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1.
Front Plant Sci ; 15: 1354141, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919815

RESUMO

Suaeda glauca Bunge produces dimorphic seeds on the same plant, with brown seeds displaying non-dormant characteristics and black seeds exhibiting intermediate physiological dormancy traits. Previous studies have shown that black seeds have a very low germination rate under natural conditions, but exogenous GA3 effectively enhanced the germination rate of black seeds. However, the physiological and molecular mechanisms underlying the effects of GA3 on S. glauca black seeds are still unclear. In this study, transcriptomic profiles of seeds at different germination stages with and without GA3 treatment were analyzed and compared, and the TTF, H2O2, O2 -, starch, and soluble sugar contents of the corresponding seed samples were determined. The results indicated that exogenous GA3 treatment significantly increased seed vigor, H2O2, and O2 - contents but decreased starch and soluble sugar contents of S. glauca black seeds during seed dormancy release. RNA-seq results showed that a total of 1136 DEGs were identified in three comparison groups and were involved mainly in plant hormone signal transduction, diterpenoid biosynthesis, flavonoid biosynthesis, phenylpropanoid biosynthesis, and carbohydrate metabolism pathway. Among them, the DEGs related to diterpenoid biosynthesis (SgGA3ox1, SgKAO and SgGA2ox8) and ABA signal transduction (SgPP2Cs) could play important roles during seed dormancy release. Most genes involved in phenylpropanoid biosynthesis were activated under GA3 treatment conditions, especially many SgPER genes encoding peroxidase. In addition, exogenous GA3 treatment also significantly enhanced the expression of genes involved in flavonoid synthesis, which might be beneficial to seed dormancy release. In accordance with the decline in starch and soluble sugar contents, 15 genes involved in carbohydrate metabolism were significantly up-regulated during GA3-induced dormancy release, such as SgBAM, SgHXK2, and SgAGLU, etc. In a word, exogenous GA3 effectively increased the germination rate and seed vigor of S. glauca black seeds by mediating the metabolic process or signal transduction of plant hormones, phenylpropanoid and flavonoid biosynthesis, and carbohydrate metabolism processes. Our results provide novel insights into the transcriptional regulation mechanism of exogenous GA3 on the dormancy release of S. glauca black seeds. The candidate genes identified in this study may be further studied and used to enrich our knowledge of seed dormancy and germination.

2.
Physiol Plant ; 176(3): e14313, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38666351

RESUMO

Bipolaris setariae is known to cause brown stripe disease in sugarcane, resulting in significant yield losses. Silicon (Si) has the potential to enhance plant growth and biotic resistance. In this study, the impact of Si on brown stripe disease was investigated across susceptible and resistant sugarcane varieties, utilizing four Si concentrations (0, 15, 30, and 45 g per barrel of Na2SiO3·5H2O). Si significantly reduced the incidence of brown stripe disease (7.41-59.23%) and alleviated damage to sugarcane growth parameters, photosynthetic parameters, and photosynthetic pigments. Submicroscopic observations revealed that Si induced the accumulation of silicified cells in leaves, reduced spore accumulation, decreased stomatal size, and protected organelles from B. setariae damage. In addition, Si increased the activity of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase), reduced reactive oxygen species production (malondialdehyde and hydrogen peroxide) and modulated the expression of genes associated with hormone signalling (PR1, TGA, AOS, AOC, LOX, PYL8, and SnRK2), leading to the accumulation of abscisic acid and jasmonic acid and inhibiting SA synthesis. Si also activated the activity of metabolism-related enzymes (polyphenol oxidase and phenylalanine ammonia lyase) and the gene expression of PAL-dependent genes (PAL, C4H, and 4CL), regulating the accumulation of metabolites, such as chlorogenic acid and lignin. The antifungal test showed that chlorogenic acid (15ug µL-1) had a significant inhibitory effect on the growth of B. setariae. This study is the first to demonstrate the inhibitory effect of Si on B. setariae in sugarcane, highlighting Si as a promising and environmentally friendly strategy for managing brown stripe disease.


Assuntos
Doenças das Plantas , Reguladores de Crescimento de Plantas , Espécies Reativas de Oxigênio , Saccharum , Silício , Saccharum/efeitos dos fármacos , Saccharum/metabolismo , Saccharum/microbiologia , Saccharum/genética , Saccharum/crescimento & desenvolvimento , Silício/farmacologia , Silício/metabolismo , Doenças das Plantas/microbiologia , Espécies Reativas de Oxigênio/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/microbiologia , Folhas de Planta/genética , Ascomicetos/fisiologia , Ascomicetos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Sequestradores de Radicais Livres/metabolismo
3.
ACS Appl Mater Interfaces ; 16(7): 8742-8750, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38340053

RESUMO

Direct formate fuel cells have gained traction due to their eco-friendly credentials and inherent safety. However, their potential is hampered by the kinetic challenges of the formate oxidation reaction (FOR) on Pd-based catalysts, chiefly due to the unfavorable adsorption of hydrogen species (Had). These species clog the active sites, hindering efficient catalysis. Here, we introduce a straightforward strategy to remedy this bottleneck by incorporating Pd with Cu to expedite the removal of Pd-Had in alkaline media. Notably, Cu plays a pivotal role in bolstering the concentration of hydroxyl adsorbates (OHad) on the surface of catalyst. These OHad species can react with Had, effectively unblocking the active sites for FOR. The as-synthesized catalyst of PdCu/C exhibits a superior FOR performance, boasting a remarkable mass activity of 3.62 A mg-1. Through CO-stripping voltammetry, we discern that the presence of Cu in Pd markedly speeds up the formation of adsorbed hydroxyl species (OHad) at diminished potentials. This, in turn, aids the oxidative removal of Pd-Had, leveraging a synergistic mechanism during FOR. Density functional theory computations further reveal intensified interactions between adsorbed oxygen species and intermediates, underscoring that the Cu-Pd interface exhibits greater oxyphilicity compared to pristine Pd. In this study, we present both experimental and theoretical corroborations, unequivocally highlighting that the integrated copper species markedly amplify the generation of OHad, ensuring efficient removal of Had. This work paves the way, shedding light on the strategic design of high-performing FOR catalysts.

4.
Int J Syst Evol Microbiol ; 73(10)2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37831063

RESUMO

Light yellowish-white colonies of a bacterial strain, designated LNNU 24178T, were isolated from the rhizosphere soil of halophyte Suaeda aralocaspica (Bunge) Freitag and Schütze grown at Shihezi district, Xinjiang, PR China. Cells were Gram-stain-negative, non-flagellum-forming, rod-shaped and non-motile. The results of phylogenetic analysis based on the 16S rRNA gene sequence indicated that LNNU 24178T represented a member of the genus Luteimonas and shared the highest sequence similarity with Luteimonas yindakuii CGMCC 1.13927T (97.1 %) and lower sequence similarity (< 97.0 %) to other known species. The genomic DNA G+C content of LNNU 24178T was 68.8 %. The average nucleotide identity (ANI) values between LNNU 24178T and Luteimonas yindakuii CGMCC 1.13927T, Luteimonas mephitis DSM 12574T, Luteimonas arsenica 26-35T and Luteimonas huabeiensis HB2T were 78.7, 78.6, 78.4 and 80.0 %, respectively. The digital DNA-DNA hybridisation (dDDH) values between LNNU 24178T and L. yindakuii CGMCC 1.13927T, L. mephitis DSM 12574T, L. arsenica 26-35T and L. huabeiensis HB2T were 22.0, 22.3, 22.2 and 23.5 %, respectively. The respiratory quinone detected in LNNU 24178T was ubiquinone-8 (Q-8). The major fatty acids (> 5.0 %) of LNNU 24178T were identified as iso-C15 : 0 (33.9 %), iso-C17 : 0 (8.7 %), iso-C11 : 0 (6.2 %), iso-C16 : 0 (5.7 %), C16 : 0 (5.3 %) and summed feature 9 (iso-C17 : 1ω9c/10-methyl C16 : 0) (21.1 %). The major polar lipids of LNNU 24178T were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), one unidentified phospholipid (PL), one unidentified glycolipid (GL) and three unidentified lipids. According to the data obtained from phenotypic, chemotaxonomic and phylogenetic analyses, strain LNNU 24178T represents a novel species of the genus Luteimonas, for which the name Luteimonas suaedae sp. nov. is proposed, with LNNU 24178T (= CGMCC 1.17331T= KCTC 62251T) as the type strain.


Assuntos
Ácidos Graxos , Rizosfera , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Fosfolipídeos
5.
Nat Commun ; 14(1): 5923, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37740028

RESUMO

Treatment of osteoporosis commonly diminishes osteoclast number which suppresses bone formation thus compromising fracture prevention. Bone formation is not suppressed, however, when bone degradation is reduced by retarding osteoclast functional resorptive capacity, rather than differentiation. We find deletion of deubiquitinase, BRCA1-associated protein 1 (Bap1), in myeloid cells (Bap1∆LysM), arrests osteoclast function but not formation. Bap1∆LysM osteoclasts fail to organize their cytoskeleton which is essential for bone degradation consequently increasing bone mass in both male and female mice. The deubiquitinase activity of BAP1 modifies osteoclast function by metabolic reprogramming. Bap1 deficient osteoclast upregulate the cystine transporter, Slc7a11, by enhanced H2Aub occupancy of its promoter. SLC7A11 controls cellular reactive oxygen species levels and redirects the mitochondrial metabolites away from the tricarboxylic acid cycle, both being necessary for osteoclast function. Thus, in osteoclasts BAP1 appears to regulate the epigenetic-metabolic axis and is a potential target to reduce bone degradation while maintaining osteogenesis in osteoporotic patients.


Assuntos
Osteoclastos , Osteogênese , Animais , Feminino , Humanos , Masculino , Camundongos , Densidade Óssea , Ciclo do Ácido Cítrico , Enzimas Desubiquitinantes , Osteogênese/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética
6.
Ecotoxicol Environ Saf ; 263: 115381, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37597288

RESUMO

Cadmium (Cd) is a toxic element that endangers crop growth and affects food safety and human health. Therefore, the study of Cd mitigation technology is important. Ultrasonic treatment can improve crop growth and enhance their ability to resist various abiotic stresses. In this study, the effect of ultrasonic treatment on alleviating sugarcane Cd stress was studied in a barrel experiment using sugarcane varieties 'ROC22' and 'LC05-136' as test materials. Sugarcane buds without ultrasonic treatment and with ultrasonic treatment (20-40 kHz mixed frequency ultrasound for 2 min, dry treatment) were planted in soil with Cd contents of 0, 50, 100, 250, and 500 mg·kg-1. Compared with non-ultrasonic treatment, Ultrasonic treatment significantly increased the activities of antioxidant enzymes in sugarcane, significantly increased the content of osmoregulation substances, significantly reduced the content of superoxide anion (the highest decreases reached 11.55%) and malondialdehyde (the highest decreases reached 20.59%), and significantly increased the expression level of metallothionein (MT)-related genes, with the expression of ScMT1 increased by 8.80-37.49% and the expression of ScMT2-1-5 increased by 1.55-69.33%. In addition, ultrasonic treatment significantly reduced the Cd contents in sugarcane roots, stems, leaves, bagasse, and juice (the highest reduction in Cd content was 49.18%). In general, ultrasonic treatment regulated the metabolism of reactive oxygen species and MT-related gene expression in sugarcane, increased the Cd tolerance of sugarcane, promoted photosynthesis in sugarcane leaves, improved root morphology, enhanced sugarcane growth, and increased cane and sugar yield.


Assuntos
Antioxidantes , Cádmio , Saccharum , Antioxidantes/metabolismo , Cádmio/toxicidade , Metalotioneína , Saccharum/efeitos dos fármacos , Saccharum/metabolismo , Saccharum/efeitos da radiação , Ondas Ultrassônicas
7.
ACS Appl Mater Interfaces ; 15(23): 28790-28798, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37268875

RESUMO

The rational design of electrocatalysts for formate oxidation reaction (FOR) in alkaline media is crucial to promote the practical applications of direct formate fuel cells (DFFCs). The FOR kinetic on palladium (Pd) based electrocatalysts is strongly hindered by unfavorably adsorbed hydrogen (Had) as the major intermediate species blocking the active sites. Herein, we report a strategy of modulating the interfacial water network of dual-site Pd/FeOx/C catalyst to significantly enhance the desorption kinetics of Had during FOR. Aberration-corrected electron microscopy and synchrotron characterizations revealed the successful construction of Pd/FeOx interfaces on carbon support as a dual-site electrocatalyst for FOR. Electrochemical tests and in situ Raman spectroscopy results showed that Had could be effectively removed from the active sites of the as-designed Pd/FeOx/C catalyst. CO-stripping voltammetry and density functional theory calculations (DFT) demonstrated that the introduced FeOx could effectively accelerate the dissociative adsorption of water molecules on active sites, which accordingly generates adsorbed hydroxyl species (OHad) to facilitate the removal of Had during FOR. This work provides a novel route to develop advanced FOR catalysts for fuel cell applications.

8.
J Plant Res ; 136(5): 631-641, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37202494

RESUMO

Environmental conditions during seed development and maturation can affect seed traits and germination behavior, yet systematic research on the effects of seed maturation time on seed traits, germination behavior and seedling emergence of cleistogamy plants is lacking. Here, we determined the difference in phenotypic characteristics of CH and CL (namely CL1, CL2 and CL3 based on maturation time, respectively) fruits/seeds that were collected from Viola prionantha Bunge, a cleistogamous perennial plant, and evaluated the effects of various environmental factors on seed germination and seedling emergence. The fruit mass, width, seed number per fruit and mean seed mass of CL1 and CL3 were greater than that of CH and CL2, while seed setting of CH was lower than that of CL1, CL2 and CL3. Germination of CH, CL1, CL2, and CL3 seeds was < 10% in the dark at 15/5 and 20/10 â„ƒ, whereas germination (0%-99.2%) of CH, CL1, CL2, and CL3 seeds changed significantly under light conditions. In contrast, more than 71% (from 71.7 to 94.2%) germination of both CH, CL1, CL2 and CL3 seeds occurred under both light/dark conditions and continuous darkness at 30/20 â„ƒ. Germination of CH, CL1, CL2 and CL3 seeds was sensitive to osmotic potential, but CL1 seeds were more resistant to osmotic stress, compared with CH, CL2 and CL3. Seedling emergence of CH seeds was more than 67% (from 67.8 to 73.3%) at a burial depth of 0 cm-2 cm, while all types of CL seeds were below 15% at a burial depth of 2 cm. Information gathered from this study indicates that CH and CL seeds of V. prionantha were different in fruit size, seed mass, thermoperiod and photoperiod sensitivity, osmotic potential tolerance and seedling emergence, especially, maturation time significantly affect phenotypic characteristics and germination behavior of CL seeds matured at different periods. These results indicate that V. prionantha adapts to unpredictable environmental conditions by developing a variety of adaptation strategies, and ensures the survival and reproduction of the populations.


Assuntos
Plântula , Viola , Germinação , Sementes , Reprodução
9.
Small ; 19(36): e2301717, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37118856

RESUMO

Internal electric field (IEF) construction is an innovative strategy to regulate the electronic structure of electrode materials to promote charge transfer processes. Despite the wide use of IEF in various applications, the underlying mechanism of its formation in an asymmetric TM-O-TM unit still remains poorly understood. Herein, the essential principles for the IEF construction at electron occupancy state level and explore its effect on hybrid capacitive deionization (HCDI) performance is systematically investigated. By triggering a charge separation in Ni-MnO2 via superexchange interactions in a coordination structure unit of Mn4+ -O2- -Ni2+ , the formation of an IEF that can enhance charge transfer during the HCDI process is demonstrated. Experimental and theoretical results confirm the electrons transfer from O 2p orbital to TM (Ni2+ and Mn4+ ) eg orbital via superexchange interactions in the basic Mn4+ -O2- -Ni2+ coordination unit. As a result of the charge redistribution, the IEF endows Ni-MnO2 with superior electron and ion transfer property. This work presents a unique material design strategy that activates the electrochemical performance, and provides insights into the formation mechanism of IEF in an asymmetric TM-O-TM unit, which has potential applications in the construction of other innovative materials.

10.
Artigo em Inglês | MEDLINE | ID: mdl-36881479

RESUMO

Direct formate fuel cells (DFFCs) have drawn tremendous attention because they are environmentally benign and have good safety. However, the lack of advanced catalysts for formate electrooxidation hinders the development and applications of DFFCs. Herein, we report a strategy of regulating the metal-substrate work function difference to effectively promote the transfer of adsorbed hydrogen (Had), thus enhancing formate electrooxidation in alkaline solutions. By introducing rich oxygen vacancies, the obtained catalysts of Pd/WO3-x-R show outstanding formate electrooxidation activity, exhibiting an extremely high peak current of 15.50 mA cm-2 with a lower peak potential of 0.63 V. In situ electrochemical Fourier transform infrared and in situ Raman measurements verify an enhanced in situ phase transition from WO3-x to HxWO3-x during the formate oxidation reaction process over the Pd/WO3-x-R catalyst. The results of experimental and density functional theory (DFT) calculations confirm that the work function difference (ΔΦ) between the metal (Pd) and substrate (WO3-x) would be regulated by inducing oxygen vacancies in the substrate, resulting in improved hydrogen spillover at the interface of the catalyst, which is essentially responsible for the observed high performance of formate oxidation. Our findings provide a novel strategy of rationally designing efficient formate electrooxidation catalysts.

11.
JBMR Plus ; 6(4): e10613, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35434449

RESUMO

Both LRF (Zbtb7a) and ThPOK (Zbtb7b) belong to the POK (BTB/POZ and Kruppel) family of transcription repressors that participate in development, differentiation, and oncogenesis. Although LRF mediates osteoclast differentiation by regulating NFATc1 expression, the principal established function of ThPOK is transcriptional control of T-cell lineage commitment. Whether ThPOK affects osteoclast formation or function is not known. We find that marrow macrophage ThPOK expression diminishes with exposure to receptor activator of NF-kB ligand (RANKL), but ThPOK deficiency does not affect osteoclast differentiation. On the other hand, enhanced ThPOK, in macrophages, substantially impairs osteoclastogenesis. Excess ThPOK binds the NFATc1 promoter and suppresses its transcription, suggesting a mechanism for its osteoclast inhibitory effect. Despite suppression of osteoclastogenesis by excess ThPOK being associated with diminished NFATc1, osteoclast formation is not rescued by NFATc1 overexpression. Thus, ThPOK appears to inhibit NFATc1 transcription and its osteoclastogenic capacity, while its depletion has no effect on the bone-resorptive cell. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

12.
Materials (Basel) ; 15(3)2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35161004

RESUMO

The utilization of construction waste soil to produce foamed concrete together with cement and a foaming agent is a promising method for waste recycling. Completely decomposed granite (CDG), which is widely available in southern China, was selected as a typical construction waste soil in foamed material production. The Taguchi method was applied to study the influence of various parameters on compressive strength, including cement dosage, CDG dosage, water to solid materials ratio (W/M), fine particles content, and gravel particles content. Analysis of variance (ANOVA) on a CDG-based sample showed that all factors have significant effects on compressive strength and the most effective parameter was cement dosage, followed in sequence by CDG dosage, W/M, gravel particles content, and fine particles content. However, only cement dosage and W/M influence the internal structure significantly during water/vacuum-immersion tests. The relationship between micro-pore structure and compressive strength suggested that with the decrease of open porosity, the compressive strength showed an increasing trend. This study reveals the possibility of CDG as a raw material for foamed lightweight soil and provides a technical reference of production procedure.

13.
ACS Appl Mater Interfaces ; 13(43): 51643-51651, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34672195

RESUMO

Direct formate fuel cells (DFFCs) as promising energy technologies have been applied for portable and wearable devices. However, for the formate oxidation reaction (FOR), the deficiency of catalysts has prevented DFFCs from practical applications. Herein, we prepared a Pd-loaded CeO2 catalyst through a simple steam treatment at 400 °C to enhance the catalytic FOR performance. In comparison with the counterpart of Pd/CeO2 without stream treatment, the as-prepared Pd/CeO2-ST catalyst has a lower onset potential of 381 mV and a lower peak potential of 0.64 V with a higher peak current of 10.62 mA cm-2. The experimental results show that the enhanced FOR properties of Pd/CeO2-ST are ascribed to the introduction of surface reactive oxygen species to the CeO2 substrate, which substantially promotes the desorption of adsorbed hydrogen (H*) intermediates. Density functional theory (DFT) calculations reveal that on the surface of CeO2, the abundant oxygen vacancies boost the OH* adsorption ability and accelerate the kinetics of the potential-limiting step. This work not only proposes a new strategy for enhancing the activity of FOR catalysts but also highlights the understanding of the FOR mechanism in alkaline media for DFFC applications.

14.
Cell Metab ; 33(2): 270-282.e8, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33278339

RESUMO

Recent studies suggest that mitochondria can be transferred between cells to support the survival of metabolically compromised cells. However, whether intercellular mitochondria transfer occurs in white adipose tissue (WAT) or regulates metabolic homeostasis in vivo remains unknown. We found that macrophages acquire mitochondria from neighboring adipocytes in vivo and that this process defines a transcriptionally distinct macrophage subpopulation. A genome-wide CRISPR-Cas9 knockout screen revealed that mitochondria uptake depends on heparan sulfates (HS). High-fat diet (HFD)-induced obese mice exhibit lower HS levels on WAT macrophages and decreased intercellular mitochondria transfer from adipocytes to macrophages. Deletion of the HS biosynthetic gene Ext1 in myeloid cells decreases mitochondria uptake by WAT macrophages, increases WAT mass, lowers energy expenditure, and exacerbates HFD-induced obesity in vivo. Collectively, this study suggests that adipocytes and macrophages employ intercellular mitochondria transfer as a mechanism of immunometabolic crosstalk that regulates metabolic homeostasis and is impaired in obesity.


Assuntos
Tecido Adiposo Branco/metabolismo , Homeostase , Macrófagos/metabolismo , Mitocôndrias/metabolismo , Obesidade/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos
15.
Cell Metab ; 32(5): 801-813.e6, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33027637

RESUMO

Adipocytes control bone mass, but the mechanism is unclear. To explore the effect of postnatal adipocyte elimination on bone cells, we mated mice expressing an inducible primate diphtheria toxin receptor (DTR) to those bearing adiponectin (ADQ)-Cre. DTR activation eliminates peripheral and marrow adipocytes in these DTRADQ mice. Within 4 days of DTR activation, the systemic bone mass of DTRADQ mice began to increase due to stimulated osteogenesis, with a 1,000% expansion by 10-14 days post-DTR treatment. This adipocyte ablation-mediated enhancement of skeletal mass reflected bone morphogenetic protein (BMP) receptor activation following the elimination of its inhibitors, associated with simultaneous epidermal growth factor (EGF) receptor signaling. DTRADQ-induced osteosclerosis is not due to ablation of peripheral adipocytes but likely reflects the elimination of marrow ADQ-expressing cells. Thus, anabolic drugs targeting BMP receptor inhibitors with short-term EGF receptor activation may be a means of profoundly increasing skeletal mass to prevent or reverse pathological bone loss.


Assuntos
Adipócitos/metabolismo , Reabsorção Óssea/metabolismo , Animais , Células Cultivadas , Camundongos , Camundongos Transgênicos
16.
JCI Insight ; 5(17)2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32879136

RESUMO

Obesity predisposes to cancer and a virtual universality of nonalcoholic fatty liver disease (NAFLD). However, the impact of hepatic steatosis on liver metastasis is enigmatic. We find that while control mice were relatively resistant to hepatic metastasis, those which were lipodystrophic or obese, with NAFLD, had a dramatic increase in breast cancer and melanoma liver metastases. NAFLD promotes liver metastasis by reciprocal activation initiated by tumor-induced triglyceride lipolysis in juxtaposed hepatocytes. The lipolytic products are transferred to cancer cells via fatty acid transporter protein 1, where they are metabolized by mitochondrial oxidation to promote tumor growth. The histology of human liver metastasis indicated the same occurs in humans. Furthermore, comparison of isolates of normal and fatty liver established that steatotic lipids had enhanced tumor-stimulating capacity. Normalization of glucose metabolism by metformin did not reduce steatosis-induced metastasis, establishing the process is not mediated by the metabolic syndrome. Alternatively, eradication of NAFLD in lipodystrophic mice by adipose tissue transplantation reduced breast cancer metastasis to that of control mice, indicating the steatosis-induced predisposition is reversible.


Assuntos
Lipólise , Neoplasias Hepáticas/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Animais , Feminino , Glucose/metabolismo , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Hepáticas/metabolismo , Metástase Neoplásica
17.
J Clin Invest ; 130(5): 2644-2656, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32310225

RESUMO

We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Energy expenditure and brown adipose tissue metabolism in Asxl2ΔLysM mice were protected from the suppressive effects of HFD, a phenomenon associated with relatively increased catecholamines likely due to their suppressed degradation by macrophages. White adipose tissue of HFD-fed Asxl2ΔLysM mice also exhibited none of the pathological remodeling extant in their control counterparts. Suppression of macrophage Asxl2 expression, via nanoparticle-based siRNA delivery, prevented HFD-induced obesity. Thus, ASXL2 controlled the response of macrophages to dietary factors to regulate metabolic homeostasis, suggesting modulation of the cells' inflammatory phenotype may impact obesity and its complications.


Assuntos
Metabolismo Energético , Células Mieloides/metabolismo , Obesidade/prevenção & controle , Proteínas Repressoras/deficiência , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Dieta Hiperlipídica/efeitos adversos , Feminino , Técnicas de Silenciamento de Genes , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Mieloides/patologia , Obesidade/metabolismo , Obesidade/patologia , Especificidade de Órgãos , RNA Interferente Pequeno/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Aumento de Peso/genética , Aumento de Peso/fisiologia
18.
Cell Rep ; 27(10): 2809-2816.e3, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167128

RESUMO

We explored the relationship of obesity and inflammatory arthritis (IA) by selectively expressing diphtheria toxin in adipose tissue yielding "fat-free" (FF) mice completely lacking white and brown fat. FF mice exhibit systemic neutrophilia and elevated serum acute phase proteins suggesting a predisposition to severe IA. Surprisingly, FF mice are resistant to K/BxN serum-induced IA and attendant bone destruction. Despite robust systemic basal neutrophilia, neutrophil infiltration into joints of FF mice does not occur when challenged with K/BxN serum. Absence of adiponectin, leptin, or both has no effect on joint disease, but deletion of the adipokine adipsin (complement factor D) completely prevents serum-induced IA. Confirming that fat-expressed adipsin modulates the disorder, transplantation of wild-type (WT) adipose tissue into FF mice restores susceptibility to IA, whereas recipients of adipsin-deficient fat remain resistant. Thus, adipose tissue regulates development of IA through a pathway in which adipocytes modify neutrophil responses in distant tissues by producing adipsin.


Assuntos
Tecido Adiposo/metabolismo , Artrite/etiologia , Artrite/metabolismo , Neutrófilos/metabolismo , Adipócitos/metabolismo , Tecido Adiposo/imunologia , Animais , Artrite/induzido quimicamente , Artrite/imunologia , Fator D do Complemento/genética , Fator D do Complemento/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Leptina/genética , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Infiltração de Neutrófilos/genética , Infiltração de Neutrófilos/imunologia , Neutrófilos/citologia , Neutrófilos/imunologia
19.
Org Lett ; 21(11): 4340-4344, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31117715

RESUMO

An NHC-catalyzed α-carbon amination of chloroaldehydes was developed. Cyclohexadiene-1,2-diimines are used as amination reagents and four-atom synthons. Our reaction affords optically enriched dihydroquinoxalines that are core structures in natural products and synthetic bioactive molecules.

20.
iScience ; 9: 175-191, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30396151

RESUMO

The mevalonate pathway is essential for the synthesis of isoprenoids and cholesterol. Adipose tissue is known as a major site for cholesterol storage; however, the role of the local mevalonate pathway and its synthesized isoprenoids remains unclear. In this study, adipose-specific mevalonate pathway-disrupted (aKO) mice were generated through knockout of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (HMGCR). aKO mice showed serious lipodystrophy accompanied with glucose and lipid metabolic disorders and hepatomegaly. These metabolic variations in aKO mice were dramatically reversed after fat transplantation. In addition, HMGCR-disrupted adipocytes exhibited loss of lipid accumulation and an increase of cell death, which were ameliorated by the supplementation of mevalonate and geranylgeranyl pyrophosphate but not farnesyl pyrophosphate and squalene. Finally, we found that apoptosis may be involved in adipocyte death induced by HMGCR down-regulation. Our findings indicate that the mevalonate pathway is essential for adipocytes and further suggest that this pathway is an important regulator of adipocyte turnover.

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