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Chronic inflammation triggers compensatory immunosuppression to stop inflammation and minimize tissue damage. Studies have demonstrated that endoplasmic reticulum (ER) stress augments the suppressive phenotypes of immune cells; however, the molecular mechanisms underpinning this process and how it links to the metabolic reprogramming of immunosuppressive macrophages remain elusive. In the present study, we report that the helper T cell 2 cytokine interleukin-4 and the tumor microenvironment increase the activity of a protein kinase RNA-like ER kinase (PERK)-signaling cascade in macrophages and promote immunosuppressive M2 activation and proliferation. Loss of PERK signaling impeded mitochondrial respiration and lipid oxidation critical for M2 macrophages. PERK activation mediated the upregulation of phosphoserine aminotransferase 1 (PSAT1) and serine biosynthesis via the downstream transcription factor ATF-4. Increased serine biosynthesis resulted in enhanced mitochondrial function and α-ketoglutarate production required for JMJD3-dependent epigenetic modification. Inhibition of PERK suppressed macrophage immunosuppressive activity and could enhance the efficacy of immune checkpoint programmed cell death protein 1 inhibition in melanoma. Our findings delineate a previously undescribed connection between PERK signaling and PSAT1-mediated serine metabolism critical for promoting immunosuppressive function in M2 macrophages.
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Estrés del Retículo Endoplásmico , eIF-2 Quinasa , Estrés del Retículo Endoplásmico/genética , Macrófagos/metabolismo , Transducción de Señal , Respuesta de Proteína Desplegada , eIF-2 Quinasa/genética , eIF-2 Quinasa/metabolismoRESUMEN
Mitochondrial DNA single nucleotide polymorphisms (mtSNPs) have been associated with a reduced risk of developing Parkinson's disease (PD), yet the underlying mechanisms remain elusive. In this study, we investigate the functional role of a PD-associated mtSNP that impacts the mitochondrial-derived peptide (MDP) Small Humanin-like Peptide 2 (SHLP2). We identify m.2158 T > C, a mtSNP associated with reduced PD risk, within the small open reading frame encoding SHLP2. This mtSNP results in an alternative form of SHLP2 (lysine 4 replaced with arginine; K4R). Using targeted mass spectrometry, we detect specific tryptic fragments of SHLP2 in neuronal cells and demonstrate its binding to mitochondrial complex 1. Notably, we observe that the K4R variant, associated with reduced PD risk, exhibits increased stability compared to WT SHLP2. Additionally, both WT and K4R SHLP2 show enhanced protection against mitochondrial dysfunction in in vitro experiments and confer protection against a PD-inducing toxin, a mitochondrial complex 1 inhibitor, in a mouse model. This study sheds light on the functional consequences of the m.2158 T > C mtSNP on SHLP2 and provides insights into the potential mechanisms by which this mtSNP may reduce the risk of PD.
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Mitocondrias , Enfermedad de Parkinson , Polimorfismo de Nucleótido Simple , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Animales , Ratones , Humanos , Polimorfismo de Nucleótido Simple/genética , Mitocondrias/metabolismo , ADN Mitocondrial/genética , Factores Protectores , Ratones Endogámicos C57BL , Neuronas/metabolismo , Modelos Animales de Enfermedad , Masculino , Complejo I de Transporte de Electrón/metabolismo , Complejo I de Transporte de Electrón/genética , Péptidos/genética , Péptidos/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Péptidos y Proteínas de Señalización IntracelularRESUMEN
Metal ions play an important role in living organisms and are involved in essential physiological activities. However, the overload state of ions can cause excess free radicals, cell damage, and even cell death. Ferroptosis and cuproptosis are specific forms of cell death that are distinct from apoptosis, necroptosis, and other regulated cell death. These unique modalities of cell death, dependent on iron and copper, are regulated by multiple cellular metabolic pathways, including steady-state metal redox treatment mitochondrial activity of lipid, amino acid and glucose metabolism, and various signaling pathways associated with disease. Although the mechanisms of ferroptosis and cuproptosis are not yet fully understood, there is no doubt that ion overload plays a crucial act in these metal-dependent cell deaths. In this review, we discussed the core roles of ion overload in ferroptosis and cuproptosis, the association between metabolism imbalance and ferroptosis and cuproptosis, the extract the diseases caused by ion overload and current treatment modalities.
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Ferroptosis , Enfermedades Renales , Muerte Celular Regulada , Humanos , Ferroptosis/genética , Apoptosis , IonesRESUMEN
Light and brassinosteroids (BR) are indispensable for plant growth and control cell division in the apical meristem. However, how external light signals cooperate with internal brassinosteroids to program root meristem development remains elusive. We reveal that the photoreceptor phytochrome B (phyB) guides the scaffold protein RACK1 to coordinate BR signaling for maintaining root meristematic activity. phyB and RACK1 promote early root meristem development. Mechanistically, RACK1 could reinforce the phyB-SPA1 association by interacting with both phyB and SPA1, which indirectly affects COP1-dependent RACK1 degradation, resulting in the accumulation of RACK1 in roots. Subsequently, RACK1 interacts with BES1 to repress its DNA-binding activity toward the target gene CYCD3;1, leading to the release of BES1-mediated inhibition of CYCD3;1 transcription, and hence the promotion of root meristem development. Our study provides mechanistic insights into the regulation of root meristem development by combination of light and phytohormones signals through the photoreceptors and scaffold proteins.
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Biosynthesis of flavonoid aglycones and glycosides is well established. However, key genes involved in their catabolism are poorly understood, even though the products of hydrolysis and oxidation play important roles in plant resistance to biotic stress. Here, we report on catabolism of dihydrochalcones (DHCs), the most abundant flavonoids in domesticated apple and wild Malus. Two key genes, BGLU13.1 and PPO05, were identified by activity-directed protein purification. BGLU13.1-A hydrolyzed phlorizin, (the most abundant DHC in domesticated apple) to produce phloretin which was then oxidized by PPO05. The process differed in some wild Malus, where trilobatin (a positional isomer of phlorizin) was mainly oxidized by PPO05. The effects of DHC catabolism on apple resistance to biotic stresses was investigated using transgenic plants. Either directly or indirectly, phlorizin hydrolysis affected resistance to the phytophagous pest two-spotted spider mite, while oxidation of trilobatin was involved in resistance to the biotrophic fungus Podosphaera leucotricha. DHC catabolism did not affect apple resistance to necrotrophic pathogens Valsa mali and Erwinia amylovara. These results suggest that different DHC catabolism pathways play different roles in apple resistance to biotic stresses. The role of DHC catabolism on apple resistance appeared closely related to the mode of invasion/damage used by pathogen/pest.
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Malus , Polifenoles , Malus/metabolismo , Florizina/metabolismo , Flavonoides/metabolismo , Estrés Fisiológico/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiologíaRESUMEN
Phloretin has different glycosylation modes in plants. Phlorizin (phloretin 2'-O-glucoside) is one of the glycosylation products of phloretin, and accumulates abundantly in apple plants. However, it is still unclear whether phlorizin is more beneficial for apple plants compared with other glycosylation products of phloretin. We created transgenic apple plants with different glycosylation modes of phloretin. In transgenic plants, the accumulation of phlorizin was partly replaced by that of trilobatin (phloretin 4'-O-glucoside) or phloretin 3',5'-di-C-glycoside. Compared with wild type, transgenic plants with less phlorizin showed dwarf phenotype, larger stomatal size, higher stomatal density and less tolerance to drought stress. Transcriptome and phytohormones assay indicate that phlorizin might regulate stomatal development and behaviour via controlling auxin and abscisic acid signalling pathways as well as carbonic anhydrase expressions. Transgenic apple plants with less phlorizin also showed less resistance to spider mites. Apple plants may hydrolyse phlorizin to produce phloretin, but cannot hydrolyse trilobatin or phloretin 3',5'-di-C-glycoside. Compared with its glycosylation products, phloretin is more toxic to spider mites. These results suggest that the glycosylation of phloretin to produce phlorizin is the optimal glycosylation mode in apple plants, and plays an important role in apple resistance to stresses.
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To present the expression of calsyntenin-1 (Clstn1) in the brain and investigate the potential mechanism of Clstn1 in lithium-pilocarpine rat seizure models. Thirty-five male SD adult rats were induced to have seizures by intraperitoneal injection of lithium chloride pilocarpine. Rats exhibiting spontaneous seizures were divided into the epilepsy (EP) group (n = 15), whereas those without seizures were divided into the control group (n = 14). Evaluate the expression of Clstn1 in the temporal lobe of two groups using Western blotting, immunohistochemistry, and immunofluorescence. Additionally, 55 male SD rats were subjected to status epilepticus (SE) using the same induction method. Rats experiencing seizures exceeding Racine's level 4 (n = 48) were randomly divided into three groups: SE, SE + control lentivirus (lentiviral vector expressing green fluorescent protein [LV-GFP]), and SE + Clstn1-targeted RNA interference lentivirus (LV-Clstn1-RNAi). The LV-GFP group served as a control for the lentiviral vector, whereas the LV-Clstn1-RNAi group received a lentivirus designed to silence Clstn1 expression. These lentiviral treatments were administered via hippocampal stereotactic injection 2 days after SE induction. Seven days after SE, Western blot analysis was performed to evaluate the expression of Clstn1 in the hippocampus and temporal lobe. Meanwhile, we observed the latency of spontaneous seizures and the frequency of spontaneous seizures within 8 weeks among the three groups. The expression of Clstn1 in the cortex and hippocampus of the EP group was significantly increased compared to the control group (p < .05). Immunohistochemistry and immunofluorescence showed that Clstn1 was widely distributed in the cerebral cortex and hippocampus of rats, and colocalization analysis revealed that it was mainly co expressed with neurons in the cytoplasm. Compared with the SE group (11.80 ± 2.17 days) and the SE + GFP group (12.40 ± 1.67 days), there was a statistically significant difference (p < .05) in the latency period of spontaneous seizures (15.14 ± 2.41 days) in the SE + Clstn1 + RNAi group rats. Compared with the SE group (4.60 ± 1.67 times) and the SE + GFP group (4.80 ± 2.05 times), the SE + Clstn1 + RNAi group (2.0 ± .89 times) showed a significant reduction in the frequency of spontaneous seizures within 2 weeks of chronic phase in rats (p < .05). Elevated Clstn1 expression in EP group suggests its role in EP onset. Targeting Clstn1 may be a potential therapeutic approach for EP management.
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Modelos Animales de Enfermedad , Pilocarpina , Ratas Sprague-Dawley , Convulsiones , Animales , Masculino , Pilocarpina/toxicidad , Ratas , Convulsiones/metabolismo , Convulsiones/inducido químicamente , Convulsiones/genética , Estado Epiléptico/inducido químicamente , Estado Epiléptico/metabolismo , Neurocalcina/metabolismo , Neurocalcina/genética , Hipocampo/metabolismo , Cloruro de Litio , Lóbulo Temporal/metabolismo , Encéfalo/metabolismoRESUMEN
PURPOSE: To investigate the value of histogram analysis of postcontrast T1-weighted (T1C) and apparent diffusion coefficient (ADC) images in predicting the grade and proliferative activity of adult intracranial ependymomas. METHODS: Forty-seven adult intracranial ependymomas were enrolled and underwent histogram parameters extraction (including minimum, maximum, mean, 1st percentile (Perc.01), Perc.05, Perc.10, Perc.25, Perc.50, Perc.75, Perc.90, Perc.95, Perc.99, standard deviation (SD), variance, coefficient of variation (CV), skewness, kurtosis, and entropy of T1C and ADC) using FireVoxel software. Differences in histogram parameters between grade 2 and grade 3 adult intracranial ependymomas were compared. Receiver operating characteristic curves and logistic regression analyses were conducted to evaluate the diagnostic performance. Spearman's correlation analysis was used to evaluate the relationship between histogram parameters and Ki-67 proliferation index. RESULTS: Grade 3 intracranial ependymomas group showed significantly higher Perc.95, Perc.99, SD, variance, CV, and entropy of T1C; lower minimum, mean, Perc.01, Perc.05, Perc.10, Perc.25, Perc.50 of ADC; and higher CV and entropy of ADC than grade 2 intracranial ependymomas group (all p < 0.05). Entropy (T1C) and Perc.10 (ADC) had a higher diagnostic performance with AUCs of 0.805 and 0.827 among the histogram parameters of T1C and ADC, respectively. The diagnostic performance was improved by combining entropy (T1C) and Perc.10 (ADC), with an AUC of 0.857. Significant correlations were observed between significant histogram parameters of T1C (r = 0.296-0.417, p = 0.001-0.044) and ADC (r = -0.428-0.395, p = 0.003-0.038). CONCLUSION: Whole-tumor histogram analysis of T1C and ADC may be a promising approach for predicting the grade and proliferative activity of adult intracranial ependymomas.
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Neoplasias Encefálicas , Ependimoma , Adulto , Humanos , Imagen de Difusión por Resonancia Magnética/métodos , Curva ROC , Neoplasias Encefálicas/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Despite previous research suggesting a potential association between cerebral small vessel disease (CSVD) and epilepsy, the precise causality and directionality between cerebral small vessel disease (CSVD) and epilepsy remain incompletely understood. We aimed to investigate the causal link between CSVD and epilepsy. METHOD: A bidirectional two-sample Mendelian randomization (MR) analysis was performed to evaluate the causal relationship between CSVD and epilepsy. The analysis included five dimensions of CSVD, namely small vessel ischemic stroke (SVS), intracerebral hemorrhage (ICH), white matter damage (including white matter hyperintensity [WMH], fractional anisotropy, and mean diffusivity), lacunar stroke, and cerebral microbleeds. We also incorporated epilepsy encompassing both focal epilepsy and generalized epilepsy. Inverse variance weighted (IVW) was used as the primary estimate while other four MR techniques were used to validate the results. Pleiotropic effects were controlled by adjusting vascular risk factors through multivariable MR. RESULT: The study found a significant association between SVS (odds ratio [OR] 1.117, PFDR = 0.022), fractional anisotropy (OR 0.961, PFDR = 0.005), mean diffusivity (OR 1.036, PFDR = 0.004), and lacunar stroke (OR 1.127, PFDR = 0.007) with an increased risk of epilepsy. The aforementioned correlations primarily occurred in focal epilepsy rather than generalized epilepsy on subgroup analysis and retained their significance in the multivariable MR analysis. CONCLUSION: Our study demonstrated that genetic susceptibility to CSVD independently elevates the risk of epilepsy, especially focal epilepsy. Diffusion tensor imaging may help screen patients at high risk for epilepsy in CSVD. Improved management of CSVD may be a significant approach in reducing the overall prevalence of epilepsy.
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Enfermedades de los Pequeños Vasos Cerebrales , Epilepsias Parciales , Epilepsia Generalizada , Epilepsia , Accidente Vascular Cerebral Lacunar , Humanos , Imagen de Difusión Tensora , Análisis de la Aleatorización Mendeliana , Imagen por Resonancia Magnética/métodos , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Epilepsia/diagnóstico por imagen , Epilepsia/epidemiología , Epilepsia/genéticaRESUMEN
To evaluate the utility of magnetic resonance imaging (MRI) histogram parameters in predicting O(6)-methylguanine-DNA methyltransferase promoter (pMGMT) methylation status in IDH-wildtype glioblastoma (GBM). From November 2021 to July 2023, forty-six IDH-wildtype GBM patients with known pMGMT methylation status (25 unmethylated and 21 methylated) were enrolled in this retrospective study. Conventional MRI signs (including location, across the midline, margin, necrosis/cystic changes, hemorrhage, and enhancement pattern) were assessed and recorded. Histogram parameters were extracted and calculated by Firevoxel software based on contrast-enhanced T1-weighted images (CET1). Differences and diagnostic performance of conventional MRI signs and histogram parameters between the pMGMT-unmethylated and pMGMT-methylated groups were analyzed and compared. No differences were observed in the conventional MRI signs between pMGMT-unmethylated and pMGMT-methylated groups (all p > 0.05). Compared with the pMGMT-methylated group, pMGMT-unmethylated showed a higher minimum, mean, Perc.01, Perc.05, Perc.10, Perc.25, Perc.50, and coefficient of variation (CV) (all p < 0.05). Among all significant CET1 histogram parameters, minimum achieved the best distinguishing performance, with an area under the curve of 0.836. CET1 histogram parameters could provide additional value in predicting pMGMT methylation status in patients with IDH-wildtype GBM, with minimum being the most promising parameter.
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Neoplasias Encefálicas , Metilación de ADN , Glioblastoma , Isocitrato Deshidrogenasa , Imagen por Resonancia Magnética , Regiones Promotoras Genéticas , Humanos , Glioblastoma/genética , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , Adulto , Metilación de ADN/genética , Anciano , Isocitrato Deshidrogenasa/genética , Estudios Retrospectivos , O(6)-Metilguanina-ADN Metiltransferasa/genéticaRESUMEN
BACKGROUND: Deep venous thrombosis (DVT) after spinal surgery has recently attracted increasing attention. Patients with spinal metastases who undergo decompression with fixation are at a high risk of developing DVT. D-dimer levels indicate the risk of DVT, and the purpose of our study was to investigate D-dimer levels as a predictor of DVT perioperatively. METHODS: We prospectively evaluated 100 patients with spinal metastases. D-dimer tests were performed twice: once before surgery and one day postoperatively. DVT was diagnosed by duplex ultrasonographic assessment of both lower extremities. Pulmonary embolisms (PEs) were diagnosed using multidetector computed tomography and pulmonary angiography. Perioperative serum D-dimer levels were compared between the DVT (+) and DVT (-) groups. The cutoff value of the D-dimer level was calculated using receiver operating characteristic analysis. RESULTS: Preoperative and postoperative DVT prevalences were 8.0% (8/100) and 6.6% (6/91), respectively, and none of the patients developed PE. Before surgery, there was no significant differences in D-dimer levels between the pre-DVT (+) and pre-DVT (-) groups. After surgery, the D-dimer level one-day postoperatively for the post-DVT (+) group (17.6 ± 11.8 mg/L) was significantly higher than that of the post-DVT (-) group (5.0 ± 4.7 mg/L). The cutoff value of the postoperative D-dimer level was 9.51(mg/L), and the sensitivity and specificity for the optimum threshold were 83.3% and 89.4%, respectively. CONCLUSIONS: Our findings suggest that preoperative D-dimer level may not be a predictor of DVT. Preoperative ultrasound examinations should be routinely performed in patients with spinal metastases. Postoperative D-dimer levels greater than 9.51(mg/L) are a predictive factor for the early diagnosis of DVT after spine surgery. TRIAL REGISTRATION: Our study was registered on Chinese Clinical Trial Registry (No.ChiCTR2000029737). Registered 11 February 2020 - Retrospectively registered, https://www.chictr.org.cn/index.aspx.
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Descompresión Quirúrgica , Productos de Degradación de Fibrina-Fibrinógeno , Neoplasias de la Columna Vertebral , Trombosis de la Vena , Humanos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Femenino , Masculino , Trombosis de la Vena/sangre , Trombosis de la Vena/etiología , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/epidemiología , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Descompresión Quirúrgica/efectos adversos , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/sangre , Adulto , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Embolia Pulmonar/sangre , Embolia Pulmonar/etiología , Embolia Pulmonar/diagnóstico , Valor Predictivo de las Pruebas , Biomarcadores/sangreRESUMEN
Two-dimensional (2D) nanosheet arrays with unidirectional orientations are of great significance for synthesizing wafer-scale single crystals. Although great efforts have been devoted, the growth of atomically thin magnetic nanosheet arrays and single crystals is still unaddressed. Here we design an interisland-distance-mediated chemical vapor deposition strategy to synthesize centimeter-scale atomically thin Fe3O4 arrays with unidirectional orientations on mica. The unidirectional alignment of nearly all the Fe3O4 nanosheets is driven by a dual-coupling-guided growth mechanism. The Fe3O4/mica interlayer interaction induces two preferred antiparallel orientations, whereas the interisland interaction of Fe3O4 breaks the energy degeneracy of antiparallel orientations. The room-temperature long-range ferrimagnetic order and thickness-tunable magnetic domain evolution are uncovered in atomically thin Fe3O4. This strategy to tune the orientations of nanosheets through the an interisland interaction can guide the synthesis of other 2D transition-metal oxides, thereby laying a solid foundation for future spintronic device applications at the integration level.
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In view of the defects in the previous detection of cuaminosulfate, which only focused on the analysis of copper ions, there is currently no analysis method available to determine the actual state of cuaminosulfate as chelated or bound. In order to investigate the dissipation and terminal residues in soil and watermelon of cuaminosulfate for food safety and environmental risk, a highly effective technique was developed to detect cuaminosulfate residues in watermelon and soil, and field experiments were conducted in China. After single-factor experiments, residual cuaminosulfate in samples was extracted by pure water, purified using a liquid-liquid approach combined with a dispersive solid-phase extraction, and detected by liquid chromatography tandem mass spectrometry (LC-MS/MS). The Box-Behnken design (BBD) study was used to find the optimal solutions for the time of liquid-liquid purification, the amount of extraction solvent, and the amounts of cleanup sorbents for the analytical method. The average recovery of the method was in the range of 80.0% to 101.1%, the average relative standard deviation (RSD) was 5.3-9.9%, and the detection limit was lower than 0.05 mg/kg. The BBD study not only improved the extraction rate of the method, but also saved time and was operated easily. The final residues of cuaminosulfate in watermelon at different sampling intervals were all lower than 0.05 mg/kg under field conditions. The cuaminosulfate in soils dissipated following exponential kinetics, with half-life values in the range of 9.39 to 12.58 days, which varied by different locations. Based on the validated method, food safety residues and soil residues can be determined rapidly and accurately.
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Residuos de Plaguicidas , Espectrometría de Masas en Tándem , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida con Espectrometría de Masas , Residuos de Plaguicidas/análisis , Límite de Detección , Extracción en Fase Sólida/métodos , Suelo/química , Cromatografía Líquida de Alta Presión/métodosRESUMEN
We here reported a highly stereoselective method for the synthesis of polysubstituted conjugated dienes from α-aryl α-diazo alkynyl ketones and pyrazole-substituted unsymmetric aminals under mild conditions, which was promoted by photo-irridation and involved with 1,6-dipolar intermediate and quadruple sigmatropic rearrangements, was successfully developed. In this transformation, the cleavage of four bonds and the recombination of five bonds were implemented in one operational step. This protocol provided a modular tool for constructing dienes from amines, pyrazoles and α-alkynyl-α-diazoketones in one-pot manner. The results of mechanistic investigation indicated that the plausible reaction path underwent the 1,6-sigmatropic rearrangement instead of the 1,5-sigmatropic rearrangement.
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This study aimed to identify the possible function and the molecular mechanism of hsa_circ_0007334 in human bone marrow mesenchymal stem cells (hBMSCs) osteogenic differentiation. The level of hsa_circ_0007334 was detected by means of quantitative real-time polymerase chain reaction (RT-qPCR). Alkaline phosphatase (ALP), RUNX2, osterix (OSX), and osteocalcin (OCN) were monitored to analyze the degree of osteogenic differentiation under routine culture or under the control of hsa_circ_0007334. The proliferation of hBMSCs was tested with a cell counting kit-8 (CCK-8) assay. The migration of hBMSCs was tested using the Transwell assay. Bioinformatics analysis was used to predict the possible targets of hsa_circ_0007334 or miR-144-3p. Dual-luciferase reporter assay system was used to analyze the combination between hsa_circ_0007334 and miR-144-3p. Hsa_circ_0007334 was upregulated in osteogenic differentiation of hBMSCs. Osteogenic differentiation increased by hsa_circ_0007334 in vitro was confirmed with levels of ALP and bone markers (RUNX2, OCN, OSX). hsa_circ_0007334 overexpression promoted osteogenic differentiation, proliferation, and migration of hBMSCs, and knockdown of hsa_circ_0007334 has the opposite effects. miR-144-3p was identified as the target of hsa_circ_0007334. The targeting genes of miR-144-3p are involved in osteogenic-differentia-tion-related biological processes (such as bone development, epithelial cell proliferation, and mesenchymal cell apoptotic prosess) and pathways (including FoxO and VEGF signaling pathway). Hsa_circ_0007334, therefore, presents itself as a promising biological for osteogenic differentiation.
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Células Madre Mesenquimatosas , MicroARNs , Humanos , MicroARNs/genética , Osteogénesis , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Diferenciación Celular , Proliferación CelularRESUMEN
Sodium-ion batteries (SIBs) have received increasing attention because of their appealing cell voltages and cost-effective features. However, the atom aggregation and electrode volume variation inevitably deteriorate the sodium storage kinetics. Here a new strategy is proposed to boost the lifetime of SIB by synthesizing sea urchin-like FeSe2 /nitrogen-doped carbon (FeSe2 /NC) composites. The robust FeN coordination hinders the Fe atom aggregation and accommodates the volume expansion, while the unique biomorphic morphology and high conductivity of FeSe2 /NC enhance the intercalation/deintercalation kinetics and shorten the ion/electron diffusion length. As expected, FeSe2 /NC electrodes deliver excellent half (387.6 mAh g-1 at 20.0 A g-1 after 56 000 cycles) and full (203.5 mAh g-1 at 1.0 A g-1 after 1200 cycles) cell performances. Impressively, an ultralong lifetime of SIB composed of FeSe2 /Fe3 Se4 /NC anode is uncovered with the cycle number exceeding 65 000. The sodium storage mechanism is clarified with the aid of density function theory calculations and in situ characterizations. This work hereby provides a new paradigm for enhancing the lifetime of SIB by constructing a unique coordination environment between active material and framework.
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Brassinosteroids (BRs) are a group of plant-specific steroid hormones, which induces the rapid nuclear localization of the positive transcriptional factors BRASSINAZOLE RESISTANT1/2 (BZR1/2). However, the mechanisms underlying the regulation of nucleocytoplasmic shuttling of BZR1 remain to be fully elucidated. In this study, we show that the scaffold protein Receptor for Activated C Kinase 1 (RACK1) from Arabidopsis is involved in BR signaling cascades through mediating the nuclear localization of BZR1, which is tightly retained in the cytosol by the conserved scaffold protein 14-3-3s. RACK1 can interact with BZR1 and competitively decrease the 14-3-3 interaction with BZR1 in cytosol, which efficiently enhances the nuclear localization of BZR1. 14-3-3 also retains RACK1 in cytosol through their interaction. Conversely, BR treatment enhances the nuclear localization of BZR1 by disrupting the 14-3-3 interaction with RACK1 and BZR1. Our study uncovers a new mechanism that integrates two kinds of conserved scaffold proteins (RACK1 and 14-3-3) coordinating BR signaling event.
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Proteínas de Arabidopsis , Arabidopsis , Fitosteroles , Proteínas de Arabidopsis/metabolismo , Proteínas de Unión al ADN/metabolismo , Arabidopsis/metabolismo , Núcleo Celular/metabolismo , Transducción de Señal , Reguladores del Crecimiento de las Plantas/metabolismo , Brasinoesteroides/metabolismo , Fitosteroles/metabolismo , Regulación de la Expresión Génica de las Plantas , Receptores de Cinasa C Activada/metabolismoRESUMEN
Light emitted by an object placed in a transparent protective cover will change its original propagation direction before entering a fringe projection profilometry (FPP) system due to the influence of light refraction. This Letter proposes refractive FPP for accurate three-dimensional (3D) shape measurement. The method derives a coordinate mapping between a 3D measurement space and a 2D space formed by an incident ray, a normal of a refractive interface, and an emergent ray. Based on the coordinate mapping, the equation of the emergent ray in the 3D space can be directly determined with the equation of the incident ray and used for 3D measurement without refraction error. For validation, an FPP system through a planar glass was established and used for 3D shape measurements of a ring board, a regular sphere, and two objects with complex surfaces. Experimental results demonstrate the effectiveness and accuracy of the proposed refractive FPP.
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Perioperative neurocognitive disorder (PND) is a common complication of surgery and anesthesia, especially among older patients. Microglial activation plays a crucial role in the occurrence and development of PND and transforming growth factor beta 1 (TGF-ß1) can regulate microglial homeostasis. In the present study, abdominal surgery was performed on 12-14 months-old C57BL/6 mice to establish a PND model. The expression of TGF-ß1, TGF-ß receptor 1, TGF-ß receptor 2, and phosphor-smad2/smad3 (psmad2/smad3) was assessed after anesthesia and surgery. Additionally, we examined changes in microglial activation, morphology, and polarization, as well as neuroinflammation and dendritic spine density in the hippocampus. Behavioral tests, including the Morris water maze and open field tests, were used to examine cognitive function, exploratory locomotion, and emotions. We observed decreased TGF-ß1 expression after surgery and anesthesia. Intranasally administered exogenous TGF-ß1 increased psmad2/smad3 colocalization with microglia positive for ionized calcium-binding adaptor molecule 1. TGF-ß1 treatment attenuated microglial activation, reduced microglial phagocytosis, and reduced surgery- and anesthesia-induced changes in microglial morphology. Compared with the surgery group, TGF-ß1 treatment decreased M1 microglial polarization and increased M2 microglial polarization. Additionally, surgery- and anesthesia-induced increase in interleukin 1 beta and tumor necrosis factor-alpha levels was ameliorated by TGF-ß1 treatment at postoperative day 3. TGF-ß1 also ameliorated cognitive function after surgery and anesthesia as well as rescue dendritic spine loss. In conclusion, surgery and anesthesia induced decrease in TGF-ß1 levels in older mice, which may contribute to PND development; however, TGF-ß1 ameliorated microglial activation and cognitive dysfunction in PND mice.
Asunto(s)
Microglía , Factor de Crecimiento Transformador beta1 , Humanos , Ratones , Animales , Lactante , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Microglía/metabolismo , Ratones Endogámicos C57BL , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Trastornos Neurocognitivos/metabolismo , Factor de Crecimiento Transformador betaRESUMEN
INTRODUCTION: EP300 is considered to be a cancer suppressor gene that plays a role in tumor development, but some studies have reported that it is not an oral squamous cell carcinoma suppressor gene, because there was neither epigenetic inactivation of the gene nor a mutation resulting in functional impairment. However, there is no relevant study on whether EP300 is the exact carcinogenic effect and its mechanisms of carcinogenic effects in oral squamous cell carcinoma. METHODS: Western blot analysis and quantitative real time polymerase chain reaction experiments verified the protein and mRNA expression of EP300 in oral squamous cell carcinoma; The effects of EP300 knockout on glucose consumption and lactic acid production were detected by glycolysis experiments; The relationship between pathway-related proteins and EP300 was verified by bioinformatics analysis and co-immunoprecipitation experiment. RESULTS: Our experimental results confirm that the protein and mRNA of EP300 are highly expressed in oral squamous cell carcinoma, and after knocking out the EP300, the glycolysis ability, invasion, migration, and other biological functions of oral squamous cell carcinoma, are inhibited at the same time. Pathway-related experiments have confirmed that EP300 plays a role in promoting cancer through the transforming growth factor-beta receptor II (TGF-ßRII)/EP300/Smad4 cascade pathway. CONCLUSION: EP300 plays a carcinogenic role in OSCC showed that the TGF-ßRII/EP300/Smad4 cascade pathway is involved in oral squamous cell carcinoma.