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1.
Proc Natl Acad Sci U S A ; 120(5): e2219091120, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36693098

RESUMO

Macrophage migration inhibitory factor (MIF) is a multifaced protein that plays important roles in multiple inflammatory conditions. However, the role of MIF in endothelial cell (EC) death under inflammatory condition remains largely unknown. Here we show that MIF actively promotes receptor-interacting protein kinase 1 (RIPK1)-mediated cell death under oxygen-glucose deprivation condition. MIF expression is induced by surgical trauma in peripheral myeloid cells both in perioperative humans and mice. We demonstrate that MIF-loaded myeloid cells induced by peripheral surgery adhere to the brain ECs after distal middle cerebral artery occlusion (dMCAO) and exacerbate the blood-brain barrier (BBB) disruption. Genetic depletion of myeloid-derived MIF in perioperative ischemic stroke (PIS) mice with MCAO following a surgical insult leads to significant reduction in ECs apoptosis and necroptosis and the associated BBB disruption. The adoptive transfer of peripheral blood mononuclear cells (PBMC) from surgical MIFΔLyz2 mice to wild-type (WT) MCAO mice also shows reduced ECs apoptosis and necroptosis compared to the transfer of PBMC from surgical MIFf  l/f  l mice to MCAO recipients. The genetic inhibition of RIPK1 also attenuates BBB disruption and ECs death compared to that of WT mice in PIS. The administration of MIF inhibitor (ISO-1) and RIPK1 inhibitor (Nec-1s) can both reduce the brain EC death and neurological deficits following PIS. We conclude that myeloid-derived MIF promotes ECs apoptosis and necroptosis through RIPK1 kinase-dependent pathway. The above findings may provide insights into the mechanism as how peripheral inflammation promotes the pathology in central nervous system.


Assuntos
Lesões Encefálicas , Fatores Inibidores da Migração de Macrófagos , Proteína Serina-Treonina Quinases de Interação com Receptores , Animais , Humanos , Camundongos , Apoptose , Morte Celular , Células Endoteliais/metabolismo , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Leucócitos Mononucleares/metabolismo , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
2.
Circulation ; 148(7): 589-606, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37203562

RESUMO

BACKGROUND: Aortic dissection (AD) is a fatal cardiovascular disorder without effective medications due to unclear pathogenic mechanisms. Bestrophin3 (Best3), the predominant isoform of bestrophin family in vessels, has emerged as critical for vascular pathological processes. However, the contribution of Best3 to vascular diseases remains elusive. METHODS: Smooth muscle cell-specific and endothelial cell-specific Best3 knockout mice (Best3SMKO and Best3ECKO, respectively) were engineered to investigate the role of Best3 in vascular pathophysiology. Functional studies, single-cell RNA sequencing, proteomics analysis, and coimmunoprecipitation coupled with mass spectrometry were performed to evaluate the function of Best3 in vessels. RESULTS: Best3 expression in aortas of human AD samples and mouse AD models was decreased. Best3SMKO but not Best3ECKO mice spontaneously developed AD with age, and the incidence reached 48% at 72 weeks of age. Reanalysis of single-cell transcriptome data revealed that reduction of fibromyocytes, a fibroblast-like smooth muscle cell cluster, was a typical feature of human ascending AD and aneurysm. Consistently, Best3 deficiency in smooth muscle cells decreased the number of fibromyocytes. Mechanistically, Best3 interacted with both MEKK2 and MEKK3, and this interaction inhibited phosphorylation of MEKK2 at serine153 and MEKK3 at serine61. Best3 deficiency induced phosphorylation-dependent inhibition of ubiquitination and protein turnover of MEKK2/3, thereby activating the downstream mitogen-activated protein kinase signaling cascade. Furthermore, restoration of Best3 or inhibition of MEKK2/3 prevented AD progression in angiotensin II-infused Best3SMKO and ApoE-/- mice. CONCLUSIONS: These findings unveil a critical role of Best3 in regulating smooth muscle cell phenotypic switch and aortic structural integrity through controlling MEKK2/3 degradation. Best3-MEKK2/3 signaling represents a novel therapeutic target for AD.


Assuntos
Dissecção Aórtica , Músculo Liso Vascular , Animais , Humanos , Camundongos , Dissecção Aórtica/genética , Sistema de Sinalização das MAP Quinases , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Fosforilação
3.
Small ; : e2310469, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38282141

RESUMO

Water splitting (or, water electrolysis) is considered as a promising approach to produce green hydrogen and relieve the ever-increasing energy consumption as well as the accompanied environmental impact. Development of high-efficiency, low-cost practical water-splitting systems demands elegant design and fabrication of catalyst-loaded electrodes with both high activity and long-life time. To this end, dimensional engineering strategies, which effectively tune the microstructure and activity of electrodes as well as the electrochemical kinetics, play an important role and have been extensively reported over the past years. Here, a type of most investigated electrode configurations is reviewed, combining particulate catalysts with 3D porous substrates (aerogels, metal foams, hydrogels, etc.), which offer special advantages in the field of water splitting. It is analyzed the design principles, structural and interfacial characteristics, and performance of particle-3D substrate electrode systems including overpotential, cycle life, and the underlying mechanism toward improved catalytic properties. In particular, it is also categorized the catalysts as different dimensional particles, and show the importance of building hybrid composite electrodes by dimensional control and engineering. Finally, present challenges and possible research directions toward low-cost high-efficiency water splitting and hydrogen production is discussed.

4.
PLoS Biol ; 19(4): e3001190, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33844686

RESUMO

Chemical insecticides have been heavily employed as the most effective measure for control of agricultural and medical pests, but evolution of resistance by pests threatens the sustainability of this approach. Resistance-conferring mutations sometimes impose fitness costs, which may drive subsequent evolution of compensatory modifier mutations alleviating the costs of resistance. However, how modifier mutations evolve and function to overcome the fitness cost of resistance still remains unknown. Here we show that overexpression of P450s not only confers imidacloprid resistance in the brown planthopper, Nilaparvata lugens, the most voracious pest of rice, but also leads to elevated production of reactive oxygen species (ROS) through metabolism of imidacloprid and host plant compounds. The inevitable production of ROS incurs a fitness cost to the pest, which drives the increase or fixation of the compensatory modifier allele T65549 within the promoter region of N. lugens peroxiredoxin (NlPrx) in the pest populations. T65549 allele in turn upregulates the expression of NlPrx and thus increases resistant individuals' ability to clear the cost-incurring ROS of any source. The frequent involvement of P450s in insecticide resistance and their capacity to produce ROS while metabolizing their substrates suggest that peroxiredoxin or other ROS-scavenging genes may be among the common modifier genes for alleviating the fitness cost of insecticide resistance.


Assuntos
Hemípteros/efeitos dos fármacos , Resistência a Inseticidas/efeitos dos fármacos , Neonicotinoides/farmacologia , Nitrocompostos/farmacologia , Oryza/parasitologia , Peroxirredoxinas/fisiologia , Adaptação Biológica/efeitos dos fármacos , Adaptação Biológica/genética , Alelos , Animais , Mapeamento Cromossômico , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Genes de Insetos/efeitos dos fármacos , Genes Modificadores/efeitos dos fármacos , Genes Modificadores/fisiologia , Estudos de Associação Genética , Aptidão Genética/efeitos dos fármacos , Hemípteros/fisiologia , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Oryza/efeitos dos fármacos , Peroxirredoxinas/genética , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade
5.
Acta Pharmacol Sin ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719954

RESUMO

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

6.
Photodermatol Photoimmunol Photomed ; 40(4): e12987, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38968385

RESUMO

BACKGROUND: Skin microbiota is essential for health maintenance. Photoaging is the primary environmental factor that affects skin homeostasis, but whether it influences the skin microbiota remains unclear. OBJECTIVE: The objective of this study is to investigate the relationship between photoaging and skin microbiome. METHODS: A cohort of senior bus drivers was considered as a long-term unilateral ultraviolet (UV) irradiated population. 16S rRNA amplicon sequencing was conducted to assess skin microbial composition variations on different sides of their faces. The microbiome characteristics of the photoaged population were further examined by photoaging guinea pig models, and the correlations between microbial metabolites and aging-related cytokines were analyzed by high-throughput sequencing and reverse transcription polymerase chain reaction. RESULTS: Photoaging decreased the relative abundance of microorganisms including Georgenia and Thermobifida in human skin and downregulated the generation of skin microbe-derived antioxidative metabolites such as ectoin. In animal models, Lactobacillus and Streptobacillus abundance in both the epidermis and dermis dropped after UV irradiation, resulting in low levels of skin antioxidative molecules and leading to elevated expressions of the collagen degradation factors matrix metalloproteinase (MMP)-1 and MMP-2 and inflammatory factors such as interleukin (IL)-1ß and IL-6. CONCLUSIONS: Skin microbial characteristics have an impact in photoaging and the loss of microbe-derived antioxidative metabolites impairs skin cells and accelerates the aging process. Therefore, microbiome-based therapeutics may have potential in delaying skin aging.


Assuntos
Microbiota , Envelhecimento da Pele , Pele , Raios Ultravioleta , Humanos , Animais , Cobaias , Pele/microbiologia , Pele/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , RNA Ribossômico 16S
7.
Cancer Sci ; 114(12): 4535-4547, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37750019

RESUMO

Papillary thyroid cancer (PTC) is the most common form of thyroid cancer and is characterized by its tendency for lymphatic metastasis, leading to a poor prognosis. Tetraspanin 1 (TSPAN1) is a member of the tetra-transmembrane protein superfamily and has been implicated in tumorigenesis and cancer metastasis in various studies. However, the role of TSPAN1 in PTC tumor development remains unclear. In this study, we aimed to investigate the impact of TSPAN1 on PTC cell behavior. Our results demonstrate that knockdown of TSPAN1 inhibits PTC cell proliferation, migration, and invasion, while overexpression of TSPAN1 has the opposite effect. These findings suggest that TSPAN1 might play a role in the tumorigenesis and invasiveness of PTC. Mechanistically, we found that TSPAN1 activates the ERK pathway by increasing its phosphorylation, subsequently leading to upregulated expression of c-Myc. Additionally, we observed that TSPAN1-ERK-c-Myc axis activation promotes glycolytic activity in PTC cells, as evidenced by the upregulation of glycolytic genes such as LDHA. Taken together, our findings indicate that TSPAN1 acts as an oncogene in PTC by regulating glycolytic metabolism. This discovery highlights the potential of TSPAN1 as a promising therapeutic target for PTC treatment. Further research in this area could provide valuable insights into the development of targeted therapies for PTC patients.


Assuntos
MicroRNAs , Neoplasias da Glândula Tireoide , Humanos , Linhagem Celular Tumoral , Neoplasias da Glândula Tireoide/patologia , Câncer Papilífero da Tireoide/patologia , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Proliferação de Células/genética , Tetraspaninas/genética , Tetraspaninas/metabolismo , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética
8.
Ecotoxicol Environ Saf ; 249: 114369, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508800

RESUMO

The use of broad-spectrum pesticides may reduce the biological control efficacy of predatory arthropods. Hence, the risks of pesticides to predators need to be evaluated. Here, we assessed the effects of a broad spectrum pyrethroid λ-cyhalothrin on a polyphagous predatory insect Eocanthecona furcellata via contact exposure route. The recommended application rate of λ-cyhalothrin was lower than the LR50 and HQ (in-field) was equal to 0.57, indicating the risk of λ-cyhalothrin to E. furcellata was low. Dried λ-cyhalothrin residue had no effect on the mortality, body weight, protein content of cuticle, or activities of major detoxification enzymes in E. furcellata. Residual of λ-cyhalothrin was only detected in the cuticle and legs of E. furcellata with a decreasing trend as time went by and no λ-cyhalothrin was detected inside the body. Additionally, a comparative transcriptome analysis was conducted to study global changes in gene expression in E. furcellata at different time points following exposure to λ-cyhalothrin-contaminated environment. A total of 57,839 unigenes with an average length of 1044 bp and an N50 of 1820 bp were obtained. In total, 118 and 109 differentially expressed genes (DEGs) at 12 h, and 60 h were identified between two groups. The DEGs were largely enriched in functional categories related to the structural constituent of cuticle. Accordingly, multiple cuticle protein-coding genes were up-regulated at 12 h after pesticide exposure. The present study stressed the importance of evaluating the compatibility between a specific pesticide (λ-cyhalothrin) and E. furcellata via simulating the releasing predators after insecticide application. The data could help optimize the pesticide use, optimizing the ecological services of E. furcellata as a BCA, and expanding its use into more areas of agriculture.


Assuntos
Heterópteros , Inseticidas , Piretrinas , Animais , Inseticidas/toxicidade , Piretrinas/toxicidade , Insetos , Nitrilas/toxicidade
9.
Nano Lett ; 22(9): 3744-3750, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35437988

RESUMO

Deciphering the precise physical mechanism of interaction between an adsorbed species and a reactive site in heterogeneous catalysis is crucial for predictive design of highly efficient catalysts. Here, using first-principles calculations we identify that the two-dimensional ferromagnetic metal organic framework of Mn2C18H12 can serve as a highly efficient single-atom catalyst for spin-triplet O2 activation and CO oxidation. The underlying mechanism is via "concerted charge-spin catalysis", involving a delicate synergetic process of charge transfer, provided by the hosting Mn atom, and spin selection, preserved through active participation of its nearest neighboring Mn atoms for the crucial step of O2 activation. The synergetic mechanism is further found to be broadly applicable in O2 adsorption on magnetic X2C18H12 (X = Mn, Fe, Co, and Ni) with a well-defined linear scaling dependence between the chemical activity and spin excitation energy. The present findings provide new insights into chemical reactions wherein spin selection plays a vital role.

10.
J Environ Manage ; 340: 117984, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37084646

RESUMO

River ecosystems interact strongly with adjacent terrestrial environments and receive dissolved organic matter (DOM) from a variety of sources, all of which are vulnerable to human activities and natural processes. However, it is unclear how and to what extent human and natural factors drive DOM quantity and quality changes in river ecosystems. Here, three fluorescence components were identified via optical techniques, including two humic-like substances and one protein-like component. The protein-like DOM was mainly accumulated in anthropogenically impacted regions, while humic-like components exhibit the opposite trend. Furthermore, the driving mechanisms of both natural and anthropogenic factors on the variations in DOM composition were investigated using partial least squares structural equation modelling (PLS-SEM). Human activities, especially agriculture, positively influence the protein-like DOM directly by enhancing anthropogenic discharge with protein signals and also indirectly by affecting water quality. Water quality directly influences the DOM composition by stimulating in-situ production through a high nutrient load from anthropogenic discharge and inhibiting the microbial humification processes of DOM due to higher salinity levels. The microbial humification processes can also be restricted directly by a shorter water residence time during the DOM transport processes. Furthermore, protein-like DOM was more sensitive to direct anthropogenic discharge than indirect in-situ production (0.34 vs. 0.25), especially from non-point source input (39.1%), implying that agricultural industry optimization may be an efficient way to improve water quality and reduce protein-like DOM accumulation.


Assuntos
Ecossistema , Rios , Humanos , Rios/química , Matéria Orgânica Dissolvida , Efeitos Antropogênicos , China , Substâncias Húmicas/análise , Espectrometria de Fluorescência
11.
Molecules ; 28(11)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37298979

RESUMO

Blumea balsamifera (L.) DC., a perennial herb in the Asteraceae family native to China and Southeast Asia, has a notable history of medicinal use due to its pharmacological properties. Using UPLC-Q-Orbitrap HRMS techniques, we systematically investigated the chemical constituents of this plant. A total of 31 constituents were identified, of which 14 were flavonoid compounds. Significantly, 18 of these compounds were identified in B. balsamifera for the first time. Furthermore, the mass spectrometry fragmentation patterns of significant chemical constituents identified in B. balsamifera were analyzed, providing important insights into their structural characteristics. The in vitro antioxidative potential of the methanol extract of B. balsamifera was assessed using DPPH and ABTS free-radical-scavenging assays, total antioxidative capacity, and reducing power. The antioxidative activity exhibited a direct correlation with the mass concentration of the extract, with IC50 values of 105.1 ± 0.503 µg/mL and 12.49 ± 0.341 µg/mL for DPPH and ABTS, respectively. For total antioxidant capacity, the absorbance was 0.454 ± 0.009 at 400 µg/mL. In addition, the reducing power was 1.099 ± 0.03 at 2000 µg/mL. This study affirms that UPLC-Q-Orbitrap HRMS can effectively discern the chemical constituents in B. balsamifera, primarily its flavonoid compounds, and substantiates its antioxidative properties. This underscores its potential utility as a natural antioxidant in the food, pharmaceutical, and cosmetics sectors. This research provides a valuable theoretical basis and reference value for the comprehensive development and utilization of B. balsamifera and expands our understanding of this medicinally valuable plant.


Assuntos
Antioxidantes , Asteraceae , Antioxidantes/farmacologia , Antioxidantes/química , Espectrometria de Massas , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Asteraceae/química , Flavonoides/química
12.
Helicobacter ; 27(2): e12879, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35124867

RESUMO

BACKGROUND: Although antimicrobial resistance (AMR) in Helicobacter pylori is a global threat to human health and the underlying molecular mechanisms have been explored previously, only a few of them are fully elucidated. MATERIALS AND METHODS: In the present study, we isolated 54 Helicobacter pylori strains from Southern China and assessed their susceptibility to five antibiotics using the agar dilution assay. Whole-genome sequencing was performed to screen the AMR genotypes of the Helicobacter pylori isolates. RESULTS: Our study revealed a high prevalence of resistance to clarithromycin (CLR), levofloxacin (LVX), and metronidazole (MTZ) in the Chinese isolates, 55.56% of which showed multidrug-resistant phenotypes. We screened for the 94 types of previously reported AMR mutations in 12 genes, but only a few of them were related to the AMR phenotype. Furthermore, we discovered four new mutations in the 23S rRNA gene and one mutation in infB related to CLR resistance. Another three mutations in gyrA and one in gyrB were closely correlated with the AMR pattern against LVX. We also demonstrated that the mutations R16C/H in rdxA, V56I in rpsU, and D54A in sodB might contribute to resistance to MTZ, which were previously reported in laboratory experiments but not found in clinical strains. We examined the concordance between the genotype and phenotype of AMR and identified several potential molecular biomarkers for predicting CLR and LVX resistance. CONCLUSIONS: Our study explored the molecular mechanisms underlying the antibiotic resistance of Helicobacter pylori isolates from Southern China. We propose further epidemiologic investigations in China.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Mutação , RNA Ribossômico 23S/genética
13.
Inorg Chem ; 61(47): 18899-18906, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36367771

RESUMO

The extreme magnetoresistance (XMR) of some compounds, challenging our understanding of magnetoresistance, is an interesting topic in condensed-matter and materials physics and future device applications. Here, we reported magnetotransport and magnetic properties of the as-grown and post-annealed TaCo2Te2 single crystals. The resistivity evolution with temperature in the two TaCo2Te2 single crystals shows a metallic behavior. Below 50 K, the XMR effect for the two crystals is found, and MR values at 3 K under 9 T are about 3.72 × 103% for the as-grown TaCo2Te2 and 5.71 × 102% for the annealed samples, larger than that of the previous report. The studies on the Hall effect of the two TaCo2Te2 single crystals indicate the multiband feature with high carrier mobilities from a two-band model. Electron and hole concentrations and mobilities of as-grown samples are comparable, while for the annealed sample, the hole concentration and mobility are larger than the electron concentration and mobility. The carrier mobilities for the two TaCo2Te2 single crystals have the same order of magnitude, ∼103 cm2 V-1 s-1. The XMR effect may be from high carrier mobilities. Magnetization of the as-grown TaCo2Te2 decreases with increasing temperature, and a weaker magnetic transition at ∼150 K is observed. The annealed TaCo2Te2 shows no magnetic transition and just a paramagnetic behavior with rising temperature. These results indicate that defects/deficiencies may play an important role in magnetotransport and magnetic properties of the two TaCo2Te2 single crystals. These results are helpful in deeply understanding the XMR mechanism and magnetic properties in TaCo2Te2 and offer a way to study the magnetic properties of the XMR Co-Te system.

14.
Phys Chem Chem Phys ; 24(29): 17832-17840, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35851386

RESUMO

Hydrogen energy is considered to be one of the most promising clean energy sources. The development of highly active, low-cost catalysts, and good stability is essential for hydrogen production. Herein, the catalytic activity of a two-dimensional ß-Sb surface doped with main-group elements (N, P, As, O, S, Se, and Te) for the hydrogen evolution reaction (HER) was investigated by density functional theory, and the catalytic activity of the ß-Sb monolayer can be improved by doping group VIA atoms. The catalytic activity of Se@Sb and O@Sb structures at the doping concentration of 2.78% and the S@Sb structure at the doping concentration of 5.56% may be as good as the Pt(111) surface, while keeping energetically stable. In addition, the catalytic performance could be optimized under biaxial strain. Further analysis suggests that the activity is caused by hole states in the lone pair electrons, which are created by the group VIA atom dopants. And our work also reveals that the density of states at the Fermi level could be an appropriate descriptor of the hydrogenation Gibbs free energy. This work not only proposes a novel non-platinum HER catalyst but also provides physical foundations for further application on antimonene-based catalysts.

15.
Eur Heart J ; 42(47): 4847-4861, 2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34570211

RESUMO

AIMS: Our previous study demonstrated that Ca2+ influx through the Orai1 store-operated Ca2+ channel in macrophages contributes to foam cell formation and atherosclerosis via the calcineurin-ASK1 pathway, not the classical calcineurin-nuclear factor of activated T-cell (NFAT) pathway. Moreover, up-regulation of NFATc3 in macrophages inhibits foam cell formation, suggesting that macrophage NFATc3 is a negative regulator of atherogenesis. Hence, this study investigated the precise role of macrophage NFATc3 in atherogenesis. METHODS AND RESULTS: Macrophage-specific NFATc3 knockout mice were generated to determine the effect of NFATc3 on atherosclerosis in a mouse model of adeno-associated virus-mutant PCSK9-induced atherosclerosis. NFATc3 expression was decreased in macrophages within human and mouse atherosclerotic lesions. Moreover, NFATc3 levels in peripheral blood mononuclear cells from atherosclerotic patients were negatively associated with plaque instability. Furthermore, macrophage-specific ablation of NFATc3 in mice led to the atherosclerotic plaque formation, whereas macrophage-specific NFATc3 transgenic mice exhibited the opposite phenotype. NFATc3 deficiency in macrophages promoted foam cell formation by potentiating SR-A- and CD36-meditated lipid uptake. NFATc3 directly targeted and transcriptionally up-regulated miR-204 levels. Mature miR-204-5p suppressed SR-A expression via canonical regulation. Unexpectedly, miR-204-3p localized in the nucleus and inhibited CD36 transcription. Restoration of miR-204 abolished the proatherogenic phenotype observed in the macrophage-specific NFATc3 knockout mice, and blockade of miR-204 function reversed the beneficial effects of NFATc3 in macrophages. CONCLUSION: Macrophage NFATc3 up-regulates miR-204 to reduce SR-A and CD36 levels, thereby preventing foam cell formation and atherosclerosis, indicating that the NFATc3/miR-204 axis may be a potential therapeutic target against atherosclerosis.


Assuntos
Aterosclerose , MicroRNAs , Animais , Aterosclerose/genética , Células Espumosas , Humanos , Leucócitos Mononucleares , Camundongos , MicroRNAs/genética , Fatores de Transcrição NFATC/genética , Pró-Proteína Convertase 9
16.
Angew Chem Int Ed Engl ; 61(32): e202207130, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35672265

RESUMO

Covalent organic frameworks (COFs) are appealing photocatalysts for toxic chemical degradation. Great efforts have been devoted to regulate the photocatalytic performance of COFs by tuning their organic building blocks, but the relationship between COF linkage and photochemical properties has rarely been explored. Herein, we report the synthesis and characterisation of a novel aminal-linked porphyrinic COF, namely Por-Aminal-COF. Por-Aminal-COF (0.25 mol %) showed excellent photocatalytic activity toward the detoxification of the sulfur mustard simulant with a half-life (t1/2 ) of 5 min, which is far lower than that of traditional imine-linked Por-COF (t1/2 =16 min). Transient absorption spectroscopy indicated that the aminal linkages of Por-Aminal-COF facilitated the intersystem crossing process. Thus, Por-Aminal-COF showed higher triplet-state generation efficiency compared with Por-COF, consequently promoting the activation of oxygen molecular to singlet oxygen.

17.
BMC Cancer ; 21(1): 753, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187411

RESUMO

BACKGROUND: Terminal differentiation-induced ncRNA (TINCR) plays an essential role in epidermal differentiation and is involved in the development of various cancers. METHODS: qPCR was used to detect the expression level of TINCR in tissues and cell lines of laryngeal squamous cell carcinoma (LSCC). The potential targets of TINCR were predicted by the bioinformation website. The expression of miR-210 and BTG2 genes were detected by qPCR, and the protein levels of BTG2 and Ki-67 were evaluated by western blot. CCK-8 assay, scratch test, and transwell chamber were used to evaluate the proliferation, invasion, and metastasis ability of LSCC cells. The relationships among TINCR, miR-210, and BTG2 were investigated by bioinformatics software and luciferase reporter assay. The in vivo function of TINCR was accessed on survival rate and tumor growth in nude mice. RESULTS: We used qRT-PCR to detect the expression of TINCR in laryngeal squamous cell carcinoma (LSCC) tissues and cells and found significantly lower levels in cancer tissues compared with adjacent tissues. Additionally, patients with high TINCR expression had a better prognosis. TINCR overexpression was observed to inhibit the proliferation and invasion of LSCC cells. TINCR was shown to exert its antiproliferation and invasion effects by adsorbing miR-210, which significantly promoted the proliferation and invasion of laryngeal squamous cells. Overexpression of miR-210 was determined to reverse the tumour-suppressive effects of TINCR. BTG2 (anti-proliferation factor 2) was identified as the target gene of miR-210, and BTG2 overexpression inhibited the proliferation and invasion of LSCC cells. BTG2 knockdown relieved the inhibitory effects of TINCR on the proliferation and invasion of LSCC. Finally, TINCR upregulation slowed xenograft tumour growth in nude mice and significantly increased survival compared with control mice. CONCLUSION: The results of this study suggest that TINCR inhibits the proliferation and invasion of LSCC by regulating the miR-210/BTG2 pathway, participates in cell cycle regulation, and may become a target for the treatment of LSCC.


Assuntos
MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Carcinoma de Células Escamosas , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Laríngeas/patologia , Camundongos , Camundongos Nus , Transfecção
18.
Nanotechnology ; 32(28)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761495

RESUMO

The transition metal sulfides/oxides have been considered as promising anode materials for lithium ion batteries due to their high theoretical capacities but have suffered limits from the unsatisfactory electronic conductivity and limited lifespan. Here, FeS micro-flowers are synthesized by hydrothermal treatment and are wared and grafted into layer-by-layer carbon nanotubes (CNT). Subsequently, FeS@Fe2O3/CNT composite films are obtained by annealing, during which the FeS micro-flowers are partially oxidized to core-shell FeS@Fe2O3micro-flowers. The FeS@Fe2O3/CNT composite electrodes exhibited high reversible capacity of 1722.4 mAh g-1(at a current density of 0.2 A g-1after 100 cycles) and excellent cycling stability (545.1 mAh g-1at a current density of 2 A g-1after 600 cycles) as self-supporting anodes. The prominent electrochemical performances are attributed to the unique reciprocal overlap architecture. This structure serves as a cushion to buffer large volume expansion during discharge/charge cycles, and ameliorates electrical conductivity. Due to their good specific capacity and cycle stability, these FeS@Fe2O3/CNT films have high potential application value to be used as high-performance anodes for lithium-ion, lithium sulfur and flexible packaging batteries.

19.
PLoS Genet ; 14(10): e1007725, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30332402

RESUMO

Symbiotic bacteria are important drivers of phenotypic diversity in insects. One of the widespread symbionts to have emerged belongs to the genus Arsenophonus, however, its biological functions in most host insects remain entirely unknown. Here we report two distinct Arsenophonus strains in the brown planthopper (BPH), Nilaparvata lugens, a major pest insect in Asian countries that causes significant economic damage through rice crop destruction. Genomic resequencing data suggested that one Arsenophonus strain (S-type) negatively affected the insecticide resistance of the host. Indeed, replacement of the resident Arsenophonus with the S-type Arsenophonus significantly decreased host insecticide resistance. Transcriptome and metabolome analysis revealed down-regulation of xenobiotic metabolism and increased amino acid accumulation in the S-type Arsenophonus infected host. This study demonstrates how a symbiont-mediated phenotypic change can occur. The results of this study will aid in developing strategies that work through imposing an ecological disadvantage on insect pests, which will be of great value for pest control in agricultural industry.


Assuntos
Enterobacteriaceae/genética , Resistência a Inseticidas/genética , Animais , Ásia , Bactérias/genética , DNA Bacteriano/genética , Hemípteros , Insetos/genética , Resistência a Inseticidas/fisiologia , Inseticidas , Polimorfismo de Nucleotídeo Único/genética , Simbiose/genética
20.
Chemistry ; 26(3): 584-591, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31725180

RESUMO

Selection of the friction electrode materials is crucial to the performance of a triboelectric nanogenerator (TENG). In the present study, a metal-organic coordination complex containing organosulfonate counteranions with electron-donating ability was synthesized through the coordination-driven self-assembly approach under mild reaction conditions and was chosen as a positive electrode material to construct a triboelectric nanogenerator, exhibiting high-output performance with a peak value of short circuit current density of 98.6 µA and an output voltage of 1180 V. As a practical application, it was shown to light up 1488 commercial green LEDs and power an anticorrosion system device to protect metals from corrosion.

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