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1.
BMB Rep ; 57(2): 98-103, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38303560

RESUMO

The mammalian sirtuin family (SIRT1-SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor [BMB Reports 2024; 57(2): 98-103].


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Sirtuínas , Animais , Humanos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/genética , Dietilnitrosamina/toxicidade , Reparo do DNA , Dano ao DNA , Sirtuínas/genética , Sirtuínas/metabolismo , Mamíferos/metabolismo
2.
Drug Resist Updat ; 73: 101054, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38277756

RESUMO

AIMS: Sirtuin 7 (SIRT7) plays an important role in tumor development, and has been characterized as a potent regulator of cellular stress. However, the effect of SIRT7 on sorafenib acquired resistance remains unclear and a possible anti-tumor mechanism beyond this process in HCC has not been clarified. We examined the therapeutic potential of SIRT7 and determined whether it functions synergistically with sorafenib to overcome chemoresistance. METHODS: Cancer Genome Atlas-liver HCC data and unbiased gene set enrichment analyses were used to identify SIRT7 as a potential effector molecule in sorafenib acquired resistance. Two types of SIRT7 chemical inhibitors were developed to evaluate its therapeutic properties when synergized with sorafenib. Mass spectrometry was performed to discover a direct target of SIRT7, DDX3X, and DDX3X deacetylation levels and protein stability were explored. Moreover, an in vivo xenograft model was used to confirm anti-tumor effect of SIRT7 and DDX3X chemical inhibitors combined with sorafenib. RESULTS: SIRT7 inhibition mediated DDX3X depletion can re-sensitize acquired sorafenib resistance by disrupting NLRP3 inflammasome assembly, finally suppressing hyperactive ERK1/2 signaling in response to NLRP3 inflammasome-mediated IL-1ß inhibition. CONCLUSIONS: SIRT7 is responsible for sorafenib acquired resistance, and its inhibition would be beneficial when combined with sorafenib by suppressing hyperactive pro-cell survival ERK1/2 signaling.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Sirtuínas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Inflamassomos/metabolismo , Inflamassomos/farmacologia , Fosforilação , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sistema de Sinalização das MAP Quinases , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Proliferação de Células , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/farmacologia , Sirtuínas/genética , Sirtuínas/metabolismo , Sirtuínas/farmacologia
3.
Pathology ; 56(3): 374-381, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38296676

RESUMO

Pellino-1 plays a role in regulating inflammation and immune responses, and its effects on tumours are complex, with different outcomes reported in various studies. Additionally, the role of Pellino-1 in diffuse large B-cell lymphoma (DLBCL) has not been thoroughly investigated. We aimed to examine the expression of Pellino-1 in tumour cells and tumour-infiltrating lymphocytes (TILs) separately and identify the clinicopathological significance of Pellino-1 expression in DLBCL. We evaluated Pellino-1 expression in 104 patients with DLBCL. The density of specific cell types was quantitatively analysed using digital image analysis after a multiplex immunofluorescence staining with Pellino-1, CD20, CD8, FOXP3, and PD-1. Pellino-1 expression was mostly observed in CD20+ tumour cells and CD8+ TILs. The high CD8+/Pellino-1+ group was significantly associated with the non-GCB subtype and higher numbers of Foxp3+ T-cells. Patients with high CD20+/Pellino-1+ and high CD8+/Pellino-1+ cell densities had significantly shorter event-free survival (EFS) rates. The multivariate Cox-regression analysis showed that CD20+/Pellino-1+ cell density and CD8+/Pellino-1+ cell density were independent poor prognostic factors for EFS. Furthermore, patients with low densities of both CD20+/Pellino-1+ and CD8+/Pellino-1+ cells demonstrated a prognosis superior to that of patients with high Pellino-1+ cell densities, either alone or in combination. Additionally, the multivariate analysis demonstrated that the combination of CD20+/Pellino-1+ and CD8+/Pellino-1+ cell densities was an independent prognostic factor for EFS and overall survival. Pellino-1 expression was observed in both tumour cells and TILs, particularly in cytotoxic T-cells, and was correlated with poor outcomes in DLBCL. Thus, Pellino-1 might have an oncogenic effect on DLBCL and might be a potential target for improving cytotoxic T-cell activity.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Linfócitos T CD8-Positivos , Linfócitos do Interstício Tumoral/patologia , Prognóstico , Fatores de Transcrição Forkhead/metabolismo
4.
Exp Mol Med ; 56(1): 100-109, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38182653

RESUMO

Soluble receptors are soluble forms of receptors found in the extracellular space. They have emerged as pivotal regulators of cellular signaling and disease pathogenesis. This review emphasizes their significance in cancer as diagnostic/prognostic markers and potential therapeutic targets. We provide an overview of the mechanisms by which soluble receptors are generated along with their functions. By exploring their involvement in cancer progression, metastasis, and immune evasion, we highlight the importance of soluble receptors, particularly soluble cytokine receptors and immune checkpoints, in the tumor microenvironment. Although current research has illustrated the emerging clinical relevance of soluble receptors, their therapeutic applications remain underexplored. As the landscape of cancer treatment evolves, understanding and targeting soluble receptors might pave the way for novel strategies for cancer diagnosis, prognosis, and therapy.


Assuntos
Relevância Clínica , Neoplasias , Humanos , Neoplasias/patologia , Imunoterapia , Microambiente Tumoral
5.
Sensors (Basel) ; 23(24)2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38139573

RESUMO

Skin-based wearable devices have gained significant attention due to advancements in soft materials and thin-film technologies. Nevertheless, traditional wearable electronics often entail expensive and intricate manufacturing processes and rely on metal-based substrates that are susceptible to corrosion and lack flexibility. In response to these challenges, this paper has emerged with an alternative substrate for wearable electrodes due to its cost-effectiveness and scalability in manufacturing. Paper-based electrodes offer an attractive solution with their inherent properties of high breathability, flexibility, biocompatibility, and tunability. In this study, we introduce carbon nanotube-based paper composites (CPC) electrodes designed for the continuous detection of biopotential signals, such as electrooculography (EOG), electrocardiogram (ECG), and electroencephalogram (EEG). To prevent direct skin contact with carbon nanotubes, we apply various packaging materials, including polydimethylsiloxane (PDMS), Eco-flex, polyimide (PI), and polyurethane (PU). We conduct a comparative analysis of their signal-to-noise ratios in comparison to conventional gel electrodes. Our system demonstrates real-time biopotential monitoring for continuous health tracking, utilizing CPC in conjunction with a portable data acquisition system. The collected data are analyzed to provide accurate heart rates, respiratory rates, and heart rate variability metrics. Additionally, we explore the feasibility using CPC for sleep monitoring by collecting EEG signals.


Assuntos
Nanotubos de Carbono , Dispositivos Eletrônicos Vestíveis , Nanotubos de Carbono/química , Pele , Eletrodos , Sono , Eletrocardiografia
6.
Nanomaterials (Basel) ; 13(22)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37999316

RESUMO

To simultaneously reduce the cost of environmental treatment of discarded food waste and the cost of energy storage materials, research on biowaste conversion into energy materials is ongoing. This work employs a solid-state thermally assisted synthesis method, transforming natural eggshell membranes (NEM) into nitrogen-doped carbon. The resulting NEM-coated LFP (NEM@LFP) exhibits enhanced electrical and ionic conductivity that can promote the mobility of electrons and Li-ions on the surface of LFP. To identify the optimal synthesis temperature, the synthesis temperature is set to 600, 700, and 800 °C. The NEM@LFP synthesized at 700 °C (NEM 700@LFP) contains the most pyrrolic nitrogen and has the highest ionic and electrical conductivity. When compared to bare LFP, the specific discharge capacity of the material is increased by approximately 16.6% at a current rate of 0.1 C for 50 cycles. In addition, we introduce innovative data-driven experiments to observe trends and estimate the discharge capacity under various temperatures and cycles. These data-driven results corroborate and support our experimental analysis, highlighting the accuracy of our approach. Our work not only contributes to reducing environmental waste but also advances the development of efficient and eco-friendly energy storage materials.

7.
Plants (Basel) ; 12(22)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-38005685

RESUMO

Cypripedium guttatum is a highly restricted terrestrial orchid that faces increasing endangerment owing to its habitat destruction and illegal collection. Compared to epiphytic orchids, terrestrial orchids such as C. guttatum have harder seed coats and more demanding in vitro germination conditions. This study aimed to develop an effective in vitro propagation system for C. guttatum to aid in its conservation. Seeds from mature capsules were subjected to various conditions, including sterilization using 1% sodium hypochlorite (NaOCl) and different light conditions, culture media, hormones, and organic supplements, to assess germination and early seedling development in vitro. Sterilization with 1% NaOCl significantly improved the germination rate, especially under dark conditions. Germination initiation occurred at 2 and 3 months in orchid seed sowing medium (OSM) and Murashige and Skoog (MS) medium, respectively. The addition of 1 mg/L naphthaleneacetic acid (NAA) further enhanced germination. However, the inclusion of organic supplements, such as apple and banana homogenates, in the culture medium led to substantial growth inhibition after 12 months. Notably, orchid maintenance medium (OMM) without organic additives proved to be the most suitable for seedling growth. The results of this study show that sterilization, appropriate light, and optimal NAA concentrations are beneficial for seed germination.

8.
Int J Mol Sci ; 24(13)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37446348

RESUMO

Ferulic acid and related hydroxycinnamic acids, used as antioxidants and preservatives in the food, cosmetic, pharmaceutical and biotechnology industries, are among the most abundant phenolic compounds present in plant biomass. Identification of novel compounds that can produce ferulic acid and hydroxycinnamic acids, that are safe and can be mass-produced, is critical for the sustainability of these industries. In this study, we aimed to obtain and characterize a feruloyl esterase (LaFae) from Lactobacillus acidophilus. Our results demonstrated that LaFae reacts with ethyl ferulate and can be used to effectively produce ferulic acid from wheat bran, rice bran and corn stalks. In addition, xylanase supplementation was found to enhance LaFae enzymatic hydrolysis, thereby augmenting ferulic acid production. To further investigate the active site configuration of LaFae, crystal structures of unliganded and ethyl ferulate-bound LaFae were determined at 2.3 and 2.19 Å resolutions, respectively. Structural analysis shows that a Phe34 residue, located at the active site entrance, acts as a gatekeeper residue and controls substrate binding. Mutating this Phe34 to Ala produced an approximately 1.6-fold increase in LaFae activity against p-nitrophenyl butyrate. Our results highlight the considerable application potential of LaFae to produce ferulic acid from plant biomass and agricultural by-products.


Assuntos
Ácidos Cumáricos , Lactobacillus acidophilus , Ácidos Cumáricos/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Plantas/metabolismo
9.
Exp Dermatol ; 32(9): 1476-1484, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37291939

RESUMO

Pellino-1 plays a crucial role in cellular proliferation and regulates inflammatory processes. This study investigated Pellino-1 expression patterns and their relationship with CD4+ T-cell subsets in psoriasis patients. Group 1 comprised primarily biopsied psoriasis lesions from 378 patients, multiplex-immunostained for Pellino-1, CD4 and representative T helper (Th) cells (T-bet [Th1], GATA3 [Th2], and RORγt [Th17] and regulatory T cell [FoxP3] markers). Ki-67 labeling was evaluated in the epidermis. Group 2 comprised 43 Pellino-1-positive cases immunostained for Pellino-1 in both lesion and non-lesion skin biopsy samples. Five normal skin biopsies served as controls. Among 378 psoriasis cases, 293 (77.5%) were positive for Pellino-1 in the epidermis. Pellino-1-positivity was higher in psoriasis lesions than in non-lesions and normal skin (52.55% vs. 40.43% vs. 3.48%, p < 0.001; H-score, 72.08 vs. 47.55 vs. 4.40, p < 0.001, respectively). Pellino-1-positive cases also had a significantly higher Ki-67 labeling index (p < 0.001). Epidermal Pellino1-positivity was significantly associated with higher RORγt+ (p = 0.001) and FoxP3+ (p < 0.001) CD4+ T cell ratios but not T-bet+ and GATA3+ CD4+ T cell ratios. Among the CD4+ Pellino-1+ T-cell subsets, the CD4+ Pellino-1+ RORγt+ ratio was significantly associated with epidermal Pellinio-1 expression (p < 0.001). Pellino-1 expression is thus increased in psoriasis lesions and associated with increased epidermal proliferation and CD4+ T-cell subset infiltration, especially Th17 cells. This suggests that Pellino-1 could be a therapeutic target that simultaneously regulates psoriasis epidermal proliferation and immune interactions.


Assuntos
Psoríase , Células Th17 , Humanos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Antígeno Ki-67/metabolismo , Epiderme/metabolismo , Psoríase/tratamento farmacológico , Proliferação de Células , Fatores de Transcrição Forkhead/metabolismo
10.
Immune Netw ; 23(2): e12, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37179750

RESUMO

Ssu72, a dual-specificity protein phosphatase, not only participates in transcription biogenesis, but also affects pathophysiological functions in a tissue-specific manner. Recently, it has been shown that Ssu72 is required for T cell differentiation and function by controlling multiple immune receptor-mediated signals, including TCR and several cytokine receptor signaling pathways. Ssu72 deficiency in T cells is associated with impaired fine-tuning of receptor-mediated signaling and a defect in CD4+ T cell homeostasis, resulting in immune-mediated diseases. However, the mechanism by which Ssu72 in T cells integrates the pathophysiology of multiple immune-mediated diseases is still poorly elucidated. In this review, we will focus on the immunoregulatory mechanism of Ssu72 phosphatase in CD4+ T cell differentiation, activation, and phenotypic function. We will also discuss the current understanding of the correlation between Ssu72 in T cells and pathological functions which suggests that Ssu72 might be a therapeutic target in autoimmune disorders and other diseases.

11.
Int J Mol Sci ; 24(9)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37176148

RESUMO

Changes in the DNA damage response (DDR) and cellular metabolism are two important factors that allow cancer cells to proliferate. DDR is a set of events in which DNA damage is recognized, DNA repair factors are recruited to the site of damage, the lesion is repaired, and cellular responses associated with the damage are processed. In cancer, DDR is commonly dysregulated, and the enzymes associated with DDR are prone to changes in ubiquitination. Additionally, cellular metabolism, especially glycolysis, is upregulated in cancer cells, and enzymes in this metabolic pathway are modulated by ubiquitination. The ubiquitin-proteasome system (UPS), particularly E3 ligases, act as a bridge between cellular metabolism and DDR since they regulate the enzymes associated with the two processes. Hence, the E3 ligases with high substrate specificity are considered potential therapeutic targets for treating cancer. A number of small molecule inhibitors designed to target different components of the UPS have been developed, and several have been tested in clinical trials for human use. In this review, we discuss the role of ubiquitination on overall cellular metabolism and DDR and confirm the link between them through the E3 ligases NEDD4, APC/CCDH1, FBXW7, and Pellino1. In addition, we present an overview of the clinically important small molecule inhibitors and implications for their practical use.


Assuntos
Neoplasias , Humanos , Ubiquitinação , Neoplasias/patologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Dano ao DNA , Ubiquitina/metabolismo , Reparo do DNA
12.
Nat Commun ; 14(1): 1097, 2023 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-36841836

RESUMO

Brown adipose tissue (BAT) plays a pivotal role in maintaining body temperature and energy homeostasis. BAT dysfunction is associated with impaired metabolic health. Here, we show that Ssu72 phosphatase is essential for mRNA translation of genes required for thermogenesis in BAT. Ssu72 is found to be highly expressed in BAT among adipose tissue depots, and the expression level of Ssu72 is increased upon acute cold exposure. Mice lacking adipocyte Ssu72 exhibit cold intolerance during acute cold exposure. Mechanistically, Ssu72 deficiency alters cytosolic mRNA translation program through hyperphosphorylation of eIF2α and reduces translation of mitochondrial oxidative phosphorylation (OXPHOS) subunits, resulting in mitochondrial dysfunction and defective thermogenesis in BAT. In addition, metabolic dysfunction in Ssu72-deficient BAT returns to almost normal after restoring Ssu72 expression. In summary, our findings demonstrate that cold-responsive Ssu72 phosphatase is involved in cytosolic translation of key thermogenic effectors via dephosphorylation of eIF2α in brown adipocytes, providing insights into metabolic benefits of Ssu72.


Assuntos
Tecido Adiposo Marrom , Fosfoproteínas Fosfatases , Termogênese , Animais , Camundongos , Aclimatação , Adaptação Fisiológica , Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Temperatura Baixa , Camundongos Knockout , Termogênese/genética , Fosfoproteínas Fosfatases/genética
13.
J Microbiol Biotechnol ; 33(3): 387-397, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36655276

RESUMO

Cytochrome P450 (CYP) is a heme-containing enzyme that catalyzes hydroxylation reactions with various substrate molecules. Steroid hydroxylases are particularly useful for effectively introducing hydroxyl groups into a wide range of steroids in the pharmaceutical industry. This study reports a newly identified CYP steroid hydroxylase (BaCYP106A6) from the bacterium Bacillus sp. and characterizes it using an in vitro enzyme assay and structural investigation. Bioconversion assays indicated that BaCYP106A1 catalyzes the hydroxylation of progesterone and androstenedione, whereas no or low conversion was observed with 11ß-hydroxysteroids such as cortisol, corticosterone, dexamethasone, and prednisolone. In addition, the crystal structure of BaCYP106A6 was determined at a resolution of 2.8 Å to investigate the configuration of the substrate-binding site and understand substrate preference. This structural characterization and comparison with other bacterial steroid hydroxylase CYPs allowed us to identify a unique Arg295 residue that may serve as the key residue for substrate specificity and regioselectivity in BaCYP106A6. This observation provides valuable background for further protein engineering to design commercially useful CYP steroid hydroxylases with different substrate specificities.


Assuntos
Bacillus , Bacillus/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Esteroide Hidroxilases/metabolismo , Esteroides/metabolismo , Progesterona/metabolismo , Especificidade por Substrato , Hidroxilação
14.
Small ; 19(3): e2205817, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36408809

RESUMO

Stretchable energy storage devices receive a considerable attention at present due to their growing demand for powering wearable electronics. A vital component in stretchable energy storage devices is its electrode which should endure a large and repeated number of mechanical deformations during its prolonged use. It is crucial to develop a technology to fabricate highly deformable electrode in an easy and an economic manner. Here, the fabrication of stretchable electrode substrates using 3D-printing technology is reported. The ink for fabricating it contains a mixture of sacrificial sugar particles and polydimethylsiloxane resin which solidifies upon thermal curing. The printed stretchable substrate attains a porous structure after leaching the sugar particles in water. The resulting printed porous stretchable substrates are then utilized as electrodes for Li-ion batteries (LIBs) after loading them with electrode materials. The batteries with stretchable electrodes exhibit a decent electrochemical performance comparable to that of the conventional electrodes. The stretchable electrodes also exhibit a stable electrochemical performance under various mechanical deformations and even after several hundreds of stretch/release cycles. This work provides a feasible route for constructing LIBs with high stretchability and enhanced electrochemical performance thereby providing a platform for realizing stretchable batteries for next generation wearable electronics.


Assuntos
Fontes de Energia Elétrica , Silicones , Íons , Eletrodos , Lítio/química , Açúcares , Impressão Tridimensional
15.
Exp Mol Med ; 54(11): 1799-1813, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36380016

RESUMO

The liver is a complicated heterogeneous organ composed of different cells. Parenchymal cells called hepatocytes and various nonparenchymal cells, including immune cells and stromal cells, are distributed in liver lobules with hepatic architecture. They interact with each other to compose the liver microenvironment and determine its characteristics. Although the liver microenvironment maintains liver homeostasis and function under healthy conditions, it also shows proinflammatory and profibrogenic characteristics that can induce the progression of hepatitis and hepatic fibrosis, eventually changing to a protumoral microenvironment that contributes to the development of hepatocellular carcinoma (HCC). According to recent studies, phosphatases are involved in liver diseases and HCC development by regulating protein phosphorylation in intracellular signaling pathways and changing the activities and characteristics of liver cells. Therefore, this review aims to highlight the importance of protein phosphatases in HCC development and in the regulation of the cellular components in the liver microenvironment and to show their significance as therapeutic targets.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Cirrose Hepática/patologia , Fosfoproteínas Fosfatases , Microambiente Tumoral
16.
Pharmaceuticals (Basel) ; 15(11)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36422559

RESUMO

Terrein is a fungal metabolite and has been known to exert anti-melanogenesis, anti-cancer, and anti-bacterial activities. However, its role in endotoxemia has never been investigated until now. In the present study, we examined the effect of terrein on lipopolysaccharide (LPS)-induced endotoxemia in mice and characterized the potential mechanisms of action. Treatment with terrein increased the survival of mice and decreased the production of inflammatory cytokines, including interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in an LPS-induced endotoxemia model. In addition, terrein suppressed the LPS-induced production of IL-1ß and IL-6 in RAW 264.7 cells, a murine macrophage-like cell line, and the mRNA expression of IL-1ß and IL-6 was also inhibited by terrein in LPS-stimulated RAW 264.7 cells. Further study demonstrated that terrein blocked LPS-induced phosphorylation of p65 subunit of nuclear factor (NF)/κB and the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) was also suppressed by terrein treatment. Collectively, these results suggest that terrein exerts a protective effect again LPS-induced endotoxemia in mice by blocking the production of inflammatory cytokines. Our results also suggest that the anti-inflammatory effect of terrein might be mediated, at least in part, by blocking the activation of NF-κB, JNK, and p38 MAPK signaling pathways.

17.
Opt Express ; 30(14): 25249-25261, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-36237059

RESUMO

We investigate the enhancement in sensitivity when measuring a weak force through the optical response of an optomechanical oscillator driven by squeezed light. In the context of a quantum sensor based on cavity-optomechanics, the sensitivity scaling measured by the quantum Fisher information for a squeezed vacuum state pump is compared to that for a coherent state pump. We show that squeezed state inputs can produce noise levels below the standard quantum limit and even the Heisenberg limit in given regimes. This study shows that new pathways can be opened for enhanced quantum sensing with optomechanical systems conducive to measuring various physical quantities such as gravitational force, acceleration, and acoustics.

18.
PeerJ ; 10: e14050, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193426

RESUMO

Endangered wetland plants are important as the potential keystone species and mediators for plant-soil interactions. Establishing conservation strategies for endangered plants is also prioritized because of the elevating extinction risk by human-induced wetland disturbances. The present study examined the factors controlling the incidence of Pterygopleurum neurophyllum, the endangered wetland plant experiencing severe habitat loss throughout Northeast Asia. Here, P. neurophyllum populations and their surrounding environments were addressed in the last natural Korean habitat to assess the possible influential factors (vegetation coverage, species richness, exotic plant species, coarse rock content, soil bulk density, and soil electroconductivity and pH) under anthropogenic wetland interventions (with or without soil disturbance). Our results showed that P. neurophyllum occurred 6 out of 32 plots in the study area. All P. neurophyllum were found in Miscanthus-dominated area, but preferred microhabitats featuring reduced vegetation coverage, increased species richness, and undisturbed soils under vegetation removal. Multimodel inference also indicated that vegetation coverage (relative importance = 1.00) and coarse rock content (relative importance = 0.70) were the major influential factors for P. neurophyllum population size, and the surviving P. neurophyllum were strictly limited to where both of them were kept lowered. Furthermore, the wetland intervention with soil disturbance had a negative effect on P. neurophyllum by creating the rocky and compacted soil surface as a result of land reclamation treatments. Conversely, the wetland intervention without soil disturbance enhanced the P. neurophyllum incidence by decreasing vegetation coverage of the overcrowding competitive plants. Overall findings reflect that the strategies to counteract habitat loss and manage the overly dense competitive plants should be necessary for conserving P. neurophyllum, as well as other wetland plants threatened by the human-induced disturbances and excessive competition intensities.


Assuntos
Espécies em Perigo de Extinção , Áreas Alagadas , Humanos , Animais , Ecossistema , Plantas , Solo/química
19.
PLoS One ; 17(9): e0274019, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36149917

RESUMO

Ornithine carbamoyltransferases (OTCs) are involved in the arginine deiminase (ADI) pathway and in arginine biosynthesis. Two OTCs in a pair are named catalytic OTC (cOTC) and anabolic OTC (aOTC). The cOTC is responsible for catalyzing the third step of the ADI pathway to catabolize citrulline into carbamoyl phosphate (CP), as well as ornithine, and displays CP cooperativity. In contrast, aOTC catalyzes the biosynthesis of citrulline from CP and ornithine in vivo and is thus involved in arginine biosynthesis. Structural and biochemical analyses were employed to investigate the CP cooperativity and unidirectional function of two sequentially similar OTCs (32.4% identity) named Ps_cOTC and Ps_aOTC from Psychrobacter sp. PAMC 21119. Comparison of the trimeric structure of these two OTCs indicated that the 80s loop of Ps_cOTC has a unique conformation that may influence cooperativity by connecting the CP binding site and the center of the trimer. The corresponding 80s loop region of in Ps_aOTC was neither close to the CP binding site nor connected to the trimer center. In addition, results from the thermal shift assay indicate that each OTC prefers the substrate for the unidirectional process. The active site exhibited a blocked binding site for CP in the Ps_cOTC structure, whereas residues at the active site in Ps_aOTC established a binding site to facilitate CP binding. Our data provide novel insights into the unidirectional catalysis of OTCs and cooperativity, which are distinguishable features of two metabolically specialized proteins.


Assuntos
Carbamoil-Fosfato , Psychrobacter , Sequência de Aminoácidos , Arginina , Sítios de Ligação , Carbamoil-Fosfato/química , Catálise , Citrulina , Cicloexanonas , Ornitina/química , Ornitina Carbamoiltransferase/metabolismo , Psychrobacter/metabolismo
20.
Nanomaterials (Basel) ; 12(18)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36144965

RESUMO

The density, microstructure, and ionic conductivity of solid electrolyte Li1.3Al0.3Ti1.7(PO4)3 (LATP) ceramics prepared by cold sintering using liquid and solid sintering additives are studied. The effects of both liquid (water and water solutions of acetic acid and lithium hydroxide) and solid (lithium acetate) additives on densification are investigated. The properties of cold-sintered LATP are compared to those of conventionally sintered LATP. The materials cold-sintered at temperatures 140-280 °C and pressures 510-600 MPa show relative density in the range of 90-98% of LATP's theoretical value, comparable or higher than the density of conventionally sintered ceramics. With the relative density of 94%, a total ionic conductivity of 1.26 × 10-5 S/cm (room temperature) is achieved by cold sintering at the temperature of 200 °C and uniaxial pressure of 510 MPa using water as additive. The lower ionic conductivities of the cold-sintered ceramics compared to those prepared by conventional sintering are attributed to the formation of amorphous secondary phases in the intergranular regions depending on the type of additives used and on the processing conditions selected.

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