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1.
Neuroendocrinology ; 114(2): 170-178, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37725912

RESUMO

INTRODUCTION: The association of serum sex hormone-binding globulin (SHBG) concentrations with dementia risk remains uncertain in middle-aged to older women. We examined associations of serum SHBG levels with incidence of all-cause dementia and its subtypes in middle-aged to older women from the large population-based UK Biobank cohort study. METHODS: Serum total SHBG levels were measured by immunoassay. The incidence of all-cause dementia and its subtypes was recorded. Cox proportional hazards models were used to calculate hazard ratios (HR) for main outcomes. RESULTS: Among 171,482 community-dwelling women (mean [SD] age was 59.9 [5.4] years, median follow-up of 11.8 years), 2,368 developed dementia, including 1,088 from Alzheimer's disease (AD), 451 from vascular dementia (VAD), and 1,609 from other dementia. After multivariable adjustments, higher serum SHBG levels were significantly associated with higher risks of all-cause dementia, AD, and other dementia (all p < 0.05). Compared to those in the lowest quartile of SHBG levels, participants in the highest quartile of SHBG levels had a higher risk of all-cause dementia (HR: 1.34; 95% confidence interval [CI]: 1.16-1.53), AD (HR: 1.32; 95% CI: 1.07-1.62), and other dementia (HR: 1.44; 95% CI: 1.21-1.70). However, this relationship was not significant for VAD (HR: 1.16; 95% CI: 0.86-1.56). CONCLUSION: These findings indicated that higher serum SHBG concentrations were independently associated with higher risks of incident all-cause dementia, as well as AD and other dementia among middle-aged to older women. No association was found for VAD.


Assuntos
Doença de Alzheimer , Globulina de Ligação a Hormônio Sexual , Idoso , Pré-Escolar , Feminino , Humanos , Pessoa de Meia-Idade , Bancos de Espécimes Biológicos , Estudos de Coortes , Estudos Prospectivos , Fatores de Risco , Biobanco do Reino Unido
2.
Opt Express ; 30(18): 33048-33067, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36242354

RESUMO

With the improvement of semiconductor processing technology, polarization sensors using division of focal plane have gradually become the mainstream method of polarization imaging. Similar to the color restoration method of the Bayer array sensor, the spatial information of polarized image is also recovered through the polarization demosaicking algorithm. In this paper, we propose a new modified Newton-residual interpolation polarization image demosaicking algorithm based on residual interpolation, which is suitable for a monochrome or color polarization filter array. First, we use the modified Newton interpolation method to generate edge-sensitive guiding images. Then, we carry out the improvement of the guide process during the residual interpolation by performing variance statistics on the local window image in the guiding process, so that the edges and flat image blocks have different guiding weights. Finally, we obtain edge-preserving results by applying these two improvements, which reduces the zipper effect and edge confusion. We compare the results of various algorithms on experimental data, demonstrating that our algorithm has impactful improvements in the evaluation metrics based on the ground-truth images.

3.
Cancer Cell Int ; 21(1): 442, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419067

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common malignant neoplasms. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a key role in the lipid remodelling and is correlated with various neoplasms. Nonetheless, the biological functions and molecular mechanisms of LPCAT1 underlying HCC remain obscure. METHODS: In the present study, we investigated the role of LPCAT1 in the progression of HCC. In-house RT-qPCR, tissue microarrays, and immunohistochemistry were performed to detect the expression levels and the clinical value of LPCAT1 in HCC. External datasets were downloaded to confirm the results. Proliferation, migration, invasiveness, cell cycle, and apoptosis assays were conducted to reveal the biological effects LPCAT1 has on SMMC-7721 and Huh7 cells. HCC differentially expressed genes and LPCAT1 co-expressed genes were identified to explore the molecular mechanisms underlying HCC progression. RESULTS: LPCAT1 showed upregulated expression in 3715 HCC specimens as opposed to 3105 non-tumour specimens. Additionally, LPCAT1 might be an independent prognostic factor for HCC. LPCAT1-knockout hampered cellular proliferation, migration, and metastasis in SMMC-7721 and Huh7 cells. More importantly, the cell cycle and chemical carcinogenesis were the two most enriched signalling pathways. CONCLUSIONS: The present study demonstrated that increased LPCAT1 correlated with poor prognosis in HCC patients and fuelled HCC progression by promoting cellular growth, migration, and metastasis.

4.
J Exp Bot ; 71(18): 5469-5483, 2020 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-32474603

RESUMO

The function of the transcription factor KNOTTED ARABIDOPSIS THALIANA7 (KNAT7) is still unclear since it appears to be either a negative or a positive regulator for secondary cell wall deposition with its loss-of-function mutant displaying thicker interfascicular and xylary fiber cell walls but thinner vessel cell walls in inflorescence stems. To explore the exact function of KNAT7, class II KNOTTED1-LIKE HOMEOBOX (KNOX II) genes in Arabidopsis including KNAT3, KNAT4, and KNAT5 were studied together. By chimeric repressor technology, we found that both KNAT3 and KNAT7 repressors exhibited a similar dwarf phenotype. Both KNAT3 and KNAT7 genes were expressed in the inflorescence stems and the knat3 knat7 double mutant exhibited a dwarf phenotype similar to the repressor lines. A stem cross-section of knat3 knat7 displayed an enhanced irregular xylem phenotype as compared with the single mutants, and its cell wall thickness in xylem vessels and interfascicular fibers was significantly reduced. Analysis of cell wall chemical composition revealed that syringyl lignin was significantly decreased while guaiacyl lignin was increased in the knat3 knat7 double mutant. Coincidently, the knat3 knat7 transcriptome showed that most lignin pathway genes were activated, whereas the syringyl lignin-related gene Ferulate 5-Hydroxylase (F5H) was down-regulated. Protein interaction analysis revealed that KNAT3 and KNAT7 can form a heterodimer, and KNAT3, but not KNAT7, can interact with the key secondary cell wall formation transcription factors NST1/2, which suggests that the KNAT3-NST1/2 heterodimer complex regulates F5H to promote syringyl lignin synthesis. These results indicate that KNAT3 and KNAT7 synergistically work together to promote secondary cell wall biosynthesis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Parede Celular/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Lignina , Proteínas Nucleares , Proteínas Repressoras/metabolismo , Fatores de Transcrição/genética
5.
Inorg Chem ; 59(17): 12858-12866, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32805998

RESUMO

We present three new hybrid layered lead(II) bromide perovskites of generic composition A2PbBr4 or AA'PbBr4 that exhibit three distinct structure types. [TzH]2PbBr4 ([TzH+] = 1,2,4-triazolium) adopts a (001)-oriented layer structure and [AaH]2PbBr4, ([AaH+] = acetamidinium) adopts a (110)-oriented type, whereas [ImH][TzH]PbBr4, ([ImH+] = imidazolium) adopts a rare (110)-oriented structure with enhanced corrugation (i.e., 3 × 3 type). The crystal structures of each are discussed in terms of the differing nature of the templating molecular species. Photoluminescent spectra for each are reported and the behaviors discussed in relation to the different structure of each composition.

6.
Ecotoxicol Environ Saf ; 200: 110742, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32470681

RESUMO

The accumulation of arsenic in rice has become a worldwide concern. In this study, dose-dependency in tissues (intestine, liver and kidney) and blood distribution of inorganic arsenicals and their methylated metabolites were investigated in male C57BL/6 mice exposed to four arsenic species (arsenite [iAs]III, arsenate [iAs]V, monomethylarsonate [MMA]V, and dimethylarsinate [DMA]V) at four doses (control [C]: 0 µg/g, simulation [S]: 0.91 µg/g, medium [M]: 9.1 µg/g and high [H]: 30 µg/g) according to the arsenical composition in rice for 8 and 16 weeks. No adverse effects were observed, while body weight gain decreased in group H. Increases in total arsenic concentrations (CtAs) and histopathological changes in the tissues occurred in all of the test groups. CtAs presented a tendency of kidney > intestine > liver > blood and were time-/dose-dependent in the liver and kidney in groups M and H. In the intestine and blood, abundant iAs (23%-28% in blood and 36%-49% in intestine) was detected in groups M and H, and CtAs decreased in group H from the 8th week to the 16th week. PMI decreased in the liver and SMI decreased in the kidney. These results indicate that the three tissues are injured through food arsenic. The intestine can also accumulate food arsenic, and the high arsenic dose will cause a deficiency in the absorbing function of the intestine. Thus, long-term exposure to arsenic-contaminated rice should be taken seriously attention.


Assuntos
Intoxicação por Arsênico , Arsenicais/farmacocinética , Animais , Arseniatos/farmacocinética , Arseniatos/toxicidade , Intoxicação por Arsênico/metabolismo , Intoxicação por Arsênico/patologia , Arsenitos/farmacocinética , Arsenitos/toxicidade , Ácido Cacodílico/farmacocinética , Ácido Cacodílico/toxicidade , Exposição Dietética , Intestinos/efeitos dos fármacos , Intestinos/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oryza/metabolismo
7.
Zhongguo Zhong Yao Za Zhi ; 45(23): 5607-5613, 2020 Dec.
Artigo em Zh | MEDLINE | ID: mdl-33496098

RESUMO

In this experiment, by determination of the HPLC characteristic spectrum of the classical prescription Qingwei San decoction, the contents of isoferulic acid, palmatine and paeonol in Qingwei San decoction and the extraction rate were investigated. The factors such as the crushing degree of decoction pieces, the amount of decocting water, the decocting time, the filter material and the decocting container involved in Qingwei San decoction process were examined to make a detailed comparison of Qingwei San's decoction processes during the development.HPLC characteristic spectrum method of Qingwei San was established, and then the decoction process parameters of Qingwei San were optimized, with the similarity of characteristic spectrum, the concentration of the index components and the extraction rate as indexes. The decoction process of Qingwei San was determined as follows: Qingwei San decoction pieces were weighed according to the prescription amount and pulverized into the most coarse powder; the powder was put in a ceramic pot, added with 225 mL water, heated to boiling, cooked for 50 minutes with gentle heat(100 W), and filtered with a layer of 300 mesh nylon cloth.The similarity of Qingwei San's characteristics pectrum of different decoction methods was all above 0.9, and the concentration of isoferulic acid, palmatine and paeonol in Qingwei San under determined decoction process was 40.74, 26.73, 65.73 µg·mL~(-1), respectively, with an extraction rate of 33.80%.The characteristic spectrum determined in this experiment can better express the information and index components of Qingwei San, and if combined with the extraction rate information, it can provide the general information, index component content and extraction information. The decoction process after detailed investigation can better reflect the quality of Qingwei San decoction, with easier control and operation. It can provide a basis for the subsequent research and development of Qingwei San decoction standard, and can also provide experimental basis and reference for the decoction process research of other classical prescriptions.


Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Pós , Prescrições , Água
8.
BMC Psychol ; 12(1): 396, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020424

RESUMO

BACKGROUND: In the cognitive-affective model of athlete burnout, anxiety is a key physiological response to stress that influences the development of burnout in athletes. Despite its importance, there has been little research on the relationship between competitive anxiety and athlete burnout, particularly regarding the mediating mechanisms. This study aimed to explore the relationship between competitive anxiety and athlete burnout, with a focus on the mediating role of general need satisfaction from self-determination theory. METHODS: The current study employed a cross-sectional design involving 618 college athletes (354 females, mean age 20.57 years), comprising 303 participants in individual sports and 315 in team sports. These participants completed the Sport Anxiety Scale-2 (SAS-2), the Athlete Burnout Questionnaire (ABQ), and the Basic Psychological Need Satisfaction Scale in General (BPNSS-G) online. Subsequently, correlation, regression, and mediation analyses were conducted using SPSS and JASP to examine the relationships between the variables. RESULTS: Regression results indicated that somatic anxiety (beta = 0.116, t = 2.21, p = 0.028) and concentration disruption (beta = 0.259, t = 5.35, p < 0.001) in competitive anxiety were positively correlated with athlete burnout. Worry in competitive anxiety was negatively correlated with competence (beta =-0.149, t=-2.70, p = 0.007) and autonomy (beta =-0.179, t=-3.25, p = 0.001) in needs satisfaction. Additionally, the regression results found that competence (beta =-0.178, t=-3.39, p = 0.001) and Autonomy (beta =-0.208, t=-4.17, p < 0.001) were negatively associated with athlete burnout. Mediation analyses revealed significant direct effects in the relationship between somatic anxiety (Effect = 0.116, p = 0.026) along with concentration disruption (Effect = 0.259, p < 0.001) and athlete burnout. In the indirect effect, worry (Effect = 0.071, p = 0.002) as well as concentration disruption (Effect = 0.082, p < 0.001) had significant effects in relation to athlete burnout, respectively. CONCLUSIONS: Overall, the current study found that somatic anxiety and concentration disruption in competitive anxiety are related to athlete burnout. Moreover, competence and autonomy in need satisfaction mediated the relationship between competitive anxiety (worry and concentration disruption) and athlete burnout. The findings of this study not only shed further light on the relationship between competitive anxiety and athlete burnout but also provide theoretical insights into the mediating mechanisms of this relationship.


Assuntos
Ansiedade , Atletas , Esgotamento Psicológico , Comportamento Competitivo , Autonomia Pessoal , Humanos , Feminino , Masculino , Atletas/psicologia , Atletas/estatística & dados numéricos , Ansiedade/psicologia , Estudos Transversais , Adulto Jovem , Universidades , Adulto , Esgotamento Psicológico/psicologia , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Satisfação Pessoal , Inquéritos e Questionários , Adolescente
9.
RSC Adv ; 14(24): 16624-16628, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38784423

RESUMO

Herein, we report a one-pot approach to diarylamines through the reductive homocoupling of nitroaromatics, employing triethylsilane as the reducing agent and Pd/NHC as the catalyst. This method enables nitroaromatics to serve both as electrophilic reagents and as precursors of nucleophilic reagents, allowing for the direct preparation of diarylamines without the need to isolate aromatic primary amines.

10.
Int J Biol Macromol ; 258(Pt 1): 128933, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38143071

RESUMO

In this study, zein-gallic acid covalent complex prepared by alkali treatment was utilized as an emulsifier to stabilize cinnamon essential oil (CEO) Pickering emulsion, and the chitosan-based (CZGE) films loaded with CEO Pickering emulsion were prepared by blending. The influences of different contents of CEO Pickering emulsion on the physical properties and biological activities of CZGE films were investigated. The results showed that Pickering emulsion had good compatibility with chitosan matrix and enhanced the interaction between film-forming matrix polymer. In addition, incorporating with CEO Pickering emulsion (15 %, v/v) significantly improved the mechanical and barrier properties of the films, and also enhanced the light transmittance and thermal stability of the films. Furthermore, the loading of emulsion also improved the antioxidant activities of the films and led to the formation of high antimicrobial property against food pathogens, and the slow-release behavior of CEO could effectively extend the biological activity of the films. These results suggested that Pickering emulsion has potential as a loading system and a plasticizer in active packaging, and the feasibility of CZGE film in food packaging.


Assuntos
Quitosana , Nanopartículas , Óleos Voláteis , Zeína , Cinnamomum zeylanicum , Ácido Gálico , Emulsões , Antibacterianos
11.
J Clin Endocrinol Metab ; 109(2): e745-e756, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-37665960

RESUMO

CONTEXT: Sex hormones have been identified as cardiovascular risk factors, whereas the relationship between sex hormones and the risk of arrhythmias in men has not yet been well studied in the prospective cohort study. OBJECTIVE: To analyze associations of serum testosterone and SHBG concentrations and calculate free testosterone (cFT) with arrhythmias in men. METHODS: Sex hormones were measured at baseline from UK Biobank. Main outcomes were incidence of atrial fibrillation/flutter (AF), ventricular arrhythmia (VA), and bradyarrhythmia (BA). RESULTS: Of 173 498 men (aged 37-73 years, followed for 11 years), 11 368 had incident AF, 1646 had incident VA, and 4788 had incident BA. Compared with the third quartiles, the lowest category of serum testosterone was associated with increased risks of AF (hazard ratio [HR], 1.06; 95% CI, 1.00-1.12) and BA (HR, 1.11; 95% CI, 1.02-1.20) after multivariable adjustment, but no VA. Likewise, similar associations were found between cFT values and AF and BA events. Furthermore, higher levels of cFT were associated with increased risks of AF (HR, 1.07; 95% CI, 1.02-1.13) and VA (HR, 1.18; 95% CI, 1.01-1.37). Higher SHBG concentrations were associated with increased risks of AF (HR, 1.44; 95% CI, 1.34-1.54), VA (HR, 1.27; 95% CI, 1.07-1.52), and BA (HR, 1.17; 95% CI ,1.05-1.29). CONCLUSIONS: Lower levels of testosterone and cFT were associated with increased risk of AF and BA. Higher cFT levels were associated with increased risk of AF and VA. Higher SHBG levels were associated with increased risk of AF, VA, and BA.


Assuntos
Fibrilação Atrial , Globulina de Ligação a Hormônio Sexual , Masculino , Humanos , Estudos Prospectivos , Biobanco do Reino Unido , Bancos de Espécimes Biológicos , Testosterona , Hormônios Esteroides Gonadais , Fibrilação Atrial/epidemiologia
12.
IEEE Trans Pattern Anal Mach Intell ; 45(11): 12738-12746, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36155475

RESUMO

Vision transformers have recently attained state-of-the-art results in visual recognition tasks. Their success is largely attributed to the self-attention component, which models the global dependencies among the image patches (tokens) and aggregates them into higher-level features. However, self-attention brings significant training difficulties to ViTs. Many recent works thus develop various new self-attention components to alleviate this issue. In this article, instead of developing complicated self-attention mechanism, we aim to explore simple approaches to fully release the potential of the vanilla self-attention. We first study the token selection behavior of self-attention and find that it suffers from a low diversity due to attention over-smoothing, which severely limits its effectiveness in learning discriminative token features. We then develop simple approaches to enhance selectivity and diversity for self-attention in token selection. The resulted token selector module can server as a drop-in module for various ViT backbones and consistently boost their performance. Significantly, they enable ViTs to achieve 84.6% top-1 classification accuracy on ImageNet with only 25M parameters. When scaled up to 81M parameters, the result can be further improved to 86.1%. In addition, we also present comprehensive experiments to demonstrate the token selector can be applied to a variety of transformer-based models to boost their performance for image classification, semantic segmentation and NLP tasks. Code is available at https://github.com/zhoudaquan/dvit_repo.

13.
Natl Sci Rev ; 10(2): nwac261, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36817840

RESUMO

The immiscible alloy Ti-Co-Gd is solidified in space by using the Electrostatic Levitation Device on board the Chinese Space Station. A sample with in-situ composite structure is obtained. The microstructure formation and gravity effect are discussed.

14.
Aging (Albany NY) ; 15(14): 6834-6847, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37462732

RESUMO

In this study we sought to analyze the critical role of oxidized phospholipid (OxPL) in the progression of calcific aortic valve disease (CAVD) with the involvement of activating transcription factor 4 (ATF4). Differentially expressed genes related to CAVD were identified using bioinformatics analysis. Expression of ATF4 was examined in mouse models of aortic valve calcification (AVC) induced by the high cholesterol (HC) diet. Valvular interstitial cells (VICs) were then isolated from mouse non-calcified valve tissues, induced by osteogenic induction medium (OIM) and co-cultured with OxPAPC-stimulated macrophages. The effect of OxPLs regulating ATF4 on the macrophage polarization and osteogenic differentiation of VICs was examined with gain- and loss-of-function experiments in VICs and in vivo. In aortic valve tissues and OIM-induced VICs, ATF4 was highly expressed. ATF4 knockdown alleviated the osteogenic differentiation of VICs, as evidenced by reduced expression of bone morphogenetic protein-2 (BMP2), osteopontin (OPN), and osteocalcin. In addition, knockdown of ATF4 arrested the AVC in vivo. Meanwhile, OxPL promoted M1 polarization of macrophages and mediated osteogenic differentiation of VICs. Furthermore, OxPL up-regulated ATF4 expression through protein kinase R-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 subunit alpha (eIF2α) pathway. In conclusion, OxPL can potentially up-regulate the expression of ATF4, inducing macrophages polarized to M1 phenotype, osteogenic differentiation of VICs and AVC, thus accelerating the progression of CAVD.


Assuntos
Estenose da Valva Aórtica , Calcinose , Animais , Camundongos , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Valva Aórtica , Estenose da Valva Aórtica/metabolismo , Calcinose/genética , Calcinose/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Retículo Endoplasmático/metabolismo , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Osteogênese/genética , Fosfolipídeos/metabolismo , Proteínas Quinases/metabolismo
15.
J Cell Commun Signal ; 17(4): 1449-1467, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37812275

RESUMO

This study aims to elucidate the role of miR-129/miR-342 loaded in exosomes derived from vascular smooth muscle cells (VSMCs) stimulated by intermittent hypoxia in calcified aortic valvular disease (CAVD). Bioinformatics analysis was conducted to identify differentially expressed miRs in VSMCs-derived exosomes and CAVD samples, and their potential target genes were predicted. VSMCs were exposed to intermittent hypoxia to induce stimulation, followed by isolation of exosomes. Valvular interstitial cells (VICs) were cultured in vitro to investigate the impact of miR-129/miR-342 on VICs' osteogenic differentiation and aortic valve calcification with eIF2α. A CAVD mouse model was established using ApoE knockout mice for in vivo validation. In CAVD samples, miR-129 and miR-342 were downregulated, while eIF2α and ATF4 were upregulated. miR-129 and miR-342 exhibited inhibitory effects on eIF2α through targeted regulation. Exosomes released from intermittently hypoxia-stimulated VSMCs contained miR-129 and miR-342. Overexpression of miR-129 and miR-342, or silencing ATF4, suppressed VICs' osteogenic differentiation and aortic valve calcification, which could be rescued by overexpressed eIF2α. Collectively, intermittent hypoxia stimulation of VSMCs leads to the secretion of exosomes that activate the miR-129/miR-342 dual pathway, thereby inhibiting the eIF2α/ATF4 axis and attenuating VICs' osteogenic differentiation and CAVD progression.

16.
Int J Cardiol ; 389: 131193, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37473815

RESUMO

BACKGROUND: The lectin pathway has been demonstrated to play a critical role in the pathological process of myocardial ischemia/reperfusion injury (IRI). Mannose-binding lectin (MBL)-associated serine protease-1 (MASP-1), especially different from other components of the lectin pathway, mediates proinflammatory and procoagulant reactions independent of complement cascades. However, the role of MASP-1 in myocardial IRI remains unknown so far. METHODS: Myocardial IRI was established with 45 min ischemia and 24 h reperfusion in mice. C1 inhibitor, as the natural inhibitor of MASP-1, was administrated at 20 IU/Kg via tail vein 5 min before surgical operation. Cardiac function and myocardial infarct size were assessed. Myocardial histology and fibrosis were evaluated by H&E and Masson staining, respectively. Deposition of MASP-1, expression of PAR-1/4 and neutrophil extracellular traps (NET) were investigated on myocardium tissue by IHC staining. Cell apoptosis was detected by TUNEL assay. Levels of myocardial enzymes and proinflammatory cytokines were determined by ELISA. RESULTS: Inhibition of MASP-1 with C1 INH improved cardiac function and alleviated myocardium tissue injury (infarct size, enzymes, histology and fibrosis) after myocardial IRI. Deposition of MASP-1 and expression PAR-1, as well as NET formation in myocardial tissue were suppressed by MASP-1 inhibitor, while PAR-4 was elevated. Levels of apoptosis, HMGB-1 and IL-6 were lower after blocking MASP-1. Yet, IL-8 and TNF-α remained unchanged. CONCLUSIONS: MASP-1, as a new contributor, played a critical role in myocardial IRI. Inhibition of MASP-1 protected myocardial tissue from IRI probably via regulation of PARs/NET pathway. This may provide a novel target strategy against myocardial IRI.


Assuntos
Traumatismo por Reperfusão Miocárdica , Camundongos , Animais , Lectina de Ligação a Manose da Via do Complemento/fisiologia , Serina Proteases Associadas a Proteína de Ligação a Manose/metabolismo , Lectinas/metabolismo , Lectinas de Ligação a Manose
17.
J Clin Endocrinol Metab ; 108(9): e850-e860, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36810801

RESUMO

CONTEXT: Relationships between insulin-like growth factor 1 (IGF-1) levels and cardiovascular disease (CVD) in the general population remain unclear. OBJECTIVE: This study aims to investigate the association of circulating IGF-1 concentrations with CVD from a population-based cohort study. METHODS: A total of 394 082 participants without CVD and cancer at baseline from UK Biobank were included with measurements of serum IGF-1 at baseline. Main outcomes were incidence of CVD, including CVD mortality, coronary heart disease (CHD), myocardial infarction (MI), heart failure (HF), and stroke. RESULTS: Over a median 11.6 years of follow-up, UK Biobank documented 35 803 incident CVD cases, including 4231 from CVD-related death, 27 051 from CHD, 10 014 from MI, 7661 from HF, and 6802 from stroke. Dose-response analysis showed a U-shaped relationship between IGF-1 levels and cardiovascular events. Compared with the third quintile of IGF-1, the lowest category of IGF-1 was associated with increased risk of CVD (hazard ratio 1.128; 95% CI, 1.093 to 1.164), CVD mortality (1.294; 1.181 to 1.418), CHD (1.118; 1.078 to 1.159), MI (1.071; 1.008 to 1.139), HF (1.185; 1.107 to 1.268), and stroke (1.149, 1.070 to 1.235); also, the highest category was associated with increased risk of CVD (1.056; 1.020 to 1.094), CVD mortality (1.111; 1.000 to 1.236), CHD (1.070; 1.028 to 1.114), MI (1.111; 1.041 to 1.187) and HF (1.098; 1.015 to 1.188) after multivariable adjustment. CONCLUSION: This study indicates that both low and high levels of circulating IGF-1 are associated with increased risk of CVD in general population. These results highlight the importance of monitoring IGF-1 status on cardiovascular health.


Assuntos
Doenças Cardiovasculares , Doença das Coronárias , Insuficiência Cardíaca , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Fator de Crescimento Insulin-Like I/metabolismo , Bancos de Espécimes Biológicos , Fatores de Risco , Infarto do Miocárdio/complicações , Insuficiência Cardíaca/epidemiologia , Doença das Coronárias/epidemiologia , Acidente Vascular Cerebral/complicações , Reino Unido/epidemiologia
18.
Int J Biol Macromol ; 253(Pt 3): 126762, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37683750

RESUMO

The lignin plays one of the most important roles in plant secondary metabolism. However, it is still unclear how lignin can contribute to the impressive height of wood growth. In this study, C3'H, a rate-limiting enzyme of the lignin pathway, was used as the target gene. C3'H3 was knocked out by CRISPR/Cas9 in Populus tomentosa. Compared with wild-type popular trees, c3'h3 mutants exhibited dwarf phenotypes, collapsed xylem vessels, weakened phloem thickening, decreased hydraulic conductivity and photosynthetic efficiency, and reduced auxin content, except for reduced total lignin content and significantly increased H-subunit lignin. In the c3'h3 mutant, the flavonoid biosynthesis genes CHS, CHI, F3H, DFR, ANR, and LAR were upregulated, and flavonoid metabolite accumulations were detected, indicating that decreasing the lignin biosynthesis pathway enhanced flavonoid metabolic flux. Furthermore, flavonoid metabolites, such as naringenin and hesperetin, were largely increased, while higher hesperetin content suppressed plant cell division. Thus, studying the c3'h3 mutant allows us to deduce that lignin deficiency suppresses tree growth and leads to the dwarf phenotype due to collapsed xylem and thickened phloem, limiting material exchanges and transport.


Assuntos
Lignina , Populus , Lignina/metabolismo , Oxigenases de Função Mista/metabolismo , Árvores , Populus/metabolismo , Sistemas CRISPR-Cas/genética , Flavonoides/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo
19.
J Am Heart Assoc ; 12(16): e030105, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37581386

RESUMO

Background The associations of oral contraceptive (OC) use with cardiovascular disease (CVD) and all-cause death remains unclear. We aimed to determine the associations of OC use with incident CVD and all-cause death. Methods and Results This cohort study included 161 017 women who had no CVD at baseline and reported their OC use. We divided OC use into ever use and never use. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs for cardiovascular outcomes and death. Overall, 131 131 (81.4%) of 161 017 participants reported OC use at baseline. The multivariable-adjusted hazard ratios for OC ever users versus never users were 0.92 (95% CI, 0.86-0.99) for all-cause death, 0.91 (95% CI, 0.87-0.96) for incident CVD events, 0.88 (95% CI, 0.81-0.95) for coronary heart disease, 0.87 (95% CI, 0.76-0.99) for heart failure, and 0.92 (95% CI, 0.84-0.99) for atrial fibrillation. However, no significant associations of OC use with CVD death, myocardial infarction, or stroke were observed. Furthermore, the associations of OC use with CVD events were stronger among participants with longer durations of use (P for trend<0.001). Conclusions OC use was not associated with an increased risk of CVD events and all-cause death in women and may even produce an apparent net benefit. In addition, the beneficial effects appeared to be more apparent in participants with longer durations of use.


Assuntos
Doenças Cardiovasculares , Humanos , Feminino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Estudos de Coortes , Fatores de Risco , Bancos de Espécimes Biológicos , Anticoncepcionais Orais/efeitos adversos , Reino Unido/epidemiologia
20.
Chem Mater ; 35(10): 3801-3814, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37251101

RESUMO

One of the great advantages of organic-inorganic metal halides is that their structures and properties are highly tuneable and this is important when optimizing materials for photovoltaics or other optoelectronic devices. One of the most common and effective ways of tuning the electronic structure is through anion substitution. Here, we report the inclusion of bromine into the layered perovskite [H3N(CH2)6NH3]PbBr4 to form [H3N(CH2)6NH3]PbBr4·Br2, which contains molecular bromine (Br2) intercalated between the layers of corner-sharing PbBr6 octahedra. Bromine intercalation in [H3N(CH2)6NH3]PbBr4·Br2 results in a decrease in the band gap of 0.85 eV and induces a structural transition from a Ruddlesden-Popper-like to Dion-Jacobson-like phase, while also changing the conformation of the amine. Electronic structure calculations show that Br2 intercalation is accompanied by the formation of a new band in the electronic structure and a significant decrease in the effective masses of around two orders of magnitude. This is backed up by our resistivity measurements that show that [H3N(CH2)6NH3]PbBr4·Br2 has a resistivity value of one order of magnitude lower than [H3N(CH2)6NH3]PbBr4, suggesting that bromine inclusion significantly increases the mobility and/or carrier concentration in the material. This work highlights the possibility of using molecular inclusion as an alternative tool to tune the electronic properties of layered organic-inorganic perovskites, while also being the first example of molecular bromine inclusion in a layered lead halide perovskite. By using a combination of crystallography and computation, we show that the key to this manipulation of the electronic structure is the formation of halogen bonds between the Br2 and Br in the [PbBr4]∞ layers, which is likely to have important effects in a range of organic-inorganic metal halides.

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