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1.
J Org Chem ; 88(20): 14274-14282, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37774417

RESUMO

An environmentally benign and efficient method for the synthesis of unsymmetrical diquinoxalin-2(1H)-ones with potential axial chirality via inexpensive copper-catalyzed, low-toxicity, and stable PIFA oxidation, rarely assisted by PhSeSePh, regioselective homocoupling of quinoxalin-2(1H)-ones under mild conditions is developed. This practical scheme is compatible with a variety of functional groups and allows the preparation of functionalized unsymmetrical dimeric quinoxalin-2(1H)-ones from readily available and safe starting materials, providing new ideas for the sustainable development of methodological studies of quinoxalin-2(1H)-ones.

2.
Proc Natl Acad Sci U S A ; 117(21): 11459-11470, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32385148

RESUMO

Genomic regions preferentially associate with regions of similar transcriptional activity, partitioning genomes into active and inactive compartments within the nucleus. Here we explore mechanisms controlling genome compartment organization in Caenorhabditis elegans and investigate roles for compartments in regulating gene expression. Distal arms of C. elegans chromosomes, which are enriched for heterochromatic histone modifications H3K9me1/me2/me3, interact with each other both in cis and in trans, while interacting less frequently with central regions, leading to genome compartmentalization. Arms are anchored to the nuclear periphery via the nuclear envelope protein CEC-4, which binds to H3K9me. By performing genome-wide chromosome conformation capture experiments (Hi-C), we showed that eliminating H3K9me1/me2/me3 through mutations in the methyltransferase genes met-2 and set-25 significantly impaired formation of inactive Arm and active Center compartments. cec-4 mutations also impaired compartmentalization, but to a lesser extent. We found that H3K9me promotes compartmentalization through two distinct mechanisms: Perinuclear anchoring of chromosome arms via CEC-4 to promote their cis association, and an anchoring-independent mechanism that compacts individual chromosome arms. In both met-2 set-25 and cec-4 mutants, no dramatic changes in gene expression were found for genes that switched compartments or for genes that remained in their original compartment, suggesting that compartment strength does not dictate gene-expression levels. Furthermore, H3K9me, but not perinuclear anchoring, also contributes to formation of another prominent feature of chromosome organization, megabase-scale topologically associating domains on X established by the dosage compensation condensin complex. Our results demonstrate that H3K9me plays crucial roles in regulating genome organization at multiple levels.


Assuntos
Caenorhabditis elegans/genética , Cromossomos/metabolismo , Histonas/metabolismo , Lisina/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Núcleo Celular/genética , Núcleo Celular/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Cromossomos/genética , Regulação da Expressão Gênica , Genoma , Heterocromatina/genética , Heterocromatina/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/genética , Lisina/genética , Metilação , Mutação , Cromossomo X/genética , Cromossomo X/metabolismo
3.
Molecules ; 28(13)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37446689

RESUMO

In recent years, Web of Science has published nearly one hundred reports per year on quinoxalin-2(1H)-ones, which have attracted great interest due to their wide applications in pharmaceutical and materials fields, especially in recyclable heterogeneous catalytic reactions for direct C-H functionalisation. This review summarises for the first time the methods and reaction mechanisms of heterogeneous catalytic reactions of quinoxalin-2(1H)-ones, including six major types of heterogeneous catalysts involved. The heterogeneous reactions of quinoxalin-2(1H)-ones are summarised by classifying different types of catalytic materials (graphitic phase carbon nitride, MOF, COF, ion exchange resin, piezoelectric materials, and microsphere catalysis). In addition, this review discusses the future development of heterogeneous catalytic reactions of quinoxalin-2(1H)-ones, including the construction of C-B/Si/P/RF/X/Se bonds by heterogeneous catalytic reactions, the enrichment of heterogeneous catalysts such as metal oxides, graphene-based composites, doped metal nanoparticles, and molecular sieve-based porous materials, asymmetric synthesis, and other areas. The aim of this review is to contribute to the development of green and sustainable heterogeneous reaction methods for quinoxalin-2(1H)-ones with applications in materials chemistry and pharmacology.


Assuntos
Óxidos , Quinoxalinas , Catálise
4.
Molecules ; 28(6)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36985484

RESUMO

The direct C-H multifunctionalization of quinoxalin-2(1H)-ones via multicomponent reactions has attracted considerable interest due to their diverse biological activities and chemical profile. This review will focus on recent achievements. It mainly covers reaction methods for the simultaneous introduction of C-C bonds and C-RF/C/O/N/Cl/S/D bonds into quinoxalin-2(1H)-ones and their reaction mechanisms. Meanwhile, future developments of multi-component reactions of quinoxalin-2(1H)-ones are envisaged, such as the simultaneous construction of C-C and C-B/SI/P/F/I/SE bonds through multi-component reactions; the construction of fused ring and macrocyclic compounds; asymmetric synthesis; green chemistry; bionic structures and other fields. The aim is to enrich the methods for the reaction of quinoxalin-2(1H)-ones at the C3 position, which have rich applications in materials chemistry and pharmaceutical pharmacology.

5.
Int J Neurosci ; 132(2): 192-200, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32762281

RESUMO

OBJECTIVE: To investigate the role and mechanism of miR-17-5p in cerebral hypoxia/reoxygenation (H/R)-induced apoptosis. METHODS: The present study used human brain microvascular endothelial cells (HBMVECs) to establish cerebral H/R model. MTT was used to measure the cell viability. Flow cytometry was used to detect the cell apoptosis. The interaction between miR-17-5p and PTEN was determined using dual luciferase reporter assay. RT-qPCR and Western blotting were used for determination of the expression of miR-17-5p, PTEN, apoptosis- and PI3K/AKT/mTOR signalling-related proteins. RESULTS: The cell viability and the expression of miR-17-5p were obviously down-regulated while the expression of PTEN was obviously up-regulated in H/R cells. The cell viability was remarkably enhanced, and the cell apoptosis induced by H/R injury was dramatically reduced when miR-17-5p was overexpressed in HBMVECs under H/R condition, which was reversed by overexpression of PTEN. Dual luciferase reporter assay showed PTEN was a direct target of miR-17-5p. Treatment of PI3K inhibitor LY294002 significantly increased the apoptosis rate of HBMVECs, and this effect was significantly reversed by transfection of miR-17-5p mimics, while further dramatically enhanced by overexpression of PTEN. CONCLUSION: MiR-17-5p could ameliorate cerebral I/R injury-induced cell apoptosis by directly targeting PTEN and regulation of PI3K/AKT/mTOR signalling.


Assuntos
Hipóxia Encefálica , MicroRNAs , Apoptose , Células Endoteliais/metabolismo , Humanos , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
6.
BMC Neurol ; 20(1): 236, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517723

RESUMO

BACKGROUND: Diffusion tensor imaging (DTI) is an effective method to identify subtle changes to normal-appearing white matter (WM). Here we analyzed the DTI data with other examinations, including motor evoked potentials (MEPs), histopathological images, and behavioral results, to reflect the lesion development in different degrees of spinal cord injury (SCI) in acute and subacute stages. METHOD: Except for 2 Sprague -Dawley rats which died from the anesthesia accident, the rest 42 female rats were randomized into 3 groups: control group (n = 6), moderate group (n = 18), and severe group (n = 18). Moderate (a 50-g aneurysm clip with 0.4-mm thickness spacer) or severe (a 50-g aneurysm clip with no spacer) contusion SCI at T8 vertebrae was induced. Then the electrophysiological assessments via MEPs, behavioral deterioration via the Basso, Beattie, and Bresnaha (BBB) scores, DTI data, and histopathology examination were analyzed. RESULTS: In this study, we found that the damage of WM myelin, MEPs amplitude, BBB scores and the decreases in the values of fractional anisotropy (FA) and axial diffusivity (AD) were more obvious in the severe injury group than those of the moderate group. Additionally, the FA and AD values could identify the extent of SCI in subacute and early acute SCI respectively, which was reflected in a robust correlations with MEPs and BBB scores. While the values of radial diffusivity (RD) showed no significant changes. CONCLUSIONS: Our data confirmed that DTI was a valuable in ex vivo imaging tool to identify damaged white matter tracts after graded SCI in rat, which may provide useful information for the early identification of the severity of SCI.


Assuntos
Imagem de Tensor de Difusão/métodos , Potencial Evocado Motor/fisiologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Anisotropia , Feminino , Ratos , Ratos Sprague-Dawley , Substância Branca/patologia , Substância Branca/fisiopatologia
7.
J Org Chem ; 84(18): 11417-11424, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31418562

RESUMO

A facile and effective alkoxylation protocol of quinoxalin-2(1H)-ones with primary or secondary alcohols via cross-dehydrogenative coupling under catalyst-free conditions has been disclosed. This method provides a powerful and convenient access to 3-alkoxylquinoxalin-2(1H)-ones in good to excellent yields by utilizing PhI(OTFA)2 as an oxidant and allows to easily obtain potential drug molecules containing 3-alkoxylquinoxalin-2(1H)-one skeletons.

8.
Int J Mol Sci ; 18(7)2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28665305

RESUMO

Obesity and its common association with type 2 diabetes, dyslipidemia, and cardiovascular diseases are worldwide epidemics. Currently, to prevent or treat obesity and associated metabolic disorders, herbal dietary supplements or medicines have attracted more and more attention owing to their relative effectiveness with fewer significant side effects. We investigate the therapeutic effects and underlying mechanisms of Plantago asiatica L. seed extract (PSE) on obesity and associated metabolic disorders in high-fat (HF) diet-induced mice. Our results displayed that PSE did not modify food intake or body weight but decreased abdominal white adipose tissue ratio, white/brown adipocyte size, serum total cholesterol, triglyceride (TG), low density lipoprotein cholesterol, free fatty acid, and hepatic TG concentrations when compared with the HF group. The levels of fasting blood glucose and glucose tolerance were improved in the PSE group when compared with the HF group. Furthermore, PSE upregulated mRNA expressions of peroxisome proliferator activated receptors (PPARs) and target genes related to fatty acid metabolism and energy expenditure in liver and adipose tissue of obese mice when compared with the HF group. PSE treatment effectively improved lipid and glucose metabolism in HF diet-induced obese mice. These effects might be attributed to the upregulation of PPAR signaling.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Obesidade/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Plantago/química , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Glucose/metabolismo , Hiperglicemia/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , PPAR gama/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 42(21): 4150-4153, 2017 Nov.
Artigo em Zh | MEDLINE | ID: mdl-29271153

RESUMO

The chemical constituents of Plantaginis Semen with hypoglycemic effect was investigated in this paper. The previous results of the in vivo hypoglycemic effect showed that 60% ethanol extract of Plantaginis Semen decreased the levels of FBG and improved the glucose tolerance in high fat diet(HFD)-induced diabetic C57BL/6 mice. Then, in the present study, the above potential bioactive extract was separated and purified by silica gel, ODS, Sephadex LH-20 column chromatography, medium pressure liquid chromatography(MPLC)and preparative HPLC. The structures of isolated compounds were identified by physicochemical properties and spectral analyses. Eight compounds were obtained and identified as 4, 4a, 5, 7a-tetrahydro-7-(hydroxymethyl)cyclopenta[c]pyran-3(1H)-one(1), iridolactone(2), pedicularislacton(3), rehmaglutin C(4), geniposidic acid(5), p-hydroxylphenylglycerol(6), 1, 2-benzenediol-4-(2-hydroxyethyl)(7), and 3-buten-2-one-4-[3-(ß-D-glucopyranosyloxy)-4-hydroxyphenyl](8). Among them, compounds 1-5 were iridoids, and 6-8 were phenolic acids. Compound 1 was a new natural product, and compounds 2-4, 6 and 8 were isolated from the Plantaginaceae family for the first time.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hipoglicemiantes/farmacologia , Plantago/química , Animais , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/tratamento farmacológico , Hidroxibenzoatos/isolamento & purificação , Hidroxibenzoatos/farmacologia , Iridoides/isolamento & purificação , Iridoides/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
10.
J Sep Sci ; 39(10): 1842-52, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27030316

RESUMO

Plantaginis Semen is commonly used in traditional medicine to treat edema, hypertension, and diabetes. The commercially available Plantaginis Semen in China mainly comes from three species. To clarify the chemical composition and distinct different species of Plantaginis Semen, we established a metabolite profiling method based on ultra high performance liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry coupled with elevated energy technique. A total of 108 compounds, including phenylethanoid glycosides, flavonoids, guanidine derivatives, terpenoids, organic acids, and fatty acids, were identified from Plantago asiatica L., P. depressa Willd., and P. major L. Results showed significant differences in chemical components among the three species, particularly flavonoids. This study is the first to provide a comprehensive chemical profile of Plantaginis Semen, which could be involved into the quality control, medication guide, and developing new drug of Plantago seeds.


Assuntos
Medicamentos de Ervas Chinesas/análise , Plantago/química , Cromatografia Líquida de Alta Pressão , Medicina Tradicional Chinesa , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
11.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 33(3): 604-8, 2016 Jun.
Artigo em Zh | MEDLINE | ID: mdl-29709167

RESUMO

Graphene and its derivatives have good physical and chemical properties and biological properties,which can promote stem cell proliferation and osteogenic differentiation,and it has antibacterial properties and drug release property.Therefore,it has broad application prospects in the field of orthopedic biomaterials.This paper mainly introduces the research progress of graphene nanocomposite materials applied in the aspects of bone tissue engineering scaffold,bone repair,bone graft materials,etc.in order to provide desirable information for the future application basis and clinical research.


Assuntos
Grafite/química , Nanocompostos/química , Osteogênese , Células-Tronco/citologia , Engenharia Tecidual , Materiais Biocompatíveis/química , Osso e Ossos , Diferenciação Celular , Proliferação de Células , Ortopedia , Alicerces Teciduais/química
12.
J Pharmacol Exp Ther ; 351(2): 474-83, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25204338

RESUMO

Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acids, and triglycerides. We investigated the effect of the specific SREBP suppressor andrographolide, a natural compound isolated from Andrographis paniculata, on the regulation of SREBP signaling by use of Western blot, reporter gene assay, and quantitative real-time polymerase chain reaction analysis. In addition, the antiobesity effects of andrographolide were evaluated in C57BL/6 mice with high-fat diet (HFD)-induced obesity. Our results showed that andrographolide downregulated the expressions of SREBPs target genes and decreased cellular lipid accumulation in vitro. Further, andrographolide (100 mg/kg per day) attenuated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin or glucose sensitivity in HFD-induced obese mice. Andrographolide effectively suppressed the respiratory quotient, energy expenditure, and oxygen consumption, which may have contributed to the decreased body-weight gain of the obese mice fed with a HFD. Consistently, andrographolide regulated SREBP target genes and metabolism-associated genes in liver or brown adipose tissue, which may have directly contributed to the lower lipid levels and enhanced insulin sensitivity. Taken together, our results indicated that andrographolide ameliorated lipid metabolism and improved glucose use in mice with HFD-induced obesity. Andrographolide has potential as a leading compound in the prevention or treatment of obesity and insulin resistance.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Diterpenos/farmacologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Animais , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Glucose/metabolismo , Células Hep G2 , Humanos , Insulina/metabolismo , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Consumo de Oxigênio/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacos
13.
J Nat Prod ; 77(7): 1594-600, 2014 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-24955889

RESUMO

Six new diterpenoids, 4-epi-7α-O-acetylscoparic acid A (1), 7α-hydroxyscopadiol (2), 7α-O-acetyl-8,17ß-epoxyscoparic acid A (3), neo-dulcinol (4), dulcinodal-13-one (5), and 4-epi-7α-hydroxydulcinodal-13-one (6), and a new flavonoid, dillenetin 3-O-(6″-O-p-coumaroyl)-ß-D-glucopyranoside (10), along with 12 known compounds, were isolated from the aerial parts of Scoparia dulcis. The 7S absolute configuration of the new diterpenoids 1-4 and 6 was deduced by comparing their NOESY spectra with that of a known compound, (7S)-4-epi-7-hydroxyscoparic acid A (7), which was determined by the modified Mosher's method. The flavonoids scutellarein (11), hispidulin (12), apigenin (15), and luteolin (16) and the terpenoids 4-epi-scopadulcic acid B (9) and betulinic acid (19) showed more potent α-glucosidase inhibitory effects (with IC50 values in the range 13.7-132.5 µM) than the positive control, acarbose. In addition, compounds 1, 11, 12, 15, 16, and acerosin (17) exhibited peroxisome proliferator-activated receptor gamma (PPAR-γ) agonistic activity, with EC50 values ranging from 0.9 to 24.9 µM.


Assuntos
Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Abietanos/química , Abietanos/farmacologia , Acarbose/farmacologia , Apigenina/química , Apigenina/farmacologia , Diterpenos/química , Flavonoides/química , Glucosídeos/química , Inibidores de Glicosídeo Hidrolases , Luteolina/química , Luteolina/farmacologia , Estrutura Molecular , PPAR gama/agonistas , Componentes Aéreos da Planta/química , Scoparia
14.
Front Neurosci ; 18: 1349512, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38379762

RESUMO

Objective: To explore the characteristics of spontaneous brain activity changes in patients with lumbar disc herniation (LDH), and help reconcile the contradictory findings in the literature and enhance the understanding of LDH-related pain. Materials and methods: PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), SinoMed, and Wanfang databases were searched for literature that studies the changes of brain basal activity in patients with LDH using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation/fraction amplitude of low-frequency fluctuation (ALFF/fALFF) analysis methods. Activation likelihood estimation (ALE) was used to perform a meta-analysis of the brain regions with spontaneous brain activity changes in LDH patients compared with healthy controls (HCs). Results: A total of 11 studies were included, including 7ALFF, 2fALFF, and 2ReHo studies, with a total of 269 LDH patients and 277 HCs. Combined with the data from the ALFF/fALFF and ReHo studies, the meta-analysis results showed that compared with HCs, LDH patients had increased spontaneous brain activity in the right middle frontal gyrus (MFG), left anterior cingulate cortex (ACC) and the right anterior lobe of the cerebellum, while they had decreased spontaneous brain activity in the left superior frontal gyrus (SFG). Meta-analysis using ALFF/fALFF data alone showed that compared with HCs, LDH patients had increased spontaneous brain activity in the right MFG and left ACC, but no decrease in spontaneous brain activity was found. Conclusion: In this paper, through the ALE Meta-analysis method, based on the data of reported rs-fMRI whole brain studies, we found that LDH patients had spontaneous brain activity changes in the right middle frontal gyrus, left anterior cingulate gyrus, right anterior cerebellar lobe and left superior frontal gyrus. However, it is still difficult to assess whether these results are specific and unique to patients with LDH. Further neuroimaging studies are needed to compare the effects of LDH and other chronic pain diseases on the spontaneous brain activity of patients. Furthermore, the lateralization results presented in our study also require further LDH-related pain side-specific grouping study to clarify this causation. Systematic review registration: PROSPERO, identifier CRD42022375513.

15.
Heliyon ; 10(5): e26934, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449658

RESUMO

Using dual polarization multiplexing alternate mark inversion (AMI) downlink signals, a novel radio over fiber (RoF) system integrating optical fiber and FSO channel is designed to adapt to applications in mountainous areas and other complex terrain areas. Optical heterodyne technology and self-mixing homodyne detection method are used to realize high sensitivity detection of the received signals after 25.1 km channel (including 1 km single-mode fiber and 100 m free space link) transmission. Moreover, polarization multiplexing technology is introduced to exponentially increase the transmission capacity of downlink signals. This scheme not only can be compatible with traditional optical fiber transmission systems, but also support the wireless optical access application of millimeter wave signals in RoF systems.

16.
Environ Sci Pollut Res Int ; 30(59): 124245-124262, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37996581

RESUMO

Recognizing the environmental development-related commitments made by the Next Eleven countries at 26th Conference of Parties (COP26), this study scrutinizes the repercussions accompanying good democratic governance, renewable energy transition, economic growth, and the ratification of the Kyoto Protocol on carbon emission figures of these emerging nations. In this regard, the period of analysis considered spans from 1990 to 2018 while the econometric analyses involve application of both parametric and non-parametric panel data estimators. Among the key findings, firstly, the outcomes from the parametric estimation methods verify that establishing better democratic governance and undergoing renewable energy transition, both independently and jointly, curb carbon emission levels, while higher economic growth and the signing of the Kyoto Protocol are responsible for boosting emissions the Next Eleven countries. Secondly, the findings derived using the non-parametric methods reveal a great deal of heterogeneity when compared with the results obtained from the parametric analysis. Notably, better democratic governance is seen to reduce carbon emissions in less and moderately polluted. Next Eleven nations, while renewable energy transition curbs emissions only in the moderately and highly polluted ones. Additionally, these variables jointly inhibit emissions only in the Next Eleven nations that are moderately polluted. Besides, better democratic governance is observed to mediate the renewable energy transition-carbon emissions nexus only for the less-polluted Next Eleven nations, while the environmental impacts of economic growth and the signing of the Kyoto Protocol vary across different emission quantiles. Accordingly, relevant policies are recommended for helping the Next Eleven countries to comply with their pledges made at the COP26.


Assuntos
Dióxido de Carbono , Energia Renovável , Dióxido de Carbono/análise , Países em Desenvolvimento , Desenvolvimento Econômico , Carbono
17.
Elife ; 122023 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-36951246

RESUMO

An evolutionary perspective enhances our understanding of biological mechanisms. Comparison of sex determination and X-chromosome dosage compensation mechanisms between the closely related nematode species Caenorhabditis briggsae (Cbr) and Caenorhabditis elegans (Cel) revealed that the genetic regulatory hierarchy controlling both processes is conserved, but the X-chromosome target specificity and mode of binding for the specialized condensin dosage compensation complex (DCC) controlling X expression have diverged. We identified two motifs within Cbr DCC recruitment sites that are highly enriched on X: 13 bp MEX and 30 bp MEX II. Mutating either MEX or MEX II in an endogenous recruitment site with multiple copies of one or both motifs reduced binding, but only removing all motifs eliminated binding in vivo. Hence, DCC binding to Cbr recruitment sites appears additive. In contrast, DCC binding to Cel recruitment sites is synergistic: mutating even one motif in vivo eliminated binding. Although all X-chromosome motifs share the sequence CAGGG, they have otherwise diverged so that a motif from one species cannot function in the other. Functional divergence was demonstrated in vivo and in vitro. A single nucleotide position in Cbr MEX can determine whether Cel DCC binds. This rapid divergence of DCC target specificity could have been an important factor in establishing reproductive isolation between nematode species and contrasts dramatically with the conservation of target specificity for X-chromosome dosage compensation across Drosophila species and for transcription factors controlling developmental processes such as body-plan specification from fruit flies to mice.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis , Animais , Camundongos , Caenorhabditis/genética , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Cromossomo X/genética , Cromossomo X/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Mecanismo Genético de Compensação de Dose
18.
Life Sci ; 331: 122042, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37634815

RESUMO

AIMS: Memory impairment is a major clinical manifestation in Alzheimer's disease (AD) patients, while regular exercise may prevent and delay degenerative changes in memory functions, and our aim is to explore the influence and molecular mechanisms of aerobic exercise on the early stages of Alzheimer's disease. MAIN METHODS: 3-month-old male APP/PS1 transgenic AD mice and C57BL/6J wild-type mice were randomly divided into four groups: wild-type and APP/PS1 mice with sedentary (WT-SED, AD-SED), and running (WT-RUN, AD-RUN) for 12-weeks. The spatial learning and memory function, RNA-sequencing, spine density, synaptic associated protein, mRNA and protein expression involved in G protein-coupled receptor 81 (GPR81) signaling pathway, and complement factors in brain were measured. KEY FINDINGS: Aerobic exercise improved spatial learning and memory in APP/PS1 mice, potentially attributed to increased dendritic spine density. Subsequently, potential underlying mechanisms were identified through RNA sequencing: regular aerobic exercise could activate the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) cAMP/PKA signaling pathway and upregulate synaptic function-related proteins to promote synaptic growth, possibly by modulating GPR81. Notably, regular aerobic exercise inhibited microglial activation, reversed the microglial phenotype, reduced the production of initiation factor C1q and central factor C3 in the complement cascade in the brain, prevented the colocalization of microglia and PSD-95, and thus prevented synaptic loss. SIGNIFICANCE: Physical exercise could play a critical role in improving cognitive function in AD by promoting synaptic growth and preventing synaptic loss, which may be related to the regulation of the GPR81/cAMP/PKA signaling pathway and inhibition of complement-mediated microglial phagocytosis of synapses.


Assuntos
Doença de Alzheimer , Humanos , Camundongos , Masculino , Animais , Lactente , Doença de Alzheimer/metabolismo , Microglia/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transdução de Sinais , Proteínas do Sistema Complemento , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Homeostase , Modelos Animais de Doenças , Hipocampo/metabolismo , Presenilina-1
19.
Biomaterials ; 300: 122207, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37352606

RESUMO

Effective recovery of peripheral nerve injury (PNI) after surgical treatment relies on promoting axon regeneration and minimizing the fibrotic response. Decellularized amniotic membrane (dAM) has unique features as a natural matrix for promoting PNI repair due to its pro-regenerative extracellular matrix (ECM) structure and anti-inflammatory properties. However, the fragile nature and rapid degradation rate of dAM limit its widespread use in PNI surgery. Here we report an engineered composite membrane for PNI repair by combining dAM with gelatin (Gel) nanofiber membrane to construct a Gel nanofiber-dAM composite membrane (Gel-dAM) through interfacial bonding. The Gel-dAM showed enhanced mechanical properties and reduced degradation rate, while retaining maximal bioactivity and biocompatibility of dAM. These factors led to improved axon regeneration, reduced fibrotic response, and better functional recovery in PNI repair. As a fully natural materials-derived off-the-shelf matrix, Gel-dAM exhibits superior clinical translational potential for the surgical treatment of PNI.


Assuntos
Nanofibras , Traumatismos dos Nervos Periféricos , Humanos , Traumatismos dos Nervos Periféricos/terapia , Gelatina/química , Nanofibras/química , Âmnio , Axônios/patologia , Regeneração Nervosa , Fibrose
20.
Sci Rep ; 12(1): 16585, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36198758

RESUMO

Temporal network link prediction is an important task in the field of network science, and has a wide range of applications in practical scenarios. Revealing the evolutionary mechanism of the network is essential for link prediction, and how to effectively utilize the historical information for temporal links and efficiently extract the high-order patterns of network structure remains a vital challenge. To address these issues, in this paper, we propose a novel temporal link prediction model with adjusted sigmoid function and 2-simplex structure (TLPSS). The adjusted sigmoid decay mode takes the active, decay and stable states of edges into account, which properly fits the life cycle of information. Moreover, the latent matrix sequence is introduced, which is composed of simplex high-order structure, to enhance the performance of link prediction method since it is highly feasible in sparse network. Combining the life cycle of information and simplex high-order structure, the overall performance of TLPSS is achieved by satisfying the consistency of temporal and structural information in dynamic networks. Experimental results on six real-world datasets demonstrate the effectiveness of TLPSS, and our proposed model improves the performance of link prediction by an average of 15% compared to other baseline methods.


Assuntos
Algoritmos
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