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1.
Nature ; 592(7853): 220-224, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33828322

RESUMO

In condensed-matter systems, higher temperatures typically disfavour ordered phases, leading to an upper critical temperature for magnetism, superconductivity and other phenomena. An exception is the Pomeranchuk effect in 3He, in which the liquid ground state freezes upon increasing the temperature1, owing to the large entropy of the paramagnetic solid phase. Here we show that a similar mechanism describes the finite-temperature dynamics of spin and valley isospins in magic-angle twisted bilayer graphene2. Notably, a resistivity peak appears at high temperatures near a superlattice filling factor of -1, despite no signs of a commensurate correlated phase appearing in the low-temperature limit. Tilted-field magnetotransport and thermodynamic measurements of the in-plane magnetic moment show that the resistivity peak is connected to a finite-field magnetic phase transition3 at which the system develops finite isospin polarization. These data are suggestive of a Pomeranchuk-type mechanism, in which the entropy of disordered isospin moments in the ferromagnetic phase stabilizes the phase relative to an isospin-unpolarized Fermi liquid phase at higher temperatures. We find the entropy, in units of Boltzmann's constant, to be of the order of unity per unit cell area, with a measurable fraction that is suppressed by an in-plane magnetic field consistent with a contribution from disordered spins. In contrast to 3He, however, no discontinuities are observed in the thermodynamic quantities across this transition. Our findings imply a small isospin stiffness4,5, with implications for the nature of finite-temperature electron transport6-8, as well as for the mechanisms underlying isospin ordering and superconductivity9,10 in twisted bilayer graphene and related systems.

2.
Mol Biol Evol ; 41(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38401527

RESUMO

Following invasion, insects can become adapted to conditions experienced in their invasive range, but there are few studies on the speed of adaptation and its genomic basis. Here, we examine a small insect pest, Thrips palmi, following its contemporary range expansion across a sharp climate gradient from the subtropics to temperate areas. We first found a geographically associated population genetic structure and inferred a stepping-stone dispersal pattern in this pest from the open fields of southern China to greenhouse environments of northern regions, with limited gene flow after colonization. In common garden experiments, both the field and greenhouse groups exhibited clinal patterns in thermal tolerance as measured by critical thermal maximum (CTmax) closely linked with latitude and temperature variables. A selection experiment reinforced the evolutionary potential of CTmax with an estimated h2 of 6.8% for the trait. We identified 3 inversions in the genome that were closely associated with CTmax, accounting for 49.9%, 19.6%, and 8.6% of the variance in CTmax among populations. Other genomic variations in CTmax outside the inversion region were specific to certain populations but functionally conserved. These findings highlight rapid adaptation to CTmax in both open field and greenhouse populations and reiterate the importance of inversions behaving as large-effect alleles in climate adaptation.


Assuntos
Adaptação Fisiológica , Inversão Cromossômica , Animais , Adaptação Fisiológica/genética , Clima , Temperatura , Insetos
3.
Phys Rev Lett ; 132(4): 046603, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38335366

RESUMO

Bernal bilayer graphene hosts even-denominator fractional quantum Hall states thought to be described by a Pfaffian wave function with non-Abelian quasiparticle excitations. Here, we report the quantitative determination of fractional quantum Hall energy gaps in bilayer graphene using both thermally activated transport and by direct measurement of the chemical potential. We find a transport activation gap of 5.1 K at B=12 T for a half filled N=1 Landau level, consistent with density matrix renormalization group calculations for the Pfaffian state. However, the measured thermodynamic gap of 11.6 K is smaller than theoretical expectations for the clean limit by approximately a factor of 2. We analyze the chemical potential data near fractional filling within a simplified model of a Wigner crystal of fractional quasiparticles with long-wavelength disorder, explaining this discrepancy. Our results quantitatively establish bilayer graphene as a robust platform for probing the non-Abelian anyons expected to arise as the elementary excitations of the even-denominator state.

4.
Br J Dermatol ; 191(3): 385-396, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-38655652

RESUMO

BACKGROUND: Psoriasis is a common chronic inflammatory disease with an unclear aetiology. Keratinocytes in psoriasis are susceptible to exogenous triggers that induce inflammatory cell death. OBJECTIVES: To investigate whether gasdermin E (GSDME)-mediated pyroptosis in keratinocytes contributes to the pathogenesis of psoriasis. METHODS: Skin samples from patients with psoriasis and from healthy controls were collected to evaluate the expression of GSDME, cleaved caspase-3 and inflammatory factors. We then analysed the data series GSE41662 to further compare the expression of GSDME between lesional and nonlesional skin samples in those with psoriasis. In vivo, a caspase-3 inhibitor and GSDME-deficient mice (Gsdme-/-) were used to block caspase-3/GSDME activation in an imiquimod-induced psoriasis model. Skin inflammation, disease severity and pyroptosis-related proteins were analysed. In vitro, tumour necrosis factor (TNF)-α-induced caspase-3/GSDME-mediated pyroptosis in the HACAT cell line was explored. RESULTS: Our analysis of the GSE41662 data series found that GSDME was upregulated in psoriasis lesions vs. normal skin. High levels of inflammatory cytokines such as interleukin (IL)-1ß, IL-6 and TNF-α were also found in psoriasis lesions. In mice in the Gsdme-/- and caspase-3 inhibitor groups, the severity of skin inflammation was attenuated and GSDME and cleaved caspase-3 levels decreased after imiquimod treatment. Similarly, IL-1ß, IL-6 and TNF-α expression was decreased in the Gsdme-/- and caspase-3 inhibitor groups. In vitro, TNF-α induced HACAT cell pyroptosis through caspase-3/GSDME pathway activation, which was suppressed by blocking caspase-3 or silencing Gsdme. CONCLUSIONS: Our study provides a novel explanation of TNF-α/caspase-3/GSDME-mediated keratinocyte pyroptosis in the initiation and -acceleration of skin inflammation and the progression of psoriasis.


Psoriasis is chronic and autoinflammatory common skin disease that affects 2­3% of the world's population. The disease is characterized by persistent inflammation in various body systems, including the skin and joints. However, the exact cause of the disease is unclear. In this study from China, we found that in people with psoriasis a protein called 'gasdermin E' (or 'GSDME') is increased in a type of skin cell called keratinocytes. In psoriasis, these keratinocytes are susceptible to a type of cell death called 'pyroptosis'. We aimed to find out whether pyroptosis caused by GSDME in keratinocytes contributes to the development of psoriasis. To do this, we looked at samples of skin from people with psoriasis and compared these to samples from healthy controls (those without psoriasis). Firstly, we investigated the levels of GSDME, another protein called caspase-3 and other inflammatory factors in the skin lesions from patients with psoriasis. Secondly, we analysed previously published data from 24 patients with psoriasis. Finally, we carried out a range of experiments to confirm our findings. We found that keratinocyte pyroptosis was mediated by the messenger proteins TNF-α/caspase-3, and that GSDME played a key role in the initiation and acceleration of skin inflammation and the progression of psoriasis. Targeting the GSDME pathway may be a novel strategy in treating psoriasis.


Assuntos
Imiquimode , Queratinócitos , Psoríase , Piroptose , Piroptose/fisiologia , Psoríase/patologia , Psoríase/metabolismo , Psoríase/imunologia , Humanos , Queratinócitos/metabolismo , Animais , Camundongos , Camundongos Knockout , Pele/patologia , Pele/metabolismo , Pele/imunologia , Caspase 3/metabolismo , Modelos Animais de Doenças , Células HaCaT , Masculino , Feminino , Proteínas de Ligação a Fosfato/metabolismo , Estudos de Casos e Controles , Regulação para Cima , Fator de Necrose Tumoral alfa/metabolismo , Gasderminas
5.
Mol Ecol ; 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37277936

RESUMO

Adaptive evolution following colonization can affect the impact of invasive species. The fall webworm (FWW) invaded China 40 years ago through a single introduction event involving a severe bottleneck and subsequently diverged into two genetic groups. The well-recorded invasion history of FWW, coupled with a clear pattern of genetic divergence, provides an opportunity to investigate whether there is any sign of adaptive evolution following the invasion. Based on genome-wide SNPs, we identified genetically separated western and eastern groups of FWW and correlated spatial variation in SNPs with geographical and climatic factors. Geographical factors explained a similar proportion of the genetic variation across all populations compared with climatic factors. However, when the two population groups were analysed separately, environmental factors explained more variation than geographical factors. SNP outliers in populations of the western group had relatively stronger response to precipitation than temperature-related variables. Functional annotation of SNP outliers identified genes associated with insect cuticle protein potentially related to desiccation adaptation in the western group and genes associated with lipase biosynthesis potentially related to temperature adaptation in the eastern group. Our study suggests that invasive species may maintain the evolutionary potential to adapt to heterogeneous environments despite a single invasion event. The molecular data suggest that quantitative trait comparisons across environments would be worthwhile.

6.
Phys Rev Lett ; 131(22): 226501, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101367

RESUMO

The phase diagram of an interacting two-dimensional electron system in a high magnetic field is enriched by the varying form of the effective Coulomb interaction, which depends strongly on the Landau level index. While the fractional quantum Hall states that dominate in the lower-energy Landau levels have been explored experimentally in a variety of two-dimensional systems, much less work has been done to explore electron solids owing to their subtle transport signatures and extreme sensitivity to disorder. Here, we use chemical potential measurements to map the phase diagram of electron solid states in N=2, N=3, and N=4 Landau levels in monolayer graphene. Direct comparison between our data and theoretical calculations reveals a cascade of density-tuned phase transitions between electron bubble phases up to two, three, or four electrons per bubble in the N=2, 3, and 4 Landau levels, respectively. Finite-temperature measurements are consistent with melting of the solids for T≈1 K.

7.
Mol Ecol ; 31(21): 5568-5580, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35984732

RESUMO

How invasive species cope with novel selective pressures with limited genetic variation is a fundamental question in molecular ecology. Several mechanisms have been proposed, but they can lack generality. Here, we addressed an alternative solution, polygenic adaptation, wherein traits that arise from multiple combinations of loci may be less sensitive to loss of variation during invasion. We tested the polygenic signal of environmental adaptation of Colorado potato beetle (CPB) introduced in Eurasia. Population genomic analyses showed declining genetic diversity in the eastward expansion of Eurasian populations, and weak population genetic structure (except for the invasion fronts in Asia). Demographic history showed that all populations shared a strong bottleneck about 100 years ago when CPB was introduced to Europe. Genome scans revealed a suite of genes involved in activity regulation functions that are plausibly related to cold stress, including some well-founded functions (e.g., the activity of phosphodiesterase, the G-protein regulator) and discrete functions. Such polygenic architecture supports the hypothesis that polygenic adaptation and potentially genetic redundancy can fuel the adaptation of CPB despite strong genetic depletion, thus representing a promising general mechanism for resolving the genetic paradox of invasion. More broadly, most complex traits based on polygenes may be less sensitive to invasive bottlenecks, thus ensuring the evolutionary success of invasive species in novel environments.


Assuntos
Besouros , Solanum tuberosum , Animais , Besouros/genética , Herança Multifatorial/genética , Espécies Introduzidas , Diester Fosfórico Hidrolases/genética
8.
BMC Med Inform Decis Mak ; 22(1): 344, 2022 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-36581862

RESUMO

BACKGROUND: Clinical diagnosis based on machine learning usually uses case samples as training samples, and uses machine learning to construct disease prediction models characterized by descriptive texts of clinical manifestations. However, the problem of sample imbalance often exists in the medical field, which leads to a decrease in classification performance of the machine learning. METHODS: To solve the problem of sample imbalance in medical dataset, we propose a hybrid sampling algorithm combining synthetic minority over-sampling technique (SMOTE) and edited nearest neighbor (ENN). Firstly, the SMOTE is used to over-sampling missed abortion and diabetes datasets, so that the number of samples of the two classes is balanced. Then, ENN is used to under-sampling the over-sampled dataset to delete the "noisy sample" in the majority. Finally, Random forest is used to model and predict the sampled missed abortion and diabetes datasets to achieve an accurate clinical diagnosis. RESULTS: Experimental results show that Random forest has the best classification performance on missed abortion and diabetes datasets after SMOTE-ENN sampled, and the MCC index is 95.6% and 90.0%, respectively. In addition, the results of pairwise comparison and multiple comparisons show that the SMOTE-ENN is significantly better than other sampling algorithms. CONCLUSION: Random forest has significantly improved all indexes on the missed abortion dataset after SMOTE-ENN sampled.


Assuntos
Aborto Induzido , Aborto Retido , Feminino , Humanos , Gravidez , Algoritmos , Aprendizado de Máquina , Algoritmo Florestas Aleatórias , Árvores de Decisões
9.
Waste Manag Res ; 40(9): 1440-1449, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35212588

RESUMO

Anaerobic digestion, one of the most currently remarkable techniques for biogas production, has provided a method of high organic solid waste disposal. Operating temperature, especially in the winter of northern city, makes biomass degradation less efficient. The microorganisms that take on the role of gas production are greatly affected by temperature. In our study, solar energy was selected for anaerobic digestion and winter was selected as the experimental environment. Anaerobic digestion was performed with solar heating and electric heating separately. Parameters were tested (pH, soluble chemical oxygen demand, total ammonia nitrogen, total volatile fatty acids), and microbial structure was monitored. The volume of methane produced was measured over 60 days. The methane yield differed by 15.92% under different conditions. It is clearly shown that methane yield can be improved by a steady temperature environment. Nevertheless, dominant bacteria and microbial structure did not seem to be much different. This study may provide more energy-saving ideas for winter anaerobic digestion projects in northern regions.


Assuntos
Eliminação de Resíduos , Energia Solar , Anaerobiose , Biocombustíveis , Reatores Biológicos , Alimentos , Calefação , Metano , Eliminação de Resíduos/métodos , Temperatura
10.
Phys Rev Lett ; 126(15): 156802, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33929240

RESUMO

We describe an experimental technique to measure the chemical potential µ in atomically thin layered materials with high sensitivity and in the static limit. We apply the technique to a high quality graphene monolayer to map out the evolution of µ with carrier density throughout the N=0 and N=1 Landau levels at high magnetic field. By integrating µ over filling factor ν, we obtain the ground state energy per particle, which can be directly compared to numerical calculations. In the N=0 Landau level, our data show exceptional agreement with numerical calculations over the whole Landau level without adjustable parameters as long as the screening of the Coulomb interaction by the filled Landau levels is accounted for. In the N=1 Landau level, a comparison between experimental and numerical data suggests the importance of valley anisotropic interactions and reveals a possible presence of valley-textured electron solids near odd filling.

11.
Diabetes Metab Res Rev ; 37(4): e3432, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400837

RESUMO

AIMS: Urinary haptoglobin (UHp) is a potential biomarker for predicting progress of diabetic kidney disease (DKD) to remedy the defects of currently used urinary albumin. The clinical application of UHp is however limited, owing to the extremely low level in urine. This study aims to establish an enzyme-linked immunosorbent assay (ELISA) kit specifically for detecting UHp in urine samples of patients with diabetes and DKD. MATERIALS AND METHODS: Supersensitive human haptoglobin antibodies were generated for ELISA kit development, and the sensitivity, specificity and reproducibility of the kit was evaluated. This kit was used to detect UHp in 246 healthy individuals and 83 patients with type 2 diabetes (T2D). The interference of blood haptoglobin genotypes on UHp measurement was analysed. RESULTS: The UHp ELISA kit had a standard curve ranging from 5 to 200 ng/ml. The low detection limit was 0.11 ng/ml. The coefficients of variation of intra- and interassay were 5.5% and 8.3%, respectively. The kit showed high accuracy with 100.9% mean recovery rate, and linearity R2  = 0.999. The reference range of UHp was 0-42.3 ng/g creatinine (0-Q95) in the healthy individuals. UHp level was significantly higher in T2D patients with microalbuminuria and macroalbuminuria than that in T2D without microalbuminuria (p < 0.01). The UHp concentration measured by this kit was not affected by haptoglobin genotypes. CONCLUSIONS: We have generated an ELISA kit to accurately detect UHp levels, which is potentially a reliable biomarker of DKD.


Assuntos
Nefropatias Diabéticas , Ensaio de Imunoadsorção Enzimática , Haptoglobinas , Biomarcadores/urina , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Haptoglobinas/urina , Humanos , Reprodutibilidade dos Testes
12.
Diabet Med ; 38(2): e14456, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33169869

RESUMO

AIM: PAX6 is a transcription factor involved in embryonic development of many organs, including the eyes and the pancreas. Mutations of PAX6 gene is the main cause of a rare disease, congenital aniridia (CA). This case-control study aims to investigate the effects of PAX6 mutations on glucose metabolism and insulin secretion in families with CA. METHODS: In all, 21 families with CA were screened by Sanger sequencing. Patients with PAX6 mutations and CA (cases) and age-matched healthy family members (controls) were enrolled. Oral glucose tolerance test (OGTT) was performed to detect diabetes or impaired glucose tolerance (IGT). Insulin and proinsulin secretion were evaluated. RESULTS: Among 21 CA families, heterozygous PAX6 mutations were detected in five families. Among cases (n = 10) from the five families, two were diagnosed with newly identified diabetes and another two were diagnosed with IGT. Among controls (n = 12), two had IGT. The levels of haemoglobin A1c were 36 ± 4 mmol/mol (5.57 ± 0.46%) and 32 ± 5 mmol/L (5.21 ± 0.54%) in the cases and the controls, respectively (p = 0.049). More importantly, levels of proinsulin in the cases were significantly higher than that of the controls, despite similar levels of total insulin. The areas under the curve of proinsulin in the cases (6425 ± 4390) were significantly higher than that of the controls (3709 ± 1769) (p = 0.032). CONCLUSION: PAX6 may participate in the production of proinsulin to insulin and heterozygous PAX6 mutations may be associated with glucose metabolism in CA patients.


Assuntos
Aniridia/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus/genética , Intolerância à Glucose/genética , Fator de Transcrição PAX6/genética , Adulto , Peptídeo C/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Intolerância à Glucose/metabolismo , Hemoglobinas Glicadas/metabolismo , Heterozigoto , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Proinsulina/metabolismo
13.
Phys Chem Chem Phys ; 23(38): 21701-21713, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34581333

RESUMO

Dimethyldodecylamine N-oxide (DDAO), a unique type of surfactant, shows high surface activity with two distinct energy states at the buried hydrophilic silica/aqueous solution interface studied by total internal reflection (TIR) Raman spectroscopy combined with ratiometric and kinetic analysis. Different from other types of surfactant, i.e., ionic and nonionic, the adsorption of DDAO demonstrates a specific critical surface aggregation concentration (csac) at 0.15 mM gives a complete surface coverage of 6.6 ± 0.3 µmol m-2, much lower than the bulk critical micellization concentration (cmc) at the same conditions (csac ≈ 0.072 cmc). A phase transition of adsorbed layers from liquid crystalline as the intermediate state to the disordered liquid phase is spectroscopically and energetically analyzed. The adsorption of DDAO on silica surfaces is described quantitatively in a potential energy curve.

14.
Phys Chem Chem Phys ; 23(8): 4944-4950, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33621292

RESUMO

Sum-frequency generation imaging microscopy combined with compressive-sensing (CS-SFG) is a powerful micro-spectroscopic technique for probing interfaces and surfaces with a spatial resolution where contrast is based on the chemical functional groups. We reported the use of the CS-SFG technique to probe the electric field due to charge accumulation and the internal electric field in operating organic field-effect transistors (OFETs) with the aluminum oxide and octadecylphosphonic acid (ODPA) self-assembled monolayer as the gate dielectric layer and 2,7-diphenyl[1]benzothieno[3,2-b][1]benzothiophene (DPh-BTBT) as the semiconductor layer. In addition, the electric field behavior was discussed by a difference in the electric field induced SFG intensity between the open-circuit and the voltage application conditions. The SFG peak of CH stretching mode derived from methyl groups of ODPA and phenyl groups of DPh-BTBT could be observed at each interface of ODPA/DPh-BTBT or DPh-BTBT/Au, respectively. Moreover, the electric field induced SFG coming from ODPA/DPh-BTBT shows the presence of intense electric field due to charge injection and accumulation near the drain and source electrode edges under the operation of OFETs. Our studies show that the electric field-induced SFG imaging technique is useful for probing the local electric field distribution or charge accumulation behavior in OFETs under operating conditions.

15.
J Immunol ; 201(12): 3514-3523, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30397034

RESUMO

Trafficking of dendritic cells (DCs) to lymph nodes (LNs) to present Ags is a crucial step in the pathogenesis of rheumatoid arthritis (RA). Matrix metalloproteinase-9 (MMP-9) is the key molecule for DC migration. Thus, blocking MMP-9 to inhibit DC migration may be a novel strategy to treat RA. In this study, we used anti-MMP-9 Ab to treat collagen-induced arthritis (CIA) in DBA/1J mice and demonstrated that anti-MMP-9 Ab treatment significantly suppressed the development of CIA via the modulation of DC trafficking. In anti-MMP-9 Ab-treated CIA mice, the number of DCs in draining LNs was obviously decreased. In vitro, anti-MMP-9 Ab and MMP-9 inhibitor restrained the migration of mature bone marrow-derived DCs in Matrigel in response to CCR7 ligand CCL21. In addition, blocking MMP-9 decreased T and B cell numbers in LNs of CIA mice but had no direct influence on the T cell response to collagen II by CD4+ T cells purified from LNs or spleen. Besides, anti-MMP-9 Ab did not impact on the expression of MHC class II, CD40, CD80, CD86, and chemokine receptors (CCR5 and CCR7) of DCs both in vivo and in vitro. Furthermore, we discovered the number of MMP-9-/- DCs trafficking from footpads to popliteal LNs was dramatically reduced as compared with wild type DCs in both MMP-9-/- mice and wild type mice. Taken together, these results indicated that DC-derived MMP-9 is the crucial factor for DC migration, and blocking MMP-9 to inhibit DC migration may constitute a novel strategy of future therapy for RA and other similar autoimmune diseases.


Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Metaloproteinase 9 da Matriz/metabolismo , Animais , Anticorpos Monoclonais/metabolismo , Movimento Celular , Células Cultivadas , Modelos Animais de Doenças , Humanos , Masculino , Metaloproteinase 9 da Matriz/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout
16.
Biochem Biophys Res Commun ; 508(2): 556-562, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30509498

RESUMO

Regulatory Factor X-box binding transcriptional factor 6 (Rfx6) plays an important role in the differentiation and development of pancreas in mammals. However, the direct target genes of Rfx6 to regulate this process were largely unknown. The present study aimed to investigate the function of Rfx6 on regulating pancreatic differentiation and development in a physiologically-relevant context. We performed the chromatin immunoprecipitation followed by the next generation sequencing analysis (ChIP-seq) using whole pancreatic tissue harvested from C57/BL6 adult mice to find target genes of Rfx6. We captured 4146 unique peaks in the genome region of the adult murine pancreas. Among all these binding peaks, a majority were located in intron or intergenic regions. We further annotated all peaks to their nearest gene, and over 1000 genes were captured as Rfx6-binding genes in the pancreas. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis found that Rfx6-binding genes to be associated with the pancreas developmental process. A portion of selected ChIP-seq targets related with pancreas differentiation including Pdx1, Neurod1, Hnf1a, Nkx6-1, St18 and Shox2 were selected and validated as true targets by independent qPCR experiments. In addition, Rfx6 can directly bind to upstream of MiR-145, MiR-195, and possibly other non-protein-coding functional RNAs to control adult mouse pancreatic differentiation. Interestingly, our study revealed that Rfx6 played an important role in insulin translation by binding to the Eif2ak1, Upf1, and Eif5. Our data provide direct target genes of Rfx6 during pancreas development and point to Rfx6 as a potential therapeutic target for improving insulin protein content.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Insulina/biossíntese , Pâncreas/crescimento & desenvolvimento , Fatores de Transcrição de Fator Regulador X/genética , Animais , Diferenciação Celular , Regulação da Expressão Gênica , Insulina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Organogênese , Pâncreas/química , Ligação Proteica , Fatores de Transcrição de Fator Regulador X/metabolismo
17.
Diabetes Metab Res Rev ; 35(4): e3123, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30604460

RESUMO

BACKGROUND: Previous works indicated that the stress on the endoplasmic reticulum (ER) affected nonalcoholic fatty liver disease (NAFLD). However, there is no clear evident on the effect of the regulation of ER stress by angiotensin-converting enzyme 2 (ACE2) on the prevention of NAFLD. METHODS: HepG2 cells were treated with thapsigargin (Tg) or palmitic acid (PA). We analysed ACE2 expression using Western-blotting analyses. ER stress-related proteins were detected in ACE2 knockout mice and Ad-ACE2-treated db/db mice by immunofluorescence or Western-blotting analyses. In ACE2-overexpression HepG2 cells, the triglyceride (TG), total cholesterol (TC), and glycogen content were detected by assay kits. Meanwhile, the expression of hepatic lipogenic proteins (ACCα, SREBP-1c, FAS, and LXRα), enzymes for gluconeogenesis (PEPCK, G6Pase, and IRS2), and IKKß/NFκB/IRS1/Akt pathway were analysed by Western-blotting analyses. RESULTS: ACE2 was significantly increased in Tg/PA-induced cultured hepatocytes. Additionally, ACE2 knockout mice displayed elevated levels of ER stress, while Ad-ACE2-treated db/db mice showed reduced ER stress in liver. Furthermore, activation of ACE2 can ameliorate ER stress, accompanied by decreased TG content, increased intracellular glycogen, and downregulated expression of hepatic lipogenic proteins and enzymes for gluconeogenesis in Tg/PA-induced hepatocytes. As a consequence of anti-ER stress, the activation of ACE2 led to improved glucose and lipid metabolism through the IKKß/NFκB/IRS1/Akt pathway. CONCLUSIONS: This is the first time documented that ACE2 had a notable alleviating role in ER stress-induced hepatic steatosis and glucose metabolism via the IKKß/NFκB/IRS1/Akt-mediated pathway. This study may further provide insight into a novel underlying mechanism and a strategy for treating NAFLD.


Assuntos
Estresse do Retículo Endoplasmático , Gluconeogênese , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Peptidil Dipeptidase A/fisiologia , Transdução de Sinais , Enzima de Conversão de Angiotensina 2 , Animais , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Triglicerídeos/metabolismo
18.
Nano Lett ; 18(10): 6611-6616, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30216077

RESUMO

The advent of black phosphorus field-effect transistors (FETs) has brought new possibilities in the study of two-dimensional (2D) electron systems. In a black phosphorus FET, the gate induces highly anisotropic 2D electron and hole gases. Although the 2D hole gas in black phosphorus has reached high carrier mobilities that led to the observation of the integer quantum Hall effect, the improvement in the sample quality of the 2D electron gas (2DEG) has however been only moderate; quantum Hall effect remained elusive. Here, we obtain high quality black phosphorus 2DEG by defining the 2DEG region with a prepatterned graphite local gate. The graphite local gate screens the impurity potential in the 2DEG. More importantly, it electrostatically defines the edge of the 2DEG, which facilitates the formation of well-defined edge channels in the quantum Hall regime. The improvements enable us to observe precisely quantized Hall plateaus in electron-doped black phosphorus FET. Magneto-transport measurements under high magnetic fields further revealed a large effective mass and an enhanced Landé g-factor, which points to strong electron-electron interaction in black phosphorus 2DEG. Such strong interaction may lead to exotic many-body quantum states in the fractional quantum Hall regime.

19.
Biochem Biophys Res Commun ; 495(1): 860-866, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29128354

RESUMO

Mitochondrial metabolism plays an essential role in the regulation of insulin release and glucose homeostasis. Evidence demonstrated that the angiotensin-converting enzyme 2 (ACE2) participates in the regulation of glucose metabolism, however, its role in mitochondrial metabolism remains unclear. The purpose of our study was to determine if ACE2 can regulate mitochondrial function in pancreatic ß-cells. We found that ACE2 over-expression restored glucose-stimulated insulin secretion (GSIS) and mitochondrial membrane potential (MMP) in the presence of H2O2 in INS-1 cells. PCR array demonstrated that ACE2 over-expression up-regulated 67 mitochondria-related genes in INS-1 cells. In pancreatic islets, ACE2 ablation attenuated intracellular calcium influx with a decrease in GSIS. Ace2-/y mice islets exhibited impaired mitochondrial respiration and lower production of ATP, along with decreased expression of genes involved in mitochondrial oxidation. In islets from db/db mice, ACE2 over-expression increased intracellular calcium influx and restored impaired mitochondrial oxidation, potentially causing an increase in GSIS. These results shed light on the potential roles of ACE2 in mitochondrial metabolism, moreover, may improve our understanding of diabetes.


Assuntos
Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Peptidil Dipeptidase A/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , Sinalização do Cálcio/fisiologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Masculino , Camundongos , Camundongos Knockout , Consumo de Oxigênio/fisiologia
20.
Langmuir ; 34(18): 5273-5278, 2018 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-29672067

RESUMO

Cooperative effects of a series of equimolar binary zwitterionic-ionic surfactant mixtures on the interfacial water structure at the air-water interfaces have been studied by sum frequency generation vibrational spectroscopy (SFG-VS). For zwitterionic surfactant palmityl sulfobetaine (SNC16), anionic surfactant sodium hexadecyl sulfate (SHS), and cationic surfactant cetyltrimethylammonium bromide (CTAB) with the same length of alkyl chain, significantly enhanced ordering of interfacial water molecules was observed for the zwitterionic-anionic surfactant mixtures SNC16-SHS, indicating that SNC16 interacts more strongly with SHS than with CTAB because of the strong headgroup-headgroup electrostatic attraction for SNC16-SHS. Meanwhile, the SFG amplitude ratio of methyl and methylene symmetric stretching modes was used to verify the stronger interaction between SNC16 and SHS. The conformational order indicator increased from 0.64 for SNC16 to 7.17 for SNC16-SHS but only 0.94 for SNC16-CTAB. In addition, another anionic surfactant sodium dodecyl sulfate (SDS) was introduced to study the influence of chain-chain interaction. Decreased SFG amplitude of interfacial water molecules for SNC16-SDS was observed. Therefore, both the headgroup-headgroup electrostatic interaction and chain-chain van der Waals attractive interaction of the surfactants play an important role in enhancing the ordering of interfacial water molecules. The results provided experimental and theoretical bases for practical applications of the surfactants.

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