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Several preclinical studies demonstrate that antitumor efficacy of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade can be improved by combination with other checkpoint inhibitors. Lymphocyte-activation gene 3 (LAG-3) is an inhibitory checkpoint receptor involved in T cell exhaustion and tumor immune escape. Here, we describe ABL501, a bispecific antibody targeting LAG-3 and PD-L1 in modulating immune cell responses against tumors. ABL501 that efficiently inhibits both LAG-3 and PD-L1 pathways enhances the activation of effector CD4+ and CD8+ T cells with a higher degree than a combination of single anti-LAG-3 and anti-PD-L1. The augmented effector T cell responses by ABL501 resulted in mitigating regulatory-T-cell-mediated immunosuppression. Mechanistically, the simultaneous binding of ABL501 to LAG-3 and PD-L1 promotes dendritic cell (DC) activation and tumor cell conjugation with T cells that subsequently mounts effective CD8+ T cell responses. ABL501 demonstrates its potent in vivo antitumor efficacy in a humanized xenograft model and with knockin mice expressing human orthologs. The immune profiling analysis of peripheral blood reveals an increased abundance of LAG-3hiPD-1hi memory CD4+ T cell subset in relapsed cholangiocarcinoma patients after gemcitabine plus cisplatin therapy, which are more responsive to ABL501. This study supports the clinical evaluation of ABL501 as a novel cancer immunotherapeutic, and a first-in-human trial has started (NCT05101109).
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Anticorpos Biespecíficos , Antígenos CD , Antígeno B7-H1 , Neoplasias , Animais , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos , Células Dendríticas , Camundongos , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Evasão Tumoral , Proteína do Gene 3 de Ativação de LinfócitosRESUMO
BACKGROUND: In this study, we tested whether a combination of radiomic features extracted from baseline pre-immunotherapy computed tomography (CT) images and clinicopathological characteristics could be used as novel noninvasive biomarkers for predicting the clinical benefits of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). METHODS: The data from 92 consecutive patients with lung cancer who had been treated with ICIs were retrospectively analyzed. In total, 88 radiomic features were selected from the pretreatment CT images for the construction of a random forest model. Radiomics model 1 was constructed based on the Rad-score. Using multivariate logistic regression analysis, the Rad-score and significant predictors were integrated into a single predictive model (radiomics nomogram model 1) to predict the durable clinical benefit (DCB) of ICIs. Radiomics model 2 was developed based on the same Rad-score as radiomics model 1.Using multivariate Cox proportional hazards regression analysis, the Rad-score, and independent risk factors, radiomics nomogram model 2 was constructed to predict the progression-free survival (PFS). RESULTS: The models successfully predicted the patients who would benefit from ICIs. For radiomics model 1, the area under the receiver operating characteristic curve values for the training and validation cohorts were 0.848 and 0.795, respectively, whereas for radiomics nomogram model 1, the values were 0.902 and 0.877, respectively. For the PFS prediction, the Harrell's concordance indexes for the training and validation cohorts were 0.717 and 0.760, respectively, using radiomics model 2, whereas they were 0.749 and 0.791, respectively, using radiomics nomogram model 2. CONCLUSIONS: CT-based radiomic features and clinicopathological factors can be used prior to the initiation of immunotherapy for identifying NSCLC patients who are the most likely to benefit from the therapy. This could guide the individualized treatment strategy for advanced NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Processamento de Imagem Assistida por Computador/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
We propose a novel dual-channel electromyography (EMG) spatio-temporal differential (DESTD) method that can estimate volitional electromyography (vEMG) signals during time-varying functional electrical stimulation (FES). The proposed method uses two pairs of EMG signals from the same stimulated muscle to calculate the spatio-temporal difference between the signals. We performed an experimental study with five healthy participants to evaluate the vEMG signal estimation performance of the DESTD method and compare it with that of the conventional comb filter and Gram-Schmidt methods. The normalized root mean square error (NRMSE) values between the semi-simulated raw vEMG signal and vEMG signals which were estimated using the DESTD method and conventional methods, and the two-tailed t-test and analysis of variance were conducted. The results showed that under the stimulation of the gastrocnemius muscle with rapid and dynamically modulated stimulation intensity, the DESTD method had a lower NRMSE compared to the conventional methods (p < 0.01) for all stimulation intensities (maximum 5, 10, 15, and 20 mA). We demonstrated that the DESTD method could be applied to wearable EMG-controlled FES systems because it estimated vEMG signals more effectively compared to the conventional methods under dynamic FES conditions and removed unnecessary FES-induced EMG signals.
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Músculo Esquelético , Estimulação Elétrica , Eletromiografia , HumanosRESUMO
The pulsed laser fragmentation in liquid (PLFL) process is a promising technique for the synthesis of carbon-based functional materials. In particular, there has been considerable attention on graphene quantum dots (GQDs) derived from multiwalled carbon nanotubes (MWCNTs) by the PLFL process, owing to the low cost and rapid processing time involved. However, a fundamental deep understanding of the formation of GQDs from MWCNTs by PLFL has still not been achieved despite the high demand. In this work, a mechanism for the formation of GQDs from MWCNTs by the PLFL process is reported, through the combination of experimental and theoretical studies. Both the experimental and computational results demonstrate that the formation of GQDs strongly depends on the pulse laser energy. Both methods demonstrate that the critical energy point, where a plasma plume is generated on the surface of the MWCNTs, should be precisely maintained to produce GQDs; otherwise, an amorphous carbon structure is favorably formed from the scattered carbons.
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To tune the electronic and optoelectronic properties of graphene quantum dots (GQDs), heteroatom doping (e.g., nitrogen (N), boron (B), and sulfur (S)) is an effective method. However, it is difficult to incorporate S into the carbon framework of GQDs because the atomic size of S is much larger than that of C atoms, compared to N and B. In this study, we report a simple and one-step method for the synthesis of sulfur-doped GQDs (S-GQDs) via the pulsed laser ablation in liquid (PLAL) process. The as-prepared S-GQDs exhibited enhanced fluorescence quantum yields (0.8% â 3.89%) with a huge improved absorption band in ultraviolet (UV) region (200 â¼ 400â nm) and excellent photo stability under the UV radiation at 360â nm. In addition, XPS results revealed that the PLAL process can effectively facilitate the incorporation of S into the carbon framework compared to those produced by the chemical exfoliation method (e.g., hydrothermal method). And also, the mechanisms related with the optical properties of S-GQDs was investigated by time-resolved photoluminescence (TRPL) spectroscopy. We believe that the PLAL process proposed in this study will serve as a simple and one-step route for designing S-GQDs and opens up to opportunities for their potential applications.
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The purpose of the present study was to assess the impact of cryoprotective media on cryopreservation of Paesun cells using loading trehalose. 30â¯mM trehalose was added after confluence of cells, and cultures were further incubated for 18â¯h at 37⯰C. Cryoprotective media was "Cryocool" for the experiment, while MEM containing 10% FBS for the control. After thawing, these cells were examined with assaying the percentage of viable cells and the recovery rate; 89.2⯱â¯1.4% and 78.8⯱â¯3.2%, respectively in the experiment group, while 33.1⯱â¯2.9% and 21.5⯱â¯2.1%, respectively in the control group. Post-thaw cells of the experiment group were examined by assaying proliferation and susceptibility to virus lines; there were no significant differences between before and after cryopreservation, while cells of control group could not be recultured. In conclusion, the cryoprotective media impacts on the effectiveness of cryopreservation using loading trehalose.
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Criopreservação/métodos , Crioprotetores/farmacologia , Trealose/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , HumanosRESUMO
In vivo animal studies are required by regulatory agencies to investigate drug safety before clinical trials. In this review, we summarize the process of selecting a relevant non-rodent species for preclinical studies. The dog is the primary, default non-rodent used in toxicology studies with multiple scientific advantages, including adequate background data and availability. Rabbit has many regulatory advantages as the first non-rodent for the evaluation of reproductive and developmental as well as local toxicity. Recently, minipigs have increasingly replaced dogs and rabbits in toxicology studies due to ethical and scientific advantages including similarity to humans and breeding habits. When these species are not relevant, nonhuman primates (NHPs) can be used as the available animal models, especially in toxicology studies investigating biotherapeutics. Particularly, based on the phylogenetic relationships, the use of New-World marmosets can be considered before Old-World monkeys, especially cynomolgus with robust historical data. Importantly, the use of NHPs should be justified in terms of scientific benefits considering target affinity, expression pattern, and pharmacological cross-reactivity. Strict standards are required for the use of animals. Therefore, this review is helpful for the selection of appropriate non-rodent in regulatory toxicology studies by providing sufficient regulatory, ethical, and scientific data for each species.
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Modelos Animais , Toxicologia/métodos , Animais , Projetos de Pesquisa , Toxicologia/éticaRESUMO
Spontaneously arising mouse mutations have served as the foundation for understanding gene function for more than 100 years. We have used exome sequencing in an effort to identify the causative mutations for 172 distinct, spontaneously arising mouse models of Mendelian disorders, including a broad range of clinically relevant phenotypes. To analyze the resulting data, we developed an analytics pipeline that is optimized for mouse exome data and a variation database that allows for reproducible, user-defined data mining as well as nomination of mutation candidates through knowledge-based integration of sample and variant data. Using these new tools, putative pathogenic mutations were identified for 91 (53%) of the strains in our study. Despite the increased power offered by potentially unlimited pedigrees and controlled breeding, about half of our exome cases remained unsolved. Using a combination of manual analyses of exome alignments and whole-genome sequencing, we provide evidence that a large fraction of unsolved exome cases have underlying structural mutations. This result directly informs efforts to investigate the similar proportion of apparently Mendelian human phenotypes that are recalcitrant to exome sequencing.
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Exoma , Mutação , Animais , Feminino , Doenças Genéticas Inatas/genética , Ligação Genética , Variação Genética , Estudo de Associação Genômica Ampla , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Camundongos , Fenótipo , Reprodutibilidade dos TestesRESUMO
In the present study, keratinase from Stenotrophomonas maltophilia R13 was used for the first time as a reducing agent for the eco-friendly synthesis of AgNPs. The keratinase produced by strain R13 was responsible for the reduction of silver ions and the subsequent formation of AgNPs. Maximum AgNP synthesis was achieved using 2 mM AgNO3 at pH 9 and 40 °C. Electron microscopy and dynamic light scattering analysis showed AgNPs were spherical and of average diameter ~ 8.4 nm. X-ray diffraction revealed that AgNPs were crystalline. FTIR indicated AgNPs were stabilized by proteins present in the crude enzyme solution of strain R13. AgNPs exhibited a broad antimicrobial spectrum against several pathogenic microorganisms, and the antimicrobial mechanism appeared to involve structural deformation of cells resulting in membrane leakage and subsequent lysis. AgNPs also displayed 1,1-diphenyl-2-picrylhydrazyl (IC50 = 0.0112 mg/ml), 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonate radical scavenging (IC50 = 0.0243 mg/ml), and anti-collagenase (IC50 = 23.5 mg/ml) activities.
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Anti-Infecciosos/química , Proteínas de Bactérias/química , Nanopartículas Metálicas/química , Peptídeo Hidrolases/química , Prata/química , Stenotrophomonas maltophilia/enzimologia , Anti-Infecciosos/farmacologia , Prata/farmacologia , Nitrato de Prata/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Epidural blood patch (EBP) has been shown to be an effective treatment option for spontaneous intracranial hypotension (SIH). We investigated whether response to the EBP was related to the distance of the injection site from the leakage site in patients with SIH. METHODS: We reviewed patients with SIH who underwent EBP at a single hospital. Patients were assigned to group R (response after EBP) or group N (no response after EBP). We then analyzed the demographics, clinical characteristics, leakage site, leakage length, EBP injection level and distance from leakage site, and injected EBP volume. RESULTS: Sixty-two patients were included in the analysis. The overall response rate to EBP was 59.7% (37 patients). The leakage length and injection distance from the leakage site did not differ between the two groups. Age, gender, body mass index, leakage site, and EBP volume did not differ significantly between the two groups. CONCLUSION: The clinical effect of EBP in SIH was not affected by leakage length or injection distance to leakage site. Further large studies must be conducted to investigate the efficacy of targeted EBP for SIH.
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Placa de Sangue Epidural/métodos , Hipotensão Intracraniana/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Vazamento de Líquido Cefalorraquidiano/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
GRM6 encodes the metabotropic glutamate receptor 6 (mGluR6) used by retinal depolarizing bipolar cells (DBCs). Mutations in GRM6 lead to DBC dysfunction and underlie the human condition autosomal recessive complete congenital stationary night blindness. Mouse mutants for Grm6 are important models for this condition. Here we report a new Grm6 mutant, identified in an electroretinogram (ERG) screen of mice maintained at The Jackson Laboratory. The Grm6nob8 mouse has a reduced-amplitude b-wave component of the ERG, which reflects light-evoked DBC activity. Sequencing identified a missense mutation that converts a highly conserved methionine within the ligand binding domain to leucine (p.Met66Leu). Consistent with prior studies of Grm6 mutant mice, the laminar size and structure in the Grm6nob8 retina were comparable to control. The Grm6nob8 phenotype is distinguished from other Grm6 mutants that carry a null allele by a reduced but not absent ERG b-wave, decreased but present expression of mGluR6 at DBC dendritic tips, and mislocalization of mGluR6 to DBC somas. Consistent with a reduced but not absent b-wave, there were a subset of retinal ganglion cells whose responses to light onset have times to peak within the range of those in control retinas. These data indicate that the p.Met66Leu mutant mGluR6 is trafficked less than control. However, the mGluR6 that is localized to the DBC dendritic tips is able to initiate DBC signal transduction. The Grm6nob8 mouse extends the Grm6 allelic series and will be useful for elucidating the role of mGluR6 in DBC signal transduction and in human disease.NEW & NOTEWORTHY This article describes a mouse model of the human disease complete congenital stationary night blindness in which the mutation reduces but does not eliminate GRM6 expression and bipolar cell function, a distinct phenotype from that seen in other Grm6 mouse models.
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Oftalmopatias Hereditárias/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Mutação de Sentido Incorreto , Miopia/metabolismo , Cegueira Noturna/metabolismo , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Células Bipolares da Retina/metabolismo , Visão Ocular/fisiologia , Animais , Dendritos/metabolismo , Dendritos/patologia , Dendritos/efeitos da radiação , Modelos Animais de Doenças , Eletrorretinografia , Proteínas de Escherichia coli , Oftalmopatias Hereditárias/genética , Oftalmopatias Hereditárias/patologia , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Transgênicos , Miopia/genética , Miopia/patologia , Cegueira Noturna/genética , Cegueira Noturna/patologia , Células Bipolares da Retina/patologia , Fatores de TranscriçãoRESUMO
Growing evidence indicates that endoplasmic reticulum (ER) stress and/or ER stress-mediated apoptosis may play a role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. The present study investigated the effects of non-cytotoxic concentrations of nitric oxide (NO) and nitrite, a metabolite of NO, on ER stress and ER stress-mediated apoptosis in Neuro-2a cells exposed to homocysteine (Hcy), an endogenous ER stress inducer. Hcy induced ER stress, as confirmed by inositol-requiring enzyme 1α (IRE1α) phosphorylation and X-box-binding protein-1 (Xbp1) mRNA splicing as well as C/EBP homologous protein (CHOP) expression, and apoptosis, as verified by Annexin V-positive cells. Surprisingly, non-cytotoxic NO (S-nitrosoglutathione) and nitrite markedly reduced Hcy-induced IRE1α phosphorylation, Xbp1 mRNA splicing, CHOP expression, and Annexin V-positive cells, indicating the cytoprotection of NO and nitrite against Hcy-induced ER stress and apoptosis. Moreover, inhibition of sGC/cGMP pathway abolished the cytoprotective effects of NO and nitrite, whereas cellular elevation of cGMP levels mimicked the cytoprotective actions of NO and nitrite. These findings provide the first evidence showing that both NO and nitrite can reduce ER stress and subsequent apoptosis via NO-sGC-cGMP pathway in neuronal cells and suggesting that NO and/or nitrite may have therapeutic value in the treatment of ER stress-associated neurodegenerative diseases.
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Apoptose/fisiologia , GMP Cíclico/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Homocisteína/administração & dosagem , Neurônios/fisiologia , Óxido Nítrico/administração & dosagem , Nitritos/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Camundongos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
Mus pahari is a wild-derived, inbred mouse strain. M. pahari colony managers observed fragility of this strain's skin resulting in separation of tail skin from the mouse if handled incorrectly. Tail skin tension testing of M. pahari resulted in significantly lowered force threshold for caudal skin rupture and loss in comparison to closely related inbred mouse species and subspecies and even more than a model for junctional epidermolysis bullosa. Histologically, the tail skin separated at the subdermal level with the dermis firmly attached to the epidermis, excluding the epidermolysis bullosa complex of diseases. The dermal collagen bundles were abnormally thickened and branched. Elastin fiber deposition was focally altered in the dermis adjacent to the hair follicle. Collagens present in the skin could not be differentiated between the species in protein gels following digestion with pepsin. Together these data suggest that M. pahari have altered extracellular matrix development resulting in separation of the skin below the level of the dermis with moderate force similar to the African spiny mouse (Acomys spp.).
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Pele/metabolismo , Pele/fisiopatologia , Cauda , Animais , Colágeno/metabolismo , Derme/metabolismo , Derme/patologia , Derme/fisiopatologia , Elasticidade , Elastina/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Pele/patologia , Especificidade da EspécieRESUMO
Hexavalent chromium (Cr(VI)) is classified as a human carcinogen. Cr(VI) has been associated with adenocarcinomas and squamous cell carcinoma of the lung. The present study shows that acute Cr(VI) treatment in human bronchial epithelial cells (BEAS-2B) increased inflammatory responses (TNF-α, COX-2, and NF-кB/p65) and expression of Nrf2. Cr(VI)-induced generation of reactive oxygen species (ROS) are responsible for increased inflammation. Despite the fact that Nrf2 is a master regulator of response to oxidative stress, silencing of Nrf2 in the acute Cr(VI) treatment had no effect on Cr(VI)-induced inflammation. In contrast, in Cr(VI)-transformed (CrT) cells, Nrf2 is constitutively activated. Knock-down of this protein resulted in decreased inflammation, while silencing of SOD2 and CAT had no effect in the expression of these inflammatory proteins. Results obtained from the knock-down of Nrf2 in CrT cells are very different from the results obtained in the acute Cr(VI) treatment. In BEAS-2B cells, knock-down of Nrf2 had no effect in the inflammation levels, while in CrT cells a decrease in the expression of inflammation markers was observed. These results indicate that before transformation, ROS plays a critical role while Nrf2 not in Cr(VI)-induced inflammation, whereas after transformation (CrT cells), Nrf2 is constitutively activated and this protein maintains inflammation while ROS not. Constitutively high levels of Nrf2 in CrT binds to the promoter regions of COX-2 and TNF-α, leading to increased inflammation. Collectively, our results demonstrate that before cell transformation ROS are important in Cr(VI)-induced inflammation and after transformation a constitutively high level of Nrf2 is important.
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Transformação Celular Neoplásica/metabolismo , Cromo/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Materials offering high energy density are currently desired to meet the increasing demand for energy storage applications, such as pulsed power devices, electric vehicles, high-frequency inverters, and so on. Particularly, ceramic-based dielectric materials have received significant attention for energy storage capacitor applications due to their outstanding properties of high power density, fast charge-discharge capabilities, and excellent temperature stability relative to batteries, electrochemical capacitors, and dielectric polymers. In this paper, we present fundamental concepts for energy storage in dielectrics, key parameters, and influence factors to enhance the energy storage performance, and we also summarize the recent progress of dielectrics, such as bulk ceramics (linear dielectrics, ferroelectrics, relaxor ferroelectrics, and anti-ferroelectrics), ceramic films, and multilayer ceramic capacitors. In addition, various strategies, such as chemical modification, grain refinement/microstructure, defect engineering, phase, local structure, domain evolution, layer thickness, stability, and electrical homogeneity, are focused on the structure-property relationship on the multiscale, which has been thoroughly addressed. Moreover, this review addresses the challenges and opportunities for future dielectric materials in energy storage capacitor applications. Overall, this review provides readers with a deeper understanding of the chemical composition, physical properties, and energy storage performance in this field of energy storage ceramic materials.
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Neuronal cell death caused by oxidative stress is common in a variety of neural diseases and can be investigated in detail in cultured HT22 neuronal cells, where the amino acid glutamate at high concentrations causes glutathione depletion by inhibition of the glutamate/cystine antiporter system, intracellular accumulation of reactive oxygen species (ROS) and eventually oxidative stress-induced neuronal cell death. Using this paradigm, we have previously reported that resveratrol (3,5,4'-trans-trihydroxystilbene) protects HT22 neuronal cells from glutamate-induced oxidative stress by inducing heme oxygenase (HO)-1 expression. Piceatannol (3,5,4',3'-trans-trihydroxystilbene), which is a hydroxylated resveratrol analog and one of the resveratrol metabolites, is estimated to exert neuroprotective effect similar to that of resveratrol. The aim of this study, thus, is to determine whether piceatannol, similarly to resveratrol, would protect HT22 neuronal cells from glutamate-induced oxidative stress. Glutamate at high concentrations induced neuronal cell death and ROS formation. Piceatannol reduced glutamate-induced cell death and ROS formation. The observed cytoprotective effect was much higher when HT22 neuronal cells were pretreated with piceatannol for 6 or 12 h prior to glutamate treatment than when pretreated for 0.5 h. Piceatannol also increased HO-1 expression and HO activity via its activation of nuclear factor-E2-related factor 2 (Nrf2). Interestingly, neuroprotective effect of piceatannol was partly (but not completely) abolished by either down-regulation of HO-1 expression or blockage of HO-1 activity. Taken together, our results suggest that piceatannol, similar to resveratrol, is capable of protecting HT22 neuronal cells against glutamate-induced cell death, at least in part, by inducing Nrf2-dependent HO-1 expression.
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Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Glutamatos/farmacologia , Heme Oxigenase-1/genética , Proteínas de Membrana/genética , Camundongos , Fator 2 Relacionado a NF-E2/genética , Interferência de RNA , RNA Interferente Pequeno , Espécies Reativas de Oxigênio , Resveratrol , Estilbenos/metabolismoRESUMO
In this study, aluminum (Al) chip matrix-based synthetic foams were fabricated by hot pressing at a semi-solid (SS) temperature. The densities of the foams ranged from 2.3 to 2.63 g/cm3, confirming that the density decreased with increasing glass hollow sphere (GHS) content. These values were approximately 16% lower than the densities of Al chip alloys without GHS. The Al chip syntactic foam microstructure fabricated by the semi-solid process comprised GHS uniformly distributed around the Al chip matrix and a spherical microstructure surrounded by the Mg2Si phase in the interior. The resulting spherical microstructure contributed significantly to the improvement of mechanical properties. Mechanical characterization confirmed that the Al chip syntactic foam exhibited a compressive strength of approximately 225-288 MPa and an energy absorption capacity of 46-47 MJ/M3. These results indicate higher compressive properties than typical Al syntactic foam. The Al chip microstructure, consisting of the Mg2Si phase and GHS, acted as a load-bearing element during compression, significantly contributing to the compressive properties of the foam. An analysis was performed using an energy-dispersive spectrometer to validate the interfacial reaction between the GHS and the matrix. The results showed that MgAl2O4 was uniformly coated around GHS, which contributed not only to the strength of the matrix, but also to the mechanical properties via the appropriate interfacial reactive coating.
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Two-photon stereolithography (TPS) is widely used for the fabrication of various three-dimensional (3D) structures with sub-micron fabrication resolution in a single fabrication process. However, TPS is unsuitable for microstructures with fine-hole patterns. The laser ablation process can be easily drilled, or made holes in various materials. However, in the case of laser ablation, the focal plane of the laser is fixed, which is limited to the processing plane. In this study, a multidirectional ablation process is studied to apply laser ablation to various processing planes of a 3D microstructure fabricated by the TPS process. A 3D hybrid fabrication process with the advantages of both TPS and laser ablation is expected to improve the fabrication efficiency. The 3D hybrid process is proposed based on a single laser source. The microstructure is fabricated using TPS, and the multi-directional ablation process creates a hole in the lateral side of the 3D microstructure. To develop the multidirectional ablation process, the reflecting mirror system should be designed to adaptably rotate the laser focal plane and guide the laser path for the target process plane. Through various examples, we demonstrate the ability of the multi-directional ablation process with various examples.
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Cudrania tricuspidata is a traditional medicinal herb in East Asia. The compounds of plants vary depending on environmental factors, such as soil, temperature, drainage, and so on. However, few to no studies have been done on the correlation among environment, growth, and compounds in C. tricuspidata. Thus, we aimed to investigate their relationship. Samples of C. tricuspidata fruit and cultivation soil were collected from 28 cultivation sites in October 2021. Six growth characteristics, eleven soil physicochemical properties, seven meteorological data points, and three active compounds were investigated in this study. We developed and validated an optimized method for quantifying active compounds using UPLC and performed correlation analysis of the environment, growth characteristics, and active compounds. The UPLC-UV method for determining active compounds was validated by measuring the linearity, LOD, LOQ, precision, and accuracy using UPLC. The LOD and LOQ were 0.01-0.03 µg/mL and 0.04-0.09 µg/mL, respectively. The precision was acceptable with RSD% values less than 2%. The recoveries ranged from 97.25 to 104.98% with RSD values <2%, within the acceptable limits. The active compounds were negatively correlated with the size of the fruit, and the growth characteristics were negatively correlated with some environmental factors. The results of this study can be used as basic data for the standard cultural practices and quality control of C. tricuspidata fruits.
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In this study, we present the energy absorption capabilities achieved through the application of hybrid lattice structures, emphasizing their potential across various industrial sectors. Utilizing Ti-6Al-4V and powder bed fusion (PBF) techniques, we fabricated distinct octet truss, diamond, and diagonal lattice structures, tailoring each to specific densities such as 10, 30, and 50%. Furthermore, through the innovative layering of diverse lattice types, we introduced hybrid lattice structures that effectively overcome the inherent energy absorption limitations of single-lattice structures. As a result, we conducted a comprehensive comparison between single-lattice structures and hybrid lattice structures of equal density, unequivocally showcasing the latter's superior energy absorption performance in terms of compression. The single-lattice structure, OT, showed an energy absorption of 42.6 J/m3, while the reinforced hybrid lattice structure, OT-DM, represented an energy absorption of 77.8 J/m3. These findings demonstrate the significant potential of hybrid lattice structures, particularly in energy-intensive domains such as shock absorption structures. By adeptly integrating various lattice architectures and leveraging their collective energy dissipation properties, hybrid lattice structures offer a promising avenue for addressing energy absorption challenges across diverse industrial applications.