant responses to environmental stress. In this study, we heterologously expressed the melon gene CmXTH11 in Arabidopsis to generate overexpressing transgenic lines, thereby elucidating the regulatory role of CmXTH11 in water stress tolerance. Using these lines of CmXTH11 (OE1 and OE2) and wild-type (WT) Arabidopsis as experimental materials, we applied water stress treatments (including osmotic stress and soil drought) and rewatering treatments to investigate the response mechanisms of melon CmXTH11 in Arabidopsis under drought stress from a physiological and biochemical perspective. Overexpression of CmXTH11 significantly improved root growth under water stress conditions. The OE lines exhibited longer roots and a higher number of lateral roots compared to WT plants. The enhanced root system contributed to better water uptake and retention. Under osmotic and drought stress, the OE lines showed improved survival rates and less wilting compared to WT plants. Biochemical analyses revealed that CmXTH11 overexpression led to lower levels of malondialdehyde (MDA) and reduced electrolyte leakage, indicating decreased oxidative damage. The activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), were significantly higher in OE lines, suggesting enhanced oxidative stress tolerance. The CmXTH11 gene positively regulates water stress tolerance in Arabidopsis by enhancing root growth, improving water uptake, and reducing oxidative damage. Overexpression of CmXTH11 increases the activities of antioxidant enzymes, thereby mitigating oxidative stress and maintaining cellular integrity under water deficit conditions. These findings suggest that CmXTH11 is a potential candidate for genetic improvement of drought resistance in crops.
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Arabidopsis , Cucumis melo , Secas , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Cucumis melo/genética , Cucumis melo/metabolismo , Cucumis melo/fisiologia , Cucumis melo/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Estresse Fisiológico , Pressão Osmótica , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Antioxidantes/metabolismo , Malondialdeído/metabolismoRESUMO
Light quality not only directly affects the photosynthesis of green plants but also plays an important role in regulating the development and movement of leaf stomata, which is one of the key links for plants to be able to carry out normal growth and photosynthesis. By sensing changes in the light environment, plants actively regulate the expansion pressure of defense cells to change stomatal morphology and regulate the rate of CO2 and water vapor exchange inside and outside the leaf. In this study, Cucumis melo was used as a test material to investigate the mitigation effect of different red, blue, and green light treatments on short-term drought and to analyze its drought-resistant mechanism through transcriptome and metabolome analysis, so as to provide theoretical references for the regulation of stomata in the light environment to improve the water use efficiency. The results of the experiment showed that after 9 days of drought treatment, increasing the percentage of green light in the light quality significantly increased the plant height and fresh weight of the treatment compared to the control (no green light added). The addition of green light resulted in a decrease in leaf stomatal conductance and a decrease in reactive oxygen species (ROS) content, malondialdehyde MDA content, and electrolyte osmolality in the leaves of melon seedlings. It indicated that the addition of green light promoted drought tolerance in melon seedlings. Transcriptome and metabolome measurements of the control group (CK) and the addition of green light treatment (T3) showed that the addition of green light treatment not only effectively regulated the synthesis of abscisic acid (ABA) but also significantly regulated the hormonal pathway in the hormones such as jasmonic acid (JA) and salicylic acid (SA). This study provides a new idea to improve plant drought resistance through light quality regulation.
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Cucumis melo , Secas , Luz , Estresse Fisiológico , Cucumis melo/fisiologia , Cucumis melo/metabolismo , Cucumis melo/efeitos da radiação , Cucumis melo/crescimento & desenvolvimento , Cucumis melo/genética , Folhas de Planta/efeitos da radiação , Folhas de Planta/metabolismo , Folhas de Planta/fisiologia , Fotossíntese/efeitos da radiação , Regulação da Expressão Gênica de Plantas , Estômatos de Plantas/fisiologia , Estômatos de Plantas/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Transcriptoma , Ácido Abscísico/metabolismo , Plântula/efeitos da radiação , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Plântula/fisiologia , Metaboloma , Luz Verde , Luz AzulRESUMO
Identifying novel molecules involved in axon regeneration of neurons in the peripheral nervous system (PNS) will be of benefit in obtaining a therapeutic strategy for repairing axon damage both in the PNS and the central nervous system (CNS). Metabolism and axon regeneration are tightly connected. However, the overall metabolic processes and the landscape of the metabolites in axon regeneration of PNS neurons are uncovered. Here, we used an ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOFMS)-based untargeted metabolomics to analyze dorsal root ganglia (DRG) metabolic characteristics at different time points post sciatic nerve injury and acquired hundreds of differentially changed metabolites. In addition, the results reveal that several metabolic pathways were significantly altered, such as 'Histidine metabolism', 'Glycine serine and threonine metabolism', 'Arginine and proline metabolism', 'taurine and hypotaurine metabolism' and so on. Given metabolite could alter a cell's or an organism's phenotype, further investigation demonstrated that N, N-dimethylglycine (DMG) has a promoting effect on the regenerative ability post injury. Overall, our data may serve as a resource useful for further understanding how metabolites contribute to axon regeneration in DRG during sciatic nerve regeneration and suggest DMG may be a candidate drug to repair nerve injury.
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Gânglios Espinais , Regeneração Nervosa , Axônios/metabolismo , Gânglios Espinais/metabolismo , Metabolômica , Regeneração Nervosa/fisiologia , Neurônios , Sarcosina/análogos & derivadosRESUMO
(R,S)-ketamine elicits rapid-acting and sustained antidepressant actions in treatment-resistant patients with depression. (R)-ketamine produces longer-lasting antidepressant effects than (S)-ketamine in rodents; however, the precise molecular mechanisms underlying antidepressant actions of (R)-ketamine remain unknown. Using isobaric Tag for Relative and Absolute Quantification, we identified nuclear receptor-binding protein 1 (NRBP1) that could contribute to different antidepressant-like effects of the two enantiomers in chronic social defeat stress (CSDS) model. NRBP1 was localized in the microglia and neuron, not astrocyte, of mouse medial prefrontal cortex (mPFC). (R)-ketamine increased the expression of NRBP1, brain-derived neurotrophic factor (BDNF), and phosphorylated cAMP response element binding protein (p-CREB)/CREB ratio in primary microglia cultures thorough the extracellular signal-regulated kinase (ERK) activation. Furthermore, (R)-ketamine could activate BDNF transcription through activation of CREB as well as MeCP2 (methyl-CpG binding protein 2) suppression in microglia. Single intracerebroventricular (i.c.v.) injection of CREB-DNA/RNA heteroduplex oligonucleotides (CREB-HDO) or BDNF exon IV-HDO blocked the antidepressant-like effects of (R)-ketamine in CSDS susceptible mice. Moreover, microglial depletion by colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 blocked the antidepressant-like effects of (R)-ketamine in CSDS susceptible mice. In addition, inhibition of microglia by single i.c.v. injection of mannosylated clodronate liposomes (MCLs) significantly blocked the antidepressant-like effects of (R)-ketamine in CSDS susceptible mice. Finally, single i.c.v. injection of CREB-HDO, BDNF exon IV-HDO or MCLs blocked the beneficial effects of (R)-ketamine on the reduced dendritic spine density in the mPFC of CSDS susceptible mice. These data suggest a novel ERK-NRBP1-CREB-BDNF pathways in microglia underlying antidepressant-like effects of (R)-ketamine.
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Ketamina , Animais , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , MAP Quinases Reguladas por Sinal Extracelular , Humanos , Ketamina/farmacologia , Ketamina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Receptores Citoplasmáticos e Nucleares , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Proteínas de Transporte VesicularRESUMO
KEY MESSAGE: We explored the phylogenomics and methylomics of NLR genes in 41 plant species and found that highly duplicated plant NLR genes are hyper methylated in non-CG context.
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Metilação de DNA , Resistência à Doença , Metilação de DNA/genética , Resistência à Doença/genética , Genes de Plantas/genéticaRESUMO
KEY MESSAGE: We analyzed the evolutionary pattern of cysteine-rich peptides (CRPs) to infer the relationship between CRP copy number and plant ecotype, and the origin of bi-domains CRPs. Plants produce cysteine-rich peptides (CRPs) that have long-lasting broad-spectrum antimicrobial activity to protect themselves from various groups of pathogens. We analyzed 240 plant genomes, ranging from algae to eudicots, and discovered that CRPs are widely distributed in plants. Our comparative genomics results revealed that CRP genes have been amplified through both whole genome and local tandem duplication. The copy number of these genes varied significantly across lineages and was associated with the plant ecotype. This may be due to their resistance to changing pathogenic environments. The conserved and lineage-specific CRP families contribute to diverse antimicrobial activities. Furthermore, we investigated the unique bi-domain CRPs that result from unequal crossover events. Our findings provide a unique evolutionary perspective on CRPs and insights into their antimicrobial and symbiosis characteristics.
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Anti-Infecciosos , Peptídeos Antimicrobianos , Cisteína/genética , Plantas/genética , Peptídeos/genética , Peptídeos/farmacologia , Anti-Infecciosos/farmacologia , Evolução Molecular , FilogeniaRESUMO
BACKGROUND: Both primary IgA nephropathy (IgAN) with and without nephrotic syndrome (NS) can present massive proteinuria (24-h urinary protein ≥3.5 g/d). The clinical significance of massive proteinuria may be different in the two entities and needs further research. METHODS: Data of 1870 patients with biopsy-proven IgAN in our hospital from January 2011 to December 2022 was retrospectively reviewed. A total of 242 IgAN patients with massive proteinuria were enrolled. Patients who presented with nephrotic syndrome at renal biopsy were included in the IgAN with NS cohort (IgAN-NS). The IgAN with nephrotic-range proteinuria cohort (IgAN-NR) consisted of 1:1 matched cases from the remaining according to age, gender, estimated glomerular filtration rate (eGFR) at baseline, and follow-up time. The clinical and pathological characteristics between the two cohorts were analyzed. RESULTS: The IgAN-NS had a significantly higher proteinuria level than the IgAN-NR (p < .001). Cluster analysis revealed that proteinuria was associated with lipids in IgAN-NS, while it was associated with inflammatory indicators in IgAN-NR. When the complete remission of proteinuria (CR) was not achieved, the Kaplan-Meier analysis showed the prognosis of IgAN-NS was significantly worse than that of IgAN-NR (p = .04). Then, our GLMM model and line chart showed that the serum albumin level of the IgAN-NR was always evidently higher than that of the IgAN-NS while the significant difference in urinary albumin/creatinine ratio between the two cohorts gradually disappeared during the short-term follow-up (1 year). Moreover, the Cox regression analysis showed that the increased serum albumin was an independent protective factor for the poor outcomes (eGFR decreased from the baseline ≥ 30% continuously or reached end-stage renal disease [ESRD]). CONCLUSION: The IgAN-NS had poorer clinicopathologic manifestation than IgAN-NR, including severer massive proteinuria. When the CR was not achieved, the prognosis of IgAN-NS was inferior to that of the IgAN-NR.
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Glomerulonefrite por IGA , Síndrome Nefrótica , Humanos , Síndrome Nefrótica/complicações , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/patologia , Estudos de Coortes , Estudos Retrospectivos , Relevância Clínica , Proteinúria/complicações , Prognóstico , Taxa de Filtração Glomerular , Albumina SéricaRESUMO
The electrowetting effect and related applications of tiny droplets have aroused widespread research interest. In this work, we report molecular dynamics simulations of confinement dynamics of nanodroplets under different droplet-surface interactions and surface distances under an external electric field. So far, the effect of the surface-droplet interactions on electric field-induced dynamics behaviors of droplets in confined spaces has not been extensively studied. Our results show that in the absence of electric field there is a critical value of surface wettability for the shape transition of droplets. Above this value, the droplet is divided into small droplets adhered on the bottom and top surfaces; below this value, the droplets are detached from the surfaces. When an external electric field is applied parallel to the surfaces, the droplet spreads on the surface along the direction of the electric field. It was found that the surface separation significantly influences the transition of the droplet shape. The steady morphology of the droplets under the electric field depends on the surface-droplet interaction and surface separation. We explore the underlying mechanism causing the morphological transition through analyzing the molecular interactions, the number of interracial molecules and the interaction force between the droplets and surfaces. These results provide basic insights into the molecular interactions of nanodroplets under different confined environments, and clues for applications of confined nanodroplets under the control of electric field.
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Eletricidade , Simulação de Dinâmica Molecular , Molhabilidade , Tamanho da PartículaRESUMO
Sulforaphane (SFN) is an organic isothiocyanate and an NF-E2-related factor-2 (Nrf2) inducer that exerts prophylactic effects on depression-like behavior in mice. However, the underlying mechanisms remain poorly understood. Brain-derived neurotrophic factor (BDNF), a neurotrophin, is widely accepted for its antidepressant effects and role in stress resilience. Here, we show that SFN confers stress resilience via BDNF upregulation and changes in abnormal dendritic spine morphology in stressed mice, which is accompanied by rectifying the irregular levels of inflammatory cytokines. Mechanistic studies demonstrated that SFN activated Nrf2 to promote BDNF transcription by binding to the exon I promoter, which is associated with increased Nrf2, and decreased methyl-CpG binding protein-2 (MeCP2), a transcriptional suppressor of BDNF, in BV2 microglial cells. Furthermore, SFN inhibited the pro-inflammatory phenotype and activated the anti-inflammatory phenotype of microglia, which was associated with increased Nrf2 and decreased MeCP2 expression in microglia of stressed mice. Hence, our findings support that Nrf2 induces BDNF transcription via upregulation of Nrf2 and downregulation of MeCP2 in microglia, which is associated with changes in the morphology of damaged dendritic spines in stressed mice. Meanwhile, the data presented here provide evidence for the application of SFN as a candidate for the prevention and intervention of depression.
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Fator Neurotrófico Derivado do Encéfalo , Microglia , Animais , Anti-Inflamatórios/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , SulfóxidosRESUMO
OBJECTIVE: This is the first study to explore the risk factors for nephropathy caused by gadolinium-based contrast agents and establish a prediction model to identify high-risk patients. METHODS: A total of 1404 patients who received gadolinium-based contrast agents in our hospital were included. The participants were randomly assigned in a 7:3 ratio to the modeling and validation groups. The modeling group was divided into a contrast-induced nephropathy group and a non-contrast-induced nephropathy group. The clinical characteristics before the use of contrast agents were compared between the two groups. The risk factors for contrast-induced nephropathy were analyzed by logistic regression. A nomogram that could predict the incidence of contrast-induced nephropathy was plotted. The validation group was used to verify the predictive model. RESULTS: The incidence of contrast-induced nephropathy caused by gadolinium-based contrast agents was 3.92% (55/1404). The logistic stepwise regression analysis showed that sex, systolic pressure (SBP), absolute neutrophil count, albumin, fasting blood glucose level, and furosemide use were significant predictors of contrast-induced nephropathy caused by gadolinium-based contrast agents. The above predictors were then included in the nomogram construction. The area under the receiver operating characteristic (ROC) curve was 0.82 (p < 0.001). The specificity and sensitivity corresponding to the optimal cutoff point (0.039) based on the area under the ROC curve were 71.9% and 80.5%, respectively. CONCLUSION: Sex, SBP, absolute neutrophil count, albumin, fasting blood glucose levels, and furosemide use are significant predictors of contrast-induced nephropathy caused by gadolinium-based contrast agents. Therefore, the incidence of contrast-induced nephropathy may be estimated by the prediction model established in this study before the use of contrast agents.
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Meios de Contraste , Nefropatias , Albuminas , Glicemia , Meios de Contraste/efeitos adversos , Feminino , Furosemida , Gadolínio/efeitos adversos , Humanos , Nefropatias/induzido quimicamente , Masculino , Curva ROC , Estudos Retrospectivos , Fatores de RiscoRESUMO
The intrinsic regeneration ability of neurons is a pivotal factor in the repair of peripheral nerve injury. Therefore, identifying the key modulators of nerve regeneration may help improve axon regeneration and functional recovery after injury. Unlike for classical transcription factors and regeneration-associated genes, the function of long noncoding RNAs (lncRNAs) in the regulation of neuronal regeneration remains mostly unknown. In this study, we used RNA-Seq-based transcriptome profiling to analyze the expression patterns of lncRNAs and mRNAs in rat dorsal root ganglion (DRG) following sciatic nerve injury. Analyses using the lncRNA-mRNA co-expression network, gene ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway databases indicated that the lncRNA Arrl1 decreases neurite outgrowth after neuronal injury. shRNA-mediated Arrl1 silencing increased axon regeneration both in vitro and in vivo and improved functional recovery of the sciatic nerve. Moreover, inhibiting an identified target gene of Arrl1, cyclin-dependent kinase inhibitor 2B (Cdkn2b), markedly promoted neurite outgrowth of DRG neurons. We also found that Arrl1 acts as a competing endogenous RNA that sponges a Cdkn2b repressor, microRNA-761 (miR-761), and thereby up-regulates Cdkn2b expression during neuron regeneration. We conclude that the lncRNA Arrl1 affects the intrinsic regeneration of DRG neurons by derepressing Cdkn2b expression. Our findings indicate a role for an lncRNA-microRNA-kinase pathway in the regulation of axon regeneration and functional recovery following peripheral nerve injury in rats.
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Regeneração Nervosa/fisiologia , Crescimento Neuronal/fisiologia , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Animais , Antagomirs/metabolismo , Axônios/metabolismo , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p15/química , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor de Quinase Dependente de Ciclina p15/metabolismo , Gânglios Espinais/citologia , Gânglios Espinais/metabolismo , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , MicroRNAs/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/patologia , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia , TranscriptomaRESUMO
Protein quality control is crucial for maintaining cellular homeostasis and its dysfunction is closely linked to human diseases. The post-translational protein quality control machinery mainly composed of BCL-2-associated athanogene 6 (BAG6) is responsible for triage of mislocalized membrane proteins (MLPs). However, it is unknown how the BAG6-mediated degradation of MLPs is regulated. We report here that PAQR9, a member of the Progesterone and AdipoQ receptor (PAQR) family, is able to modulate BAG6-mediated triage of MLPs. Analysis with mass spectrometry identified that BAG6 is one of the major proteins interacting with PAQR9 and such interaction is confirmed by co-immunoprecipitation and co-localization assays. The protein degradation rate of representative MLPs is accelerated by PAQR9 knockdown. Consistently, the polyubiquitination of MLPs is enhanced by PAQR9 knockdown. PAQR9 binds to the DUF3538 domain within the proline-rich stretch of BAG6. PAQR9 reduces the binding of MLPs to BAG6 in a DUF3538 domain-dependent manner. Taken together, our results indicate that PAQR9 plays a role in the regulation of protein quality control of MLPs via affecting the interaction of BAG6 with membrane proteins.
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Homeostase/genética , Proteínas de Membrana/genética , Chaperonas Moleculares/genética , Receptores de Progesterona/genética , Humanos , Proteínas de Membrana/química , Chaperonas Moleculares/química , Ligação Proteica/genética , Domínios Proteicos/genética , Transporte Proteico/genética , Proteínas Proto-Oncogênicas c-bcl-2/química , Proteínas Proto-Oncogênicas c-bcl-2/genética , Receptores de Progesterona/química , Ubiquitinação/genética , Ubiquitinas/química , Ubiquitinas/genéticaRESUMO
Adenosylmethionine decarboxylase 1 (AMD1) is a key enzyme involved in biosynthesis of polyamines including spermidine and spermine. The potential function of AMD1 in human gastric cancers is unknown. We analyzed AMD1 expression level in 319 human gastric cancer samples together with the adjacent normal tissues. The protein expression level of AMD1 was significantly increased in human gastric cancer samples compared with their corresponding para-cancerous histological normal tissues (P < 0.0001). The expression level of AMD1 was positively associated with Helicobactor pylori 16sRNA (P < 0.0001), tumor size (P < 0.0001), tumor differentiation (P < 0.05), tumor venous invasion (P < 0.0001), tumor lymphatic invasion (P < 0.0001), blood vessel invasion (P < 0.0001), and tumor lymph node metastasis (TNM) stage (P < 0.0001). Patients with high expression of AMD1 had a much shorter overall survival than those with normal/low expression of AMD1. Knockdown of AMD1 in human gastric cancer cells suppressed cell proliferation, colony formation and cell migration. In a tumor xenograft model, knockdown of AMD1 suppressed the tumor growth in vivo. Inhibition of AMD1 by an inhibitor SAM486A in human gastric cancer cells arrested cell cycle progression during G1-to-S transition. Collectively, our studies at the cellular, animal and human levels indicate that AMD1 has a tumorigenic effect on human gastric cancers and affect the prognosis of the patients.
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Adenocarcinoma/patologia , Adenosilmetionina Descarboxilase/metabolismo , Carcinogênese/patologia , Infecções por Helicobacter/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/microbiologia , Adenocarcinoma/mortalidade , Adenosilmetionina Descarboxilase/antagonistas & inibidores , Adenosilmetionina Descarboxilase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Amidinas/farmacologia , Animais , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Indanos/farmacologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Poliaminas/metabolismo , Prognóstico , Estômago/patologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/mortalidade , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Detection of hydrogen peroxide (H2O2) produced by living cells is very significant to fully understand its roles in cellular physiology, as well as providing reliable diagnosis of pathological conditions. However, in situ detection of H2O2 released from adherent cells in cellular culture medium is still insufficiently achieved. Here, we report an electrochemical platform for in situ detection of H2O2 produced by adherent cells in cellular culture medium. It is based on the use of organic electrochemical transistor (OECT) fabricated on a flexible poly(ethylene terephthalate) substrate and Transwell support. A screen-printed carbon paste electrode was modified with carbon nanotubes and platinum nanoparticles and served as the gate of the device. Under optimal conditions, this device exhibits good modulation and sensitivity. It works in the 0.5 µM to 0.1 mM H2O2 concentration range and has a 0.2 µM detection limit. The cells were seeded and grew on the Transwell membrane. Upon being stimulated by N-formylmethionyl-leucyl-phenylalanine peptide, H2O2 produced by the adherent cells diffused into the bottom chamber of the Transwell and was in situ detected by OECT. Moreover, evaluating in vitro cytotoxicity of the nanomaterial using the OECT-Transwell platform was realized. This simple electrochemical platform would be of great interest for in vitro cytotoxicity, cellular physiology study, and diagnosis of pathological conditions.
Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Peróxido de Hidrogênio/análise , Nanoestruturas/toxicidade , Testes de Toxicidade/instrumentação , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Desenho de Equipamento , Ouro/toxicidade , Grafite/toxicidade , Humanos , Polietilenotereftalatos/química , Transistores EletrônicosRESUMO
Ecological compensation is an important economic tool for the control and management of ecological and environmental problems. The accurate assessment of the amount of compensation is the key factor in the implementation of ecological compensation schemes. However, due to the complex and various ecological and environmental problems caused by groundwater overexploitation, there is no scientific quantitative method. Emergy theory is a new method to quantitatively study the relationship between environmental resources and social economy. Based on the literature review of ecological compensation for groundwater overexploitation, this paper puts forward a new evaluation method for using emergy loss as groundwater overexploitation ecological compensation. The emergy system diagram of environmental problems caused by overexploitation of groundwater is constructed. And the calculation methods of the emergy loss of eco-environmental problems caused by groundwater overexploitation, such as land subsidence (collapse), salt water intrusion, surface runoff reduction, vegetation deterioration, and groundwater pollution, were presented, respectively. Taking Zhengzhou as an example, the total amount of ecological compensation for groundwater overexploitation in 2014 was equivalent to 853 × 106 US dollars. The largest loss of land subsidence is 816 × 106 US dollars, which accounts for 95.64% of the total loss. It can be seen that land subsidence is the most serious in the eco-environmental problems caused by overexploitation of groundwater in Zhengzhou.
Assuntos
Conservação dos Recursos Hídricos/métodos , Água Subterrânea , China , Conservação dos Recursos Hídricos/economia , Conservação dos Recursos Hídricos/estatística & dados numéricos , Ecossistema , Modelos Econômicos , Poluição da ÁguaRESUMO
Molecular dynamics simulations have been used to predict the transport dynamics of fluids through nanochannels with polymer patterning surfaces. The effects of different parameters, such as separation between polymer stripes, solvent quality, and direction and strength of the electric field, were explored in terms of electroosmotic flow transport characteristics, conformational dynamics of the polymer brush and ion distribution. Anisotropic electrokinetic transport becomes significant due to the surface patterning of polymers when the direction of the electric field is changed. At the separation between adjacent polymer stripes comparable to the chain length, local strong flow close to the bare surfaces weakens dramatically under the electric field along the stripe direction. However, when the electric field is switched to the direction perpendicular to the stripes, the flow is enhanced considerably. The coupling of the polymer solvent quality further richens and complicates the transport behaviors. We explain the physical mechanism of the electroosmotic flow in complex polymer patterning channels by analyzing the interrelationship among various properties.