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1.
Ann Palliat Med ; 10(9): 9702-9714, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628896

RESUMO

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is highly prevalent in type 2 diabetes mellitus (T2DM) patients and can rapidly progress to steatohepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). Accurate evaluation and proper management of MAFLD can help prevent adverse liver outcomes. Here we evaluated the precision of the FibroTouch (FT) in the staging of liver steatosis and fibrosis in patients with MAFLD combined with T2DM using two indicators: controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). METHODS: Eighty-five adult MAFLD combined with T2DM patients were selected at our center from July 2016 to July 2019 and underwent liver puncture biopsy for histopathology and the FT assay simultaneously. Two blinded pathologists independently reviewed the samples. The severity of fatty liver was classified using two scoring systems: the nonalcoholic fatty liver disease activity score (NAS) and the fibrosis score. Scores were then assessed following the Pathology Working Group of the NASH Clinical Research Network of the National Institutes of Health. Similarly, the severity of nonalcoholic steatohepatitis (NASH) was classified using the European Steatosis Activity Fibrosis (SAF) system. The FT assay was applied to obtain the LSM and the CAP. FT accuracy in diagnosing steatosis and fibrosis was determined by the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUROC). RESULTS: Using biopsy analysis as the gold standard, the AUROCs and cutoff values of CAP in diagnosing liver steatosis were as follows: 0.84 (95% CI: 0.67-1.01) and 278 dB/m for S ≥ S1, 0.88 (95% CI: 0.81-0.95) and 305 dB/m for S ≥ S2, 0.89 (95% CI: 0.82-0.95) and 307 dB/m for S ≥ S3. The AUROCs and cutoff values of LSM in diagnosing liver fibrosis were as follows: 0.76 (95% CI: 0.66-0.86) for F ≥ F2, 0.81 (95% CI: 0.71-0.91) and 13.8 kPa for F ≥ F3, 0.92 (95% CI: 0.85-1.00) and 20.1 kPa for F ≥ F4. CONCLUSIONS: In patients of MAFLD with T2DM, CAP and LSM obtained by FT are highly accurate in assess liver steatosis and fibrosis, respectively, with AUROC values ranging from 0.76 to 0.92.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Técnicas de Imagem por Elasticidade , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Cirrose Hepática , Estados Unidos
3.
BMC Complement Med Ther ; 21(1): 222, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479552

RESUMO

BACKGROUND: Increasing attention has been paid to the effect of Epimedium on the nervous system, particularly anti-depression function. In the present study, we applied network pharmacology to introduce a testable hypothesis on the multi-target mechanisms of Epicedium against depression. METHODS: By reconstructing the network of protein-protein interaction and drug-component-target, we predicted the key protein targets of Epicedium for the treatment of depression. Then, through molecular docking, the interaction of the main active components of Epicedium and predicted candidate targets were verified. RESULTS: Nineteen active compounds were selected from Epicedium. There were 200 targets associated with Epicedium and 537 targets related to depression. The key targets of Epicedium for treating depression were IL6, VEGFA, AKT1, and EGF. According to gene ontology functional enrichment analysis, 22 items of biological process (BP), 13 items of cell composition (CC) and 9 items of molecular function (MF) were obtained. A total of 56 signaling pathways (P < 0.05) were identified by Kyoto Encyclopedia of Genes and Genomes analysis, mainly involving depression-related pathways such as dopaminergic synapse, TNF signaling pathway, and prolactin signaling pathway. The results of molecular docking showed that the most important activity components, including luteoklin, quercetin and kaempferol, were well combined with the key targets. CONCLUSIONS: Luteoklin, quercetin, kaempferol and other active compounds in Epicedium can regulate multiple signaling pathways and targets such as IL6, AKT1, and EGF, therefore playing therapeutic roles in depression.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34505945

RESUMO

PURPOSE: Obtaining tumour-free margins is critical for avoiding re-excision and reducing local recurrence following breast-conserving surgery; however, it remains challenging. Imaging-guided surgery provides precise detection of residual lesions and assists surgical resection. Herein, we described water-soluble melanin nanoparticles (MNPs) conjugated with cyclic Arg-Gly-Asp (cRGD) peptides for breast cancer photoacoustic imaging (PAI) and surgical navigation. METHODS: The cRGD-MNPs were synthesised and characterized for morphology, photoacoustic characteristics and stability. Tumour targeting and toxicity of cRGD-MNPs were determined by using either breast cancer cells, MDA-MB-231 tumour-bearing mice or the FVB/N-Tg (MMTV-PyVT) 634Mul/J mice model. PAI was used to locate the tumour and guide surgical resection in MDA-MB-231 tumour-bearing mice. RESULTS: The cRGD-MNPs exhibited excellent in vitro and in vivo tumour targeting with low toxicity. Intravenous administration of cRGD-MNPs to MDA-MB-231 tumour-bearing mice showed an approximately 2.1-fold enhancement in photoacoustic (PA) intensity at 2 h, and the ratio of the PA intensity at the tumour site to that in the surrounding normal tissue was 3.2 ± 0.1, which was higher than that using MNPs (1.7 ± 0.3). Similarly, the PA signal in the spontaneous breast cancer increased ~ 2.5-fold at 2 h post-injection of cRGD-MNPs in MMTV-PyVT transgenic mice. Preoperative PAI assessed tumour volume and offered three-dimensional (3D) reconstruction images for accurate surgical planning. Surgical resection following real-time PAI showed high consistency with histopathological analysis. CONCLUSION: These results highlight that cRGD-MNP-mediated PAI provide a powerful tool for breast cancer imaging and precise tumour resection. cRGD-MNPs with fine PA properties have great potential for clinical translation.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34490578

RESUMO

Sustainability is a strategic choice for the transition to a green economy in China. Improving green total factor energy efficiency (GTFEE) is the key to realizing the dual targets of energy-saving and economic growth. This paper empirically tests the nonlinear effects of environmental regulation on technical innovation affecting GTFEE by using panel data of 271 prefecture-level cities in China from 2004 to 2019. Meanwhile, a system GMM approach is used to verify the channels through which technical innovation affects GTFEE. Finally, the spatial and temporal characteristics of technical innovation affecting GTFEE are analyzed from the perspective of environmental regulation. The empirical results are as follows: (1) Technical innovation can significantly improve GTFEE. However, this improvement effect is a threshold characteristic; when environmental regulation is above the threshold value, technical innovation has a greater improvement effect on GTFEE. (2) Besides directly influencing GTFEE, technical innovation can also indirectly influence GTFEE via channels such as economic growth effect, industrial structure upgrading effect, and foreign investment effect. Meanwhile, indirect influence channels also show environmental regulation heterogeneity. (3) The number of cities crossing the threshold of environmental regulation in China increases year by year, which helps technical innovation play a role in improving GTFEE. However, there are still a small number of cities that do not cross the threshold during the sample period, which should attract the attention of local governments.

6.
PLoS Pathog ; 17(9): e1009901, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34506605

RESUMO

Neddylation, an important type of post-translational modification, has been implicated in innate and adapted immunity. But the role of neddylation in innate immune response against RNA viruses remains elusive. Here we report that neddylation promotes RNA virus-induced type I IFN production, especially IFN-α. More importantly, myeloid deficiency of UBA3 or NEDD8 renders mice less resistant to RNA virus infection. Neddylation is essential for RNA virus-triggered activation of Ifna gene promoters. Further exploration has revealed that mammalian IRF7undergoes neddylation, which is enhanced after RNA virus infection. Even though neddylation blockade does not hinder RNA virus-triggered IRF7 expression, IRF7 mutant defective in neddylation exhibits reduced ability to activate Ifna gene promoters. Neddylation blockade impedes RNA virus-induced IRF7 nuclear translocation without hindering its phosphorylation and dimerization with IRF3. By contrast, IRF7 mutant defective in neddylation shows enhanced dimerization with IRF5, an Ifna repressor when interacting with IRF7. In conclusion, our data demonstrate that myeloid neddylation contributes to host anti-viral innate immunity through targeting IRF7 and promoting its transcriptional activity.

7.
Sci Rep ; 11(1): 18922, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556699

RESUMO

Maximizing grain yields with effective fertilization technologies and minimizing nitrogen losses is essential in agroecosystems. In this research, we conducted a two-year field experiment to explore whether dripline spacing and fertilization rate would affect maize grain yield. Two dripline spacings (i.e., one drip line per row of maize with a row space of 60 cm and one drip line per two rows of maize) and two fertilization rates (i.e., high fertilization level: N, 180 kg ha-1; P2O5, 90 kg ha-1; and K2O, 90 kg ha-1 and low level: N, 139.5 kg ha-1; P2O5, 76.5 kg ha-1; and K2O, 76.5 kg ha-1) were employed in this research. The results showed that maize yield was significantly affected by both dripline spacing and fertilization rate. The maize yield was 10.2% higher in the treatment with one drip line per two rows than that in the treatment with one drip line per row. Maize yield increased by 10.9% at the high fertilization level compared to that at the low fertilization level. The quantity of cumulative ammonia volatilization was reduced by 15.1% with one drip line per two rows compared to that with one drip line per row, whereas it increased by 26.9% at the high fertilization level compared with that at the low fertilization level. These results indicated that one drip line per two rows with a high fertilization rate increased the yield and could reduce the environmental burden, which may be economically beneficial and environmentally sound for maize fertigation for green agricultural development.

8.
Biomed Pharmacother ; 143: 112118, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34481378

RESUMO

Cardiovascular diseases (CVD) are a significant cause of human health harm. In the past, stem cell therapy was reported to have functional defects, such as immune rejection, tumorigenicity, and infusion toxicity. Exosomes are extracellular vesicles with lipid bilayer membrane structure, containing proteins, lipids, mRNA, miRNA, DNA, and other molecules, which can mediate various biological functions such as immune response, inflammatory response, cell migration, and differentiation intercellular communication. Exosomal miRNAs have outstanding advantages in disease diagnosis and curative effect prediction. Likewise, paracrine factors could also mediate the main therapeutic effect of mesenchymal stem cells. Research has shown that mesenchymal stem cell-derived micro-exosomes, which may come from stem cells, accumulate in the ischemic tissue and regulate cell proliferation, apoptosis, inflammation, and angiogenesis sites of myocardial injury after being transplanted. This review reviewed the molecular mechanisms of exosomes and internal microRNAs derived from mesenchymal stem cells in cardiac ischemic injury repair.

9.
Pharmacol Biochem Behav ; 210: 173269, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34487773

RESUMO

Previous studies have shown that prenatal stress (PS) can potentially contribute to depression-like behavior in offspring and that this effect may be moderated by cross-fostering. However, the underlying mechanism of this effect remains to be determined. This study aimed to determine the effect of cross-fostering on the expression of EAAT2 and the SNARE complex in the hippocampus and the prefrontal cortex of PS offspring rats and to demonstrate functional effects on depression-like behavior. The impacts of cross-fostering were functionally assessed using the sucrose preference test (SPT), the forced swimming test (FST) and the elevated plus maze (EPM). Quantitative real-time PCR was used to determine changes in the expression of EAAT2 and SNAREs mRNA in the hippocampus and the prefrontal cortex of offspring rats. PS offspring rats showed significantly decreased sucrose preference and prolonged immobility time, while cross-fostering effectively increased sucrose preference and shorten the time of immobility. The expression of EAAT2 mRNA in PS offspring rats was markedly reduced, whilst the core mRNA expression of the SNARE complex increased. Our results provide strong evidence demonstrating that cross-fostering can alleviate depression-like behavior and regulate the abnormal expression levels of EAAT2 mRNA and SNARE complex in the hippocampus and the prefrontal cortex of PS offspring rats. Our findings contribute to further understanding of the pathogenesis of PS-induced depression and may help to inform the future development of novel treatment approaches.

10.
Int J Pharm ; 607: 120947, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34358541

RESUMO

With ideal optical properties, semiconducting polymer quantum dots (SPs) have become a research focus in recent years; a considerable number of studies have been devoted to the application of SPs in non-invasive and biosafety phototherapy with near-infrared (NIR) lasers. Nevertheless, the relatively poor stability of SPs in vitro and in vivo remains problematic. PCPDTBT was chosen to synthesize photothermal therapy (PTT) and photodynamic therapy (PDT) dual-model SPs, considering its low band gap and desirable absorption in the NIR window. For the first time, cetrimonium bromide was used as a stabilizer to guarantee the in vitro stability of SPs, and as a template to prepare SP hybrid mesoporous silica nanoparticles (SMs) to achieve long-term stability in vivo. The mesoporous structure of SMs was used as a reservoir for the hypoxia-activated prodrug Tirapazamine (TPZ). SMs were decorated with polyethylene glycol-folic acid (SMPFs) to specifically target activated macrophages in rheumatoid arthritis (RA). Upon an 808 nm NIR irradiation, the SMPFs generate intracellular hyperthermia and excessive singlet oxygen. Local hypoxia caused by molecular oxygen consumption simultaneously activates the cytotoxicity of TPZ, which effectively kills activated macrophages and inhibits the progression of arthritis. This triple PTT-PDT-chemo synergistic treatment suggests that SMPFs realize the in vivo application of SPs and may be a potential nano-vehicle for RA therapy with negligible side-toxicity.


Assuntos
Artrite Reumatoide , Hipertermia Induzida , Nanopartículas , Fotoquimioterapia , Artrite Reumatoide/tratamento farmacológico , Ácido Fólico , Humanos , Fototerapia , Terapia Fototérmica , Polímeros , Dióxido de Silício
11.
J Tradit Chin Med ; 41(4): 617-623, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34392655

RESUMO

OBJECTIVE: To investigate the efficacy of Sijunzi decoction () on limb weakness in a rat model of spleen Qi deficiency (SQD), and to study its effect on mitophagy in skeletal muscle through adenosine monophosphate-activated protein kinase (AMPK) / unc-51 like autophagy activating kinase 1 (ULK1) signaling. METHODS: SQD model rats were produced by fasting combined with forced swimming method for 15 d. After model assessment, rats were randomly divided into four groups of 10 [low/middle/high (L/M/H) Sijunzi decoction dose groups and a normal saline (S) group]. Limb holding power (HP) and body mass (BM) were measured after 2 weeks of treatment. Following euthanasia, quadriceps femoris were dissected and myofiber and mitochondrial morphology were observed by transmission electron microscopy (TEM). Mitochondrial membrane potential (MMP), adenosine triphosphatase (ATP) and reactive oxygen species (ROS) levels were determined using colorimetric methods, and immunoblot analysis of Microtubule-associated protein light chain 3 (LC3) and Sequestosome 1 (p62) was performed to monitor mitophagy and AMPK/ULK1 signaling. RESULTS: Compared with control (C) group rats, in the S group, HP was reduced, the myofiber Z line was disordered, mitochondria were scattered, and numerous vacuoles and mitophagy were observed. MMP and ATP levels were reduced, ROS levels were elevated, and LC3B expression, and p-AMPKα (Thr172)/AMPKα, p-ULK1 (Ser555)/ULK1, and p-Raptor (Ser792)/Raptor ratios were increased, while p62 expression and p-mTOR (Ser2448)/mTOR and p-ULK1 (Ser757)/ULK1 ratios were decreased. After treatment, compared with the S group, HP was improved in M and H groups but not in the L group. Mitophagy was reduced in M, H and L groups but the Z line was disordered and vacuolization remained in the L group. ATP levels were elevated in M, H and L groups, and MMPs were elevat-ed in M and H groups but not in the L group. ROS levels were decreased in M, H and L groups, as were LC3B expression and p-Raptor (Ser792)/Raptor ratios, while p62 expression and p-mTOR (Ser2448)/mTOR and p-ULK1 (Ser757)/ULK1 ratios were increased in M and H groups but not in the L group. p-AMPKα (Thr172)/AMPKα and p-ULK1 (Ser555)/ULK1 ratios were decreased in M, H and L groups. CONCLUSIONS: Sijunzi decoction improved HP, possibly by inhibiting mitophagy via suppression of AMPK/ULK1 signaling. This restored mitochondrial morphology and improved oxidative phosphorylation, which contributed to recovery of limb weakness in SQD model rats.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34382763

RESUMO

All-inorganic halide perovskite nanocrystals (PNCs) have received increasing attention due to their excellent optical properties. However, the inherent instability and the large amount of volatile organic compounds during the production process have severely limited their applications. In this research, we employed the microfluidic electrostatic spinning method to synthesize polyvinylpyrrolidone (PVP)-based PNC (CsPbBr3/PVP) powders directly by spinning chemistry, where the fibers serve as reactors. Thus, 20.1 g of CsPbBr3/PVP powders was obtained, which exhibits good fluorescent properties and high stability. Based on these excellent properties, several new applications were explored, including 3D printing, direct encapsulants for light-emitting diodes, and fluorescent coatings. It should be noted that the powder showed distinct advantages in 3D printing, allowing the fabrication of a series of fluorescent patterns, which offers a new candidate for fluorescent 3D printable materials. This work not only opens up an optimal way for facile production of fluorescent powders by the spinning chemistry strategy, but also provides a new perspective for various application directions, especially for 3D printing.

13.
PLoS One ; 16(8): e0255476, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34339449

RESUMO

Financial bubbles have always been a topic of long-term concern for economists. Understanding bubble phenomenon and dating the period of bubbles in real time can provide an early warning diagnosis for financial bubbles and help regulatory authorities to control it and maintain market order. The generalized sup ADF (GSADF) and backward sup ADF (BSADF) tests with flexible window width can effectively detect and date periodically collapsing bubbles in real time. Based on the financial present value model, this paper applies right-tail recursive ADF test to test multiple bubbles in China's multi-level stock market. Unlike the other researches in China, the ratios of the real stock prices' natural logarithm to the real dividends' natural logarithm are used for our testing instead of stock price index. Empirical results show that there are 8 bubbles in the Main-Board Market, 6 bubbles in the Small and Medium Enterprises Board (SMEs), and 4 bubbles in the Growth Enterprise Market (GEM). These bubbles are liquidity-driven and presuppose a loose credit cycle, with the exception of bubbles in 2014-2015. The frequent emergence of bubbles in a short time indicates that China's stock market is still emerging market. In addition, frequent fluctuations imply there is a serious "herd effect" and a lack of monitoring mechanism for bubble risk. This study not only enrich the real-time dynamic research on periodical bubbles of China's stock market, but also provide an empirical reference for investors' investment choices, financial decisions of listed companies and warning mechanism of regulatory authorities.

14.
Environ Health Perspect ; 129(8): 87001, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34347531

RESUMO

BACKGROUND: Air pollution may be associated with elevated dementia risk. Prior research has limitations that may affect reliability, and no studies have evaluated this question in a population-based cohort of men and women in the United States. OBJECTIVES: We evaluated the association between time-varying, 10-y average fine particulate matter (PM2.5) exposure and hazard of all-cause dementia. An additional goal was to understand how to adequately control for age and calendar-time-related confounding through choice of the time axis and covariate adjustment. METHODS: Using the Adult Changes in Thought (ACT) population-based prospective cohort study in Seattle, we linked spatiotemporal model-based PM2.5 exposures to participant addresses from 1978 to 2018. Dementia diagnoses were made using high-quality, standardized, consensus-based protocols at biennial follow-ups. We conducted multivariable Cox proportional hazards regression to evaluate the association between time-varying, 10-y average PM2.5 exposure and time to event in a model with age as the time axis, stratified by apolipoprotein E (APOE) genotype, and adjusted for sex, education, race, neighborhood median household income, and calendar time. Alternative models used calendar time as the time axis. RESULTS: We report 1,136 cases of incident dementia among 4,166 individuals with nonmissing APOE status. Mean [mean ± standard deviation (SD)] 10-y average PM2.5 was 10.1 (±2.9) µg/m3. Each 1-µg/m3 increase in the moving average of 10-y PM2.5 was associated with a 16% greater hazard of all-cause dementia [1.16 (95% confidence interval: 1.03, 1.31)]. Results using calendar time as the time axis were similar. DISCUSSION: In this prospective cohort study with extensive exposure data and consensus-based outcome ascertainment, elevated long-term exposure to PM2.5 was associated with increased hazard of all-cause dementia. We found that optimal control of age and time confounding could be achieved through use of either age or calendar time as the time axis in our study. Our results strengthen evidence on the neurodegenerative effects of PM2.5. https://doi.org/10.1289/EHP9018.

15.
Theor Appl Genet ; 134(10): 3287-3303, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34410456

RESUMO

KEY MESSAGE: Two CO paralogs in Brassica napus were confirmed and shown distinct expression pattern and function in promoting flowering and allelic variation s within BnaCO.A10 were found closely associated with ecotype divergence. CONSTANS (CO) is a key gene that responds to photoperiod and in Arabidopsis can promote flowering under long-day (LD) conditions. Brassica napus L. is a major oil crop and close relative of Arabidopsis, and arose via allopolyploidization from the diploids B. rapa (A genome) and B. oleracea (C genome). In this study, we confirmed that B. napus has two CO genes located on the A10 (BnaCO.A10) and C9 (BnaCO.C9) chromosomes. Significant differences in level and temporal pattern of transcription, as well as in protein function, of these homoeologous may have resulted from sequence variation in the promoter as well as in the coding region. Apart from two insertions of 527 bp and 2002 bp in the promoter of BnaCO.C9 that function as transcriptional enhancers, this gene is otherwise highly conserved in both promoter and coding region. However, BnaCO.A10 was classified into two haplotypes and transgene analysis in Arabidopsis and backcross analysis in rapeseed indicated that the winter-type haplotype had a greater effect in promoting flowering than the spring type. We discuss the contribution of CO alleles to species evolution, and for eco-geographic radiation following crop domestication, alongside scope for managing this locus in future breeding.


Assuntos
Brassica napus/crescimento & desenvolvimento , Cromossomos de Plantas/genética , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Fenótipo , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Alelos , Brassica napus/genética , Mapeamento Cromossômico/métodos , Ecótipo , Evolução Molecular , Flores/genética , Fotoperíodo , Filogenia , Melhoramento Vegetal , Proteínas de Plantas/genética , Locos de Características Quantitativas , Estações do Ano , Fatores de Transcrição/genética
16.
Int J Pharm ; 607: 120939, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34310953

RESUMO

This paper presents a generic framework of Model Driven Design (MDD) with its application for a twin screw granulation process using a mechanistic-based population balance model (PBM). The process kernels including nucleation, breakage, layering and consolidation are defined in the PBM. A recently developed breakage kernel is used with key physics incorporated in the model formulation. Prior to granulation experiments, sensitivity analysis of PBM parameters is performed to investigate the variation of model outputs given the input parameter variance. The significance of liquid to solid ratio (L/S ratio), nucleation and breakage parameters is identified by sensitivity analysis. The sensitivity analysis dramatically reduces the number of fitting parameters in PBM and only nine granulation experiments are required for model calibration and validation. A model validation flowchart is proposed to elucidate the evolution of kinetic rate parameters associated with L/S ratio and screw element geometry. The presented MDD framework for sensitivity analysis, parameter estimation, model verification and validation can be generalized and applied for any particulate process.


Assuntos
Modelos Teóricos , Tecnologia Farmacêutica , Parafusos Ósseos , Calibragem , Composição de Medicamentos , Tamanho da Partícula
17.
Eur J Pharmacol ; 908: 174317, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34270989

RESUMO

Endothelial cell dysfunction is a prominent feature of diabetic cardiovascular complications, and endothelial cell senescence is considered to be an important contributor to endothelial dysfunction. Discoidin domain receptor 1 (DDR1) has been reported to be involved in atherogenesis and cerebral ischemia/reperfusion injury. In this study, we aimed to explore the role of DDR1 in endothelial cell senescence under diabetic conditions and elucidate the underlying mechanisms. A diabetic rat model was established by a single intraperitoneal injection of streptozocin (STZ) (60 mg/kg), which showed an increase in senescence-associated ß-galactosidase (SA-ß-gal) staining signal of thoracic aortic endothelium, impaired vascular structure and function, accompanied by an up-regulation of DDR1. Next, we verified the role of DDR1 in endothelial senescence and the underlying mechanisms in high glucose-treated human umbilical vein endothelial cells (HUVECs). Consistent with the in vivo findings, high glucose induced endothelial senescence, impaired endothelial function and elevated DDR1 expression, accompanied by the elevation of senescence-related genes p53 and p21 expression, and these effects were reversed by DDR1 siRNA. DDR1 has been documented to be a potential target of miR-199a-3p. Here, we found that miR-199a-3p was down-regulated by high glucose in the aorta tissue and HUVECs, while miR-199a-3p mimic significantly suppressed increased endothelial senescence and elevated DDR1 induced by high glucose. In conclusion, our data demonstrated that miR-199a-3p/DDR1/p53/p21 signaling pathway was involved in endothelial senescence under diabetic conditions, and therapeutic targeting DDR1 would be exploited to inhibit endothelial senescence owing to high glucose exposure.

18.
Cytogenet Genome Res ; 161(5): 272-277, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34289478

RESUMO

The genus Dracaena is the main source of dragon's blood, which is a plant resin and has been used as traditional medicine since ancient times in different civilizations. However, the chromosome numbers and karyotypes present in this genus remain poorly understood. In this study, fluorescence in situ hybridization (FISH) using oligonucleotide probes for ribosomal DNAs (5S and 45S rDNA) and telomeric repeats (TTTAGGG)3 was applied to analyze 4 related species: Dracaena terniflora Roxb., Dracaena cambodiana Pierre ex Gagnep., Aizong (Dracaena sp.), and Dracaena cochinchinensis (Lour.) S.C. Chen. In all 4 species, both 5S and 45S rDNA showed hybridization signals in the paracentromeric region of a pair of chromosomes; the sizes of the 45S rDNA signals were larger than those of the 5S rDNA. Importantly, the telomeric repeat signals were located in the telomeric regions of almost all chromosomes. The results indicated that the chromosome number of all 4 Dracaena species is 2n = 40, and the lengths of the mitotic metaphase chromosomes range from 0.99 to 2.98 µm. Our results provide useful cytogenetic information, which will be beneficial to future studies in genome structure of the genus Dracaena.


Assuntos
Mapeamento Cromossômico/métodos , Cromossomos de Plantas/química , Dracaena/genética , Cariótipo , Centrômero , China , Dracaena/classificação , Hibridização in Situ Fluorescente/métodos , Cariotipagem/métodos , Filogeografia , RNA Ribossômico/genética , RNA Ribossômico 5S/genética , Telômero
19.
Artigo em Inglês | MEDLINE | ID: mdl-34318673

RESUMO

Cu/SiO2 hybrid bonding with planarized dielectric and isolated metal connections can realize ultradense interconnects (e.g., ≤1 µm) by eliminating the microbumps and underfill through the direct bonding of Cu-Cu and SiO2-SiO2. However, the low-temperature bonding of Cu-Cu (oxide-free surface) and SiO2-SiO2 (hydroxylated surface) is difficult to be compatible in a mechanism. We circumvent this contradiction by constructing a co-hydroxylated functional surface on a Cu/SiO2 hybrid platform. By combining and optimizing the protocol of Ar/O2 plasma activation and formic acid solution immersion, an -OH active layer was successfully established on the Cu and SiO2 surfaces simultaneously, and the increased total surface area provided more adsorption sites for hydroxyl groups. A Cu-Cu interface with sufficient atom diffusion, substantial grain growth, and fewer microvoids was obtained at 200 °C. Notably, the carbon-related interlayer that may degrade the interfacial performance could be effectively inhibited across the optimized SiO2-SiO2 interface even if organic acid was introduced in the protocol. This low-temperature Cu/SiO2 hybrid bonding via a co-hydroxylated strategy may inspire the development of a memory-centric chip architecture and functional integrated circuits delivering a monolithic-like performance in the future hyperscaling era.

20.
Ecotoxicol Environ Saf ; 221: 112469, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34198190

RESUMO

Glutathione S-transferase (GST) is the key enzyme in glutathione (GSH) synthesis, and plays a crucial role in copper (Cu) detoxification. Nonetheless, its regulatory mechanisms remain largely unclear. In this study, we identified a Cu-induced glutathione S-transferase 1 (TaGST1) gene in wheat. Yeast one-hybrid (Y1H) screened out TaWRKY74, which was one member from the WRKY transcription factor family. The bindings between TaGST1 promoter and TaWRKY74 were further verified by using another Y1H and luciferase assays. Expression of TaWRKY74 was induced more than 30-folds by Cu stress. Functions of TaWRKY74 were tested by using transiently silence methods. In transiently TaWRKY74-silenced wheat plants, TaWRKY74 and TaGST1 expression, GST activity, and GSH content was significantly inhibited by 25.68%, 19.88%, 27.66%, and 12.68% in shoots, and 53.81%, 52.11%, 23.47%, and 17.11% in roots, respectively. However, contents of hydrogen peroxide, malondialdehyde, or Cu were significantly increased by 2.58%, 12.45%, or 37.74% in shoots, and 25.24%, 53.84%, and 103.99% in roots, respectively. Notably, exogenous application of GSH reversed the adverse effects of transiently TaWRKY74-silenced wheat plants during Cu stress. Taken together, our results suggesting that TaWRKY74 regulated TaGST1 expression and affected GSH accumulation under Cu stress, and could be useful to ameliorate Cu toxicity for crop food safety.


Assuntos
Cobre/toxicidade , Glutationa Transferase/metabolismo , Glutationa/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Triticum/efeitos dos fármacos , Fatores de Transcrição/genética , Triticum/genética , Triticum/metabolismo , Técnicas do Sistema de Duplo-Híbrido , Leveduras/genética
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