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1.
Artigo em Inglês | MEDLINE | ID: mdl-34806874

RESUMO

Recently, photoassisted charging has been demonstrated as a green and sustainable approach to successfully enhance the capacitance of supercapacitors with low cost and good efficiency. However, their light-induced capacitance enhancement is relatively low and is lost quickly when the illumination is off. In this work, a novel active material system is developed for supercapacitors with the photoassisted charging capability by the decoration of a small amount of Bi2WO6 nanoparticles on an h-WO3 submicron rod surface in situ, which forms a typical type II band alignment heterostructure with a close contact interface through the co-sharing of W atoms between h-WO3 submicron rods and Bi2WO6 nanoparticles. The photogenerated charge carrier separation and transfer are largely enhanced in the h-WO3/Bi2WO6 submicron rod electrode, which subsequently allows more charge carriers to participate in its photoassisted charging process to largely enhance its capacitance improvement under simulated solar illumination than that of the h-WO3 submicron rod electrode. Furthermore, the h-WO3/Bi2WO6 submicron rod electrode could retain its photoinduced capacitance enhancement in the dark for an extended period of time from the photocatalytic memory effect. Thus, our work provides a solution to the two major drawbacks of reported supercapacitors with the light-induced capacitance enhancement property, and supercapacitors based on active materials with the photocatalytic memory effect could be utilized in various technical fields.

2.
Pestic Biochem Physiol ; 179: 104958, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34802537

RESUMO

Isoxaflutole (IXF), a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, causes injury to crops leading to reductions in grain yield. In order to solve the phytotoxicity caused by IXF, the present work evaluated the protective response of the substituted quinoxaline derivatives as potential safeners on Zea mays. The bioassay results showed that all of the test compounds displayed protection against IXF. In particular, safener I-6 exhibited excellent safener activity against IXF injury via enhancing glutathione (GSH) content, glutathione S transferases (GSTs) and cytochrome P450 monooxygenases (CYP450) activity. The tested compounds induced the activity of CYP450 and GSTs in Z. mays. The physicochemical properties and ADMET properties of safener I-6, benoxacor and diketonitrile (DKN, IXF metabolite) were compared to predict pharmaceutical behavior. The present work demonstrates that the safener I-6 could be considered as a potential candidate for developing novel safeners in the future.


Assuntos
Herbicidas , Herbicidas/toxicidade , Quinoxalinas/toxicidade , Zea mays
3.
Pest Manag Sci ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34719096

RESUMO

BACKGROUND: 4-Hydroxyphenyl pyruvate dioxygenase (EC 1.13.11.27, HPPD) is one of the important target enzymes used to address the issue of weed control. HPPD-inhibiting herbicides can reduce the carotenoid content in plants and hinder photosynthesis, eventually causing albinism and death. Exploring novel HPPD-inhibiting herbicides is a significant direction in pesticide research. In the process of exploring new high-efficiency HPPD inhibitors, a series of novel quinoxaline derivatives were designed and synthesized using an active fragment splicing strategy. RESULTS: The title compounds were unambiguously characterized by infrared, 1 H NMR, 13 C NMR, and high-resolution mass spectroscopy. The results of the in vitro tests indicated that the majority of the title compounds showed potent inhibition of Arabidopsis thaliana HPPD (AtHPPD). Preliminary bioevaluation results revealed that a number of novel compounds displayed better or excellent herbicidal activity against broadleaf and monocotyledonous weeds. Compound III-5 showed herbicidal effects comparable to those of mesotrione at a rate of 150 g of active ingredient (ai)/ha for post-emergence application. The results of molecular dynamics verified that compound III-5 had a more stable protein-binding ability. Molecular docking results showed that compound III-5 and mesotrione shared homologous interplay with the surrounding residues. In addition, the enlarged aromatic ring system adds more force, and the hydrogen bond formed can enhance the synergy with π-π stacking. CONCLUSIONS: The present work indicates that compound III-5 may be a potential lead structure for the development of new HPPD inhibitors.

4.
ACS Appl Mater Interfaces ; 13(36): 42861-42869, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34473469

RESUMO

Ni(OH)2-based materials are widely studied in oxygen evolution reaction (OER), but no related synthesis, electrocatalytic application, or theoretical analysis of Sn4+-doped Ni(OH)2 has been reported. In this work, Sn-Ni(OH)2 with a homogeneously distributed nanosheet array was synthesized through a one-step hydrothermal process. It displays a hugely enhanced catalytic activity compared to undoped Ni(OH)2 throughout the OER and hydrogen evolution reaction (HER) processes. The overpotentials at 100 mA cm-2 of Sn-Ni(OH)2 are 312 mV (OER) and 298 mV (HER), which are lower than the corresponding 396 and 427 mV of Ni(OH)2, respectively. In addition, Sn-Ni(OH)2 can deliver stable large current densities (at ≈500 and ≈1000 mA cm-2) for the long-term (>100 h) chronoamperometry testing. Moreover, Sn-Ni(OH)2 illustrates catalytic activity comparable to that of a commercial Pt/C||RuO2 electrode pair during the overall water splitting course. Both experimental phenomena and relevant computed theoretical data confirm that the enhanced water splitting activity is mainly due to the introduced Sn4+ site, which acts as the active center activates the nearby Ni sites during the OER, while acting as the most active reaction site that participates in the HER. Although the doped Sn4+ has two different effects on OER and HER proceedings, water splitting performance of Sn-Ni(OH)2 has been conspicuously improved.

5.
Environ Pollut ; 291: 118120, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34520951

RESUMO

Polyethylene (PE) and polypropylene (PP) microplastics (MPs), as carriers, can bind with pesticides, which propose harmful impacts to aqueous ecosystems. Meanwhile, carbofuran and carbendazim (CBD), two widely used carbamate pesticides, are toxic to humans because of the inhibition of acetylcholinesterase activity. The interaction between two MPs and two pesticides could start in farmland and be maintained during transportation to the ocean. Herein, the adsorption behavior and mechanism of carbofuran and carbendazim (CBD) by PE and PP MPs were investigated via characterization and density functional theory (DFT) simulation. The adsorption kinetic and thermodynamic data were best described by pseudo-second-order kinetics and the Freundlich models. The adsorption behaviors of individual carbofuran/CBD on both MPs were very similar. The CBD adsorption rate and capacity of PE and PP MPs were higher than those of carbofuran. This phenomenon explained the lower negative effects of DOM (oxalic acid, glycine (Gly)) on CBD adsorption relative to those of carbofuran. The presence of oxalic acid and Gly decreased the PE adsorption by 20.40-48.02% and the PP adsorption by 19.27-42.11%, respectively. It indicated the significance of DOM in carbofuran cycling. The adsorption capacities were negatively correlated with MPs size, indicating the importance of specific surficial area. Fourier transformation infrared spectroscopy before and after adsorption suggested that the adsorption process did not produce any new covalent bond. Instead, intermolecular van der Waals forces were one of the primary adsorption mechanisms of carbofuran and CBD by MPs, as evidenced by DFT calculations. Based on the zeta potential, the electrostatic interaction explained the higher adsorption CBD by MPs than carbofuran.


Assuntos
Praguicidas , Poluentes Químicos da Água , Acetilcolinesterase , Adsorção , Teoria da Densidade Funcional , Ecossistema , Humanos , Microplásticos , Tamanho da Partícula , Plásticos , Polietileno , Polipropilenos , Poluentes Químicos da Água/análise
6.
J Dairy Sci ; 104(12): 12830-12844, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34538488

RESUMO

Bovine mammary epithelial cells undergo an increase in metabolic rate, mitochondrial dysfunction, and oxidative stress after calving. Nuclear factor erythroid 2-related factor 2 (NFE2L2), a master regulator of cellular redox homeostasis, plays crucial roles in the regulation of mitochondrial function. The objective of this study was to investigate the role of NFE2L2 on mitochondrial function in bovine mammary epithelial cells under hyperlipidemic conditions. Three experiments were conducted as follows: (1) the immortalized bovine mammary epithelial cell line MAC-T was treated with various concentrations of free fatty acids (FFA; 0, 0.6, 1.2, or 2.4 mM) for 24 h to induce stress; (2) MAC-T cells were transfected with small interfering RNA targeting NFE2L2 (si-NFE2L2) and scrambled nontarget negative control (si-Control) for 48 h; and (3) MAC-T cells were pretreated with 10 µM sulforaphane (SFN), an activator of NFE2L2, for 24 h followed by treatment with 1.2 mM FFA for an additional 24 h. Results indicated that exogenous FFA challenge induced linear and quadratic increases in concentrations of mitochondrial reactive oxygen species (ROS). Compared with 0 mM FFA, mitochondrial membrane potential, mRNA abundance of oxidative phosphorylation complexes (CO I-V), protein abundance of nuclear respiratory factor 1 (NRF1), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), mitochondrial transcription factor A (TFAM), and NFE2L2 along with the contents of ATP, mitochondrial DNA (mtDNA), and total mitochondria were greater in the MAC-T challenged with 0.6 mM FFA group, but lower in the 1.2 and 2.4 mM FFA cultures. Knockdown of NFE2L2 via small interfering RNA led to greater mitochondrial ROS content and lower mitochondrial membrane potential along with contents of ATP, mtDNA, and total mitochondria. The SFN pretreatment upregulated protein abundance of NFE2L2 and attenuated the downregulation of NFE2L2 induced by FFA. Pretreatment with SFN attenuated the downregulation induced by FFA of PGC-1α, NRF1, and TFAM protein abundance along with contents of mtDNA and total mitochondria. Furthermore, SFN pretreatment attenuated the upregulation of mitochondrial ROS content, the downregulation of mitochondrial membrane potential, and the decreases in ATP, mtDNA, and mitochondrial content induced by FFA. Overall, data indicated that FFA inhibit NFE2L2, resulting in mitochondrial dysfunction and ROS production in bovine mammary epithelial cells. Thus, NFE2L2 may be a promising therapeutic target against metabolic challenge-driven mitochondrial dysfunction and oxidative stress in bovine mammary epithelial cells.


Assuntos
Ácidos Graxos não Esterificados , Estresse Oxidativo , Animais , Bovinos , Células Epiteliais , Ácidos Graxos não Esterificados/metabolismo , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
7.
Environ Res ; 204(Pt A): 111826, 2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34375658

RESUMO

High sulphide concentrations can be toxic to denitrifying and desulphurising microorganisms. In this study, bioaugmentation was used to solve this problem. Pseudomonas sp. gs1 can tolerate 400 mg/L sulphide and converts most of the sulphide into elemental sulphur after 4 h. A solid inoculum of Pseudomonas sp. h1 was prepared. Two reactors, that is, one with and one without inoculum, were simultaneously run for 60 days. Bioreactor II to which bacterial inoculum was added reached a good treatment performance on day 3. The elemental sulphur concentration of the effluent was 342.6 mg/L. It was maintained at 245.3-333.8 mg/L during the subsequent operation. In contrast, reactor I without inoculants achieved the same performance on day 50. High-throughput sequencing shows that Pseudomonas and Azoarcus are the dominant genera. The abundance of the genus Pseudomonas and related denitrifying sulphur-oxidising bacteria in reactor I increases with the operation time. This phenomenon was confirmed by testing the sqr and gltA genes. The quantitative fluorescence PCR test also proves that the addition of bacteria leads to a rapid increase in the sulphur oxidation and carbon metabolism of the activated sludge in the reactor.

8.
Environ Res ; 204(Pt A): 111946, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34453896

RESUMO

This study aims to compare the effects of different carbon sources on sulfur-oxidizing denitrifying microorganisms by using glucose, ethanol, and acetate as carbon sources. Under the same chemical oxygen demand Cr (CODCr), nitrate, and sulfide concentrations, the removal rate of nitrate and total organic carbon, and the yield of elemental sulfur in a static experiment and a continuous flow reactor with glucose as the carbon source were lower than those with ethanol and acetic acid as the carbon source. The core sulfur-oxidizing denitrifying bacteria that use glucose as the carbon source were Azoarcus, Geoalkalibacter, and Mangroviflexus; those that use ethanol as the carbon source were Arcobacter, Pseudomonas, and Thauera; those that use acetate as the carbon source were Pseudomonas and Azoarcus. The metabolic activity of microorganisms that use different carbon sources was explained by functional gene detection. The fluctuation of gltA, a functional gene indicating heterotrophic metabolism of microorganisms, was small in three reactors, but that of the sulfur oxidation gene, Sqr, in the reactor with acetic acid as the carbon source was larger. Our results suggest that acetate is a more suitable carbon source for denitrification-desulfurization systems.

9.
Biomark Res ; 9(1): 56, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233760

RESUMO

BACKGROUND: Contemporary to the rapidly evolving landscape of cancer immunotherapy is the equally changing understanding of immune tumor microenvironments (TMEs) which is crucial to the success of these therapies. Their reliance on a robust host immune response necessitates clinical grade measurements of immune TMEs at diagnosis. In this study, we describe a stable tumor immunogenic profile describing immune TMEs in multiple tumor types with ability to predict clinical benefit from immune checkpoint inhibitors (ICIs). METHODS: A tumor immunogenic signature (TIGS) was derived from targeted RNA-sequencing (RNA-seq) and gene expression analysis of 1323 clinical solid tumor cases spanning 35 histologies using unsupervised analysis. TIGS correlation with ICI response and survival was assessed in a retrospective cohort of NSCLC, melanoma and RCC tumor blocks, alone and combined with TMB, PD-L1 IHC and cell proliferation biomarkers. RESULTS: Unsupervised clustering of RNA-seq profiles uncovered a 161 gene signature where T cell and B cell activation, IFNg, chemokine, cytokine and interleukin pathways are over-represented. Mean expression of these genes produced three distinct TIGS score categories: strong (n = 384/1323; 29.02%), moderate (n = 354/1323; 26.76%), and weak (n = 585/1323; 44.22%). Strong TIGS tumors presented an improved ICI response rate of 37% (30/81); with highest response rate advantage occurring in NSCLC (ORR = 36.6%; 16/44; p = 0.051). Similarly, overall survival for strong TIGS tumors trended upward (median = 25 months; p = 0.19). Integrating the TIGS score categories with neoplastic influence quantified via cell proliferation showed highly proliferative and strong TIGS tumors correlate with significantly higher ICI ORR than poorly proliferative and weak TIGS tumors [14.28%; p = 0.0006]. Importantly, we noted that strong TIGS and highly [median = not achieved; p = 0.025] or moderately [median = 16.2 months; p = 0.025] proliferative tumors had significantly better survival compared to weak TIGS, highly proliferative tumors [median = 7.03 months]. Importantly, TIGS discriminates subpopulations of potential ICI responders that were considered negative for response by TMB and PD-L1. CONCLUSIONS: TIGS is a comprehensive and informative measurement of immune TME that effectively characterizes host immune response to ICIs in multiple tumors. The results indicate that when combined with PD-L1, TMB and cell proliferation, TIGS provides greater context of both immune and neoplastic influences on the TME for implementation into clinical practice.

10.
Front Pharmacol ; 12: 666860, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305588

RESUMO

FGF5 and FGF18 are key factors in the regulation of the hair follicle cycle. FGF5 is overexpressed during the late anagen phase and serves as a crucial regulatory factor that promotes the anagen-to-catagen transition in the hair follicle cycle. FGF18, which is overexpressed during the telogen phase, mainly regulates the hair follicle cycle by maintaining the telogen phase and inhibiting the entry of hair follicles into the anagen phase. The inhibition of FGF5 may prolong the anagen phase, whereas the inhibition of FGF18 may promote the transition of the hair follicles from the telogen phase to the anagen phase. In the present study, we used siRNA to suppress FGF5 or FGF18 expression as a way to inhibit the activity of these genes. Using qPCR, we showed that FGF5-targeting siRNA modified by cholesterol was more effective than the same siRNA bound to a cell-penetrating peptide at suppressing the expression of FGF5 both in vitro and in vivo. We then investigated the effects of the cholesterol-modified siRNA targeting either FGF5 or FGF18 on the hair follicle cycle in a depilated area of the skin on the back of mice. The cholesterol-modified siRNA, delivered by intradermal injection, effectively regulated the hair follicle cycle by inhibiting the expression of FGF5 and FGF18. More specifically, intradermal injection of a cholesterol-modified FGF5-targeted siRNA effectively prolonged the anagen phase of the hair follicles, whereas intradermal injection of the cholesterol-modified FGF18-targeted siRNA led to the mobilization of telogen follicles to enter the anagen phase earlier. The inhibitory effect of the cholesterol-modified FGF18-targeted siRNA on FGF18 expression was also evaluated for a topically applied siRNA. Topical application of a cream containing the cholesterol-modified FGF18-targeted siRNA on a depilated area of the skin of the back of mice revealed comparable inhibition of FGF18 expression with that observed for the same siRNA delivered by intradermal injection. These findings suggested that alopecia could be prevented and hair regrowth could be restored either through the intradermal injection of cholesterol-modified siRNA targeting FGF5 or FGF18 or the topical application of FGF18 siRNA.

11.
Pestic Biochem Physiol ; 177: 104897, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34301359

RESUMO

To seek novel and safe protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors with excellent herbicidal activity. A series of novel phenoxypyridine derivatives containing natural product coumarins with allelopathy were designed and synthesized based on bioisosterism and active subunit combination in this research. Compounds W3.1 and W3.4, with the half-maximal inhibitory concentration (IC50) value of 0.02653 mg/L and 0.01937 mg/L, respectively, displayed excellent herbicidal activity in greenhouse. Their herbicidal activity was similar to commercial herbicide oxyfluorfen (IC50 = 0.04943 mg/L). The best field inhibitory effect of compounds W3.1 and W3.4 recorded was at doses of 450 g ai/ha and 300 g ai/ha, respectively. Compound W3.4 had the best herbicidal activity among all the target compounds in this paper. Molecular docking analysis revealed that compounds W3.1 and W3.4 could form a hydrogen bonds with the amino acid AGR-98 and a π-π superposition with the amino acid PHE-398, respectively, which was similar to the oxyfluorfen. The crop selectivity tests results indicated that maize, cotton and soybean showed high tolerance to compound W3.4. Compound W3.4 reduced the Ca and Cb contents of wheat and rice, but had less effect on maize, cotton and soybean. Selectivity of compound W3.4 in maize, cotton and soybean were appeared to be due to reduced absorption of the herbicide compared to wheat and rice. Compound W3.4 deserves further attention as a candidate structure for new herbicides.


Assuntos
Produtos Biológicos , Herbicidas , Alelopatia , Cumarínicos/farmacologia , Inibidores Enzimáticos/farmacologia , Herbicidas/toxicidade , Simulação de Acoplamento Molecular , Oxirredutases , Plantas Daninhas , Relação Estrutura-Atividade
12.
Stem Cell Res Ther ; 12(1): 384, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233729

RESUMO

In recent years, mesenchymal stem cells (MSCs) have been used to improve cardiac function and attenuate adverse ventricular remodeling of the ischemic myocardium through paracrine effects and immunoregulation functions. In combination with cell sheet technology, MSCs could be more easily transplanted to the ischemic area. The long-term retention of MSCs in the affected area was realized and significantly improved the curative effect. In this review, we summarized the research and the applications of MSC sheets to the treatment of ischemic heart tissue. At present, many types of MSCs have been considered as multipotent cells in the treatment of heart failure, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose-derived mesenchymal stem cells (AD-MSCs), umbilical cord-derived mesenchymal stem cells (UC-MSCs), and skeletal myoblasts (SMs). Since UC-MSCs have few human leukocyte antigen-II and major histocompatibility complex class I molecules, and are easy to isolate and culture, UC-MSC sheets have been proposed as a candidate for clinical applications to ischemic heart disease.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Isquemia Miocárdica , Diferenciação Celular , Humanos , Isquemia Miocárdica/terapia , Cordão Umbilical , Remodelação Ventricular
13.
Ann Transl Med ; 9(12): 994, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34277794

RESUMO

Background: Fibroblast growth factor (FGF) 14 is a member of the FGF family that is mainly expressed in the central nervous system. FGF14 has a close association with the occurrence of neurodegenerative conditions; however, its significance in Alzheimer's disease (AD) has yet to be evaluated. Therefore, we sought to obtain a large amount of exogenous FGF14 protein and explore its effect in a cellular model of AD. Methods: FGF14 protein was expressed in an Escherichia coli system using gene recombination technology. Purified protein was obtained through washing and renaturation of inclusion bodies combined with nickel column affinity chromatography. The AD model was established via Aß25-35-induced injury in PC12 cells. Changes in the levels of lactate dehydrogenase and malondialdehyde were detected, and the neuroprotective effect of recombinant human FGF14 (rhFGF14) was evaluated through double-fluorescence staining and flow cytometry apoptosis detection. For further exploration of rhFGF14-mediated regulation of mitogen-activated protein kinase (MAPK) signaling, western blot was employed. Results: We successfully induced large amounts of insoluble rhFGF14. Following solubilization and refolding of the rhFGF14 from inclusion bodies, high purity rhFGF14 was purified by Nickel affinity column chromatography. The results showed that rhFGF14 alleviated Aß25-3-induced PC12 cell injury by inhibiting the phosphorylation of p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase, thus suppressing the MAPK signaling pathway. Conclusions: FGF14 performed a neuroprotective role in our in vitro AD model via its inhibition of MAPK signaling, highlighting its potential as a therapeutic drug for neurodegenerative conditions.

14.
J Agric Food Chem ; 69(30): 8366-8379, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34310139

RESUMO

Fenoxaprop-p-ethyl (FE), a type of acetyl-CoA carboxylase (ACCase) inhibitor, has been extensively applied to a variety of crop plants. It can cause damage to wheat (Triticum aestivum) even resulting in the death of the crop. On the prerequisite of not reducing herbicidal efficiency on target weed species, herbicide safeners selectively protect crops from herbicide injury. Based on fragment splicing, a series of novel substituted pyrazole derivatives was designed to ultimately address the phytotoxicity to wheat caused by FE. The title compounds were synthesized in a one-pot way and characterized via infrared spectroscopy, 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and high-resolution mass spectrometry. The bioactivity assay proved that the FE phytotoxicity to wheat could be reduced by most of the title compounds. The molecular docking model indicated that compound IV-21 prevented fenoxaprop acid (FA) from reaching or acting with ACCase. The absorption, distribution, metabolism, excretion, and toxicity predictions demonstrated that compound IV-21 exhibited superior pharmacokinetic properties to the commercialized safener mefenpyr-diethyl. The current work revealed that a series of newly substituted pyrazole derivatives presented strong herbicide safener activity in wheat. This may serve as a potential candidate structure to contribute to the further protection of wheat from herbicide injury.


Assuntos
Ésteres , Herbicidas , Herbicidas/toxicidade , Simulação de Acoplamento Molecular , Pirazóis/toxicidade , Recombinação Genética
15.
Free Radic Biol Med ; 172: 622-632, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34252538

RESUMO

Macrophages and microglia (M/Ms) in the injured spinal cord maintain a predominantly neurotoxic M1 phenotype that is disadvantageous to repair in the development of spinal cord injury (SCI). It has been reported that tumor necrosis factor (TNF) that polarize M/Ms toward M1 state in various disorders. In this study, we found that ablation of TNF endorsed the beneficial conversion from M1 to M2 phenotype and improved the mitochondrial metabolism in vivo and in vitro. In addition, PGC-1α that accumulates in TNF null mice, a major participant of mitochondrial metabolism, downregulated ROS activity and the expressions of M1-specific mRNA. Moreover, the absence of TNF upgraded the morphology and quantity of damaged mitochondria and rapidly switched to M2 phenotype as compare to administration of N-Acetyl-l-cysteine (NAC). Furthermore, systemic application of TPEN showed that increased ratio of M1 M/Ms. These combined results supporting predominant and prolonged TNF expression that is destructive to recovery after SCI. These results indicated that TNF would have great potential immunomodulatory for the treatment of SCI.


Assuntos
Microglia , Fator de Necrose Tumoral alfa , Animais , Humanos , Macrófagos/metabolismo , Camundongos , Microglia/metabolismo , Mitocôndrias , Medula Espinal , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
16.
Int J Biol Macromol ; 185: 876-889, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34237364

RESUMO

The integrity of the epidermal barrier and the maintenance of barrier homeostasis depend on the dynamic balance between the proliferation and differentiation of keratinocytes. Calcium (Ca2+) plays a crucial role in maintaining a balance of these two processes as well as in the formation of an epidermal permeability barrier. In this study, we showed that topical application of oat ß-glucan (OG) could ameliorate epidermal hyperplasia and accelerate the recovery of the epidermal barrier by promoting epidermal differentiation. Mechanistic studies revealed a positive interaction between OG and the dectin-1 receptor, and this interaction could lead to an upregulated expression of the calcium-sensing receptor (CaSR) via activation of the downstream ERK and p38 pathways. This consequently increased the sensitivity of keratinocytes to extracellular Ca2+ under the condition of calcium loss following the disruption of the epidermal barrier, resulting in the maintenance of normal keratinocyte differentiation in the epidermis, and ultimately promoting the recovery of the epidermal barrier. These findings clearly demonstrated the healing effect of OG on a physically damaged epidermal barrier. Thus, OG could be considered a valuable component in the development of skin repair agents.


Assuntos
Avena/química , Queratinócitos/citologia , Lectinas Tipo C/metabolismo , Receptores de Detecção de Cálcio/metabolismo , beta-Glucanas/efeitos adversos , Animais , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células HaCaT , Humanos , Hiperplasia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Lectinas Tipo C/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Receptores de Detecção de Cálcio/genética , Regulação para Cima , beta-Glucanas/farmacologia
17.
Adv Mater ; 33(36): e2102421, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34302393

RESUMO

Domain wall motion in ferroics, similar to dislocation motion in metals, can be tuned by well-concepted microstructural elements. In demanding high-power applications of piezoelectric materials, the domain wall motion is considered as a lossy hysteretic mechanism that should be restricted. Current applications for so-called hard piezoelectrics are abundant and hinge on the use of an acceptor-doping scheme. However, this mechanism features severe limitations due to enhanced mobility of oxygen vacancies at moderate temperatures. By analogy with metal technology, the authors present here a new solution for electroceramics, where precipitates are utilized to pin domain walls and improve piezoelectric properties. Through a sequence of sintering, nucleation, and precipitate growth, intragranular precipitates leading to a fine domain structure are developed as shown by transmission electron microscopy, piezoresponse force microscopy, and phase-field simulation. This structure impedes the domain wall motion as elucidated by electromechanical characterization. As a result, the mechanical quality factor is increased by ≈50% and the hysteresis in electrostrain is suppressed considerably. This is even achieved with slightly increased piezoelectric coefficient and electromechanical coupling factor. This novel process can be smoothly implemented in industrial production processes and is accessible to simple laboratory experimentation for microstructure optimization and implementation in various ferroelectric systems.

18.
Sci Adv ; 7(27)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34215590

RESUMO

Mesenchymal stem cell (MSC)-based therapy to combat diabetic-associated metabolic disorders is hindered by impoverished cell survival and limited therapeutic effects under high glucose stress. Here, we genetically engineered MSCs with Exendin-4 (MSC-Ex-4), a glucagon-like peptide-1 (GLP-1) analog, and demonstrated their boosted cellular functions and antidiabetic efficacy in the type 2 diabetes mellitus (T2DM) mouse model. Mechanistically, MSC-Ex-4 achieved self-augmentation and improved survival under high glucose stress via autocrine activation of the GLP-1R-mediated AMPK signaling pathway. Meanwhile, MSC-Ex-4-secreted Exendin-4 suppressed senescence and apoptosis of pancreatic ß cells through endocrine effects, while MSC-Ex-4-secreted bioactive factors (e.g., IGFBP2 and APOM) paracrinely augmented insulin sensitivity and decreased lipid accumulation in hepatocytes through PI3K-Akt activation. Furthermore, we encapsulated MSC-Ex-4 in 3D gelatin microscaffolds for single-dose administration to extend the therapeutic effect for 3 months. Together, our findings provide mechanistic insights into Exendin-4-mediated MSCs self-persistence and antidiabetic activity that offer more effective MSC-based therapy for T2DM.

19.
Front Pharmacol ; 12: 655281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163354

RESUMO

Objective: Exposure to ultraviolet B (UVB) can cause skin damage through oxidative stress, DNA damage, and apoptosis. Keratinocyte growth factor (KGF) has been shown to reduce the content of intracellular reactive oxygen species (ROS) following UVB exposure, a role that is crucial for the efficient photoprotection of skin. The present study evaluated the photoprotective effect of KGF-2 on UVB-induced skin damage and explored its potential molecular mechanism. Methods: To evaluate the effect of KGF-2 on UVB-induced damage ex vivo, a human epidermal full-thickness skin equivalent was pretreated without or with KGF-2 and then exposed to UVB and the levels of histopathological changes, DNA damage, inflammation, and apoptosis were then evaluated. The ability of KGF-2 to protect the cells against UVB-inflicted damage and its effect on ROS production, apoptosis, and mitochondrial dysfunction were determined in HaCaT cells. Results: Pretreatment of the epidermis with KGF-2 ameliorated the extent of photodamage. At the cellular level, KGF-2 could attenuate ROS production, apoptosis, DNA damage, and mitochondrial dysfunction caused by UVB exposure. KGF-2 could also activate the aryl hydrocarbon receptor (AhR) to trigger the Nrf2 signaling pathway. Conclusion: Taken together, our findings suggested that KGF-2 could ameliorate UVB-induced skin damage through inhibiting apoptosis, reducing oxidative stress, and preventing DNA damage and mitochondrial dysfunction via regulating AhR/Nrf2 signaling pathway.

20.
Pest Manag Sci ; 77(10): 4785-4798, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34161678

RESUMO

BACKGROUND: In recent years, protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors have been widely studied as important agricultural herbicides. Our research focused on the design and synthesis of novel PPO inhibitor herbicides, through linking of a diphenylether pyridine bioisostere structure to substituted coumarins, which aims to enhance environmental and crop safety while retaining high efficacy. RESULTS: A total of 21 compounds were synthesized via acylation reactions and all compounds were characterized using infrared, 1 H NMR, 13 C NMR, and high-resolution mass spectra. The respective configurations of compounds IV-6 and IV-12 were also confirmed using single crystal X-ray diffraction. The bioassay results showed that the title compounds displayed notable herbicidal activity, particularly compound IV-6 which displayed better herbicidal activity in greenhouse and field experiments, crop selectivity and safety for cotton and soybean compared with the commercial herbicide oxyfluorfen. CONCLUSION: The work revealed that compound IV-6 deserves further attention as a candidate structure for a novel and safe herbicide. © 2021 Society of Chemical Industry.


Assuntos
Produtos Biológicos , Herbicidas , Cumarínicos/farmacologia , Herbicidas/farmacologia , Protoporfirinogênio Oxidase/metabolismo , Relação Estrutura-Atividade
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