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1.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731817

RESUMO

MCPH1 has been identified as the causal gene for primary microcephaly type 1, a neurodevelopmental disorder characterized by reduced brain size and delayed growth. As a multifunction protein, MCPH1 has been reported to repress the expression of TERT and interact with transcriptional regulator E2F1. However, it remains unclear whether MCPH1 regulates brain development through its transcriptional regulation function. This study showed that the knockout of Mcph1 in mice leads to delayed growth as early as the embryo stage E11.5. Transcriptome analysis (RNA-seq) revealed that the deletion of Mcph1 resulted in changes in the expression levels of a limited number of genes. Although the expression of some of E2F1 targets, such as Satb2 and Cdkn1c, was affected, the differentially expressed genes (DEGs) were not significantly enriched as E2F1 target genes. Further investigations showed that primary and immortalized Mcph1 knockout mouse embryonic fibroblasts (MEFs) exhibited cell cycle arrest and cellular senescence phenotype. Interestingly, the upregulation of p19ARF was detected in Mcph1 knockout MEFs, and silencing p19Arf restored the cell cycle and growth arrest to wild-type levels. Our findings suggested it is unlikely that MCPH1 regulates neurodevelopment through E2F1-mediated transcriptional regulation, and p19ARF-dependent cell cycle arrest and cellular senescence may contribute to the developmental abnormalities observed in primary microcephaly.


Assuntos
Pontos de Checagem do Ciclo Celular , Senescência Celular , Inibidor p16 de Quinase Dependente de Ciclina , Camundongos Knockout , Microcefalia , Animais , Camundongos , Senescência Celular/genética , Microcefalia/genética , Microcefalia/metabolismo , Microcefalia/patologia , Pontos de Checagem do Ciclo Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/deficiência , Fator de Transcrição E2F1/genética , Fator de Transcrição E2F1/metabolismo , Fibroblastos/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
2.
Small ; : e2310724, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429241

RESUMO

The portfolio of extraordinary fire retardancy, mechanical properties, dielectric/electric insulating performances, and thermal conductivity (λ) is essential for the practical applications of epoxy resin (EP) in high-end industries. To date, it remains a great challenge to achieve such a performanceportfolio in EP due to their different and even mutually exclusive governing mechanisms. Herein, a multifunctional additive (G@SiO2 @FeHP) is fabricated by in situ immobilization of silica (SiO2 ) and iron phenylphosphinate (FeHP) onto the graphene (G) surface. Benefiting from the synergistic effect of G, SiO2 and FeHP, the addition of 1.0 wt% G@SiO2 @FeHP enables EP to achieve a vertical burning (UL-94) V-0 rating and a limiting oxygen index (LOI) of 30.5%. Besides, both heat release and smoke generation of as-prepared EP nanocomposite are significantly suppressed due to the condensed-phase function of G@SiO2 @FeHP. Adding 1.0 wt% G@SiO2 @FeHP also brings about 44.5%, 61.1%, and 42.3% enhancements in the tensile strength, tensile modulus, and impact strength of EP nanocomposite. Moreover, the EP nanocomposite exhibits well-preserved dielectric and electric insulating properties and significantly enhanced λ. This work provides an integrated strategy for the development of multifunctional EP materials, thus facilitating their high-performance applications.

3.
Water Res ; 229: 119465, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36513019

RESUMO

Sulfate radical (SO4●-) based advanced oxidation is considered as a promising pretreatment strategy to degrade organic pollutants and thereby mitigate the membrane fouling in the membrane process. In this study, heat-activated persulfate (PS) activation was integrated with the membrane distillation (MD) process for the alleviation of membrane fouling in treatment of wastewater treatment plant (WWTP) secondary effluent and surface water. In-depth understanding of the molecular fate during membrane fouling control process was performed by using a non-targeted screening method of two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOF-MS) coupling with multiple characterizations. It was found that the heat-activated PS activation pretreatment could effectively degrade the dissolved organic matter (DOM) and change its molecular conformation, wherein the relative abundance of oxygen-containing substances was remarkably increased through oxygenation reactions. Moreover, the refractory organics with higher molecular weight (MW) and unsaturation degree were more inclined to be destroyed, following by partial mineralization during pretreatment process. It was also identified that oxygen-deficient compounds and the molecular formulas featuring higher double bond equivalent (DBE) values and lower MW tended to be deposited on the membrane surface to cause the membrane fouling. In particular, the aliphatic substances were the predominant components irrespective of membrane foulant samples from secondary effluent or surface water. Meanwhile, the complexation between organic compounds and high valence cations as well as the precipitation of inorganics were restrained owing to the reduction of DOM concentration and the transformation of molecular structure, consequently leading to reduced membrane fouling. This study is believed to further provide new insight into the membrane fouling control mechanism at molecular level.


Assuntos
Destilação , Purificação da Água , Temperatura Alta , Ultrafiltração/métodos , Membranas Artificiais , Purificação da Água/métodos , Oxigênio , Água
4.
J Hazard Mater ; 443(Pt B): 130306, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36345065

RESUMO

Prechlorination routinely applied for the treatment of algae-laden raw water has received extensive attention due to its influence on water quality and aquatic microbes. In this study, prechlorination experiments with different doses were conducted in sets of model raw water distribution systems. With the elevated dose of chlorine and prolonged hydraulic retention time (HRT), the ratio of intact algal cells decreased, and the stability of water enhanced. Dissolved organic carbon (DOC) and nitrogen (DON) increased when chlorine dose elevated from 0 to 0.5 mg/L but decreased with elevations from 0.5 to 2.0 mg/L, while UV254 showed a monotonically increasing tendency. DOC, DON and extracellular microcystin-LR increase initially and decrease thereafter with the prolonged HRT. Notably, the effects of prechlorination on extracellular polymeric substances aggregation behavior on pipe walls and microbial community composition was revealed, providing more profound understanding of the community dynamics in this engineered system. This study helped optimize strategies to improve the stability and efficiency of pretreatment of algae-laden water.


Assuntos
Cloro , Matriz Extracelular de Substâncias Poliméricas , Microcistinas , Biofilmes
5.
Sci Total Environ ; 856(Pt 1): 158434, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36075431

RESUMO

The introduce of a nanomaterial interlayer between the substrate and polyamide is identified as a promising strategy to construct highly performed membranes. Two-dimensional (2D) materials are potential candidates as interlayer for advanced thin-film nanocomposite interlayer (TFNi) membranes. Nevertheless, low permeability, selectivity and long-term stability are still critical issues in TFNi membrane manufacture. Herein, a scalable approach for constructing TFNi membranes was implemented using stacked MXene nanosheets as interlayer, wherein the Fe3O4 nanoparticles worked as the sacrificial template to regulate the interlayer spacing of the 2D channels. SEM, XPS, water contact angle, and zeta potential were used to characterize the physical and chemical properties of prepared TFNi membranes, and the results shows that the presence of MXene interlayer increased the hydrophilicity, thinness and roughness of polyamide layer compared to that of pure TFC membranes. Besides, the enlarged interlayer channel after the sacrifice of the Fe3O4 nanoparticles greatly boosted the transport of the water molecules. The resultant membranes exhibited nearly double fold of water flux (66.4 ± 3.45 L·m-2·h-1) and higher selective separation factor (48.4) compared with those prepared without interlayer, while the outstanding salt rejection (>97 %) was maintained. This work achieves an innovative strategy for multifunctional polyamide nanofiltration membrane construction.


Assuntos
Nanocompostos , Nylons , Salinidade , Membranas Artificiais , Água
6.
Int J Mol Sci ; 23(16)2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36012290

RESUMO

Head and neck squamous cell carcinomas (HNSCCs) are a type of cancer originating in the mucosal epithelium of the mouth, pharynx, and larynx, the sixth most common cancer in the world. However, there is no effective treatment for HNSCCs. More than 90% of HNSCCs overexpress epidermal growth factor receptors (EGFRs). Although small molecule inhibitors and monoclonal antibodies have been developed to target EGFRs, few EGFR-targeted therapeutics are approved for clinical use. Ferroptosis is a new kind of programmed death induced by the iron catalyzed excessive peroxidation of polyunsaturated fatty acids. A growing body of evidence suggests that ferroptosis plays a pivotal role in inhibiting the tumor process. However, whether and how ferroptosis-inducers (FINs) play roles in hindering HNSCCs are unclear. In this study, we analyzed the sensitivity of different HNSCCs to ferroptosis-inducers. We found that only tongue squamous cell carcinoma cells and laryngeal squamous cell carcinoma cells, but not nasopharyngeal carcinoma cells, actively respond to ferroptosis-inducers. The different sensitivities of HNSCC cells to ferroptosis induction may be attributed to the expression of KRAS and ferritin heavy chain (FTH1) since a high level of FTH1 is associated with the poor prognostic survival of HNSCCs, but knocked down FTH1 can promote HNSCC cell death. Excitingly, the ferroptosis-inducer RSL3 plays a synthetic role with EGFR monoclonal antibody Cetuximab to inhibit the survival of nasopharyngeal carcinoma cells (CNE-2), which are insensitive to both ferroptosis induction and EGFR inhibition due to a high level of FTH1 and a low level of EGFR, respectively. Our findings prove that FTH1 plays a vital role in ferroptosis resistance in HNSCCs and also provide clues to target HNSCCs resistant to ferroptosis induction and/or EGFR inhibition.


Assuntos
Carcinoma de Células Escamosas , Ferroptose , Neoplasias de Cabeça e Pescoço , Neoplasias da Língua , Anticorpos Monoclonais/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Neoplasias da Língua/tratamento farmacológico
7.
RSC Adv ; 12(17): 10267-10279, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35424976

RESUMO

Removing salt from dye/salt mixtures using nanofiltration (NF) membranes needs to be improved to ensure high permeability, high selectivity, and antifouling performance. In this study, we used an interfacial polymerization (IP) technique to create a novel thin-film nanocomposite NF membrane by introducing two-dimensional MXene Ti3C2T x into the polyamide (PA) layer. Enhanced IP reaction rate facilitated the overflow of residual solvent from the fresh PA layer's edge due to the MXene-mediated IP strategy, resulting considerable bubble-like nodules on the membrane surface. The unique nanostructure of PA effective layer could be tuned by controlling the MXene concentration in aqueous phase solution, which finally promoted the obtained membranes with superb permselectivity. In this way, the water permeability was elevated to a maximum value of 45.12 L m-1 h-1, nearly 1.58-fold compared to the PA-pristine membrane. Moreover, the Ti3C2T x /NF membrane exhibited a superior dye/monovalent salt separation coefficient of 820, outperforming the pristine PA membrane and other NF membranes in the literature. Additionally, the MXene-assisted IP strategy designed an effective dye anti-fouling hydration layer, which played a crucial role in fouling resistance. This work illustrates a novel use of Ti3C2T x to successfully regulate high-performance TFN PA membranes for potential application in dye/salt separation.

8.
Chemosphere ; 294: 133728, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35085609

RESUMO

New two-dimensional (2D) material MXene based lamellar membranes constructed from 2D MXene nanosheets have shown promising potential for water treatment with excellent selective property and high water flux. However, the effect of lateral size of MXene nanosheets on the membrane property and performance was rarely considered. Herein, the MXene nanosheets with different lateral size (552.3 nm, 397.5 nm and 281.8 nm) segregated via adjusting centrifugation conditions were used to prepare MXene membranes. XRD and cross-sectional SEM images confirmed that the resulting MXene membranes had the similar d-spacing and thickness. The MXene membrane with the smallest lateral size, MXene(S)-M, owned the largest surface roughness with reduced surface hydrophilicity. Lateral size determined mass transfer pathway and transfer resistance, which consequently influenced the water permeance and rejection of MXene membranes for dyeing wastewater treatment. MXene(S)-M with the shortest mass transfer pathway had the high water permeance while the MXene membrane with larger lateral size (MXene(L)-M and MXene(M)-M), possessing longer mass transport pathway, promoted high dye rejection.


Assuntos
Águas Residuárias , Purificação da Água , Corantes , Estudos Transversais , Titânio
9.
ChemSusChem ; 15(3): e202102352, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-34811943

RESUMO

Downsizing the catalyst to atom scale offers an effective way to maximize the atom utilization efficiency for electrocatalytic nitrogen reduction reaction (NRR). Herein, single-atomic ruthenium (Ru) anchored on a chemically activated Ti3 C2 with O-terminated groups (Ti3 C2 O) was designed to catalyze the NRR process. The catalyst achieved a superior activity and selectivity with ammonia yield rate of 27.56 µg h-1 mg-1 and faradaic efficiency of 23.3 % at a low potential of -0.20 V versus the reversible hydrogen electrode. According to the atomic resolution images from aberration-corrected scanning transmission electron microscopy, Ru sites on Ti3 C2 O achieved good dispersion on atomic scale. X-ray photoelectron spectroscopy analysis further demonstrated that the O-termination groups were successfully activated. Density functional theory calculations combined with experiments revealed that single Ru sites binding to four oxygen were the main reaction centers that permitted the hydrogenation of *NNH2 to *NHNH2 in a novel distal/alternating hybrid path while reducing the energy barrier of the potential-limiting step to 0.78 eV from 0.96 eV in the distal path alone or 1.18 eV in the alternating path alone, thereby significantly promoting the NRR dynamics.

10.
Chemosphere ; 283: 131180, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34467942

RESUMO

The raw water distribution systems (RWDSs) play key roles in urban water supply systems. The changes of disinfection byproducts (DBPs) precursors of trihalomethanes (THMs), haloacetic acids (HAAs) and halogenated acetaldehydes (HALs) in the RWDS in Taihu Basin were investigated by formation potentials. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) method and 454-pyrosequencing were employed to study the variation of molecular characteristics of low molecular weight-dissolved organic matter (LMW-DOM) and microbial communities of pipeline biofilms respectively, which played crucial roles in the variation of DBPs precursors. The results showed that both DBPs precursors and the molecular characteristics of LMW-DOM in the RWDS had changed. Moreover, the LMW-DOM could be an indicator due to the good positive correlation with precursors of HAAs and HALs. Specifically, the LMW-DOM showed continuous accumulation in the RWDS. The LMW-DOM tended to possess higher m/z and more CH2 or long alkyl chains while pre-chlorination controlled this trend. The LMW-DOM in the pre-chlorinated pipe section also possessed higher saturation. Additionally, lignins served as an important part of DBPs precursors and dominated the LMW-DOM. The microbial diversity decreased in the RWDS, and the abundance and diversity of the microbial community in the pre-chlorinated section were significantly lower than those in the no-chlorinated section. Finally, most DBPs precursors had positive correlation with dominant phylum and genus in RWDS. This study reveals variation of DBPs precursors, LMW-DOM and microbial pipeline biofilms as well, and provide important data for further research on raw water safety and stability in RWDSs.


Assuntos
Desinfetantes , Microbiota , Poluentes Químicos da Água , Purificação da Água , Desinfetantes/análise , Desinfecção , Halogenação , Trialometanos/análise , Água , Poluentes Químicos da Água/análise
11.
J Hazard Mater ; 420: 126686, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34329104

RESUMO

Photocatalysis and peroxymonosulfate (PMS) based advanced oxidation processes (AOP) are emerging technology for the degradation of refractory organic pollutant in the field of water treatment. Here we report a novel CoO@TiO2/MXene (CTM) hybrid through a facile sonication-hydrothermal method for efficient degradation of phenol via an integrated PMS activation-photocatalysis process. Benefiting from the proper position and superior suitability of the band structure, a dual interfacial charge transport channel was constructed, boosting the separation of photo-generated charge carriers and generating sufficient potential difference for redox reaction. Accordingly, the CTM hybrid not only possessed the outstanding photocatalytic activity but also dramatically accelerated PMS activation to generate considerable reactive radicals. As a result, over 96% phenol degradation was achieved in the 10% CTM/PMS/Vis system within 15 min. The radical quenching test and EPR analysis reveal that SO4•-, O2•- and 1O2 were predominant reactive species involved in the catalytic process. Moreover, the damaged chemical structure of CoO during PMS activation could be healed by the photo-actuated Co(II) regeneration to allow for continuous and stable catalytic process. This study offers a promising perspective for the rational design of competent and stable hybrid heterojunction catalyst to construct PMS activation-photocatalysis processes for the efficient degradation of organic contaminants.


Assuntos
Luz , Peróxidos , Fenóis , Titânio
12.
Front Aging Neurosci ; 13: 786199, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35153719

RESUMO

MRE11, RAD50, and NBS1 form the MRN complex in response to DNA damage to activate ATM, a gene responsible for Ataxia-Telangiectasia (A-T). Loss of any components of the MRN complex compromises cell life. Mutations in MRE11, RAD50, and NBS1 cause human genomic instability syndromes Ataxia-Telangiectasia-like disorder (A-TLD), NBS-like disorder (NBSLD), and Nijmegen Breakage Syndrome (NBS), respectively. Among other pathologies, neuronal deficits, including microcephaly, intellectual disabilities, and progressive cerebellar degeneration, are common in these disorders. Nbs1 deletion in neural stem cells of mouse models resulted in cerebellar atrophy and ataxia, mimicking the A-T syndrome suggesting an etiological function of MRN-mediated DDR in neuronal homeostasis and neuropathology. Here we show that deletion of Nbs1 or Mre11 specifically in Purkinje neurons of mouse models (Nbs1-PCΔ and Mre11-PCΔ, respectively) is compatible with cerebellar development. Deleting Nbs1 in Purkinje cells disrupts the cellular localization pattern of MRE11 or RAD50 without inducing apparent DNA damage, albeit impaired DNA damage response (judged by 53BP1 focus formation) to ionizing radiation (IR). However, neither survival nor morphology of Purkinje cells and thus locomotor capabilities is affected by Nbs1 deletion under physiological conditions. Similarly, deletion of Mre11 in Purkinje cells does not affect the numbers or morphology of Purkinje cells and causes no accumulation of DNA damage. Mre11-deleted Purkinje cells have regular intrinsic neuronal activity. Taken together, these data indicate that the MRN complex is not essential for the survival and functionality of postmitotic neurons such as Purkinje cells. Thus, cerebellar deficits in MRN defect-related disorders and mouse models are unlikely to be a direct consequence of loss of these factors compromising DDR in postmitotic neurons such as Purkinje cells.

13.
Ultrason Sonochem ; 72: 105411, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33321403

RESUMO

In this work, as a new strategy, ultrasound/H2O2/MOF system was firstly applied by environmental-benign Fe-MOFs (MIL-53, MIL-88B and MIL-101) for tetracycline hydrochloride removal. The syntheticFe-MOFs were characterized by XRD, FTIR, SEM, XPS, N2 sorption-desorption isotherms and CO-FTIR. MIL-88B demonstrated the best catalytic performance because of its highest amount of Lewis acid sites. Influencing factors, contrast experiment, and corresponding dynamics were carried out to obtain the best experimental conditions and reaction system. Under optimal conditions ([Tetracyclinehydrochloride] = 10 mg/L, [MIL-88B] = 0.3 g/L, [H2O2] = 44 mM, [ultrasound power] = 60 W, and pH = 5.0), the-first-order kinetic rate constant k was calculated to be 0.226 min-1, higher than the simple combination of the ultrasound system (0.004) and MIL-88B/H2O2 system (0.163), indicating the importance of synergistic effect between ultrasound and Fenton reaction. EPR test and quenching experiment proved that ·OH is mainly responsible for tetracycline hydrochloride removal. The major reaction path is the adsorption and decomposition of H2O2 by coordinative unsaturated iron sites on Fe-MOF, but it is not the only path. The direct decomposition of H2O2 and the cavitation effect caused by ultrasound also contribute to the generation of OH.

14.
J Fish Dis ; 44(5): 613-625, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33220160

RESUMO

The major histocompatibility complex (MHC) genes play a key role in immune response in vertebrates. In this study, an MHC I alpha homolog gene (PfMHC Ⅰα) from pufferfish (Takifugu obscurus) was identified and its subcellular localization and expression patterns of PfMHC Ⅰα after challenge in vivo and in vitro were analysed. The open reading frame of PfMHC Ⅰα was 1,089 bp in length, encoding 362 aa. The immunofluorescence result revealed that PfMHC Ⅰα was presented on the membrane of lymphocytes. qRT-PCR analysis indicated that PfMHC Ⅰα was expressed in all examined tissues, with the highest expression in skin, followed by the expression in gills and whole blood. After challenge of Aeromonas hydrophila or polyinosinic: polycytidylic acid (Poly I:C) in vitro, the expression levels of PfMHC Ⅰα on pufferfish kidney lymphocytes were significantly up-regulated, with the highest expression level at 48 hr post-challenge. After infection with A. hydrophila or Poly I:C in vivo, the expression levels of PfMHC Ⅰα in the skin, whole blood and kidneys were significantly up-regulated. Taken together, it is speculated that PfMHC Ⅰα associates with resistance to both intracellular and extracellular antigens and plays an important role in the host response against pathogen infection in pufferfish.


Assuntos
Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Genes MHC Classe I/genética , Genes MHC Classe I/imunologia , Imunidade/genética , Takifugu/genética , Takifugu/imunologia , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Doenças dos Peixes/microbiologia , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Filogenia , Poli I-C/farmacologia , Alinhamento de Sequência/veterinária
15.
Nucleic Acids Res ; 48(19): 10924-10939, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33010171

RESUMO

NBS1 is a critical component of the MRN (MRE11/RAD50/NBS1) complex, which regulates ATM- and ATR-mediated DNA damage response (DDR) pathways. Mutations in NBS1 cause the human genomic instability syndrome Nijmegen Breakage Syndrome (NBS), of which neuronal deficits, including microcephaly and intellectual disability, are classical hallmarks. Given its function in the DDR to ensure proper proliferation and prevent death of replicating cells, NBS1 is essential for life. Here we show that, unexpectedly, Nbs1 deletion is dispensable for postmitotic neurons, but compromises their arborization and migration due to dysregulated Notch signaling. We find that Nbs1 interacts with NICD-RBPJ, the effector of Notch signaling, and inhibits Notch activity. Genetic ablation or pharmaceutical inhibition of Notch signaling rescues the maturation and migration defects of Nbs1-deficient neurons in vitro and in vivo. Upregulation of Notch by Nbs1 deletion is independent of the key DDR downstream effector p53 and inactivation of each MRN component produces a different pattern of Notch activity and distinct neuronal defects. These data indicate that neuronal defects and aberrant Notch activity in Nbs1-deficient cells are unlikely to be a direct consequence of loss of MRN-mediated DDR function. This study discloses a novel function of NBS1 in crosstalk with the Notch pathway in neuron development.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neurogênese , Neurônios/metabolismo , Receptores Notch/metabolismo , Hidrolases Anidrido Ácido/metabolismo , Animais , Células Cultivadas , Dano ao DNA , Reparo do DNA , Embrião de Mamíferos , Fibroblastos , Proteína Homóloga a MRE11/metabolismo , Camundongos , Neurônios/citologia
16.
Fish Shellfish Immunol ; 106: 252-262, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32735858

RESUMO

Caspases are evolutionarily conserved proteases, which are inextricably linked with the apoptosis and immune system in mammals. However, the expression pattern and function of some caspases remain largely unknown in pufferfish. In this study, three different pufferfish caspases (caspase-2 (Pfcasp-2), caspase-3 (Pfcasp-3), and caspase-8 (Pfcasp-8)) were characterized, and their expression patterns and functions were determined following Aeromonas hydrophila infection. The open reading frames of Pfcasp-2, -3, and -8 are 1,320, 846, and 1455 bp, respectively. Analyses of sequence alignment and phylogenetic tree showed that casp-2, -3, and -8 share 52%-65%, 33%-40%, 63%-78% overall sequence identities with those of other vertebrates, respectively. 3D structures of Pfcasp-2, -3, and -8 enjoy conservation in core area together, while each owns a distinctive profile. Comparisons of deduced amino acid sequences indicated that Pfcaspases possessed the caspase domain and conserved active sites like 'HG' and 'QACXG' (X for R or G). qRT-PCR results revealed that Pfcasp-2, -3, and -8 were expressed constitutively in a wide range of organs, especially in immune-related organs including whole blood and kidney. In vitro, the expressions of the three caspases (Pfcasp-2, 3, and -8) and immune-related genes (IgM and IL-8) were significantly up-regulated in kidney leukocytes after A. Hydrophila challenge and inhibitors treatment. The expressions of Pfcasp-2 and Pfcasp-3 were successfully inhibited in the kidney leukocytes by Ac-DEVD-CHO (an inhibitor to caspase-3), but the expression of Pfcasp-8 was not affected. Cellular localization analysis showed that the distribution of Pfcasp-2, -3, and -8 was in cytoplasm. Further, overexpression of Pfcasp-2, -3, or -8 was found to cause DNA damage and apoptosis, suggesting that three caspases may be related to apoptosis and mediate different apoptosis pathways in pufferfish. Moreover, the expressions of these caspases were also up-regulated in whole blood and kidney after A. hydrophila challenge, indicating their possible involvement in the immune response against A. hydrophia stimulation. Taken together, the results of this study suggest that the caspase-2,-3, and -8 may play an important role in the apoptosis and immune response in pufferfish.


Assuntos
Caspases/genética , Caspases/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade/genética , Perciformes/genética , Perciformes/imunologia , Sequência de Aminoácidos , Animais , Caspases/química , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Filogenia , Alinhamento de Sequência/veterinária , Takifugu
17.
ACS Nano ; 14(7): 9125-9135, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32589400

RESUMO

The design of nanosheets interlayer between the substrate and polyamide layer has attracted growing attention to improve the performance of thin-film composite membranes. However, the membrane size is limited by current fabrication methods such as vacuum filtration. Herein, a high-performance MXene (Ti3C2Tx) interlayered polyamide forward osmosis (FO) membrane is fabricated based on a combination of a facile and scalable brush-coating of MXene on nylon substrates and the interfacial polymerization process. The as-prepared FO membrane shows high water permeability of 31.8 L m-2 h-1 and low specific salt flux of 0.27 g L-1 using 2.0 mol L-1 sodium chloride as the draw solution. This is attributed to the adjustment of substrate properties and the polyamide layer by coating of MXene as well as the facilitation of water transportation by the interlayer distances between Ti3C2Tx. The membrane also exhibits a good organic solvent forward osmosis performance with high ethanol flux as 9.5 L m-2 h-1 and low specific salt flux of 0.4 g L-1 using 2.0 mol L-1 lithium chloride as the draw solution. Moreover, the MXene interlayered FO membrane demonstrates a feasible application in real seawater desalination and industrial textile wastewater treatment. This work presents an effective approach to fabricating nanomaterials interlayered FO membranes with superior performance for both desalination and organic solvent recovery.

18.
Theranostics ; 10(13): 5704-5718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483413

RESUMO

Rationale: Epstein-Barr virus (EBV) is the causative pathogen for infectious mononucleosis and many kinds of malignancies including several lymphomas such as Hodgkin's lymphoma, Burkitt's lymphoma and NK/T cell lymphoma as well as carcinomas such as nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBV-GC). However, to date no available prophylactic vaccine was launched to the market for clinical use. Methods: To develop a novel vaccine candidate to prevent EBV infection and diseases, we designed chimeric virus-like particles (VLPs) based on the hepatitis B core antigen (HBc149). Various VLPs were engineered to present combinations of three peptides derived from the receptor binding domain of EBV gp350. All the chimeric virus-like particles were injected into Balb/C mice for immunogenicity evaluation. Neutralizing titer of mice sera were detected using an in vitro cell model. Results: All chimeric HBc149 proteins self-assembled into VLPs with gp350 epitopes displayed on the surface of spherical particles. Interestingly, the different orders of the three epitopes in the chimeric proteins induced different immune responses in mice. Two constructs (149-3A and 149-3B) induced high serum titer against the receptor-binding domain of gp350. Most importantly, these two VLPs elicited neutralizing antibodies in immunized mice, which efficiently blocked EBV infection in cell culture. Competition analysis showed that sera from these mice contained antibodies to a major neutralizing epitope recognized by the strong neutralizing mAb 72A1. Conclusion: Our data demonstrate that HBc149 chimeric VLPs provide a valuable platform to present EBV gp350 antigens and offer a robust basis for the development of peptide-based candidate vaccines against EBV.


Assuntos
Anticorpos Neutralizantes/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Imunização/métodos , Animais , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/sangue , Epitopos/genética , Epitopos/imunologia , Infecções por Vírus Epstein-Barr/prevenção & controle , Herpesvirus Humano 4/metabolismo , Herpesvirus Humano 4/patogenicidade , Imunoglobulina G/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Vacinação/métodos , Vacinas/farmacologia , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/imunologia
19.
ACS Appl Mater Interfaces ; 12(8): 9209-9218, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32019305

RESUMO

The heterogeneous Fenton-like process is regarded as a promising approach to produce reactive oxygen species for water purification and environmental remediation. Here, we report a simple and rational strategy for the design of an efficient catalyst by reducing the dimensionality instead of changing the composition or structure. Based on theoretical and experimental evidence, considerable active sites were exposed on the low-dimensional Ti3C2Tx monolayer surface and showed outstanding reactivity toward peroxymonosulfate activation, which was mainly because of the superior compatibility between the highest occupied molecular orbital of catalysts and lowest unoccupied molecular orbital of Oxone. Stimulated emission depletion super-resolution microscopy innovatively provided visual insights into the spatiotemporal heterogeneous activation process and revealed that the unilaminar Ti3C2Tx nanosheet exhibited preferable reaction dynamics relative to its inert bulk counterpart, with an aqueous 2,4-dichlorophenoxyacetic acid degradation rate ∼376 times higher than that when using bulk Ti3C2Tx as the activator.

20.
RSC Adv ; 10(42): 25186-25199, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35517444

RESUMO

A high-flux thin film nanocomposite (TFN) nanofiltration (NF) membrane for low pressure operation (3.5 bar) was fabricated by blending purified amino-functionalized single-walled carbon nanotubes (NH2-SWCNTs) with piperazine (PIP) as aqueous phase monomers through interfacial polymerization (IP). The surface properties and structures of the polyamide (PA) active layer were suitably tailored by introducing different amounts of NH2-SWCNTs into the PA layer. It was found that the homogeneous incorporation of NH2-SWCNTs facilitated a more integral PA layer along with improved roughness, hydrophilicity, and surface charge of the modified membranes, which could be validated by membrane characterisation including SEM, AFM, ATR-FTIR, XPS, zeta potential and water contact angle measurements. Based on cross-flow NF tests, the optimized ultra-thin NH2-SWCNT-TFN membranes with 0.002 wt% of NH2-SWCNTs exhibited outstanding water permeability of up to 17.8 L m-2 h-1 bar-1, 71.1% higher than that of the pristine membrane, along with high MgSO4 rejection of 91.0% and Na2SO4 rejection of 96.34%. Meanwhile, NH2-SWCNT-TFN membranes also showed excellent long-term stability and antifouling ability. This work demonstrates a facile strategy to fabricate a scalable, low-pressure and ultra-thin TFN membrane with excellent performance.

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