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HIV-1 infection remains a public health problem with no cure. Although antiretroviral therapy (ART) is effective for suppressing HIV-1 replication, it requires lifelong drug administration due to a stable reservoir of latent proviruses and may cause serious side effects and drive the emergence of drug-resistant HIV-1 variants. Gene therapy represents an alternative approach to overcome the limitations of conventional treatments against HIV-1 infection. In this study, we constructed and investigated the antiviral effects of an HIV-1 Tat-dependent conditionally replicating adenovirus, which selectively replicates and expresses the diphtheria toxin A chain (Tat-CRAds-DTA) in HIV-1-infected cells both in vitro and in vivo. We found that Tat-CRAds-DTA could specifically induce cell death and inhibit virus replication in HIV-1-infected cells mediated by adenovirus proliferation and DTA expression. A low titer of progeny Tat-CRAds-DTA was also detected in HIV-1-infected cells. In addition, Tat-CRAds-DTA showed no apparent cytotoxicity to HIV-1-negative cells and demonstrated significant therapeutic efficacy against HIV-1 infection in a humanized mouse model. The findings in this study highlight the potential of Tat-CRAds-DTA as a new gene therapy for the treatment of HIV-1 infection.
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Adenoviridae , Toxina Diftérica , Terapia Genética , Vectores Genéticos , Infecciones por VIH , VIH-1 , Replicación Viral , Productos del Gen tat del Virus de la Inmunodeficiencia Humana , Humanos , VIH-1/genética , Toxina Diftérica/genética , Animales , Adenoviridae/genética , Infecciones por VIH/terapia , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/metabolismo , Ratones , Terapia Genética/métodos , Vectores Genéticos/genética , Modelos Animales de Enfermedad , Línea Celular , Células HEK293 , Expresión Génica , Fragmentos de PéptidosRESUMEN
BACKGROUND: Hot flashes are a common side effect of endocrine therapy (ET) that contribute to poor quality of life and decreased treatment adherence. METHODS: Patients with breast cancer wo were receiving ET and experiencing hot flashes were enrolled through three parallel, randomized trials conducted in the United States, China, and South Korea. Participants were randomized to either immediate acupuncture (IA) or delayed acupuncture control (DAC). IA participants received 20 acupuncture sessions over 10 weeks, whereas DAC participants received usual care, then crossed over to acupuncture with a reduced intensity. The primary end point was a change in score on the endocrine symptom subscale of the Functional Assessment of Cancer Therapy (FACT)-Endocrine Symptoms between baseline and week 10. Secondary end points included the hot flash score and the FACT-Breast score. A planned pooled analysis of individual patient data was performed using longitudinal mixed models. RESULTS: In total, 158 women with stage 0-III breast cancer were randomized (United States, n = 78; China, n = 40; South Korea, n = 40). At week 10, IA participants reported statistically significant improvements in the endocrine symptom subscale score (mean change ± standard error: 5.1 ± 0.9 vs. 0.2 ± 1.0; p = .0003), the hot flash score (-5.3 ± 0.9 vs. -1.4 ± 0.9; p < .003), and the FACT-Breast total score (8.0 ± 1.6 vs. -0.01 ± 1.6; p = .0005) compared with DAC participants. The effect of the acupuncture intervention differed by site (p = .005). CONCLUSIONS: Acupuncture led to statistically and clinically meaningful improvements in hot flashes, endocrine symptoms, and breast cancer-specific quality of life in women undergoing ET for breast cancer in the United States, China, and South Korea.
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Terapia por Acupuntura , Neoplasias de la Mama , Sofocos , Calidad de Vida , Humanos , Femenino , Sofocos/terapia , Sofocos/inducido químicamente , Neoplasias de la Mama/terapia , Neoplasias de la Mama/complicaciones , Persona de Mediana Edad , Terapia por Acupuntura/métodos , Adulto , Anciano , República de Corea , Receptores de Estrógenos/metabolismo , Resultado del Tratamiento , China , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/uso terapéutico , Estados UnidosRESUMEN
BACKGROUND: Chemoresistant cancer cells frequently exhibit a state of chronically activated endoplasmic reticulum (ER) stress. Engaged with ER stress, the unfolded protein response (UPR) is an adaptive reaction initiated by the accumulation of misfolded proteins. Protein disulfide isomerase (PDI) is a molecular chaperone known to be highly expressed in glioblastomas with acquired resistance to temozolomide (TMZ). We investigate whether therapeutic targeting of PDI provides a rationale to overcome chemoresistance. METHODS: The activity of PDI was suppressed in glioblastoma cells using a small molecule inhibitor CCF642. Either single or combination treatment with TMZ was used. We prepared nanoformulation of CCF642 loaded in albumin as a drug carrier for orthotopic tumour model. RESULTS: Inhibition of PDI significantly enhances the cytotoxic effect of TMZ on glioblastoma cells. More importantly, inhibition of PDI is able to sensitise glioblastoma cells that are initially resistant to TMZ treatment. Nanoformulation of CCF642 is well-tolerated and effective in suppressing tumour growth. It activates cell death-triggering UPR beyond repair and induces ER perturbations through the downregulation of PERK signalling. Combination treatment of TMZ with CCF642 significantly reduces tumour growth compared with either modality alone. CONCLUSION: Our study demonstrates modulation of ER stress by targeting PDI as a promising therapeutic rationale to overcome chemoresistance.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/farmacología , Glioblastoma/patología , Apoptosis , Respuesta de Proteína Desplegada , Proteína Disulfuro Isomerasas/genética , Proteína Disulfuro Isomerasas/metabolismo , Albúminas , Línea Celular Tumoral , Resistencia a Antineoplásicos , Neoplasias Encefálicas/patologíaRESUMEN
BACKGROUND: Ischemia-reperfusion injury is a key complication following lung transplantation. The clinical application of ex vivo lung perfusion (EVLP) to assess donor lung function has significantly increased the utilization of "marginal" donor lungs with good clinical outcomes. The potential of EVLP on improving organ quality and ameliorating ischemia-reperfusion injury has been suggested. METHODS: To determine the effects of ischemia-reperfusion and EVLP on gene expression in human pulmonary microvascular endothelial cells and epithelial cells, cell culture models were used to simulate cold ischemia (4 °C for 18 h) followed by either warm reperfusion (DMEM + 10% FBS) or EVLP (acellular Steen solution) at 37 °C for 4 h. RNA samples were extracted for bulk RNA sequencing, and data were analyzed for significant differentially expressed genes and pathways. RESULTS: Endothelial and epithelial cells showed significant changes in gene expressions after ischemia-reperfusion or EVLP. Ischemia-reperfusion models of both cell types showed upregulated pro-inflammatory and downregulated cell metabolism pathways. EVLP models, on the other hand, exhibited downregulation of cell metabolism, without any inflammatory signals. CONCLUSION: The commonly used acellular EVLP perfusate, Steen solution, silenced the activation of pro-inflammatory signaling in both human lung endothelial and epithelial cells, potentially through the lack of serum components. This finding could establish the basic groundwork of studying the benefits of EVLP perfusate as seen from current clinical practice.
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Trasplante de Pulmón , Daño por Reperfusión , Humanos , Perfusión/efectos adversos , Células Endoteliales , Pulmón/metabolismo , Trasplante de Pulmón/efectos adversos , Células Epiteliales , IsquemiaRESUMEN
Ex vivo lung perfusion (EVLP) has increased donor lung utilization through assessment of "marginal" lungs prior to transplantation. To develop it as a donor lung reconditioning platform, prolonged EVLP is necessary, and new perfusates are required to provide sufficient nutritional support. Human pulmonary microvascular endothelial cells and epithelial cells were used to test different formulas for basic cellular function. A selected formula was further tested on an EVLP cell culture model, and cell confluence, apoptosis, and GSH and HSP70 levels were measured. When a cell culture medium (DMEM) was mixed with a current EVLP perfusate-Steen solution, DMEM enhanced cell confluence and migration and reduced apoptosis in a dose-dependent manner. A new EVLP perfusate was designed and tested based on DMEM. The final formula contains 5 g/L Dextran-40 and 7% albumin and is named as D05D7A solution. It inhibited cold static storage and warm reperfusion-induced cell apoptosis, improved cell confluence, and enhanced GSH and HSP70 levels in human lung cells compared to Steen solution. DMEM-based nutrient-rich EVLP perfusate could be a promising formula to prolong EVLP and support donor lung repair, reconditioning and further improve donor lung quality and quantity for transplantation with better clinical outcome.
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Técnicas de Cultivo de Célula , Células Endoteliales , Humanos , Proteínas HSP70 de Choque Térmico , Nutrientes , Reperfusión , PulmónRESUMEN
BACKGROUND: Erythrophagocytosis by reparative monocyte-derived macrophage contributes to hematoma clearance and neurological recovery after intracerebral hemorrhage (ICH). Vitamin D (VitD) is a neuroprotective hormone and regulates the differentiation of monocyte-derived macrophage from monocytes. In this study, we examined the effects of VitD supplementation on monocyte-derived macrophage and hematoma clearance in rodent with ICH. METHODS: Neurobehavioral functions and hematoma volume were assessed using a collagenase injection model in both young- and middle-aged mice with or without VitD treatment given 2 hours post-ICH induction. We used flow cytometry to analyze CD36 expression and macrophage and undifferentiated monocyte cell numbers during in vivo erythrophagocytosis in collagenase and autologous blood injection models. Western blot analysis and immunofluorescence were used to assess the expression levels of the PPAR-γ (peroxisome proliferator-activated receptor γ)-CD36 axis and CD206. A macrophage differentiation study was conducted on murine bone marrow-derived monocytes. RESULTS: VitD promoted neurological recovery and facilitated hematoma clearance in both young- and middle-aged mice after ICH. Within the perihematomal region, mature macrophages, rather than undifferentiated monocytes, expressed higher levels of CD36 in driving erythrocyte clearance. VitD increased the macrophage number but decreased the monocyte number and elevated the levels of CD36 and PPAR-γ in the brain. In vitro, VitD accelerated the differentiation of reparative macrophages from bone marrow-derived monocytes. CONCLUSIONS: VitD promotes reparative macrophage differentiation, facilitates hematoma clearance, and improves neurobehavioral performance in mice with ICH, suggesting that VitD should be further examined as a potentially promising treatment for ICH.
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Microglía , Vitamina D , Animales , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Hematoma/tratamiento farmacológico , Hematoma/metabolismo , Humanos , Ratones , PPAR gamma/metabolismo , Vitamina D/farmacologíaRESUMEN
Reciprocity is prevalent across human societies, but individuals are heterogeneous regarding their reciprocity propensity. Although a large body of task-based brain imaging measures has shed light on the neural underpinnings of reciprocity at group level, the neural basis underlying the individual differences in reciprocity propensity remains largely unclear. Here, we combined brain imaging and machine learning techniques to individually predict reciprocity propensity from resting-state brain activity measured by fractional amplitude of low-frequency fluctuation. The brain regions contributing to the prediction were then analyzed for functional connectivity and decoding analyses, allowing for a data-driven quantitative inference on psychophysiological functions. Our results indicated that patterns of resting-state brain activity across multiple brain systems were capable of predicting individual reciprocity propensity, with the contributing regions distributed across the salience (e.g., ventrolateral prefrontal cortex), fronto-parietal (e.g., dorsolateral prefrontal cortex), default mode (e.g., ventromedial prefrontal cortex), and sensorimotor (e.g., supplementary motor area) networks. Those contributing brain networks are implicated in emotion and cognitive control, mentalizing, and motor-based processes, respectively. Collectively, these findings provide novel evidence on the neural signatures underlying the individual differences in reciprocity, and lend support the assertion that reciprocity emerges from interactions among regions embodied in multiple large-scale brain networks.
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Mapeo Encefálico , Imagen por Resonancia Magnética , Humanos , Encéfalo/fisiología , Corteza Prefrontal/diagnóstico por imagen , Individualidad , Vías Nerviosas/fisiologíaRESUMEN
The rapid development of the internet of things is accompanied by a large number of equipment deployment. When the equipment fails or reaches its service life, tons of e-waste will be generated. Therefore, there is an urgent need to find environmentally friendly and effective ways to recycle and treat e-waste. In this paper, a method of classification detection and resource utilization of waste electronic components based on the triboelectric nanogenerator (TENG) is proposed, which provides a novel idea for electronic waste treatment. We studied the output voltage characteristics of different kinds of TENG based on waste electronic components subject to different environmental loadings. The output characteristics of TENG are explored, reflecting the e-waste categories and processing environment. TENG is also connected with hundreds of light-emitting diodes (LEDs) through rectifier bridge circuit, and the output performance of TENG is characterized by the number and intensity of LEDs.
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The high-throughput production of the eco-friendly MIL-88A(Fe) was achieved under mild reaction conditions with normal pressure and temperature. The as-prepared MIL-88A(Fe) exhibited efficient photo-Fenton catalytic ofloxacin (OFL) degradation upon visible light irradiation with good stability and reusability. The OFL (20.0 mg/L) was completely degraded within 50 min under visible light with the aid of MIL-88A(Fe) (0.25 g/L) and H2O2 (1.0 mL/L) in aqueous solution (pH = 7.0). The hydroxyl radicals (·OH) are the main active species during the photo-Fenton oxidation process. Meanwhile, the degradation intermediates and the corresponding degradation pathways were identified and proposed with the aid of both ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and density functional theory (DFT) calculations. Finally, the degradation product library was firstly established to identify intermediate transformation products (TPs) with their variation of concentration, and their corresponding toxicologic activities were assessed via Toxtree and T.E.S.T software as well. Finally, the MIL-88A is efficient and stable with four cycles' catalysis operations, demonstrating good potential for water treatment.
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Ofloxacino , Purificación del Agua , Catálisis , Peróxido de Hidrógeno/química , Ofloxacino/toxicidad , Purificación del Agua/métodosRESUMEN
The photoion-photoion coincidence (PIPICO) is a simple and effective approach for the selection of correlated fragments in a specific dissociating channel in molecules. We propose here a charge-encoded multi-photoion coincidence (cMUPICO) method, in analogy to traditional PIPICO, however in which the charge of individual fragments is taken into account. The cMUPICO method allows for clearly displaying coincident channels for dissociation channels containing three more fragments with unequal charge states, invisible in the traditional PIPICO. As a demonstration, three-body fragmentation dynamics of CO2 in strong IR laser fields is analyzed, and 11 dissociation channels are effectively identified, five of which are first found with cMUPICO. The present results show that cMUPICO is a powerful and practical tool for distinguishing various dissociation channels with multiply charged multi-photoions.
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Multi-ionization and subsequent Coulomb explosion (CE) of the N2O molecule irradiated by a linearly polarized 800 nm laser field is investigated by a reaction microscope, where a number of CE channels of N2Oq+ with q ≤ 5 for two-body fragmentation and q ≤ 8 for three-body fragmentation were observed. For two-body CE, by analyzing the internuclear separations extracted from kinetic energy releases (KERs), dissociation branching fractions, and laser intensity dependence, interestingly, we found that fragmentation N2O5+ â N3+ + NO2+ is produced directly from dissociating N2O3+ via non-sequential stairstep ionization, whereas most of the others result from the sequential stairstep ionization. For three-body CE, 25 fragmentation channels of N2Oq+ (q = 3-8) are distinguished in the present charge-encoded multi-photoion coincidence plot, and the concerted fragmentation mechanism is nominated in a typical Dalitz plot. With the help of the numerical computation with the measured KERs and momentum correlation angles, the geometric structures of molecular ions prior to fragmentation are reconstructed, which display the bending motion and simultaneous two-bond stretching before the CE. Increasing of the bond length for high charged N2Oq+ indicates the dominating stairstep ionization in the three-body fragmentation.
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Trust forms the basis of virtually all interpersonal relationships. Although significant individual differences characterize trust, the driving neuropsychological signatures behind its heterogeneity remain obscure. Here, we applied a prediction framework in two independent samples of healthy participants to examine the relationship between trust propensity and multimodal brain measures. Our multivariate prediction analyses revealed that trust propensity was predicted by gray matter volume and node strength across multiple regions. The gray matter volume of identified regions further enabled the classification of individuals from an independent sample with the propensity to trust or distrust. Our modular and functional decoding analyses showed that the contributing regions were part of three large-scale networks implicated in calculus-based trust strategy, cost-benefit calculation, and trustworthiness inference. These findings do not only deepen our neuropsychological understanding of individual differences in trust propensity, but also provide potential biomarkers in predicting trust impairment in neuropsychiatric disorders.
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Conectoma/métodos , Sustancia Gris/anatomía & histología , Sustancia Gris/fisiología , Individualidad , Imagen por Resonancia Magnética/métodos , Red Nerviosa/fisiología , Percepción Social , Pensamiento/fisiología , Confianza , Adolescente , Adulto , Femenino , Juegos Experimentales , Sustancia Gris/diagnóstico por imagen , Humanos , Masculino , Red Nerviosa/diagnóstico por imagen , Adulto JovenRESUMEN
It has been suggested by multiple studies (postmortem studies, invasive animal studies, and diffusion tensor imaging in the human brain) that the thalamus is important for communication among cortical regions. Many functional magnetic resonance imaging (fMRI) studies, including noninvasive and whole-brain studies, have reported thalamic co-activation with several cognitive control-related cortical systems. This forms a complex network that may be important for advanced cognitive control-related processes, such as working memory and attention. Nevertheless, how the thalamus communicates with the cognitive control-related network in the intact human brain is an essential question and needs further investigation. To address this question, we conducted a study using dynamic functional connectivity analysis and effective connectivity analysis based on fMRI data from young, healthy adult participants. The results showed that the middle thalamus exhibited both high in- and out-degree regarding the complex network related to cognitive control during both rest and task conditions. Furthermore, intrinsic communication via the middle thalamic regions showed dynamically co-varying patterns, and the thalamic regions showed high flexibility in dynamic community analysis. These results indicated that the mid-thalamic region is an important station for communication between nodes in cognitive control-related networks.
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Imagen de Difusión Tensora , Tálamo , Corteza Cerebral/diagnóstico por imagen , Cognición , Humanos , Imagen por Resonancia Magnética , Vías Nerviosas/diagnóstico por imagen , Tálamo/diagnóstico por imagenRESUMEN
Patients with major depressive disorder (MDD) suffer impairment in the transmission and integration of internal and external information sources. Accumulating evidence suggests that the temporoparietal junction (TPJ) is important for multiple cognitive and social functions and may act as a key node for the integration of internal and external information. Therefore, the TPJ's aberrant interaction mechanism may underpin MDD psychopathology. To answer this question, we conducted a comprehensive study using resting-state functional magnetic imaging data recorded from 74 patients with MDD and 69 normal controls. First, we examined whether TPJ was the most prominent region with altered functional/effective connectivity with multiple depression-related regions/networks, based on either zero-lag correlations or temporal mutual information (total interdependence and Granger causality) measurements. Accordingly, we derived a network model that depicts alterations of TPJ-connectivity in patients with MDD. Lastly, we performed a cross-approach comparison demonstrating more conducive indicators in delineating the network alteration model. Functional/effective connectivity between the TPJ and major functional networks that govern internal and external-driven information resources was attenuated in patients with MDD. TPJ acts like a key node for information-inflow and integration of multiple information streams. Therefore, dysfunctional connectivity indicators may serve as effective biomarkers for MDD. MDD is associated with the breakdown of the TPJ interaction model and its connections with the default mode network and the task-positive network.
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Trastorno Depresivo Mayor , Encéfalo , Mapeo Encefálico , Trastorno Depresivo Mayor/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Vías Nerviosas/diagnóstico por imagenRESUMEN
Principle components analysis (PCA) can be used to detect repeating co-variant patterns of resting-state dynamic functional connectivity (DFC) of brain networks, accompanied with sliding-window technique. However, the robustness of PCA-based DFC-state extraction (DFC-PCA) is poorly studied. We investigated the reliability of PCA results and improved the robustness of DFC-PCA for a limited sample size. We first established how PCA-based DFC results varied with sample size and PC order in five rounds of bootstrapping with different sample sizes. The consistency across trials increased with increasing sample size and/or decreasing PC order. We then developed a framework based on PC matching and reordering to obtain a more reliable estimation of co-variant DFC patterns. With either the identical template generated by the surrogate dataset itself or with the external template obtained from existing results, the perceptual hash algorithm was used to reorder PCs according to their patterns. After order correction, reliable results were obtained by averaging across trials within each surrogate dataset. This newly developed framework allowed simultaneous measurement and improvement of DFC-PCA. This consistency could also be used as a criterion for PC selection and interpretation to support the reliability and validity of the conclusion.
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Encéfalo , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Humanos , Análisis de Componente Principal , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To investigate the effects of interleukin-17(IL-17) antibody on polarization of adipose tissue macrophages(ATM) in mice fed with high-fat diet(HFD) exposed to bisphenol A(BPA). METHODS: Four week-old male C57 BL/6 mice were divided into control group, IgG group, IL-17 antibody group, 1000 nmol/L BPA group, 1000 nmol/L BPA+IgG group, and 1000 nmol/L BPA+IL-17 antibody group according to random number table method. Eight mice per group were fed with HFD and BPA was exposed by drinking water. The IgG group and the 1000 nmol/L BPA+IgG group were intraperitoneally injected with 100 µg IgG antibody once a week, and the IL-17 group and the 1000 nmol/L BPA+IL-17 antibody group were intraperitoneally injected with 100 µg IL-17 antibody once a week. After 16 weeks, the mice were sacrificed, and serum samples were collected for serum separation. Leptin level was measured by enzyme-linked immunosorbent assay(ELISA). The expression of IL-1ß, IL-6 and monocyte chemoattractant protein-1(MCP-1)inflammatory cytokines were observed by immunohistochemistry(IHC) of adipose tissue of epididymis. The activity of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1)was measured by ELISA, and the proportion of M1 and M2 ATMs was measured by flow cytometry(FCM). The expression of CD11 c and CD206 mRNA was measured by qRT-PCR. RESULTS: Compared with the control group, serum leptin, the expressions of inflammatory cytokines IL-6, IL-1ß and MCP-1 in adipose tissue were increased in 1000 nmol/L BPA group, the proportion of M1 type ATM was increased(22.000%±0.500% vs. 31.467%±0.379%), iNOS activity was increased, CD11 c mRNA expression was increased, Arg-1 activity was decreased, CD206 mRNA expression was decreased, the differences were statistically significant(P<0.05), but the proportion of M2 type ATM was decreased insignificantly(P>0.05). There was no significant change in IgG group. Compared with 1000 nmol/L BPA group, IgG+1000 nmol/L BPA group had no significant change. In 1000 nmol/L BPA+IL-17 antibody group, serum leptin was decreased, the expressions of inflammatory factors IL-6, IL-1ß and MCP-1 in adipose tissue were down-regulated, and the proportion of M1 type ATM was decreased(31.467%±0.379% vs. 22.933%±0.153%), iNOS activity was decreased, CD11 c mRNA expression was decreased, and the proportion of M2 type ATM was increased(4.847%±0.655% vs. 7.840%±0.555%), Arg-1 activity was enhanced, and CD206 mRNA expression was up-regulated, the differences were statistically significant(P<0.05). CONCLUSION: IL-17 antibody may reduce the secretion of ATM inflammatory factors by inhibiting the polarization of ATM to M1 type, thus improving the inflammation of adipose tissue in BPA-infected HFD-fed mice.
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Dieta Alta en Grasa , Interleucina-17 , Tejido Adiposo , Animales , Compuestos de Bencidrilo , Dieta Alta en Grasa/efectos adversos , Interleucina-17/genética , Macrófagos , Masculino , Ratones , Ratones Endogámicos C57BL , FenolesRESUMEN
Currently, most two-dimensional (2D) metal halide perovskites are of the Ruddlesden-Popper type and contain the thermally unstable methylammonium (MA) molecules, which leads to inferior photovoltaic performance and mild stability. Here we report a new type of MA-free formamidinium (FA) based low-dimensional perovskites, featuring a general formula of (PDA)(FA)n-1 Pbn I3n+1 with propane-1,3-diammonium (PDA) as the organic spacer cation. The perovskite films with well-oriented crystal grains are attained under the assistance of the FACl additive, where the role of Cl is investigated through the grazing-incidence X-ray diffraction technique. The photovoltaic device based on the optimized (PDA)(FA)3 Pb4 I13 film demonstrates a remarkable power conversion efficiency of 13.8 %, the highest record for the FA-based 2D perovskite solar cells. In addition, compared to (PDA)(MA)3 Pb4 I13 , the MA-containing analogue and a renowned stable 2D perovskite, both the (PDA)(FA)3 Pb4 I13 films and their derived devices exhibit exceedingly higher thermal stability.
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Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms due to the selective loss of midbrain dopaminergic neurons. The evidence for a chronic inflammatory reaction mediated by microglial cells in the brain is particularly strong in PD. In our previous study, we have shown that brain-specific microRNA-124 (miR-124) is significantly down-regulated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and that it can also inhibit neuroinflammation during the development of PD. However, further investigation is required to understand whether the abnormal expression of miR-124 regulates microglial activation. In this study, we found that the expression of sequestosome 1 (p62) and phospho-p38 mitogen-activated protein kinases (p-p38) showed a significant increase in LPS-treated immortalized murine microglial cell line BV2 cells in an MPTP-induced mouse model of PD. Knockdown of p62 could suppress the secretion of proinflammatory cytokines and p-p38 of microglia. Besides, inhibition of p38 suppressed the secretion of proinflammatory cytokines and promoted autophagy in BV2 cells. Moreover, our study is the first to identify a unique role of miR-124 in mediating the microglial inflammatory response by targeting p62 and p38 in PD. In the microglial culture supernatant transfer model, the knockdown of p62 in BV2 cells prevented apoptosis and death of human neuroblastoma cell lines SH-SY5Y (SH-SY5Y) cells following microglia activation. In addition, the exogenous delivery of miR-124 could suppress p62 and p-p38 expression and could also attenuate the activation of microglia in the substantia nigra par compacta of MPTP-treated mice. Taken together, our data suggest that miR-124 could inhibit neuroinflammation during the development of PD by targeting p62, p38, and autophagy, indicating that miR-124 could be a potential therapeutic target for regulating the inflammatory response in PD.-Yao, L., Zhu, Z., Wu, J., Zhang, Y., Zhang, H., Sun, X., Qian, C., Wang, B., Xie, L., Zhang, S., Lu, G. MicroRNA-124 regulates the expression of p62/p38 and promotes autophagy in the inflammatory pathogenesis of Parkinson's disease.
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Inflamación/metabolismo , MicroARNs/metabolismo , Enfermedad de Parkinson/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Autofagia/efectos de los fármacos , Autofagia/fisiología , Línea Celular , Línea Celular Tumoral , Citocinas/metabolismo , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/fisiología , Humanos , Inflamación/inducido químicamente , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Microglía/metabolismo , Neuroblastoma/metabolismoRESUMEN
Arylnitrenium ions have gained attention for their high reactivity toward guanosine, which in some cases has been linked to carcinogenesis. Although many studies have examined covalent addition reactions between arylnitrenium ions and guanosine, there is still some uncertainty regarding the attack position of nitrenium ions on guanosine and its derivatives. In this paper, we employ nanosecond transient absorption and nanosecond time-resolved resonance Raman spectroscopy to investigate the reaction between the N,N-di(4-bromophenyl) nitrenium ion (2) and guanosine. Our time-resolved spectroscopic results and photochemical product analysis results show that the reaction of guanosine with 2 generates an N7 intermediate that subsequently undergoes rearrangement and deprotonation to produce a C8 adduct. Comparing these results to our previous study between the 2-fluorenylnitrenium ion and guanosine indicates that the structure and properties of arylnitrenium ions are able to influence the reaction pathways and intermediate structures.
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Guanosina , Espectrometría Raman , IonesRESUMEN
Photochemical/photocatalytic reaction, one of the aging pathway of biochar in soil, not only changed the physicochemical properties of biochar, but also affected the migration and transformation of pollutants. Wheat straw biochar was photocatalytic aged in a Fenton-like system using organic acid as buffer solution under light sources, the organic carbon release and surface chemical changes of biochar were investigated to illustrate the adsorption behaviors. With Fe(III) or α-Fe2O3 added, the total organic carbon (TOC) of aged biochar solution was influenced more by buffer system than light sources, with the highest of 420.59 mg L-1 in citric acid system. The production of the hydroxyl radical (OH·) at citric/Fe(III) system was higher than the oxalic/Fe(III) system under the Hg lamp and showed an increasing trend with time. With light exposure, the porous structure of the biochar altered and surface area increased from 7.613 to 29.74 m2 g-1. Meanwhile, the adsorption of cadmium ion by biochar aged in citric/Fe(III) system also showed an increased adsorption capacity with a maximum of 73.54 mg g-1. So, a well understanding of biochar physicochemical properties changes under natural ecosystem was undoubtedly useful for scientific assessment the long-term feasibility of biochar as soil remediation.