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1.
PeerJ ; 10: e12664, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35036088

RESUMO

The CRISPR/Cas9-mediated genome editing system has been used extensively to engineer targeted mutations in a wide variety of species. Its application in banana, however, has been hindered because of the species' triploid nature and low genome editing efficiency. This has delayed the development of a DNA-free genome editing approach. In this study, we reported that the endogenous U6 promoter and banana codon-optimized Cas9 apparently increased mutation frequency in banana, and we generated a method to validate the mutation efficiency of the CRISPR/Cas9-mediated genome editing system based on transient expression in protoplasts. The activity of the MaU6c promoter was approximately four times higher than that of the OsU6a promoter in banana protoplasts. The application of this promoter and banana codon-optimized Cas9 in CRISPR/Cas9 cassette resulted in a fourfold increase in mutation efficiency compared with the previous CRISPR/Cas9 cassette for banana. Our results indicated that the optimized CRISPR/Cas9 system was effective for mutating targeted genes in banana and thus will improve the applications for basic functional genomics. These findings are relevant to future germplasm improvement and provide a foundation for developing DNA-free genome editing technology in banana.

2.
World J Pediatr ; 2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35066802

RESUMO

BACKGROUND: This study aimed to investigate the performance of handmade tri-leaflet expanded polytetrafluoroethylene (ePTFE) conduits in the absence of a suitable homograft. METHODS: Patients who underwent right ventricular outflow tract reconstruction with tri-leaflet ePTFE conduits or homografts between December 2016 and August 2020 were included. The primary endpoint was the incidence of moderate or severe conduit stenosis (≥ 36 mmHg) and/or moderate or severe insufficiency. The secondary endpoint was the incidence of severe conduit stenosis (≥ 64 mmHg) and/or severe insufficiency. RESULTS: There were 102 patients in the ePTFE group and 52 patients in the homograft group. The median age was younger [34.5 (interquartile range: 20.8-62.8) vs. 60.0 (interquartile range: 39.3-81.0) months, P = 0.001] and the median weight was lower [13.5 (10.0-19.0) vs. 17.8 (13.6-25.8) kg, P = 0.003] in the ePTFE group. The conduit size was smaller (17.9 ± 2.2 vs. 20.5 ± 3.0 mm, P < 0.001) and the conduit Z score was lower (1.48 ± 1.04 vs. 1.83 ± 1.05, P = 0.048) in the ePTFE group. There was no significant difference in the primary endpoints (log rank, P = 0.33) and secondary endpoints (log rank, P = 0.35). Multivariate analysis identified lower weight at surgery [P = 0.01; hazard ratio: 0.75; 95% confidence interval (CI) 0.59-0.94] and homograft conduit use (P = 0.04; hazard ratio: 8.43; 95% CI 1.14-62.29) to be risk factors for moderate or severe conduit insufficiency. No risk factors were found for moderate or severe conduit stenosis or conduit dysfunction on multivariate analysis. CONCLUSION: Handmade tri-leaflet ePTFE conduits showed acceptable early and midterm outcomes in the absence of a suitable homograft, but a longer follow-up is needed.

3.
Phytomedicine ; 96: 153886, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35026512

RESUMO

BACKGROUND: Total coumarins extracted from Hydrangea. Paniculata, Sieb (HP) have showed renal protective effect in several experimental acute and chronic kidney diseases. PURPOSE: The aim of current study is to evaluate renal protective effect of HP against cationized-BSA (c-BSA) induced experimental membranous nephritis (MN), and further investigate its underlying mechanisms. METHODS: Rat MN model was established by intravenous injection of 5 mg c-BSA for consecutive 14 days, and after albuminuria confirmed, HP was orally administrated with 7.5, 15, 30 mg/kg for nine weeks. The renal function was measured and histopathological injuries were observed. RNA sequencing was used to analyze the altered signaling pathways in kidneys. Pharmacokinetics was performed to investigate the pharmacodynamics of major ingredients in HP and possible metabolites. Discover X platform helped to clarify the possible molecular mechanisms of major compound in HP. RESULTS: HP administration could significantly improve the renal function, and ameliorate the dyslipidemia and histopathological injuries. mRNA sequencing demonstrated that HP had anti-inflammation and anti-fibrosis effects possible through down-regulating the complement activation and PI3K-AKT pathways. Pharmacokinetics demonstrated that skimmin and 7-hydoxycoumarin (7-HC) were major compound or metabolite in plasma after oral administration. Based on Discover X platform, we confirmed that skimmin and 7-HC inhibited the   IL10 production by inflammatory macrophages through blocking PI3K-AKT and NFκB signaling pathways. Finally, we demonstrated that HP protected tubulointerstitium from complement attack by reducing the C3 self-production and auto-cleavage in tubular cells. CONCLUSIONS: HP has a renal protective effect, and its drug development may provide one alternative strategy to treat immune-mediated nephropathy.

4.
J Ethnopharmacol ; 288: 115004, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35051603

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Esculetin is a bioactive compound of medicinal herb Hydrangea paniculata, and has showed anti-oxidation and anti-inflammation bioactivities. Renal local oxidative stress and inflammation are import contributors for progression of lupus nephritis (LN). AIM OF THE STUDY: In the present study, the renal protective effect of esculetin against LN was evaluated using MRL/lpr mice. MATERIALS AND METHODS: MRL/lpr mice were orally administrated with esculetin (20 mg/kg and 40 mg/kg) from 10 to 20 weeks and then renal function and kidney pathology were analyzed. RESULTS: Esculetin significantly attenuated renal impairment in MRL/lpr mice by reducing blood urea nitrogen (BUN), serum creatinine (Scr) and albuminuria, and ameliorated the glomerular hypertrophy, tubular interstitial fibrosis and mononuclear cell infiltration into interstitium. mRNA microarray suggested that esculetin could significantly down-regulate complement cascade, inflammation and fibrosis pathway, and up-regulate Nrf2-related anti-oxidation genes. Most surprising finding in the current study was that esculetin could inhibit the complement activation both in classical and alternative pathway using in vitro hemolysis assay, further enzyme assay suggested that esculetin blocked the C3 convertase (C4b2a) to exert this inhibitory capability. Molecular docking predicted that esculetin had four conventional hydrogen bonds interacting with C4b2a, and CDOCKER energy is relatively lower. Luciferase reporter gene demonstrated that esculetin could activate Nrf2 signaling pathway, and further flow cytometry confirmed that anti-oxidation bioactivity of esculetin was dependent on Nrf2 activation. On the other hand, esculetin could inhibit NFκB nuclear translocation and TGFß-smad3 profibrosis pathway. CONCLUSION: Esculetin shows beneficial effect on LN progression, and it may be a good natural leading compound for design of chemical compounds to treat LN.

5.
Nano Lett ; 22(1): 494-500, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34964627

RESUMO

Nonvolatile optoelectronic memories based on organic-inorganic hybrid perovskites have appeared as powerful candidates for next-generation soft electronics. Here, ambipolar SnO transistor-based nonvolatile memories with multibit memory behavior (11 storage states, 120 nC state-1) and ultralong retention time (>105 s) are demonstrated for which an Al2O3/two-dimensional Ruddlesden-Popper perovskite (2D PVK) heterostructure dielectric architecture is employed. The unique storage features are attributed to suppressed gate leakage by Al2O3 layer and hopping-like ionic transport in 2D PVK with varying activation energy under different light intensities. The photoinduced field-effect mechanism enables top-gated transistor operation under illumination, which would not be achieved under dark. As a result, the device exhibits remarkable photoresponsive characteristics, including ultrahigh specific detectivity (2.7 × 1015 Jones) and broadband spectrum distinction capacity (375-1064 nm). This study offers valuable insight on the PVK-based dielectric engineering for information storage and paves the way toward multilevel broadband-response optoelectronic memories.

6.
Stem Cell Res ; 57: 102606, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34864221

RESUMO

Waardenburg syndrome type I (WS1) is a human autosomal dominant genetic disease characterized by sensorineural hearing loss, pigmentary abnormalities, and dystopia canthorum. In this study, we generated an induced pluripotent stem cell (iPSC) line using non-integrative Sendai viral reprogramming technology from the peripheral blood mononuclear cells (PBMCs) of a 29-year-old woman affected with WS1, caused by a heterozygous frameshift mutation in the PAX3 (NM_181459.4:c.123del). This iPSC line carrying the same mutation displays a nomal karyotype, expresses pluripotent markers, and shows differentiation capacity in vitro.

7.
BMC Anesthesiol ; 21(1): 313, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893026

RESUMO

BACKGROUND: This study aimed to determine whether ultrasound-guided continuous erector spinae plane block (ESPB) had an effect on opioid consumption and postoperative rehabilitation in patients undergoing video-assisted thoracic surgery (VATS). METHODS: In this prospective study, 120 patients aged 20-70 years who underwent elective VATS were randomly allocated to one of three groups: group C (general anesthesia with patient-controlled intravenous analgesia [PCIA]), group T (general anesthesia with patient-controlled epidural analgesia [PCEA]), or group E (general anesthesia with continuous ESPB and PCIA). Perioperative opioid consumption, visual analog scale (VAS) scores, preoperative and postoperative Quality of Recovery-15 scores, and postoperative opioid-related adverse events were all assessed. RESULTS: Intraoperative sufentanil consumption in groups T and E was significantly lower than that in group C (both P < 0.001), and the postoperative sufentanil consumption in group E was also significantly lower than that in group C (P = 0.001). Compared with group C, the VAS scores at rest or during coughing immediately out of the post-anesthesia care unit at 6 h, 12 h, and 24 h postoperatively were significantly lower in group T (P < 0.05). However, the VAS scores at rest at 6 h and 12 h postoperatively in group E were lower than those of group C (P < 0.05), but were significantly higher than those of group T at all study times (P < 0.05). CONCLUSION: Ultrasound-guided continuous ESPB significantly reduced perioperative opioid consumption during VATS and improved postoperative rehabilitation. However, these effects were inferior to those of thoracic epidural anesthesia. TRIAL REGISTRATION: The present study was prospectively registered at http://www.chictr.org/cn /(registration number: ChiCTR1900023050 ); registration date: May 82,019.

8.
Nat Commun ; 12(1): 6978, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34848709

RESUMO

Reversing the thermal induced sintering phenomenon and forming high temperature stable fine dispersed metallic centers with unique structural and electronic properties is one of the ever-lasting targets of heterogeneous catalysis. Here we report that the dispersion of metallic Ni particles into under-coordinated two-dimensional Ni clusters over γ-Mo2N is a thermodynamically favorable process based on the AIMD simulation. A Ni-4nm/γ-Mo2N model catalyst is synthesized and used to further study the reverse sintering effect by the combination of multiple in-situ characterization methods, including in-situ quick XANES and EXAFS, ambient pressure XPS and environmental SE/STEM etc. The under-coordinated two-dimensional layered Ni clusters on molybdenum nitride support generated from the Ni-4nm/γ-Mo2N has been demonstrated to be a thermally stable catalyst in 50 h stability test in CO2 hydrogenation, and exhibits a remarkable catalytic selectivity reverse compared with traditional Ni particles-based catalyst, leading to a chemo-specific CO2 hydrogenation to CO.

9.
Invest Ophthalmol Vis Sci ; 62(15): 30, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34967855

RESUMO

Purpose: The development of myopia in guinea pigs can be inhibited by attenuating scleral hypoxia by increasing choroidal blood perfusion (ChBP). In this study, we reduced ChBP through surgical and pharmacological methods to determine the effect on myopia development. We also determined whether ChBP was reduced by quinpirole, a drug that enhances form-deprivation myopia (FDM). Methods: ChBP was reduced in the right eyes of guinea pigs via transection of the temporal ciliary arteries or daily injections of phenylephrine into the inferior peribulbar space for one week during normal ocular growth. Other guinea pigs were subjected to two weeks of monocular FDM-with facemasks, along with daily injections of quinpirole, a dopamine D2 receptor agonist, to enhance the FDM. Changes in refraction, axial length, ChBP, and choroidal thickness (ChT) were measured in both treated and fellow eyes of the treatment and control groups. Scleral hypoxia labeling with pimonidazole adducts and α-smooth muscle actin (α-SMA) protein were also measured. Results: Surgical and pharmacological reduction of ChBP induced myopia development in the treated eyes. These treatments rendered the scleral hypoxia and increased scleral α-SMA expression. Furthermore, quinpirole injections, which increased the magnitude of myopia, augmented the FDM-associated reductions in ChBP and ChT and increased the levels of scleral hypoxia and α-SMA protein. Conclusions: Decreased ChBP in guinea pigs leads to scleral hypoxia and scleral myofibroblast transdifferentiation with increased α-SMA expression, ultimately resulting in myopia development. In future clinical trials, ChBP reduction can serve as a potential biomarker for early detection of myopia development.


Assuntos
Corioide/irrigação sanguínea , Miopia/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Actinas/metabolismo , Animais , Comprimento Axial do Olho , Velocidade do Fluxo Sanguíneo , Western Blotting , Corioide/efeitos dos fármacos , Corioide/patologia , Artérias Ciliares/cirurgia , Angiografia por Tomografia Computadorizada , Modelos Animais de Doenças , Agonistas de Dopamina/farmacologia , Eletrorretinografia , Cobaias , Hipóxia/metabolismo , Músculo Liso/metabolismo , Miopia/metabolismo , Fenilefrina/farmacologia , Quimpirol/farmacologia , Receptores de Dopamina D2/metabolismo , Refração Ocular/fisiologia , Esclera/metabolismo , Tomografia de Coerência Óptica
10.
Artigo em Inglês | MEDLINE | ID: mdl-34931971

RESUMO

Lipid metabolism disorder plays a fundamental role in the pathogenesis of atherosclerosis. As the largest metabolic organ of the human body, liver has a key role in lipid metabolism by influencing fat production, fat decomposition, and the intake and secretion of serum lipoproteins. Numerous clinical and experimental studies have indicated that the dysfunction of hepatic lipid metabolism is closely tied to the onset of atherosclerosis. However, the identity and functional role of hepatic lipid metabolism responsible for these associations remain unknown. This review presented that cholesterol synthesis, cholesterol transport, and the metabolism of triglyceride, lipoproteins, and fatty acids are all associated with hepatic lipid metabolism and atherosclerosis. Moreover, we also discussed the roles of gut microbiota, inflammatory response, and oxidative stress in the pathological association between hepatic lipid metabolism and atherosclerosis. These significant evidences support strongly that hepatic lipid metabolism disorders may increase the risk of atherosclerosis.

11.
Front Microbiol ; 12: 786464, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34970243

RESUMO

Natural flavonoids, formononetin and ononin, possess antioxidant, antibacterial, anti-inflammatory and neuroprotective effects. Many complications caused by SARS-CoV-2 make patients difficult to recover. Flavonoids, especially formononetin and ononin, have the potential to treat SARS-CoV-2 and improve myocardial injury. However, their poor water solubility, poor oral absorption, high toxicity, and high-cost purification limit industrial practical application. Succinylation modification provides a solution for the above problems. Formononetin-7-O-ß-(6″-O-succinyl)-D-glucoside (FMP), a new compound, was succinyl glycosylated from formononetin by the organic solvent tolerant bacteria Bacillus amyloliquefaciens FJ18 in a 10.0% DMSO (v/v) system. The water solubility of the new compound was improved by over 106 times compared with formononetin, which perfectly promoted the application of formononetin and ononin. The conversion rate of formononetin (0.5 g/L) was almost 94.2% at 24 h, while the yield of formononetin-7-O-ß-(6″-O-succinyl)-D-glucoside could achieve 97.2%. In the isoproterenol (ISO)-induced acute ischemia mice model, the myocardial injury was significantly improved with a high dose (40 mg/kg) of formononetin-7-O-ß-(6″-O-succinyl)-D-glucoside. The lactate dehydrogenase level was decreased, and the catalase and superoxide dismutase levels were increased after formononetin-7-O-ß-(6″-O-succinyl)-D-glucoside treatment. Thus, formononetin-7-O-ß-(6″-O-succinyl)-D-glucoside has high water solubility, low toxicity, and shows significant antimyocardial ischemia effects.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(12): 1242-1249, 2021 Dec 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34911607

RESUMO

OBJECTIVES: To investigate the incidence of preterm birth and risk factors for preterm birth. METHODS: A prospective cohort study was performed for the pregnant women in early pregnancy and their spouses, who underwent prenatal examination for the first time in Hunan Provincial Maternal and Child Health Care Hospital from May 2014 to December 2016 and decided to be hospitalized for delivery. A questionnaire survey was performed to collect exposure information possibly related to preterm birth. The hospital's medical record system was used for information verification and to record the pregnancy outcome. A multivariate logistic regression analysis was used to investigate the risk factors for preterm birth. RESULTS: A total of 6 764 pregnant women with complete data were included, and the incidence rate of preterm birth was 17.09%. The multivariate logistic regression analysis showed that a history of adverse pregnancy outcomes, eating areca nut before pregnancy, a history of pregnancy complications, a history of hepatitis, no folate supplementation during pregnancy, medication during pregnancy, active smoking and passive smoking during pregnancy, drinking during pregnancy, unbalanced diet during pregnancy, high-intensity physical activity during pregnancy, and natural conception after treatment of infertility or assisted conception as the way of conception were risk factors for preterm birth (P<0.05). Additionally, the pregnant women whose spouses were older, had a higher body mass index or smoked had an increased risk for preterm birth (P<0.05). A higher level of education of pregnant women or their spouses and lower gravidity were protective factors against preterm birth (P<0.05). CONCLUSIONS: There are many risk factors for preterm birth. Special attention should be paid to the life behaviors of pregnant women during pregnancy, and health education should be strengthened for pregnant women and their spouses to develop good living habits and reduce the incidence of preterm births.


Assuntos
Nascimento Prematuro , Poluição por Fumaça de Tabaco , Criança , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Prospectivos , Fatores de Risco
13.
Mol Ther Nucleic Acids ; 26: 1466-1478, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34938601

RESUMO

Zinc-finger nucleases (ZFNs), transcription activator-like endonucleases (TALENs), and CRISPR-associated Cas9 endonucleases are three major generations of genome editing tools. However, no parallel comparison about the efficiencies and off-target activity of the three nucleases has been reported, which is critical for the final clinical decision. We for the first time developed the genome-wide unbiased identification of double-stranded breaks enabled by sequencing (GUIDE-seq) method in ZFNs and TALENs with novel bioinformatics algorithms to evaluate the off-targets. By targeting human papillomavirus 16 (HPV16), we compared the performance of ZFNs, TALENs, and SpCas9 in vivo. Our data showed that ZFNs with similar targets could generate distinct massive off-targets (287-1,856), and the specificity could be reversely correlated with the counts of middle "G" in zinc finger proteins (ZFPs). We also compared the TALENs with different N-terminal domains (wild-type [WT]/αN/ßN) and G recognition modules (NN/NH) and found the design (αN or NN) to improve the efficiency of TALEN inevitably increased off-targets. Finally, our results showed that SpCas9 was more efficient and specific than ZFNs and TALENs. Specifically, SpCas9 had fewer off-target counts in URR (SpCas9, n = 0; TALEN, n = 1; ZFN, n = 287), E6 (SpCas9, n = 0; TALEN, n = 7), and E7 (SpCas9, n = 4; TALEN, n = 36). Taken together, we suggest that for HPV gene therapies, SpCas9 is a more efficient and safer genome editing tool. Our off-target data could be used to improve the design of ZFNs and TALENs, and the universal in vivo off-target detection pipeline for three generations of artificial nucleases provided useful tools for genome engineering-based gene therapy.

14.
Oxid Med Cell Longev ; 2021: 7007933, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745421

RESUMO

Gastric cancer is a highly malignant tumor with poor survival rate. Ferroptosis, a newly defined regulated cell death, is closely related to several tumors. Introduction of ferroptosis is promising for cancer treatments. However, the predictive role of ferroptosis in GC remains elusive. In this study, we screened the ferroptosis-related genes which were differentially expressed between normal and GC tissues. Then, based on these differentially expressed genes (DEGs), the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions were applied to construct the 10-gene prognostic signature (SP1, MYB, ALDH3A2, KEAP1, AIFM2, ITGB4, TGFBR1, MAP1LC3B, NOX4, and ZFP36) in TCGA training dataset. Based on the median risk score, all GC patients in TCGA training dataset and GSE84437 testing dataset were classified into a high- or low-risk group. GC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P < 0.001). Combined with the clinical characteristics, the risk score was proven as an independent factor for predicting the OS of GC patients. Besides, the GC patients in the high- or low-risk group showed significantly different GO and KEGG functional enrichments, somatic mutation, fractions of immune cells, and immunotherapy response. Then, the expression levels of these genes in signature were further verified in the GC cell lines and our own GC samples (30-paired tumor/normal tissues). Furthermore, the effects of ferroptosis inducer Erastin on these 10 ferroptosis-related genes in GC cell lines were also explored in our study. In conclusion, our study constructed a prognostic signature of 10 ferroptosis-related genes, which could well predict the prognosis and immunotherapy for GC patients.

15.
J Magn Reson Imaging ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797007

RESUMO

BACKGROUND: Small vessel disease (SVD) shares common vascular risk factors with large artery disease (LAD). However, little is known about the relationship between intracranial artery stenosis and SVD burden. PURPOSE: To investigate whether SVD burden correlates with severity of intracranial LAD. STUDY TYPE: Retrospective. POPULATION: Five hundred and sixteen patients with LAD of arterial circulation were enrolled from one hospital, including 384 males (59 ± 11 years) and 132 females (60 ± 12 years). FIELD STRENGTH/SEQUENCE: 3 T. T1 -weighted fast spin echo (T1 W FSE), T2 W FSE, T2 fluid attenuated inversion recovery, diffusion-weighted imaging, susceptibility-weight imaging, and time-of-flight magnetic resonance angiography. ASSESSMENT: The LAD was divided into mild stenosis (<30%), moderate stenosis (30%-69%), and severe stenosis (≥70%). The Standard for Reporting Vascular Changes on Neuroimaging criteria was used to rate the SVD burden according to the level of white matter hyperintensity (WMH), perivascular space (PVS), cerebral microbleed (CMB), and lacunes. STATISTICAL TESTS: Lilliefors test, ANOVA, chi-squared test, Mann-Whitney U test, Wilcoxon signed rank test, Bonferroni test, Spearman's correlation, logistic regression, and Cohen's kappa test. RESULTS: The grade scores for centrum semiovale PVS (CS-PVS) were positively correlated with the degree of stenosis (R = 0.413), whereas the presence of severe basal ganglia PVS (BG-PVS) was associated with CMB (R = 0.508), lacunes (R = 0.365), and severe WMH (R = 0.478). In multivariate analysis, severe CS-PVS (adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 1.9-4.8) and lacunes (aOR, 2.1; 95% CI, 1.3-3.4) were associated with severe stenosis of LAD. In addition, CS-PVS was related to severe stenosis in a dose-dependent manner: when CS-PVS score was 3 and 4, the aORs of severe stenosis were 1.9 and 7.7, respectively. DATA CONCLUSION: The severity of LAD in anterior circulation is associated with SVD burden, which suggests that different SVD burden may be used for risk stratification in LAD. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

16.
Pharmacol Res ; 175: 105989, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34800628

RESUMO

Chronic cerebral ischemia (CCI) refers to long-term hypoperfusion of cerebral blood flow with the main clinical manifestations of progressive cognitive impairment. The pathological mechanism of CCI is complex, and there is a lack of effective treatments. Salvianolic acid A (SalA) is a neuroprotective extract of Salvia miltiorrhiza with the effects of anti-inflammation and anti-apoptosis. In this study, the effect of SalA on cognitive function and Drd2/Cryab/NF-κB signaling pathway in rats with CCI was investigated. Morris water maze and open field test were used to observe the effects of SalA on the cognitive function of CCI rats. The pathological changes in the brain were observed by HE, Nissl, and LFB staining. TUNEL staining, enzyme-linked immunosorbent assay, and western blot analysis were used to detect the inflammatory and apoptosis in the cortex and hippocampus. The expression of Drd2/Cryab/NF-κB pathway-related molecules and Drd2 localization were detected by western blotting and dual immunofluorescence, respectively. SH-SY5Y cells were exposed to chronic hypoglycemic and hypoxic injury in vitro, and Drd2 inhibitor haloperidol was used to verify the involved pathway. The results showed that SalA could improve the cognitive function of CCI rats, reduce pathological damage of cortex and hippocampus, inhibit neuroinflammation and apoptosis, and suppress the activation of NF-κB by regulating Drd2/Cryab pathway. And SalA inhibited NF-κB activation and nuclear translocation in SH-SY5Y cells by upregulating Drd2/Cryab pathway, which was reversed by haloperidol interference. In conclusion, SalA could relieve CCI-induced cognitive impairment in rats, at least partly through the Drd2/Cryab/NF-κB pathway.

17.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34675076

RESUMO

Myopia is a leading cause of visual impairment and blindness worldwide. However, a safe and accessible approach for myopia control and prevention is currently unavailable. Here, we investigated the therapeutic effect of dietary supplements of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on myopia progression in animal models and on decreases in choroidal blood perfusion (ChBP) caused by near work, a risk factor for myopia in young adults. We demonstrated that daily gavage of ω-3 PUFAs (300 mg docosahexaenoic acid [DHA] plus 60 mg eicosapentaenoic acid [EPA]) significantly attenuated the development of form deprivation myopia in guinea pigs and mice, as well as of lens-induced myopia in guinea pigs. Peribulbar injections of DHA also inhibited myopia progression in form-deprived guinea pigs. The suppression of myopia in guinea pigs was accompanied by inhibition of the "ChBP reduction-scleral hypoxia cascade." Additionally, treatment with DHA or EPA antagonized hypoxia-induced myofibroblast transdifferentiation in cultured human scleral fibroblasts. In human subjects, oral administration of ω-3 PUFAs partially alleviated the near-work-induced decreases in ChBP. Therefore, evidence from these animal and human studies suggests ω-3 PUFAs are potential and readily available candidates for myopia control.

18.
Nanoscale ; 13(38): 16113-16121, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34633011

RESUMO

The magnetic tunneling junction (MTJ) controlled by electric field as an alternate approach for energy efficiency is the highlight for nonvolatile RAM, while there is still a lack of research on resistance manipulation with the electric field in nanoscale MTJs. In this study, we integrated nanoscale MTJs on the (011) orientated Pb(Mg1/3Nb2/3)0.7Ti0.3O3 (PMN-PT) ferroelectric substrates and systematically investigated the magnetoresistance as a function of the magnetic field and electric field. A single domain state of the nanoscale MTJ was demonstrated by the experimental result and theoretical simulation. Afterward, the obvious electric field control of R-H curves was obtained and explained by the competition between magnetoelastic energy and shape anisotropy. More importantly, simulation results also predicted that the switching pathway of magnetic moments under the magnetic field is strongly dependent on the applied electric field, displaying the electric field control of chiral switching in the nano-MTJ. Our work is a milestone in the realization of the emerging dubbed straintronics field.

19.
ISA Trans ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34686370

RESUMO

Hot metal silicon content (HMSC) is usually utilized to measure the quality of hot metal and reflect the thermal status of blast furnace (BF) system. However, most state-of-the-arts ignore the time-varying behavior of BF ironmaking process, which are impractical. Accordingly, a novel dual ensemble online sequential extreme learning machine (DE-OS-ELM) is proposed to establish the online estimation model of HMSC, which can update the data-driven model with the latest operation data. Specifically, an online learning method with recursive modification is first proposed based on OS-ELM (referred to as RM-OS-ELM) to address the modeling with uncertainty. To heel, a dynamic forgetting factor is presented for the dynamic tracking capability enhancement and convergence acceleration. Furthermore, a final updating rule for sequential implementation is constructed by combining the output weights of OS-ELM and RM-OS-ELM based on their corresponding contributions on modeling. Considering the modeling accuracy and curve trend consistency, multiobjective parameter optimization model is also implemented to achieve the satisfactory performance. By taking the proposed DE-OS-ELM, the estimation model of HMSC is established using industrial data. Comprehensive experiments demonstrate that DE-OS-ELM-based HMSC estimation model is more feasible and practical.

20.
J Asian Nat Prod Res ; : 1-7, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647847

RESUMO

Quercetin (1) was converted into quercetin 7-O-succinyl glucoside (2) by used Bacillus amyloliquefaciens FJ18 as a solvent-resistant whole-cell biocatalyst. The structure of the new compound was confirmed by LC-MS analysis and NMR spectroscopy. The water-solubility of this novel quercetin 7-O-succinyl glucoside (2) was approximately 1000 times higher than that of native quercetin (2). Quercetin (1) and quercetin 7-O-succinyl glucoside (2) exhibited significant DPPH scavenging capacity with IC50 values of 23.55 and 36.05 µM, respectively. Both compounds showed moderate cytotoxic effects against the two human cancer cell lines (MCF-7 and HepG2) with IC50 values ranging from 39.45-63.38 µM.

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