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1.
Proc Natl Acad Sci U S A ; 119(34): e2202835119, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35969765

RESUMO

Aprotic Li-O2 batteries are a promising energy storage technology, however severe side reactions during cycles lead to their poor rechargeability. Herein, highly reactive singlet oxygen (1O2) is revealed to generate in both the discharging and charging processes and is deterimental to battery stability. Electron-rich triphenylamine (TPA) is demonstrated as an effective quencher in the electrolyte to mitigate 1O2 and its associated parasitic reactions, which has the tertiary amine and phenyl groups to manifest excellent electrochemical stability and chemical reversibility. It reacts with electrophilic 1O2 to form a singlet complex during cycles, and it then quickly transforms to a triplet complex through nonradiative intersystem crossing (ISC). This efficiently accelerates the conversion of 1O2 to the ground-state triplet oxygen to eliminate its derived side reactions, and the regeneration of TPA. These enable the Li-O2 battery with obviously reduced overvoltages and prolonged lifetime for over 310 cycles when coupled with a RuO2 catalyst. This work highlights the ISC mechanism to quench 1O2 in Li-O2 battery.

2.
Proc Natl Acad Sci U S A ; 118(17)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33879619

RESUMO

Aprotic lithium-oxygen (Li-O2) batteries have gained extensive interest in the past decade, but are plagued by slow reaction kinetics and induced large-voltage hysteresis. Herein, we use a plasmonic heterojunction of Au nanoparticle (NP)-decorated C3N4 with nitrogen vacancies (Au/NV-C3N4) as a bifunctional catalyst to promote oxygen cathode reactions of the visible light-responsive Li-O2 battery. The nitrogen vacancies on NV-C3N4 can adsorb and activate O2 molecules, which are subsequently converted to Li2O2 as the discharge product by photogenerated hot electrons from plasmonic Au NPs. While charging, the holes on Au NPs drive the reverse decomposition of Li2O2 with a reduced applied voltage. The discharge voltage of the Li-O2 battery with Au/NV-C3N4 is significantly raised to 3.16 V under illumination, exceeding its equilibrium voltage, and the decreased charge voltage of 3.26 V has good rate capability and cycle stability. This is ascribed to the plasmonic hot electrons on Au NPs pumped from the conduction bands of NV-C3N4 and the prolonged carrier life span of Au/NV-C3N4 This work highlights the vital role of plasmonic enhancement and sheds light on the design of semiconductors for visible light-mediated Li-O2 batteries and beyond.

3.
J Am Chem Soc ; 145(3): 1564-1571, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36635874

RESUMO

Metal-organic frameworks (MOFs) are emerging as attractive electrode materials for lithium-ion batteries, owing to their fascinating features of sustainable resources, tunable chemical components, flexible molecular skeletons, and renewability. However, they are faced with a limited number of redox-active sites and unstable molecular frameworks during electrochemical processes. Herein, we design a novel two-dimensional (2D) iron(III)-tetraamino-benzoquinone (Fe-TABQ) with dual redox centers of Fe cations and TABQ ligands for high-capacity and stable lithium storage. It is constructed of square-planar Fe-N2O2 linkages and phenylenediamine building blocks, between which the Fe-TABQ chains are connected by multiple hydrogen bonds, and then featured as an extended π-d-conjugated 2D structure. The redox chemistry of both Fe3+ cations and TABQ anions is revealed to render its remarkable specific capacity of 251.1 mAh g-1. Benefiting from the intrinsic robust Fe-N(O) bonds and reinforced Li-N(O) bonds during cycling, Fe-TABQ delivers high capacity retentions over 95% after 200 cycles at various current densities. This work will enlighten more investigations for the molecular designs of advanced MOF-based electrode materials.

4.
Small ; 19(49): e2304187, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37603387

RESUMO

Layered manganese-based oxides (LMOs) are promising cathode materials for sodium-ion batteries (SIBs) due to their versatile structures. However, the Jahn-Teller effect of Mn3+ induces severe distortion of MnO6 octahedra, and the resultant low symmetry is responsible for the gliding of MnO2 layers and then inferior multiple-phase transitions upon Na+ extraction/insertion. Here, hexagonal P2-Na0.643 Li0.078 Mn0.827 Ti0.095 O2 is synthesized through the incorporation of Li and Ti into the distorted orthorhombic P'2-Na0.67 MnO2 to function as a phase-transition-free oxide cathode. It is revealed that Li in both the transition-metal and Na layers enhances the covalency of Mn-O bonds and allows degeneracy of Mn 3d eg orbitals to favor the formation of hexagonal phase, and the high strength of Ti-O bonds reduces the electrostatic interaction between Na and O for suppressed Na+ /vacancy rearrangements. These collectively lead to a whole-voltage-range solid-solution reaction between 1.8 and 4.3 V with a small volume variation of 1.49%. This rewards its excellent cycling stability (capacity retention of 90% after 500 cycles) and rate capability (89 mAh g-1 at 2000 mA g-1 ).

5.
FASEB J ; 36(11): e22599, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36250902

RESUMO

Emerging evidence suggest that C3aR plays important roles in homeostasis, host defense and disease. Although it is known that C3aR is protective in several models of acute bacterial infections, the role for C3aR in chronic infection is largely unknown. Here we show that C3aR is protective in experimental chronic pyelonephritis. Global C3aR deficient (C3ar-/- ) mice had higher renal bacterial load, more pronounced renal histological lesions, increased renal apoptotic cell accumulation, tissue inflammation and extracellular matrix deposition following renal infection with uropathogenic E. coli (UPEC) strain IH11128, compared to WT control mice. Myeloid C3aR deficient (Lyz2-C3ar-/- ) mice exhibited a similar disease phenotype to global C3ar-/- mice. Pharmacological treatment with a C3aR agonist reduced disease severity in experimental chronic pyelonephritis. Furthermore, macrophages of C3ar-/- mice exhibited impaired ability to phagocytose UPEC. Our data clearly demonstrate a protective role for C3aR against experimental chronic pyelonephritis, macrophage C3aR plays a major role in the protection, and C3aR is necessary for phagocytosis of UPEC by macrophages. Our observation that C3aR agonist curtailed the pathology suggests a therapeutic potential for activation of C3aR in chronic infection.


Assuntos
Infecções por Escherichia coli , Pielonefrite , Receptores de Complemento , Animais , Camundongos , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/patologia , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia , Rim/microbiologia , Rim/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Pielonefrite/imunologia , Pielonefrite/microbiologia , Pielonefrite/patologia , Pielonefrite/prevenção & controle , Escherichia coli Uropatogênica/patogenicidade , Receptores de Complemento/agonistas , Receptores de Complemento/deficiência , Receptores de Complemento/genética , Receptores de Complemento/imunologia , Matriz Extracelular/metabolismo
6.
Mol Cell Proteomics ; 20: 100013, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33568340

RESUMO

Aspergillus flavus (A. flavus), a pathogenic fungus, can produce carcinogenic and toxic aflatoxins that are a serious agricultural and medical threat worldwide. Attempts to decipher the aflatoxin biosynthetic pathway have been hampered by the lack of a high-quality genome annotation for A. flavus. To address this gap, we performed a comprehensive proteogenomic analysis using high-accuracy mass spectrometry data for this pathogen. The resulting high-quality data set confirmed the translation of 8724 previously predicted genes and identified 732 novel proteins, 269 splice variants, 447 single amino acid variants, 188 revised genes. A subset of novel proteins was experimentally validated by RT-PCR and synthetic peptides. Further functional annotation suggested that a number of the identified novel proteins may play roles in aflatoxin biosynthesis and stress responses in A. flavus. This comprehensive strategy also identified a wide range of posttranslational modifications (PTMs), including 3461 modification sites from 1765 proteins. Functional analysis suggested the involvement of these modified proteins in the regulation of cellular metabolic and aflatoxin biosynthetic pathways. Together, we provided a high-quality annotation of A. flavus genome and revealed novel insights into the mechanisms of aflatoxin production and pathogenicity in this pathogen.


Assuntos
Aflatoxinas/metabolismo , Aspergillus flavus/genética , Proteínas Fúngicas/genética , Genoma Fúngico , Aspergillus flavus/metabolismo , Cromatografia Líquida , Proteínas Fúngicas/metabolismo , Peptídeos/metabolismo , Processamento de Proteína Pós-Traducional , Proteogenômica , Proteoma , Espectrometria de Massas em Tandem
7.
Chem Soc Rev ; 51(6): 1846-1860, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35195634

RESUMO

Rechargeable lithium-oxygen (Li-O2) batteries are promising energy storage devices due to their high theoretical energy density. However, the sluggish kinetics of the oxygen reduction and evolution reactions (ORR/OER) at the cathodes results in large polarization and low energy efficiency. Although advances have been achieved in electrode material designs and battery configurations, large discharge/charge voltage gaps remain. The introduction of light into Li-O2 batteries has been demonstrated to boost the reaction kinetics of the ORR/OER, leading to enhanced electrochemical performances, but the understanding of the photoelectrochemical process at oxygen cathodes is limited. This tutorial review focuses on the recent findings regarding photoinvolved oxygen cathodes, battery configurations, and the stability of Li-O2 batteries, aiming to provide a fundamental understanding of photoinvolved Li-O2 batteries. The challenges and perspectives are discussed in light of the interdisciplinary nature of photochemistry, materials chemistry, electrochemistry, computation, spectroscopy, and surface science.

8.
Angew Chem Int Ed Engl ; 62(31): e202305828, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37278545

RESUMO

Lithium-sulfur (Li-S) batteries are considered as promising candidates for next-generation energy storage systems in view of the high theoretical energy density and low cost of sulfur resources. The suppression of polysulfide diffusion and promotion of redox kinetics are the main challenges for Li-S batteries. Herein, we design and prepare a novel type of ZnCo-based bimetallic metal-organic framework nanoboxes (ZnCo-MOF NBs) to serve as a functional sulfur host for Li-S batteries. The hollow architecture of ZnCo-MOF NBs can ensure fast charge transfer, improved sulfur utilization, and effective confinement of lithium polysulfides (LiPSs). The atomically dispersed Co-O4 sites in ZnCo-MOF NBs can firmly capture LiPSs and electrocatalytically accelerate their conversion kinetics. Benefiting from the multiple structural advantages, the ZnCo-MOF/S cathode shows high reversible capacity, impressive rate capability, and prolonged cycling performance for 300 cycles.

9.
J Am Chem Soc ; 144(50): 23239-23246, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36474358

RESUMO

Non-aqueous Li-O2 batteries have aroused considerable attention because of their ultrahigh theoretical energy density, but they are severely hindered by slow cathode reaction kinetics and large overvoltages, which are closely associated with the discharge product of Li2O2. Herein, hexagonal conductive metal-organic framework nanowire arrays of nickel-hexaiminotriphenylene (Ni-HTP) with quadrilateral Ni-N4 units are synthesized to incorporate Ru atoms into its skeleton for NiRu-HTP. The atomically dispersed Ru-N4 sites manifest strong adsorption for the LiO2 intermediate owing to its tunable d-band center, leading to its high local concentration around NiRu-HTP. This favors the formation of film-like Li2O2 on NiRu-HTP with promoted electron transfer and ion diffusion across the cathode-electrolyte interface, facilitating its reversible decomposition during charge. These allow the Li-O2 battery with NiRu-HTP to deliver a remarkably reduced charge/discharge polarization of 0.76 V and excellent cyclability. This work will enrich the design philosophy of electrocatalysts for regulation of kinetic behaviors of oxygen redox.

10.
Environ Microbiol ; 24(11): 5596-5610, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36059183

RESUMO

Aspergillus flavus is a ubiquitous saprotrophic soil-borne pathogenic fungus that causes crops contamination with the carcinogen aflatoxins. Although sirtuin E (SirE) is known to be a NAD-dependent histone deacetylase involved in global transcriptional regulation. Its biological functions in A. flavus are not fully understood. To explore the effects of SirE, we found that SirE was located in the nucleus and increased the level of H3K56 acetylation. The ΔsirE mutant had the most severe growth defect in the sirtuin family. The RNA-Seq revealed that sirE was crucial for secondary metabolism production as well as genetic information process and oxidation-reduction in A. flavus. Further analysis revealed that the ΔsirE mutant increased aflatoxin production. Both the sirE deletion and H3K56 mutants were highly sensitive to DNA damage and oxidative stresses, indicating that SirE was required for DNA damage and redox reaction by the H3K56 locus. Furthermore, the ΔsirE mutant displayed high sensitivity to osmotic stress and cell wall stress, but they may not be associated with the H3K56. Finally, the catalytic activity site N192 of SirE was required for regulating growth, deacetylase function and aflatoxin production. Together, SirE is essential for histone deacetylation and biological function in A. flavus.


Assuntos
Aflatoxinas , Sirtuínas , Aspergillus flavus/metabolismo , Aflatoxinas/genética , Sirtuínas/genética , Sirtuínas/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Dano ao DNA
11.
Chem Eng J ; 438: 135589, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35261557

RESUMO

Nearly 200 million people have been diagnosed with COVID-19 since the outbreak in 2019, and this disease has claimed more than 5 million lives worldwide. Currently, researchers are focusing on vaccine development and the search for an effective strategy to control the infection source. This work designed a detection platform based on Surface-Enhanced Raman Spectroscopy (SERS) by introducing acetonitrile and calcium ions into the silver nanoparticle reinforced substrate system to realize the rapid detection of novel coronavirus. Acetonitrile may amplify the calcium-induced hot spots of silver nanoparticles and significantly enhanced the stability of silver nanoparticles. It also elicited highly sensitive SERS signals of the virus. This approach allowed us to capture the characteristic SERS signals of SARS-CoV-2, Human Adenovirus 3, and H1N1 influenza virus molecules at a concentration of 100 copies/test (PFU/test) with upstanding reproduction and signal-to-noise ratio. Machine learning recognition technology was employed to qualitatively distinguish the three virus molecules with 1000 groups of spectra of each virus. Acetonitrile is a potent internal marker in regulating the signal intensity of virus molecules in saliva and serum. Thus, we used the SERS peak intensity to quantify the virus content in saliva and serum. The results demonstrated a satisfactory linear relationship between peak intensity and protein concentration. Collectively, this rapid detection method has a broad application prospect in clinical diagnosis of viruses, management of emergent viral infectious diseases, and exploration of the interaction between viruses and host cells.

12.
Nano Lett ; 21(10): 4209-4216, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33970640

RESUMO

Passive cooling materials that spontaneously cool an object are promising choices for mitigating the global energy crisis. However, these cooling effects are usually weakened or lost when dust contaminates the surface structure, greatly restricting their applications. In this work, a robust hierarchical porous polytetrafluoroethylene (PTFE) film with coral-like micro/nanostructures is generated by a facile and efficient femtosecond laser ablation technique. Owing to its unique micro/nanostructures, the as-prepared surface exhibits an outstanding self-cleaning function for various liquids with ultralow adhesion. This self-cleaning characteristic enhances the durability of its passive cooling effect. It is demonstrated that the titanium (Ti) sheet covered with laser-ablated PTFE film can realize a maximum temperature decrease of 4 and 10 °C compared to the Ti sheet covered with pristine PTFE film and uncovered, respectively. This study reveals that femtosecond laser micromachining is a facile and feasible avenue to produce robust self-cleaning passive cooling devices.

13.
Angew Chem Int Ed Engl ; 61(30): e202205045, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35533111

RESUMO

Metallic Na is a promising anode for rechargeable batteries, however, it is plagued by an unstable solid electrolyte interphase (SEI) and Na dendrites. Herein, a robust anion-derived SEI is constructed on Na anode in a high-concentration 1,2-dimethoxyethane (DME) based electrolyte with a cosolvent hydrofluoroether, which effectively restrains Na dendrite growth. The hydrofluoroether can tune the solvation configuration of the electrolyte from three-dimensional network aggregates to solvent-cation-anion clusters, enabling more anions to enter and reinforce the inner solvation sheath and their stepwise decomposition. The gradient inorganic-rich SEI leads to a reduced energy barrier of Na+ migration and enhanced interfacial kinetics. These render the Na||Na3 V2 (PO4 )3 battery with an excellent rate capability of 79.9 mAh g-1 at 24 C and a high capacity retention of 94.2 % after 6000 cycles at 2 C. This highlights the modulation of the electrode-electrolyte interphase chemistry for advanced batteries.

14.
Angew Chem Int Ed Engl ; 61(8): e202114293, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-34921706

RESUMO

Aprotic Li-O2 batteries have attracted extensive attention in the past decade owing to their high theoretical energy density; however, they are obstructed by the sluggish reaction kinetics at the cathode and large voltage hysteresis. We regulate the spin state of partial Ni2+ metal centers (t2g 6 eg 2 ) of conductive nickel catecholate framework (NiII -NCF) nanowire arrays to high-valence Ni3+ (t2g 6 eg 1 ) for NiIII -NCF. The spin-state modulation enables enhanced nickel-oxygen covalency in NiIII -NCF, which facilitates electron exchange between the Ni sites and oxygen adsorbates and accelerates the oxygen redox kinetics. Upon discharging, the high affinity of Ni3+ sites with the intermediate LiO2 promotes formation of nanosheet-like Li2 O2 in the void space among NiIII -NCF nanowires. The Li-O2 battery based on NiIII -NCF offers remarkably reduced discharge/charge voltage gaps, superior rate capability, and a long cycling stability of over 200 cycles. This work highlights the importance of electron spin state on the redox kinetics and will provide insight into electronic structure regulation of electrocatalysts for Li-O2 batteries and beyond.

15.
Angew Chem Int Ed Engl ; 61(12): e202116699, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35018699

RESUMO

Li-O2 batteries have aroused considerable interest in recent years, however they are hindered by high kinetic barriers and large overvoltages at cathodes. Herein, a step-scheme (S-scheme) junction with hematite on carbon nitride (Fe2 O3 /C3 N4 ) is designed as a bifunctional catalyst to facilitate oxygen redox for a visible-light-involved Li-O2 battery. The internal electric field and interfacial Fe-N bonding in the heterojunction boost the separation and directional migration of photo-carriers to establish spatially isolated redox centers, at which the photoelectrons on C3 N4 and holes on Fe2 O3 remarkably accelerate the discharge and charge kinetics. These enable the Li-O2 battery with Fe2 O3 /C3 N4 to present an elevated discharge voltage of 3.13 V under illumination, higher than the equilibrium potential 2.96 V in the dark, and a charge voltage of 3.19 V, as well as superior rate capability and cycling stability. This work will shed light on rational cathode design for metal-O2 batteries.

16.
J Am Chem Soc ; 143(4): 1941-1947, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33467851

RESUMO

Li-O2 batteries are considered the ultimate energy storage technology for their potential to store large amounts of electrical energy in a cost-effective and simple platform. Large overpotentials for the formation and oxidation of Li2O2 during discharging and charging have thus far confined this technology to a scientific curiosity. Herein, we consider the role of catalytic intervention in the reversibility of the cathode reactions and find that semiconducting metal-organic polymer nanosheets composed of cobalt-tetramino-benzoquinone (Co-TABQ) function as a bifunctional catalyst that facilitates the kinetics of the cathode reactions under visible light. Upon discharging, we report that O2 is first adsorbed on the Co atoms of Co-TABQ and accepts electrons under illumination from the dz2 and dxz orbitals of Co atoms in the π2p* orbitals, which facilitates reduction to LiO2. The LiO2 is further shown to undergo a second reduction to the discharge product of Li2O2. In the reverse charge, the holes generated in the dz2 orbitals of Co are mobilized under the action of the applied voltage to enable the fast decomposition of Li2O2 to O2 and Li+. Under illumination, the Li-O2 battery exhibits respective discharge and charge voltages of 3.12 and 3.32 V for a round-trip efficiency of 94.0%. Our findings imply that the orbital interaction of metal ions with ligands in Co-TABQ nanosheets dictates the light harvesting and oxygen electrocatalysis for the Li-O2 battery.

17.
Environ Microbiol ; 23(9): 5334-5348, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34097354

RESUMO

Ras subfamily proteins are molecular switches in signal transduction pathways of many eukaryotes that regulate a variety of cellular processes. Here, the Ras subfamily, encoded by six genes, was identified in Aspergillus flavus: rasA, rasB, rasC, rab-33, rheb and rsr1. The rsr1 deletion mutant (∆rsr1), rheb deletion mutant (∆rheb) and double deletion mutant (∆rheb/rsr1) displayed significantly decreased growth and sporulation. Sclerotia formation was significantly decreased for ∆rheb or ∆rheb/rsr1 but increased for ∆rsr1. Aflatoxin production was significantly increased in ∆rheb but decreased in ∆rsr1 and ∆rheb/rsr1. We found that rsr1 and rheb are crucial for the pathogenicity of A. flavus. Quantitative proteomics identified 520 differentially expressed proteins (DEPs) for the ∆rsr1 mutant and 133 DEPs for the ∆rheb mutant. These DEPs were annotated in multiple biological processes and KEGG pathways in A. flavus. Importantly, we identified the cytokinesis protein SepA in the protein-protein interaction network of rsr1, and deletion mutants showed that SepA has pleiotropic effects on growth and AF biosynthesis, which may depend on Rsr1 for regulation in A. flavus. Our results indicated that these Ras subfamily proteins exhibited functional redundancy with each other but there were also differences in A. flavus.


Assuntos
Aflatoxinas , Aspergillus flavus , Aspergillus flavus/genética , Aspergillus flavus/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Virulência/genética , Proteínas ras
18.
Environ Microbiol ; 22(7): 2792-2810, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32250030

RESUMO

Reactive oxygen species (ROS) induce the synthesis of a myriad of secondary metabolites, including aflatoxins. It raises significant concern as it is a potent environmental contaminant. In Aspergillus flavus., antioxidant enzymes link ROS stress response with coordinated gene regulation of aflatoxin biosynthesis. In this study, we characterized the function of a core component of the antioxidant enzyme catalase (CTA1) of A. flavus. Firstly, we verified the presence of cta1 corresponding protein (CTA1) by Western blot analysis and mass-spectrometry based analysis. Then, the functional study revealed that the growth, sporulation and sclerotia formation significantly increased, while aflatoxins production and virulence were decreased in the cta1 deletion mutant as compared with the WT and complementary strains. Furthermore, the absence of the cta1 gene resulted in a significant rise in the intracellular ROS level, which in turn added to the oxidative stress level of cells. A further quantitative proteomics investigation hinted that in vivo, CTA1 might maintain the ROS level to facilitate the aflatoxin synthesis. All in all, the pleiotropic phenotype of A. flavus CTA1 deletion mutant revealed that the antioxidant system plays a crucial role in fungal development, aflatoxins biosynthesis and virulence.


Assuntos
Aflatoxinas/biossíntese , Aspergillus flavus/enzimologia , Aspergillus flavus/patogenicidade , Catalase/metabolismo , Virulência/genética , Antioxidantes/metabolismo , Aspergillus flavus/genética , Catalase/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Estresse Oxidativo/genética , Espécies Reativas de Oxigênio/metabolismo , Deleção de Sequência , Virulência/efeitos dos fármacos
19.
Cancer Cell Int ; 20: 315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32694937

RESUMO

BACKGROUND: Accumulating amount of evidence has highlighted the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in tumor pathogenesis. However, the roles of long non coding RNAs (lncRNAs) in the lncRNA-related ceRNA network of intrahepatic cholangiocarcinoma (ICC) still remain enigmatic. The current study aims to identify prognostic factors in the lncRNA-related ceRNA network of ICC. METHODS: The transcriptome sequencing data of lncRNAs, messenger RNA (mRNA) and microRNA (miR) were downloaded from the SRA and TCGA databases. Differentially expressed lncRNAs (DElncRNAs), DEmiRs and DEmRNAs were identified and adopted to construct an lncRNA-miR-mRNA ceRNA network. ICC-associated DEmRNAs were adopted to construct the protein-protein interaction (PPI) network. The expression of the top 6 genes in the hub module was validated with mRNA transcriptome sequencing data and ICC-related gene expression dataset GSE45001, followed by GO and KEGG pathway enrichment analysis. The relationship between the hub gene-associated ceRNA network and the overall survival of patients with ICC was predicted by conducting a Kaplan-Meier survival analysis. RESULTS: Sixty co-expressed DEmRNAs were identified in the ceRNA network. The top 6 hub genes consisted of downregulated FOS, IGF2, FOXO1 and NTF3, upregulated IGF1R, and insignificantly downregulated HGF in ICC tissues, when compared to that of normal adjacent tissues, followed by the successful construction of lncRNA-miR-hub network consisting of 86 ceRNA modules. MME-AS1 and hsa-miR-182 were associated with overall survival in ICC patients. FOS, IGF1R, IGF2, FOXO1, and NTF3 might target "TGF-ß signaling pathway", "the hedgehog signaling pathway", "retinol metabolism", or "type II diabetes mellitus" pathways respectively. CONCLUSION: These results indicate that FOS, IGF1R, IGF2, FOXO1, and NTF3 were useful prognostic factors in determining the prognosis of patients with ICC.

20.
J Clin Lab Anal ; 34(9): e23362, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32463132

RESUMO

PURPOSE: To explore the effects of PAK4/LIMK1/Cofilin-1 signaling pathway on the proliferation, invasion, and migration of human osteosarcoma cells. METHODS: The expression of PAK4/LIMK1/Cofilin-1 was detected by immunohistochemistry in osteosarcoma tissues. The osteosarcoma cell line MG63 was transfected and divided into Mock, Control siRNA, si-PAK4, LIMK1, and si-PAK4+LIMK1 groups. Then, the cellular biological features of MG63 cells were detected by CCK-8, wound-healing, Transwell, and flow cytometry methods. The relationship of PAK4 and LIMK1 was performed by co-immunoprecipitation test, and the protein expression of PAK4/LIMK1/Cofilin-1 was determined by Western blotting. Finally, the effect of PAK4 on the growth of osteosarcoma was verified by subcutaneous transplantation model of osteosarcoma in nude mice. RESULTS: The expression of PAK4/LIMK1/Cofilin-1 in both osteosarcoma tissues and cells was up-regulated. Positive PAK4, LIMK1, and Cofilin-1 expressions in osteosarcoma were associated with the clinical stage, distant metastasis, and tumor grade. The MG63 cell viability, migration, and invasion, as well as the expression of PAK4, p-LIMK/LIMK, and p-Cofilin-1/Cofilin-1, were restrained by the knock down of PAK4 while it promoted apoptosis. PAK4 silencing also suppressed the growth of subcutaneous transplanted tumor in nude mice. Co-immunocoprecipitation showed that LIMK and PAK4 protein can form complex in osteosarcoma cells. Besides, LIMK1 overexpression reversed the inhibition effect of PAK4 siRNA on the growth of osteosarcoma cells. CONCLUSION: The expression of PAK4/LIMK1/Cofilin-1 pathway in osteosarcoma tissues was up-regulated. Thus, PAK4 inhibition may restrict the osteosarcoma cell proliferation, invasion, and migration but promote its apoptosis via decreasing the activity of LIMK1/Cofilin-1 pathway.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/patologia , Cofilina 1/metabolismo , Regulação Neoplásica da Expressão Gênica , Quinases Lim/metabolismo , Osteossarcoma/patologia , Quinases Ativadas por p21/metabolismo , Adulto , Animais , Apoptose , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Movimento Celular , Proliferação de Células , Cofilina 1/genética , Feminino , Humanos , Quinases Lim/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Osteossarcoma/genética , Osteossarcoma/metabolismo , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem , Quinases Ativadas por p21/genética
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