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1.
Eur J Pharmacol ; 900: 174067, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33811838

RESUMEN

Bovine endometritis is one of the major postpartum diseases associated with infertility and subfertility, decreasing the benefit of dairy industry. It is important to develop alternate therapies for endometritis in the context of drug residues in the milk and hormone disorder in the estrous cycle. α7 nicotine acetylcholine receptor has been identified as the core of 'cholinergic anti-inflammatory pathway (CAP)', which is a potential drug target to inflammatory diseases. However, there has been still no study on its anti-inflammatory effects and mechanism on lipopolysaccharide (LPS)-induced bovine endometritis. This study aimed to demonstrate the underlying anti-inflammatory effects and mechanism of α7-nACh receptor on LPS-induced inflammation in bovine endometrial tissues cultured in vitro. The results suggested that activation of α7-nACh receptor significantly suppressed the mRNA expression levels of interleukin 1ß (IL-1ß), IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) in bovine endometrial tissues. Western blot and enzyme-linked immunosorbent assay (ELISA) detection results showed that activation of α7-nACh receptor inhibited LPS-induced phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Moreover, α7-nACh receptor agonist decreased the expression of cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1(mPGES-1), as well as prostaglandin E2 (PGE2) secretion. Interestingly, in COX-2 inhibition experiment, activation of α7-nACh receptor increased COX-2 expression and PGE2 production, compared with COX-2 inhibitor treatment. In conclusion, activation of the cholinergic system through α7-nACh receptor agonist has suppressed inflammation of bovine endometrial tissues via JAK2/STAT3 pathway and potential COX-2-derived PGE2.

2.
Demography ; 58(1): 247-272, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33834238

RESUMEN

Despite much interest in how parenthood contributes to the gender pay gap, prior research has rarely explored firms' roles in shaping the parenthood pay penalty or premium. The handful of studies that investigated parenthood's effects within and across firms generally compared parents and their childless peers at a given time and failed to account for unobserved heterogeneity between the two groups. Such comparisons also cannot inform how having children may alter individuals' earnings trajectories within and across firms. Using 26 rounds of the National Longitudinal Survey of Youth 1979 and fixed-effects models, we examine how being a mother or father is linked to earnings growth within and across firms. We find that women's pay decreases as they become mothers and that the across-employer motherhood penalty is larger than the within-employer penalty. By contrast, fatherhood is associated with a pay premium, and the within-employer fatherhood premium is considerably greater than the across-employer one. We argue that these results are consistent with the discrimination explanation of the motherhood penalty and fatherhood premium. Because employers are likely to trust women who become mothers while working for them more than new recruits who are mothers, their negative bias against mothers would be more salient when evaluating the latter, which could result in a larger between-organizational motherhood penalty. Conversely, employers' likely greater trust in existing workers who become fathers than fathers they hire from elsewhere may amplify their positive bias favoring fathers in assessing the former, which could explain the greater within-firm fatherhood premium.

3.
Proc Natl Acad Sci U S A ; 118(14)2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33811139

RESUMEN

One third of the western population suffers from nonalcoholic fatty liver disease (NAFLD), which may ultimately develop into hepatocellular carcinoma (HCC). The molecular event(s) that triggers the disease are not clear. Current understanding, known as the multiple hits model, suggests that NAFLD is a result of diverse events at several tissues (e.g., liver, adipose tissues, and intestine) combined with changes in metabolism and microbiome. In contrast to this prevailing concept, we report that fatty liver could be triggered by a single mutated protein expressed only in the liver. We established a transgenic system that allows temporally controlled activation of the MAP kinase p38α in a tissue-specific manner by induced expression of intrinsically active p38α allele. Here we checked the effect of exclusive activation in the liver. Unexpectedly, induction of p38α alone was sufficient to cause macrovesicular fatty liver. Animals did not become overweight, showing that fatty liver can be imposed solely by a genetic modification in liver per se and can be separated from obesity. Active p38α-induced fatty liver is associated with up-regulation of MUC13, CIDEA, PPARγ, ATF3, and c-jun mRNAs, which are up-regulated in human HCC. Shutting off expression of the p38α mutant resulted in reversal of symptoms. The findings suggest that p38α plays a direct causative role in fatty liver diseases and perhaps in other chronic inflammatory diseases. As p38α activity was induced by point mutations, it could be considered a proto-inflammatory gene (proto-inflammagene).

5.
Eur J Pharmacol ; : 174077, 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33798601

RESUMEN

This study investigated the hemodynamic effect of Bay 60-7550, a phosphodiesterase type 2 (PDE2) inhibitor, in healthy rat hearts both in vivo and ex vivo and its underlying mechanisms. In vivo rat left ventricular pressure-volume loop, Langendorff isolated rat heart, Ca2+ transient of left ventricular myocyte and western blot experiments were used in this study. The results demonstrated that Bay 60-7550 (1.5 mg/kg, i.p.) increased the in vivo rat heart contractility by enhancing stroke work, cardiac output, stroke volume, end-diastolic volume, heart rate, and ejection fraction. The simultaneous aortic pressure recording indicated that the systolic blood pressure was increased and diastolic blood pressure was decreased by Bay 60-7550. Also, the arterial elastance which is proportional to the peripheral vessel resistance was significantly decreased. Bay 60-7550 (0.001, 0.01, 0.1, 1 µmol/l) also enhanced the left ventricular development pressure in non-paced and paced modes with a decrease of heart rate in non-paced model. Bay 60-7550 (1 µmol/l) increased SERCA2a activity and SR Ca2+ content and reduced SR Ca2+ leak rate. Furthermore, Bay 60-7550 (0.1 µmol/l) increased the phosphorylation of phospholamban at 16-serine without significantly changing the phosphorylation levels of phospholamban at 17-threonine and RyR2. Bay 60-7550 increased the rat heart contractility and reduced peripheral arterial resistance may be mediated by increasing the phosphorylation of phospholamban and dilating peripheral vessels. PDE2 inhibitors which result in a positive inotropic effect and a decrease in peripheral resistance might serve as a target for developing agents for the treatment of heart failure in clinical settings.

6.
Pharmaceutics ; 13(3)2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33800235

RESUMEN

Antibiotic resistance is a significant crisis that threatens human health and safety worldwide. There is an urgent need for new strategies to control multidrug-resistant (MDR) bacterial infections. The latest breakthrough in gene-editing tools based on CRISPR/Cas9 has potential application in combating MDR bacterial infections because of their high targeting ability to specifically disrupt the drug resistance genes that microbes use for infection or to kill the pathogen directly. Despite the potential that CRISPR/Cas9 showed, its further utilization has been hampered by undesirable delivery efficiency in vivo. Nanotechnology offers an alternative way to overcome the shortcomings of traditional delivery methods of therapeutic agents. Advances in nanotechnology can improve the efficacy and safety of CRISPR/Cas9 components by using customized nanoparticle delivery systems. The combination of CRISPR/Cas9 and nanotechnology has the potential to open new avenues in the therapy of MDR bacterial infections. This review describes the recent advances related to CRISPR/Cas9 and nanoparticles for antimicrobial therapy and gene delivery, including the improvement in the packaging and localizing efficiency of the CRISPR/Cas9 components in the NP (nanoparticle)/CRISPR system. We pay particular attention to the strengths and limitations of the nanotechnology-based CRISPR/Cas9 delivery system to fight nosocomial pathogens.We highlight the need for more scientific research to explore the combinatorial efficacy of various nanoparticles and CRISPR technology to control and prevent antimicrobial resistance.

7.
Antioxidants (Basel) ; 10(3)2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33801821

RESUMEN

To expand the applications and enhance the stability and bioactivity of resveratrol (RE), and to simultaneously include the potential health benefits of short chain fatty acids (SCFA) esters of RE were prepared by Steglich reactions with acetic, propionic, and butyric acids, respectively. RE and the esterified RE-SCFA products (including RAE, RPE, and RBE) were analyzed using nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), differential thermal analysis (DTA), and liquid chromatography-mass spectrometry (LC-MS). The FTIR and 13C NMR spectra of the esterified products included ester-characteristic peaks at 1751 cm-1 and 171 ppm, respectively. Moreover, the peaks in the range of 1700 to 1600 cm-1 in the FTIR spectra of the esterified products indicated that the esterification of RE-SCFA was successful. The TGA results revealed that the RE-SCFA esters decomposed at lower temperatures than RE. The peaks in the LC-MS profiles of the esterified products indicated the formation of mono- and diesters, and the calculated monoester synthesis rates ranged between 45.81 and 49.64%. The RE esters inhibited the Cu2+-induced low-density lipoprotein oxidation reaction, exhibited antioxidant activity in bulk oil, and effectively inhibited the hydroxyl radical-induced DNA scission. Moreover, the RE-SCFA esters had better hydrogen peroxide scavenging activity than RE. Our results are the first in the literature to successfully including short chain fatty acids in the esters of resveratrol, and the products could be used as a functional food ingredient in processed foods or can be used as dietary supplements to promote health.

8.
Micromachines (Basel) ; 12(3)2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33802243

RESUMEN

The development of fan-out packaging technology for fine-pitch and high-pin-count applications is a hot topic in semiconductor research. To reduce the package footprint and improve system performance, many applications have adopted packaging-on-packaging (PoP) architecture. Given its inherent characteristics, glass is a good material for high-speed transmission applications. Therefore, this study proposes a fan-out wafer-level packaging (FO-WLP) with glass substrate-type PoP. The reliability life of the proposed FO-WLP was evaluated under thermal cycling conditions through finite element simulations and empirical calculations. Considering the simulation processing time and consistency with the experimentally obtained mean time to failure (MTTF) of the packaging, both two- and three-dimensional finite element models were developed with appropriate mechanical theories, and were verified to have similar MTTFs. Next, the FO-WLP structure was optimized by simulating various design parameters. The coefficient of thermal expansion of the glass substrate exerted the strongest effect on the reliability life under thermal cycling loading. In addition, the upper and lower pad thicknesses and the buffer layer thickness significantly affected the reliability life of both the FO-WLP and the FO-WLP-type PoP.

9.
Artículo en Inglés | MEDLINE | ID: mdl-33792891

RESUMEN

The non-response model in Knott et al. (1991, Statistician, 40, 217) can be represented as a tree model with one branch for response/non-response and another branch for correct/incorrect response, and each branch probability is characterized by an item response theory model. In the model, it is assumed that there is only one source of non-responses. However, in questionnaires or educational tests, non-responses might come from different sources, such as test speededness, inability to answer, lack of motivation, and sensitive questions. To better accommodate such more realistic underlying mechanisms, we propose a a tree model with four end nodes, not all distinct, for non-response modelling. The Laplace-approximated maximum likelihood estimation for the proposed model is suggested. The validation of the proposed estimation procedure and the advantage of the proposed model over traditional methods are demonstrated in simulations. For illustration, the methodologies are applied to data from the 2012 Programme for International Student Assessment (PISA). The analysis shows that the proposed tree model has a better fit to PISA data than other existing models, providing a useful tool to distinguish the sources of non-responses.

10.
J Clin Pathol ; 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33649140

RESUMEN

AIM: Various approaches have been reported for distinguishing separate primary lung adenocarcinomas from intrapulmonary metastases in patients with two lung nodules. The aim of this study was to determine whether histological assessment is reliable and accurate in distinguishing separate primary lung adenocarcinomas from intrapulmonary metastases using routine molecular findings as an adjunct. METHODS: We studied resected tumour pairs from 32 patients with lung adenocarcinomas in different lobes. In 15 of 32 tumour pairs, next-generation sequencing (NGS) for common driver mutations was performed on both nodules. The remainder of tumour pairs underwent limited NGS, or EGFR genotyping. Tumour pairs with different drivers (or one driver/one wild-type) were classified as molecularly unrelated, while those with identical low-frequency drivers were classified as related. Three pathologists independently and blinded to the molecular results categorised tumour pairs as related or unrelated based on histological assessment. RESULTS: Of 32 pairs, 15 were classified as related by histological assessment, and 17 as unrelated. Of 15 classified as related by histology, 6 were classified as related by molecular analysis, 4 were unrelated and 5 were indeterminate. Of 17 classified as unrelated by histology, 14 were classified as unrelated by molecular analysis, none was related and 3 were indeterminate. Histological assessment of relatedness was inaccurate in 4/32 (12.5%) tumour pairs. CONCLUSIONS: A small but significant subset of two-nodule adenocarcinoma pairs is inaccurately judged as related by histological assessment, and can be proven to be unrelated by molecular analysis (driver gene mutations), leading to significant downstaging.

11.
J Clin Med ; 10(4)2021 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-33668430

RESUMEN

BACKGROUND: Protein-bound uremic toxins are associated with cardiovascular disease and mortality in patients with chronic kidney disease. We investigated their association with clinical outcomes in patients undergoing chronic hemodialysis (CHD). METHODS: A prospective cohort study was conducted on 86 Taiwanese patients undergoing CHD. The predictors were indoxyl sulfate and p-cresyl sulfate concentrations, with each analyzed as three tertiles. Outcomes were cardiovascular events and all-cause mortality. RESULTS: During a 25-month follow up period, there were 23 cardiovascular events and seven all-cause mortality events. In the crude survival analysis, the second indoxyl sulfate tertile was shown to be a powerful predictor of cardiovascular events compared with the third tertile (hazard ratio (HR), 3.14; 95% confidence interval (CI), 1.10-8.94), and the first tertile was shown to have a poor but insignificant cardiovascular outcome (HR, 1.09; 95% CI, 0.30-4.00). Moreover, the predictive power of the second indoxyl sulfate tertile for cardiovascular events remained after adjustment for confounders (HR, 5.42; 95% CI, 1.67-17.60). CONCLUSIONS: An inverse U-curve relationship was observed between the total serum indoxyl sulfate level and cardiovascular events in our CHD patients. A large-scale study is needed to confirm this relationship.

12.
Materials (Basel) ; 14(4)2021 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-33671672

RESUMEN

The properties of alfalfa-derived biochars etched with phosphoric (PBC) or hydrochloric acid (ClBC) compared with raw materials (BC) were examine in this paper. SEM, FT-IR, XRD, BET and elemental analysis were performed to characterize the micromorphology and chemical structure comprehensibly. The results showed that the porous structure was enhanced, and surface area was increased via etching with inorganic acids. Batch adsorption experiments were performed for sulfamethoxazole (SMX) to biochars. The experimental data showed that modified biochars exhibited higher adsorption capacity for SMX, i.e., the adsorption quantity of ClBC and PBC had risen by 38% and 46%. The impact on pH values suggested that the physisorption, including pore-filling and electrostatic interaction, might be applied to original biochar. In addition, chemisorption also played a role, including hydrogen bonding, π-π electron donor acceptor interaction (π-π EDA), and so on. Furthermore, both pH and coexisting ions also had a certain effect on sorption. Enhancement of the electrostatic attraction between biochar and SMX might also account for the enhanced capacity of SMX at pH < 7, and coexisting ions could decrease the amount of SMX adsorbed onto biochars, mainly because of competition for adsorption sites.

13.
Artículo en Inglés | MEDLINE | ID: mdl-33674440

RESUMEN

We investigated the prevalence and transmission of NDM-producing Enterobacteriaceae in fecal samples of geese and environmental samples from a goose farm in Southern China. The samples were cultivated on MacConkey agar plates supplemented with meropenem. Individual colonies were examined for bla NDM and bla NDM-positive bacteria were characterized based on WGS data from the Illumina and ONT platforms. Of 117 samples analyzed, the carriage rates for NDM-positive Enterobacteriaceae were 47.1, 18 and 50% in geese, inanimate environments (sewage, soil, fodder and dust) and mouse samples, respectively. Two variants (4 bla NDM-1 and 40 bla NDM-5) were found among 44 bla NDM-positive Enterobacteriaceae, which belonged to 8 species and Escherichia coli was the most prevalent (50%). WGS analysis revealed that bla NDM co-existed with diverse antibiotic resistance genes (ARGs). Population structure analysis showed that most E. coli and Enterobacter sp. isolates were highly heterogeneous while most Citrobacter sp. and P. stuartii isolates possessed extremely high genetic similarity. Additionally, bla NDM-5-positive ST4358/ST48 E. coli isolates were found to be clonally spread between the geese and environment and were highly genetically similar to those reported from ducks, farm environments and humans in China. Plasmid analysis indicated that IncX3 pHNYX644-1-like (n=40) and untypable pM2-1-like plasmids (n=4) mediated bla NDM spread. pM2-1-like plasmids possessed diverse ARGs including bla NDM-1, the arsenical and mercury resistance operons and the maltose operon. Our findings revealed that the goose farm is a reservoir for NDM-positive Enterobacteriaceae. The bla NDM contamination of wild mice and the novel pM2-1-like plasmid described in this study likely adds to the risk for dissemination of bla NDM and associated resistance genes.Importance: The carbapenem-resistant bacteria, in particular NDM-producing Enterobacteriaceae, has become a great threat to global public. These bacteria have been found not only in hospital and community environments, but also among food animal production chains, which are recognized as reservoirs for NDM-producing Enterobacteriaceae. However, the dissemination of NDM-producing bacteria in the waterfowl farm has been less well explored. Our study demonstrated that horizontal spread of bla NDM-carrying plasmids and the partial clonal spread of bla NDM-positive Enterobacteriaceae contributed to widespread contamination of bla NDM in the goose farm ecosystem, including mouse. Furthermore, we found a novel and transferable bla NDM-1-carrying MDR plasmid that possessed multiple environmental adaptation-related genes. The outcomes of this study contribute to a better understanding of the prevalence and transmission of bla NDM-producing Enterobacteriaceae among diverse niches in the farm ecosystem.

14.
Artículo en Inglés | MEDLINE | ID: mdl-33709618

RESUMEN

OBJECTIVES: This study aimed to assess the short-term results of stress urinary incontinence (SUI) in women undergoing laparoscopic sacrocolpopexy (LSC) with and without midurethral sling (MUS). METHODS: This retrospective study was conducted from July 2012 to December 2017. Women with stage 3 or 4 in the Pelvic Organ Prolapse Quantification (POP-Q) who underwent LSC were recruited. Multichannel urodynamic studies were performed in all women. Assessment included pre- and postoperative POP-Q stages, urodynamic parameters, peri- and postoperative complications, and symptoms. RESULTS: One hundred and eighteen patients met the inclusion criteria in total. A total of 19.5% (23/118) of them had concomitant MUS. The mean follow-up duration was 16.9 ±  16.0 (range 3-69) months. Meanwhile, 33.9% (40/118) of the patients were diagnosed with overt SUI, and 50% (20/40) underwent MUS. In the concomitant MUS group, the rate of having postoperative SUI was only 5% (1/20). Patients diagnosed with SUI and without concomitant MUS had a 45% rate (9/20), and 25% of them (5/20) received MUS later. Preoperatively, 16.1% (19/118) of the patients were diagnosed with occult SUI. Among the patients without anti-incontinence sling during prolapse surgery, 25% (4/16) of them complained about having SUI during the follow-up. However, none of the women required subsequent anti-incontinence surgery. Postoperative de novo SUI occurred to 13.6% (16/118) of them. None of the patients received further operation. Based on the preoperative and postoperative urodynamic studies in the combination surgery group, a significant improvement was observed in the pad test. CONCLUSIONS: The combination of LSC with MUS procedure is likely to be beneficial in selected patients.

15.
Thorac Cancer ; 2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33724695

RESUMEN

Very little data exists on salvage surgery in previously unresectable or metastatic disease treated with initial immunotherapy. Only a handful of case reports/series regarding surgery for advanced lung cancer after immunotherapy mention the technical challenges involved. We report the case of a 67-year-old female with a left lung squamous cell lung cancer revealed by computed tomography-guided biopsy. Treatment started with chemotherapy followed by immunotherapy in which a partial response was recorded. Subsequent salvage lingulectomy with the thoracoscopic approach was performed. The patient fully recovered and shows no sign of recurrence at follow-up 16 months on. Our case discusses the surgical tactics involved in the procedure, highlights similar findings encountered in the literature, and contributes to the few reports therein.

16.
Artículo en Inglés | MEDLINE | ID: mdl-33646444

RESUMEN

OBJECTIVE: To investigate the outcomes of cerebrospinal fluid (CSF) diversion in lung cancer patients with leptomeningeal carcinomatosis (LMC). METHODS: A retrospective review of consecutive lung cancer patients with LMC suffering from increased intracranial pressure (IICP) and hydrocephalus between February 2017 and February 2020. We evaluated the survival benefit of CSF diversion surgery and assessed the outcomes of treatments administered post-LMC in terms of overall survival and shunt-related complications. RESULTS: The study cohort included 50 patients (median age: 59 years). Ventricular peritoneal (VP) shunts were placed in 33 patients, and lumbar peritoneal (LP) shunts were placed in 7 patients. Programmable shunts were placed in 36 patients. Shunt adjustment was performed in 19 patients. Kaplan-Meier analysis revealed that shunt placement increased overall survival from 1.95 months to 6.21 months (p = 0.0012) and increased Karnofsky Performance Scores (KPS) from 60 to 70. Univariate analysis revealed no difference between VP or LP shunts in terms of survival. No differences in post-shunt systemic treatments (tyrosine kinase inhibitors (TKIs) or systemic treatments) were observed in overall survival. Shunt-related complications were noted in 7 patients, including shunt obstruction (n = 4), infection (n = 1), and over-drainage (n = 2). CONCLUSION: CSF diversion (VP or LP shunt) appears to be an effective and safe treatment for lung cancer patients with LMC and hydrocephalus. Programmable shunts should be considered for complex cases, which commonly require pressure adjustments as the disease progresses.

17.
Mar Pollut Bull ; 166: 112230, 2021 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-33711606

RESUMEN

Twenty biota species were collected from the Northern Beibu Gulf to understand the heavy metal pollution status and biomagnification characteristics. Mean concentrations (µg/g) of Mn, Zn, Pb, Cr, Ni, As, Cu, and Cd in the biota species were 0.99, 38.33, 0.14, 0.079, 0.085, 51.10, 7.92, and 0.21, respectively. As levels in most biota species exceeded the corresponding guidelines. Crabs were detected with high metal accumulation ability for each heavy metal except Pb. The ranges of δ15N and δ13C in organisms were from 8.0‰ to 15.6‰ and from -21.4‰ to -15.6‰, respectively. Cr, Mn, Ni, and As showed potential biomagnification trends in the food webs. The EDI values of these elements decreased by the sequence of As > Zn > Cu > Mn > Cd > Pb > Ni > Cr. High THQ and CR values for As indicated a potential health risk by consumption of these aquatic products.

18.
Life Sci ; 277: 119435, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33781829

RESUMEN

AIMS: Acute pancreatitis (AP) is a common inflammatory disorder with high incidence and mortality. AMPK-SIRT1 pathway is involved in a variety of diseases, but its role in AP remains elusive. This study was aimed to explore the role of AMPK-SIRT1 pathway in AP. MAIN METHODS: AP models in vivo and vitro were constructed by intraperitoneal administration of L-arginine and caerulein-stimulated respectively. Rat serum amylase, IL-6 and TNF-α were determined by ELISA. The expression levels of AMPK, SIRT1, Beclin-1, LC3 and p62 were determined by qRT-PCR and western blot. The number of autophagosome was checked by transmission electron microscope. KEY FINDINGS: Compared with NC rats, serum amylase, IL-6 and TNF-α were increased in AP rats. The expressions of AMPK and SIRT1 were decreased, while Beclin-1, LC3II/Iratio and p62 were markedly increased in AP rats. After activation of AMPK by metformin, expressions of p-AMPKα, SIRT1 were significantly raised, while expressions of Beclin-1, LC3 II/I, p62, TNF-α, IL-6 were reduced, and the number of autophagosome was decreased significantly in caerulein-stimulated AR42J cells. The inhibition of AMPK by compound C obtained opposite results. SIGNIFICANCE: During AP occurrence, p-AMPK and SIRT1 were down-regulated, leading to the accumulation of p62, increase of autophagic vacuoles, damage of autophagy, and the occurrence of inflammation. It hinted that activation of AMPK restored impaired autophagy and inhibited inflammation reaction by up-regulating SIRT1. Our findings might provide important theoretical basis for explaining the pathogenesis of AP and investigating therapeutic target to treat and prevent AP.

20.
ACS Nano ; 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33787215

RESUMEN

Single-atom catalysts (SACs) with magnetic elements as the active center have been widely exploited for efficient electrochemical conversions. Understanding the catalytic role of spin, and thus modulating the spin density of a single-atom center, is of profound fundamental interest and technological impact. Here, we synthesized ferromagnetic single Co atom catalysts on TaS2 monolayers (Co1/TaS2) as a model system to explore the spin-activity correlation for the oxygen evolution reaction (OER). A single Co atom adsorbed at the hollow site (CoHS) with spin-polarized electronic states serves as the active site for OER, whose spin density can be regulated by its neighboring single Co site via tuning the Co loading. Both experimental and theoretical results reveal the spin density-dependent OER activity that an optimal spin density of CoHS can be achieved with a neighboring hetero-single CoTa site (substitution of Ta by Co) for a superior OER performance, in contrast to a homo-single CoHS site, which creates an excessive spin density over vicinal CoHS. An optimized spin density of CoHS results in an optimal binding energy of oxygen species for the OER. Establishing the spin-activity correlation in SACs may create a descriptor for designing efficient magnetic SACs for renewable energy conversions.

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