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1.
ACS Appl Mater Interfaces ; 16(12): 14421-14433, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38497587

RESUMO

Injectable antibacterial and osteoinductive hydrogels have received considerable attention for promoting bone regeneration owing to their versatile functionalities. However, a current hydrogel with antibacterial, osteoinductive, and antioxidant properties by a facile method for periodontitis treatment is still missing. To overcome this issue, we designed an injectable hydrogel system (GPM) composed of gelatin, Ti3C2Tx MXene nanosheets, and poly-l-lysine using a simple enzymatic cross-linking technique. Physicochemical characterization demonstrated that the GPM hydrogel matrix exhibited excellent stability, moderate tissue adhesion ability, and good mechanical behavior. The GPM hydrogels significantly inhibited the growth of Porphyromonas gingivalis, scavenged reactive oxygen species, attenuated inflammatory responses, and enhanced bone tissue regeneration. Intriguingly, the arrangement of the junctional epithelium, alveolar bone volume, and alveolar bone height in the GPM-treated periodontal disease group recovered to that of the healthy group. Therefore, our injectable hydrogel system with versatile functions may serve as an excellent tissue scaffold for the treatment of periodontitis.


Assuntos
Periodontite , Humanos , Nanogéis , Espécies Reativas de Oxigênio , Periodontite/tratamento farmacológico , Hidrogéis/farmacologia , Hidrogéis/química , Antibacterianos/farmacologia
2.
ACS Appl Mater Interfaces ; 16(5): 5486-5503, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38284176

RESUMO

Cranial bone defects remain a major clinical challenge, increasing patients' life burdens. Tricarboxylic acid (TCA) cycle metabolites play crucial roles in facilitating bone tissue regeneration. However, the development of TCA cycle metabolite-modified biomimetic grafts for skull bone regeneration still needs to be improved. The mechanism underlying the release of TCA cycle metabolites from biomaterials in regulating immune responses and mesenchymal stem cell (MSC) fate (migration and differentiation) remains unknown. Herein, this work constructs biomimetic hydrogels composed of gelatin and chitosan networks covalently cross-linked by genipin (CGG hydrogels). A series of TCA cycle metabolite-coordinated CGG hydrogels with strong mechanical and antiswelling performances are subsequently developed. Remarkably, the citrate (Na3Cit, Cit)-coordinated CGG hydrogels (CGG-Cit hydrogels) with the highest mechanical modulus and strength significantly promote skull bone regeneration in rat and murine cranial defects. Mechanistically, using a transgenic mouse model, bulk RNA sequencing, and single-cell RNA sequencing, this work demonstrates that CGG-Cit hydrogels promote Gli1+ MSC migration via neutrophil-secreted oncostatin M. Results also indicate that citrate improves osteogenesis via enhanced histone H3K9 acetylation on osteogenic master genes. Taken together, the immune microenvironment- and MSC fate-regulated CGG-Cit hydrogels represent a highly efficient and facile approach toward skull bone tissue regeneration with great potential for bench-to-bedside translation.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Humanos , Ratos , Camundongos , Animais , Histonas , Ciclo do Ácido Cítrico , Acetilação , Neutrófilos/metabolismo , Regeneração Óssea , Crânio/metabolismo , Diferenciação Celular , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Citratos
3.
Clin Res Hepatol Gastroenterol ; 47(7): 102157, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37321321

RESUMO

BACKGROUND: Recurrent hepatocellular carcinoma (RHCC) is commonly treated with transcatheter arterial chemoembolization (TACE) combined with microwave ablation (MWA) or repeated hepatectomy(RH), but the optimal treatment strategy is still controversial. This study aimed to compare the efficacy and safety of TACE-MWA and RH in RHCC patients after initial radical hepatectomy. METHODS: A total of 210 RHCC patients were included between June 2014 and January 2021, with 126 patients in the TACE-MWA group and 84 patients in the RH group. The primary endpoints were median repeat recurrence-free survival (rRFS) and overall survival (OS), and the secondary endpoint was complications. Propensity-score matching (PSM) was conducted to minimize bias. Subgroup analysis based on recurrence patterns (recurrence time and tumor size) was performed, and prognostic factors were studied. RESULTS: Before PSM, the RH group had better median OS (37.0 vs 26.0 months, P<0.001) and rRFS (15.0 vs 14.0 months, P = 0.003). After PSM, the RH group also had a better median OS (33.5 vs 29.0 months, P = 0.038), but there was no significant difference in median rRFS between the two groups (14.0 vs 13.0 months, P = 0.099). Subgroup analysis showed that when RHCC diameter>5 cm, RH had a better median OS (33.5 vs 25.0 months, P = 0.013) and rRFS (14.0 vs 10.9 months, P = 0.030). When the RHCC diameter was≤5 cm, there was no significant difference in the median OS (37.0 vs 31.0 months, P = 0.338) and rRFS (15.0 vs 17.0 months, P = 0.758) between the two groups. When RHCC relapses in the early stage (≤2 years), there is no significant difference in the median OS (26.0 vs 26.0 months, P = 0.310) and rRFS (12.0 vs 10.5 months, P = 0.089) between the two groups. When RHCC relapses in the late stage (>2 years), the RH group has better median OS (41.0 vs 33.0 months, P<0.001) and rRFS (30.0 vs 20.0 months, P = 0.010). CONCLUSION: Individualized therapy is necessary for RHCC. TACE -MWA may be a good choice for RHCC with early recurrence or tumor diameter ≤5 cm. However, RH should be the first choice for RHCC with late recurrence or tumor diameter>5 cm.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Pontuação de Propensão , Resultado do Tratamento , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia
4.
ACS Appl Mater Interfaces ; 15(26): 31243-31255, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37350582

RESUMO

Increased intracranial pressure after traumatic brain injury (TBI) is an urgent problem in clinical practice. A pliable hydrogel is preferred for cranioplasty applications after TBI since it can protect brain tissue and promote bone healing. Nevertheless, biohydrogels for cranial bone regeneration still face challenges of poor mechanical properties, large swelling ratios, and low osteogenesis activity. Herein, inspired by Hofmeister effects, biopolymer hydrogels composed of protein and polysaccharides were treated with a Hofmeister series including a series of monovalent and divalent anions. Our results reveal that the divalent anion-cross-linked biohydrogels exhibit stronger mechanical properties and lower swelling ratios compared with monovalent-anion treated gels. Intriguingly, the divalent HPO42- anion induced biohybrid hydrogels with excellent mechanical behaviors (3.7 ± 0.58 MPa, 484 ± 76.7 kPa, and 148.3 ± 6.85 kJ/m3), anti-swelling capability (16.7%), and gradual degradation ability, significantly stimulating osteogenic differentiation and in vivo cranial bone regeneration. Overall, this study may provide new insights into the design of biomimetic hydrogels for treating cranial bone defects after TBI.


Assuntos
Regeneração Óssea , Osteogênese , Crânio , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Encéfalo
5.
Aging Dis ; 14(5): 1511-1532, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37196113

RESUMO

Cells are constantly exposed to various mechanical environments; therefore, it is important that they are able to sense and adapt to changes. It is known that the cytoskeleton plays a critical role in mediating and generating extra- and intracellular forces and that mitochondrial dynamics are crucial for maintaining energy homeostasis. Nevertheless, the mechanisms by which cells integrate mechanosensing, mechanotransduction, and metabolic reprogramming remain poorly understood. In this review, we first discuss the interaction between mitochondrial dynamics and cytoskeletal components, followed by the annotation of membranous organelles intimately related to mitochondrial dynamic events. Finally, we discuss the evidence supporting the participation of mitochondria in mechanotransduction and corresponding alterations in cellular energy conditions. Notable advances in bioenergetics and biomechanics suggest that the mechanotransduction system composed of mitochondria, the cytoskeletal system, and membranous organelles is regulated through mitochondrial dynamics, which may be a promising target for further investigation and precision therapies.

6.
Panminerva Med ; 65(4): 506-510, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33860654

RESUMO

INTRODUCTION: Hepatocellular carcinoma (HCC) is the sixth most common cancer globally, and a major unresolved medical issue. According to the guideline recommendations of the European Association for the Study of the Liver in 2018 and the American Society for Clinical Oncology (ASCO) Guideline, nivolumab is a reasonable option for appropriate advanced stage HCC. EVIDENCE ACQUISITION: We searched the PubMed, Embase and CNKI (China National Knowledge Infrastructure) databases for all articles within a range of published years from 2010 to 2020 of nivolumab in advanced hepatocellular carcinoma and carried out this meta-analysis on all published studies to estimate prognostic factors of nivolumab in advanced hepatocellular carcinoma. EVIDENCE SYNTHESIS: Finally, 6 studies with 627 advanced hepatocellular carcinoma patients treated with nivolumab met the inclusion criteria for this study. Our results indicated that α-fetoprotein (AFP), eastern Cooperative Oncology Group (ECOG) performance status, Child­Pugh Class, portal vein invasion, protein induced by vitamin K absence­II (PIVKA­II), and albumin­bilirubin (ALBI) score were prognostic factor of nivolumab in advanced hepatocellular carcinoma; however, hepatitis C virus (HBV) infection, Barcelona Clinic Liver Cancer (BCLC) stage, and extrahepatic metastasis were not significant prognostic factors. CONCLUSIONS: Our meta-analysis indicated the potential prognostic factor of nivolumab in advanced hepatocellular carcinoma. However, ongoing clinical and translational research may provide us a better understanding of the prognostic factor and mechanisms.


Assuntos
Carcinoma Hepatocelular , Hepatite C , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Nivolumabe/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Prognóstico , Estudos Retrospectivos
7.
Front Cell Dev Biol ; 11: 1261117, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38567385

RESUMO

The coordination between actin and microtubule network is crucial, yet this remains a challenging problem to dissect and our understanding of the underlying mechanisms remains limited. In this study, we used travelling waves in the cell cortex to characterize the collective dynamics of cytoskeletal networks. Our findings show that Cdc42 and F-BAR-dependent actin waves in mast cells are mainly driven by formin-mediated actin polymerization, with the microtubule-binding formin FH2 domain-containing protein 1 (FHDC1) as an early regulator. Knocking down FHDC1 inhibits actin wave formation, and this inhibition require FHDC1's interaction with both microtubule and actin. The phase of microtubule depolymerization coincides with the nucleation of actin waves and microtubule stabilization inhibit actin waves, leading us to propose that microtubule shrinking and the concurrent release of FHDC1 locally regulate actin nucleation. Lastly, we show that FHDC1 is crucial for multiple cellular processes such as cell division and migration. Our data provided molecular insights into the nucleation mechanisms of actin waves and uncover an antagonistic interplay between microtubule and actin polymerization in their collective dynamics.

8.
Front Immunol ; 11: 459, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32292404

RESUMO

The c-Jun NH2-terminal kinases (JNKs) are an evolutionarily conserved family of serine/threonine protein kinases that play critical roles in the pathological process in species ranging from insects to mammals. However, the function of JNKs in bacteria-induced intestinal inflammation is still poorly understood. In this study, a fish JNK (CiJNK) pathway was identified, and its potential roles in bacterial muramyl dipeptide (MDP)-induced intestinal inflammation were investigated in Ctenopharyngodon idella. The present CiJNK was found to possess a conserved dual phosphorylation motif (TPY) in a serine/threonine protein kinase (S_TKc) domain and to contain several potential immune-related transcription factor binding sites, including nuclear factor kappa B (NF-κB), activating protein 1 (AP-1), and signal transducer and activator of downstream transcription 3 (STAT3), in its 5' flanking regions. Quantitative real-time PCR results revealed that the mRNA levels of the JNK pathway genes in the intestine were significantly upregulated after challenge with a bacterial pathogen (Aeromonas hydrophila) and MDP in a time-dependent manner. Additionally, the JNK pathway was found to be involved in regulating the MDP-induced expression levels of inflammatory cytokines (IL-6, IL-8, and TNF-α) in the intestine of grass carp. Moreover, the nutritional dipeptide carnosine and Ala-Gln could effectively alleviate MDP-induced intestinal inflammation by regulating the intestinal expression of JNK pathway genes and inflammatory cytokines in grass carp. Finally, fluorescence microscopy and dual-reporter assays indicated that CiJNK could associate with CiMKK4 and CiMKK7 involved in the regulation of the AP-1 signaling pathway. Overall, these results provide the first experimental demonstration that the JNK signaling pathway is involved in the intestinal immune response to MDP challenge in C. idella, which may provide new insight into the pathogenesis of inflammatory bowel disease.


Assuntos
Aeromonas hydrophila/fisiologia , Carpas/metabolismo , Infecções por Bactérias Gram-Negativas/metabolismo , Inflamação/metabolismo , Intestinos/imunologia , Acetilmuramil-Alanil-Isoglutamina/imunologia , Animais , Antígenos de Bactérias/imunologia , Carpas/microbiologia , Citocinas/metabolismo , Proteínas de Peixes/metabolismo , Mediadores da Inflamação/metabolismo , MAP Quinase Quinase 4/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo
9.
Front Physiol ; 11: 79, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32116786

RESUMO

Oligopeptide transporter 1 (Pept1) is located on the brush border membrane of the intestinal epithelium and plays an important role in dipeptide and tripeptide absorption from protein digestion. In this study, we cloned and characterized the cDNA sequence of Janus kinase 2 (JAK2) from Ctenopharyngodon idella. The expression patterns of JAK2 in various tissues and developmental stages were characterized by quantitative real-time PCR (qRT-PCR). The mRNA expression levels of JAK2 and Pept1 regulated by leptin in the intestine were also analyzed in vitro and in vivo. The cDNA sequence of JAK2 is 3378 bp in length, and the mRNA of JAK2 was broadly expressed in all tissues and embryonic stages of C. idella analyzed. In addition, we found that leptin regulated expression of JAK2 and Pept1 in the intestine; Pept1 expression was down-regulated by the JAK2 inhibitor AG490 in vivo and in vitro. Furthermore, luciferase experiments showed that overexpression of the JAK2 gene significantly upregulated the activity of the Pept1 5' regulatory sequence in C. idella. In conclusion, these results may help in elucidating the regulatory effect of the leptin-mediated JAK2 pathway on intestinal Pept1 expression in C. idella and the molecular mechanism of peptide transport by the intestinal transporter Pept1 in fishes.

10.
Proc Natl Acad Sci U S A ; 116(44): 22347-22352, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31611410

RESUMO

Observing the structure and regeneration of the myelin sheath in peripheral nerves following injury and during repair would help in understanding the pathogenesis and treatment of neurological diseases caused by an abnormal myelin sheath. In the present study, transmission electron microscopy, immunofluorescence staining, and transcriptome analyses were used to investigate the structure and regeneration of the myelin sheath after end-to-end anastomosis, autologous nerve transplantation, and nerve tube transplantation in a rat model of sciatic nerve injury, with normal optic nerve, oculomotor nerve, sciatic nerve, and Schwann cells used as controls. The results suggested that the double-bilayer was the structural unit that constituted the myelin sheath. The major feature during regeneration was the compaction of the myelin sheath, wherein the distance between the 2 layers of cell membrane in the double-bilayer became shorter and the adjacent double-bilayers tightly closed together and formed the major dense line. The expression level of myelin basic protein was positively correlated with the formation of the major dense line, and the compacted myelin sheath could not be formed without the anchoring of the lipophilin particles to the myelin sheath.


Assuntos
Bainha de Mielina/ultraestrutura , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/metabolismo , Animais , Axônios/metabolismo , Axônios/ultraestrutura , Bainha de Mielina/metabolismo , Traumatismos dos Nervos Periféricos/patologia , Ratos
11.
Artigo em Inglês | MEDLINE | ID: mdl-31176866

RESUMO

Cysteine oxygenase (CDO) is a mononuclear nonhemoglobin enzyme that catalyzes the production of taurine through the cysteine (Cys) pathway and plays a key role in the biosynthesis of taurine in mammals. However, the function of CDOs in bony fish remains poorly understood. In this study, we cloned CDO genes (CaCDO1 and CaCDO2) from Carassius auratus. The cDNA sequences of both CaCDO1 and CaCDO2 encoded putative proteins with 201 amino acids, which included structural features typical of the CDO protein family. Multiple sequence alignment and phylogenetic analysis showed that CaCDO1 and CaCDO2 shared high sequence identities and similarities with C. carpio homologs. Quantitative real-time polymerase chain reaction (qRT-PCR) results revealed that CaCDO1 and CaCDO2 were both broadly expressed in all selected tissues and developmental stages in C. auratus but had differing mRNA levels. In addition, compared to those of the taurine-free group, the in vivo mRNA expression levels of both CaCDO1 and CaCDO2 significantly decreased with increasing dietary taurine levels from 1.0 to 9.0 g/kg. Furthermore, in vitro taurine treatments showed similar inhibitory effects on the expression of CaCDO1 and CaCDO2 in the intestines of C. auratus. Our results also showed that the mRNA expression of CaCDO2 in the intestines was higher than that of CaCDO1 in response to in vivo and in vitro taurine supplementation. Overall, these data may provide new insights into the regulation of fish CDO expression and provide valuable knowledge for improving dietary formulas in aquaculture.


Assuntos
Cisteína Dioxigenase/genética , Cisteína Dioxigenase/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Carpa Dourada/genética , Carpa Dourada/metabolismo , Taurina/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA Complementar/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Carpa Dourada/crescimento & desenvolvimento , Isoenzimas/genética , Isoenzimas/metabolismo , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Taurina/farmacologia , Distribuição Tecidual
12.
Fish Shellfish Immunol ; 84: 795-801, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30393177

RESUMO

Mitogen-activated protein kinase kinase 6 (MKK6) is an essential component of the p38MAPK signaling pathway, which is involved in the modulation of inflammation, cell apoptosis and survival responses in mammals. However, the function of MKK6s in teleosts is still unclear. In this study, a fish MKK6 homolog (CiMKK6) was first identified from the grass carp (Ctenopharyngodon idella), a freshwater fish. CiMKK6 cDNA encodes a putative protein of 357 amino acids that contains conserved structural characteristics of the MKK6 family, including the S_TKc domain, SVAKT motif and DVD site. The deduced CiMKK6 protein exhibits high sequence homology with other reported fish MKK6s and shares the closest relationship with MKK6 from Danio rerio. Quantitative real-time PCR (qRT-PCR) analysis revealed that CiMKK6 mRNA was widely expressed in all tested tissues and stages of embryonic development. Additionally, the transcript levels of CiMKK6 in the intestine were significantly upregulated in response to bacterial muramyl dipeptide (MDP) and L-Ala-γ-D-Glu-meso-diaminopimelic acid (Tri-DAP) stimulation. Moreover, subcellular localization analysis indicated that CiMKK6 was distributed in both the cytoplasm and the nucleus of HEK293T cells. Finally, overexpression of CiMKK6 significantly enhanced the transcriptional activity of the AP-1 reporter gene in HEK293T cells. Overall, these findings may help better clarify the immune function of teleost MKK6s and provide new insight into the immune defense mechanisms of grass carp.


Assuntos
Proteínas de Bactérias/imunologia , Carpas/genética , Carpas/imunologia , Imunidade Inata/genética , MAP Quinase Quinase 6/genética , Animais , Proteínas de Bactérias/administração & dosagem , Dipeptídeos/administração & dosagem , Dipeptídeos/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Células HEK293 , Humanos , MAP Quinase Quinase 6/metabolismo , Oligopeptídeos/administração & dosagem , Oligopeptídeos/imunologia , Distribuição Aleatória
13.
Nano Lett ; 18(10): 6255-6264, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30193069

RESUMO

Grain refinement to the nano/ultrafine-grained regime can make metals several times stronger, but this process is usually accompanied by a dramatic loss of ductility. Such strength-ductility trade-off originates from a lack of strain-hardening capacity in tiny grains. Here, we present a strategy to regain the strain-hardening ability of high-strength metals by incorporation of extrinsic nanofillers at grain boundaries. We demonstrate that the dislocation storage ability in Cu grains can be considerably improved through this novel grain-boundary engineering approach, leading to a remarkably enhanced strain-hardening capacity and tensile ductility (uniform elongation). Experiments and large-scale atomistic simulations reveal that a key benefit of incorporated nanofillers is a reduction in the grain-boundary energy, enabling concurrent dislocation storage near the boundaries and in the Cu grain interior during straining. The strategy of grain-boundary engineering through nanofillers is easily controllable, generally applicable, and may open new avenues for producing nanostructured metals with extraordinary mechanical properties.

14.
FASEB J ; 32(1): 289-303, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28883043

RESUMO

Free fatty acid receptors 2 and 3 (FFAR2/FFA2/GPR43 and FFAR3/FFA3/GPR41) are mammalian receptors for gut microbiota-derived short-chain fatty acids (SCFAs). These receptors are promising drug targets for obesity, colitis, colon cancer, asthma, and arthritis. Here, we demonstrate that FFAR2 and FFAR3 interact to form a heteromer in primary human monocytes and macrophages via proximity ligation assay, and during heterologous expression in HEK293 cells via bimolecular fluorescence complementation and fluorescence resonance energy transfer. The FFAR2-FFAR3 heteromer displayed enhanced cytosolic Ca2+ signaling (1.5-fold increase relative to homomeric FFAR2) and ß-arrestin-2 recruitment (30-fold increase relative to homomeric FFAR3). The enhanced heteromer signaling was attenuated by FFAR2 antagonism (CATPB), Gαq inhibition (YM254890), or Gαi inhibition (pertussis toxin). Unlike homomeric FFAR2/3, the heteromer lacked the ability to inhibit cAMP production but gained the ability to induce p38 phosphorylation in HEK293 and inflammatory monocytes via a CATPB- and YM254890-sensitive mechanism. Our data, taken together, reveal that FFAR2 and FFAR3 may interact to form a receptor heteromer with signaling that is distinct from the parent homomers-a novel pathway for drug targeting.-Ang, Z., Xiong, D., Wu, M., Ding, J. L. FFAR2-FFAR3 receptor heteromerization modulates short-chain fatty acid sensing.


Assuntos
Ácidos Graxos Voláteis/metabolismo , Receptores de Superfície Celular/química , Receptores de Superfície Celular/metabolismo , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Sinalização do Cálcio , Colite/metabolismo , AMP Cíclico/biossíntese , Transferência Ressonante de Energia de Fluorescência , Células HEK293 , Humanos , Macrófagos/metabolismo , Obesidade/metabolismo , Fosforilação , Multimerização Proteica , Receptores de Superfície Celular/genética , Receptores Acoplados a Proteínas G/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , beta-Arrestina 2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Dev Cell ; 43(4): 507-521.e4, 2017 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-29161594

RESUMO

Assembly of the endocytic machinery is a constitutively active process that is important for the organization of the plasma membrane, signal transduction, and membrane trafficking. Existing research has focused on the stochastic nature of endocytosis. Here, we report the emergence of the collective dynamics of endocytic proteins as periodic traveling waves on the cell surface. Coordinated clathrin assembly provides the earliest spatial cue for cortical waves and sets the direction of propagation. Surprisingly, the onset of clathrin waves, but not individual endocytic events, requires feedback from downstream factors, including FBP17, Cdc42, and N-WASP. In addition to the localized endocytic assembly at the plasma membrane, intracellular clathrin and phosphatidylinositol-3,4-bisphosphate predict the excitability of the plasma membrane and modulate the geometry of traveling waves. Collectively, our data demonstrate the multiplicity of clathrin functions in cortical pattern formation and provide important insights regarding the nucleation and propagation of single-cell patterns.


Assuntos
Membrana Celular/metabolismo , Clatrina/metabolismo , Endocitose/fisiologia , Actinas/metabolismo , Animais , Proteínas de Transporte/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Transporte Proteico
16.
Sci Rep ; 6: 33801, 2016 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-27647264

RESUMO

By using CuO/graphene-oxide/CuO sandwich-like nanosheets as the building blocks, bulk nacre-inspired copper matrix nano-laminated composite reinforced by molecular-level dispersed and ordered reduced graphene oxide (rGO) with content as high as ∼45 vol% was fabricated via a combined process of assembly, reduction and consolidation. Thanks to nanoconfinement effect, reinforcing effect, as well as architecture effect, the nanocomposite shows increased specific strength and at least one order of magnitude greater recoverable deformation ability as compared with monolithic Cu matrix.

17.
Nanoscale ; 8(12): 6636-45, 2016 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-26939904

RESUMO

Aqueous hybrid capacitors (HCs) suffer from sacrificed power density and long cycle life due to the insufficient electric conductivity and poor chemical stability of the battery-type electrode material. Herein, we report a novel NH4-Co-Ni phosphate with a stable hierarchical structure combining ultrathin nanopieces and single crystal microplatelets in one system, which allows for a synergistic integration of two microstructures with different length scales and different energy storage mechanisms. The microplatelets with a stable single crystal structure store charge through the intercalation of hydroxyl ions, while the ultrathin nanopieces store charge through surface redox reaction providing enhanced specific capacitance. Furthermore, the large single crystal can bridge the small nanopieces forming continuous electronic conduction paths as well as ionic conduction channels, and facilitate both electron and ion transportation in the hierarchical structure. The HC cell based on the as prepared material and a 3D hierarchical porous carbon delivers a high energy density of 29.6 Wh kg(-1) at a high power density of 11 kW kg(-1). Particularly, an ultralong cycle life along with 93.5% capacitance retention after 10,000 charge-discharge cycles is achieved, which is outstanding among the state-of-the-art aqueous HC cells.

19.
Sci Rep ; 6: 17613, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26833204

RESUMO

A novel hybridized phosphate is developed through a mild hydrothermal method to construct high performance asymmetric supercapacitor. Single layered (Ni,Co)3(PO4)2·8H2O nanoslices (∼1 nm) and single crystal (NH4)(Ni,Co)PO4·0.67H2O microplatelets are obtained through a template sacrificial method and dissolution recrystallization approach respectively in one step. This unique hybridized structure delivers a maximum specific capacitance of 1128 F g(-1) at current density of 0.5 A g(-1). The asymmetric supercapacitor (ASC) based on the hybrid exhibits a high energy density of 35.3 Wh kg(-1) at low power density, and still holds 30.9 Wh kg(-1) at 4400 W kg(-1). Significantly, the ASC manifests very high cycling stability with 95.6% capacitance retention after 5000 cycles. Such excellent electrochemical performance could be attributed to the synergistic effect of the surface redox reaction from the ultrathin nanoslices and ion intercalation from the single crystal bulk structure. This material represents a novel kind of electrode material for the potential application in supercapacitors.

20.
ACS Appl Mater Interfaces ; 8(3): 1992-2000, 2016 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-26742692

RESUMO

Nanolayered structures present significantly enhanced electrochemical performance by facilitating the surface-dependent electrochemical reaction processes for supercapacitors, which, however, causes capacitance fade upon cycling due to their poor chemical stability. In this work, we report a simple and effective approach to develop a stable, high performance electrode material by integrating 2D transition metal hydroxide and reduced graphene oxide sheets at nanometer scale. Specifically, a hybrid nanolayer of Ni-Co hydroxide @reduced graphene oxide (Ni,Co-OH/rGO) with an average thickness of 1.37 nm is synthesized through an easy one-pot hydrothermal method. Benefiting from the face to face contact model between Ni-Co hydroxide and rGO sheets, such unique structure presents superior specific capacitance and cycling performance as compared to the pure Ni-Co hydroxide nanolayers. An asymmetric supercapacitor based on Ni,Co-OH/rGO and three-dimensional (3D) hierarchical porous carbon is developed, exhibiting a high energy density of 56.1 Wh kg(-1) along with remarkable cycling stability (80% retention after 17 000 cycles), which holds great promise for practical applications in energy storage devices.

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