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1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35553511

RESUMO

Hypertension (HTN) is common in diabetes mellitus (DM) and substantially increases the risk for diabetic nephropathy. Current therapies only slow the progression to end-stage renal disease (ESRD) in hypertensive-diabetic patients rather than halt it. Thus, new insights into the mechanisms of this disease are needed. To investigate the mechanisms by which HTN and DM interact to promote renal injury, we developed a model combining streptozotocin (STZ)-induced type 1 DM and inter-renal aorta constriction (AC)-induced HTN in male Wistar rats. In this model (Wistar-DM+AC), both kidneys are exposed to the same levels of hyperglycemia, circulating hormones, and neural influences, but the left kidney below the AC has normal to slightly reduced blood pressure (BP), while the right kidney above the AC is exposed to elevated BP. To assess the roles of mitochondrial-derived reactive oxygen species (ROS) and mitochondrial dysfunction in causing kidney injury, Wistar-DM+AC rats were also treated with saline vehicle or mito-TEMPO, a mitochondrial-targeted antioxidant, for 6 weeks starting 2 weeks after AC surgery (0.4mg/kg/day, osmotic mini-pump). Eight weeks after AC or sham surgery, glomerular filtration rate (GFR) and urinary albumin excretion (UAE) in left and right kidneys were measured separately by collecting urine from each kidney to evaluate the change of renal function. Mitochondrial oxygen consumption rate and superoxide generation from the cortex of left and right kidneys were measured simultaneously by Oroboros high-resolution respirometry. Kidneys exposed to DM or HTN alone had only mild glomerular injury and slightly increased UAE. In contrast, right kidneys from Wistar-DM+AC rats which had been exposed to DM plus HTN for 8 weeks had much greater increases in UAE (3.4±0.7 vs1.9±1.3 µg/min), significantly reduced GFR (0.5±0.1 vs 0.7±0.1 ml/min/g of kidney weight) as well as reduced mitochondrial oxygen consumption rate and increased mitochondrial ROS generation compared to left kidneys of Wistar-DM+AC rats. In Wistar-DM+AC rats that received mitoTEMPO treatment, the right kidneys exposed to the same levels of elevated BP and blood glucose had lower albumin excretion (1.7±0.3 µg/min), higher GFR (1.3±0.2 ml/min/g of kidney weight), and preserved mitochondrial oxygen consumption with reduced mitochondrial-derived ROS compared to the right kidneys of vehicle-treated Wistar-DM+AC rats. These results suggest that mitochondrial-derived ROS may contribute to kidney injury when HTN is superimposed on DM. Pharmacological inhibition of mitochondrial ROS generation attenuates kidney injury and may be a potential therapeutic strategy for diabetic nephropathy.

2.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35554281

RESUMO

BACKGROUND: Macrophages play a critical role in left ventricular (LV) remodeling after myocardial infarction (MI), and limiting macrophage-mediated inflammatory responses while enhancing reparative roles is a promising therapeutic strategy. Monocyte-derived M1 macrophages mediate the early inflammatory response, while M2 macrophages mediate the later wound healing and scar formation phase. Metabolic reprogramming from glycolysis to mitochondrial oxidative phosphorylation mediates M1 to M2 polarization. We hypothesized that metabolic reprogramming occurs in macrophages over the course of post-MI remodeling, and that blocking macrophage glycolysis attenuates post-MI inflammation. METHODS: MI was induced in adult (16-20 week old) male C57BL/6J mice by permanent ligation of the left coronary artery for 1, 3, or 7 days, and cardiac function was assessed by echocardiography. Macrophages were extracted from the LV infarct area by immunomagnetic sorting. Macrophage metabolic flux was assessed by Extracellular Flux Analysis (Seahorse); upon glucose administration, glycolysis was measured by extracellular acidification rate (ECAR) while glucose oxidation was measured by oxygen consumption (OCR). Leukocyte subtypes (neutrophils, monocytes, resident macrophages) were assessed by flow cytometry. Real-time PCR was used to assess gene expression by relative mRNA levels. To specifically block macrophage glycolysis, LysMCre mice were crossed with mice floxed for Slc2a1, the major macrophage glucose transporter, to generate macrophage-Slc2a1 null mice. RESULTS: MI led to LV contractile dysfunction (decreased ejection fraction; days 1, 3, and 7 versus day 0), thinning of the infarct wall (days 1, 3, and 7) and non-infarct wall (day 7), and dilation (increased internal diameter at diastole and end-diastolic volume; day 7). At day 1, increased neutrophils (Ly6G+) and monocytes (Ly6Chi ) were observed in the infarcted LV; at day 7, neutrophils and monocytes returned to baseline levels and the majority of macrophages were resident M2 subtype (Ly6Clow versus day 1). Day 1 macrophages showed elevated glycolysis (ECAR versus day 0) and increased mRNA levels of the M1 marker Il1b (versus day 3 and 7); day 3 macrophages showed increased glycolysis (ECAR versus day 0) and decreased glucose oxidation (versus day 0); day 7 macrophages showed decreased glycolysis (ECAR versus day 1 and 3) and increased glucose oxidation (OCR versus day 1 and 3), and increased Slc2a1 mRNA, Krebs cycle genes (Pdha1, Idh1/2, Sdha/bmRNA), pentose phosphate pathway genes (G6pd2/x, Pgd, Rpia, Taldo1 mRNA), and Il10 (M2 marker) mRNA. In macrophage-Slc2a1 null mice, macrophage glycolysis was decreased and glucose oxidation increased at day 3, and infarct levels of Il1b were decreased compared to floxed controls. CONCLUSIONS: Our results indicate that time-dependent macrophage metabolic reprogramming occurs over the MI remodeling process, and that blocking macrophage glycolysis may be a promising strategy for limiting post-MI inflammation and adverse remodeling.

3.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35554786

RESUMO

Important adverse changes in cardiac energy metabolism occur after ischemia/reperfusion injury (I/R), contributing to the worsening of cardiac function and development of heart failure. We recently showed that leptin, via its actions on the central nervous system (CNS), improves left ventricular (LV) function in a model of heart failure induced by permanent ligation of the left anterior descending coronary artery (LAD). In the present study, we examined whether the CNS- effects of leptin protect against myocardial I/R injury, and if chronic intracerebroventricular (ICV) leptin infusion improves cardiac substrate utilization, assessed by markers of myocardial fatty acid (FA) and glucose oxidation, NAD+/NADH redox state and plasma levels of ß-hydroxybutyrate (ß-HOB). Male Wistar rats were instrumented with an ICV cannula in the brain lateral ventricle. After recovery and baseline assessment of cardiac function by echocardiography (ECHO), myocardial I/R was induced by temporary (60 min) ligation of the LAD. Vehicle (saline, 0.5 µL/hr) or leptin (0.62 µg/hr) was infused chronically for 28 days starting 20 min after reperfusion using osmotic minipumps connected to the ICV cannula. ECHO assessment of cardiac function was performed weekly. At the end of week 4, +dP/dtmax was accessed by LV catheterization. Hearts and plasma samples were collected for evaluation of CD36, PPAR-δ, PDK4 and p-PDH1/PDH1 by western blot and cardiac NAD+/NADH ratio and plasma levels of ß-OHB were measured by ELISA. Our results showed that ICV leptin treatment improved cardiac function as evidenced by increased ejection fraction 4 weeks after I/R (46±3 vs. 26±3 %) and +dP/dtmax (10387±1686 vs. 5022±442 mmHg/s) when compared with vehicle-treated rats. ICV leptin infusion also significantly increased cardiac protein expression of CD36 (1.4±0.1 vs. 1.0±0.1 au), PPAR-δ (1.8±0.1vs. 1.0±0.01 au), PDK4 (1.8±0.1 vs. 1.0±0.1 au) and p-PDH1/PDH1 (2.2±0.3 vs. 1.0±0.2 au) when compared with vehicle-treated animals. In addition, ICV leptin infusion increased cardiac NAD+/NADH ratio (6.8±2 vs. 1.02±0.3 pmol/µL) and reduced plasma levels of ß-OHB (18.2±3 vs. 62.8±7.0 nmol/µL). These results demonstrate that chronic ICV leptin infusion improves cardiac function following I/R injury and suggest that leptin's CNS-mediated cardioprotective effects may involve improved myocardial FA oxidation and NAD+/NADH redox state, reducing the reliance on ketone bodies (ß-OHB) as an energy source.

4.
Artigo em Inglês | MEDLINE | ID: mdl-35537100

RESUMO

TRPC6, a member of the TRPC family, is expressed in the hypothalamus and modulates cell Ca2+ influx. However, the role of TRPC6 in controlling metabolic and cardiovascular functions under normal conditions has not been previously determined. Thus, the impacts of TRPC6 deletion on energy balance, metabolic and cardiovascular regulation as well as the anorexic responses to leptin and melanocortin 3/4 receptor (MC3/4R) activation were investigated in this study. Extensive cardiometabolic phenotyping was conducted in male and female TRPC6 knock out (KO) and control mice from 6 to 24 weeks of age to assess mechanisms by which TRPC6 influences regulation of energy balance and blood pressure (BP). We found that TRPC6 KO mice are heavier with greater adiposity, hyperphagic, and have reduced energy expenditure, impaired glucose tolerance, hyperinsulinemia, and increased liver fat compared to controls. TRPC6 KO mice also have smaller brains, reduced POMC mRNA levels in the hypothalamus, and impaired anorexic response to leptin but not to MC3/4R activation. BP and heart rate, assessed by telemetry, were similar in TRPC6 KO and control mice, and BP responses to air-jet stress were attenuated in TRPC6 KO mice despite increased body weight and metabolic disorders that normally raise BP and increase BP responses to stress. Our results provide evidence for a novel and important role of TRPC6 in controlling energy balance, adiposity, and glucose homeostasis, which suggests that normal TRPC6 function may be necessary to link weight gain and hyperleptinemia with BP responses to acute stress.

5.
Mater Today Bio ; 15: 100275, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35572854

RESUMO

Peri-implantitis, the major cause of implant failure, is an inflammatory destructive disease due to the dysbiotic polymicrobial communities at the peri-implant sites. Therefore, it is highly warranted to develop the implant materials with antimicrobial properties and investigate their effects on oral microbiota. However, most of the relevant studies were performed in vitro, and insufficient to provide the comprehensive assessment of the antimicrobial capacity of the implant materials in vivo. Herein, we introduce an innovative approach to evaluate the in vivo antibacterial properties of the most commonly used implant materials, titanium with different nanostructured surfaces, and investigate their antibacterial mechanism via the next-generation sequencing (NGS) technology. We firstly prepared the titanium implants with three different surfaces, i) mechanical polishing (MP), ii) TiO2 nanotubes (NT) and iii) nanophase calcium phosphate embedded to TiO2 nanotubes (NTN), and then characterized them using scanning electron microscopy (SEM), energy-dispersive X-ray spectrometer (EDS), X-ray photoelectron spectroscopy (XPS), confocal laser scanning microscopy (CLSM) and surface hydrophilicity analysis. Afterwards, the implants were placed in the beagle dogs' mouths to replace the pre-extracted premolar and molar teeth for eight weeks through implant surgery. The supra- and sub-mucosal plaques were collected and subjected to 16S rRNA gene/RNA sequencing and data analysis. It was found that the nanostructured surfaces in NT and NTN groups showed significantly increased roughness and decreased water contact angles compared to the MP group, while the XPS data further confirmed the successful modifications of TiO2 nanotubes and the subsequent deposition of nanophase calcium phosphate. Notably, the nanostructured surfaces in NT and NTN groups had limited impact on the diversity and community structure of oral microbiota according to the 16S rRNA sequencing results, and the nanostructures in NTN group could down-regulate the genes associated with localization and locomotion based on Gene Ontology (GO) terms enrichment analysis. Moreover, the differentially expressed genes (DEGs) were associated with microbial metabolism, protein synthesis and bacterial invasion of epithelial cells. Taken together, this study provides a new strategy to evaluate the antibacterial properties of the biomedical materials in vivo via the high-throughput sequencing and bioinformatic approaches, revealing the differences of the composition and functional gene expressions in the supra- and sub-mucosal microbiome.

6.
Curr Pediatr Rep ; : 1-12, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35540721

RESUMO

Purpose of Review: A multisystem inflammatory condition occurring in children and adolescents with COVID-19 has become increasingly recognized and widely studied globally. This review aims to investigate and synthesize evolving evidence on its clinical characteristics, management, and outcomes in pediatric patients. Recent Findings: We retrieved data from PubMed, EMBASE, Cochrane Library, WHO COVID-19 Database, Google Scholar, and preprint databases, covering a timeline from December 1, 2019, to July 31, 2021. A total of 123 eligible studies were included in the final descriptive and risk factor analyses. We comprehensively reviewed reported multisystem inflammatory syndrome in children (MIS-C) cases from published and preprint studies of various designs to provide an updated evidence on epidemiology, clinical, laboratory and imaging findings, management, and short-term outcomes. Latest evidence suggests that African black and non-Hispanic white are the two most common ethnic groups, constituting 24.89% (95% CI 23.30-26.48%) and 25.18% (95% CI 23.51-26.85%) of the MIS-C population, respectively. Typical symptoms of MIS-C include fever (90.85%, 95% CI 89.86-91.84%), not-specified gastrointestinal symptoms (51.98%, 95% CI 50.13-53.83%), rash (49.63%, 95% CI 47.80-51.47%), abdominal pain (48.97%, 95% CI 47.09-50.85%), conjunctivitis (46.93%, 95% CI 45.17-48.69%), vomiting (43.79%, 95% CI 41.90-45.68%), respiratory symptoms (41.75%, 95% CI 40.01-43.49%), and diarrhea (40.10%, 95% CI 38.23-41.97%). MIS-C patients are less likely to develop conjunctivitis (OR 0.27, 95% CI 0.11-0.67), cervical adenopathy (OR 0.21, 95% CI 0.07-0.68), and rash (OR 0.44, 95% CI 0.26-0.77), in comparison with Kawasaki disease patients. Our review revealed that the majority of MIS-C cases (95.21%) to be full recovered while only 2.41% died from this syndrome. We found significant disparity between low- and middle-income countries and high-income countries in terms of clinical outcomes. Summary: MIS-C, which appears to be linked to COVID-19, may cause severe inflammation in organs and tissues. Although there is emerging new evidence about the characteristics of this syndrome, its risk factors, and clinical prognosis, much remains unknown about the causality, the optimal prevention and treatment interventions, and long-term outcomes of the MIS-C patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s40124-022-00264-1.

7.
Dig Dis Sci ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35546206

RESUMO

BACKGROUND AND AIMS: High-quality intestinal preparation could promote intestinal cleanliness and lead to more accurate diagnosis, which patients will benefit from. This study aimed to explore the effectiveness of walking exercise and intestinal cleansing interval in bowel preparation before colonoscopy. METHODS: A randomized controlled single blind study was conducted during August 2021 to February 2022. Patients requiring colonoscopy were randomly divided into three groups: 0 step, 5000 steps or 10,000 steps during the intestinal preparation. Participants took the same intestinal cleansing drugs 4-6 h prior to the procedure: 2L-dose polyethylene glycol (PEG). RESULTS: A total of 300 patients were enrolled in the experiment (100 patients per group), and the baseline information of the three groups was close. The BBPS of right (0-step group vs 5,000-step group vs 10,000-step group: 1.78 ± 0.65 vs 1.88 ± 0.54 vs 2.36 ± 0.69, p < 0.001), transverse (0-step group vs 5,000-step group vs 10,000-step group: 2.09 ± 0.78 vs 2.18 ± 0.61 vs 2.59 ± 0.71, p < 0.001) and left (0-step group vs 5,000-step group vs 10,000-step group: 2.01 ± 0.91 vs 2.24 ± 0.59 vs 2.51 ± 0.60, p < 0.001) colon in 10,000-step group were significantly higher than others, respectively. And we also drew the same conclusion in the aspect of ADR. The adverse events and patients' satisfaction had no differences between the two groups. Moreover, intestinal cleansing interval (< 5.12 h) was only effective in BBPS of right colon (p < 0.001) and left colon (p = 0.039). CONCLUSIONS: This study suggested that participants took 10,000-step walking exercise and took PEG 5.12 h prior to the procedure were effective in routine pre-procedure cleanout for standard colonoscopy. NAME OF REGISTRY: Effect of starting time of bowel cleansing and walking exercise after bowel cleansing on bowel preparation: A prospective randomized controlled study. REGISTRATION NUMBER: ChiCTR2100049214.

8.
Nanotechnology ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35550370

RESUMO

Studying two-dimensional (2D) materials using transmission electron microscopy (TEM) is necessary and very important in many aspects. However, some 2D materials are not resistant to acids or alkalis, which are widely used in normal wet transfer techniques to transfer the exfoliated 2D nanosheets onto the TEM grids. On the other hand, dry stamping method can damage the holey carbon film on the TEM grids. In this article, we present a non-destructive, efficient, and widely applicable transfer method for preparing the TEM samples of the exfoliated 2D materials. Our method only uses the heat-release tape, PMMA, and blue Nitto tape. Neither acid nor alkali is involved in our method, therefore, impurities and damage can be avoided to the greatest extent. The method is also very efficient and can be accomplished in less than 30 min after the exfoliation of the 2D materials. This method is particularly useful for preparing the TEM samples of the 2D materials that are not resistant to acids and alkalis. The present method is also applicable to various 2D materials and various substrates.

10.
Sci Total Environ ; : 155874, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35568173

RESUMO

Copper ion (Cu2+) and zinc ion (Zn2+) are widely co-existent in anaerobic digestion effluent as typical contaminants. This work aims to explore how Cu2+-Zn2+ association affects physiological properties of S. platensis using Schlösser medium (SM) and sterilized anaerobic digestion effluent (SADE). Microalgae cells viability, biochemical properties, uptake of Cu2+ and Zn2+, and risk assessment associated with the biomass reuse as additives to pigs were comprehensively assessed. Biomass production ranged from 0.03 to 0.28 g/L in SM and 0.63 to 0.79 g/L in SADE due to the presence of Cu2+ and Zn2+. Peak value of chlorophyll-a and carotenoid content during the experiment decreased by 70-100% and 40-100% in SM, and by 70-77% and 30-55% in SADE. Crude protein level reduced by 4-41% in SM and by 65-75% in SADE. The reduction ratio of these compounds was positively related to the Cu2+ and Zn2+ concentrations. Maximum value of saturated and unsaturated fatty acids was both obtained at 0.3 Cu + 2.0 Zn (50.8% and 22.8%, respectively) and 25% SADE reactors (33.8% and 27.7%, respectively). Uptake of Cu in biomass was facilitated by Zn2+ concentration (> 4.0 mg/L). Risk of S. platensis biomass associated with Cu2+ was higher than Zn2+. S. platensis from SM (Cu2+ ≤ 0.3 mg/L and Zn2+ ≤ 4.0 mg/L) and diluted SADE (25% and 50% SADE) reactors could be used as feed additives without any risk (hazard index <1), which provides sufficient protein and fatty acids for pig consumption. These results revealed the promising application of using S. platensis for bioremediation of Cu2+ and Zn2+ in anaerobic digestion effluent and harvesting biomass for animal feed additives.

11.
Water Res ; 219: 118589, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35597222

RESUMO

The aperiodic changes in the quantity and community of planktonic and particle-associated bacteria have hampered the understanding and management of microbiological water quality in drinking water distribution systems. In this study, online sampling was combined with the microbial fingerprint-based SourceTracker2 to capture and trace the spatiotemporal variations in planktonic and particle-associated bacteria in an unchlorinated distribution system. The results showed that spatially, the particle load significantly increased, while in contrast, the quantity of particle-associated bacteria decreased sharply from the treatment plant to the distribution network. Similar to the trend of particle-associated bacterial diversity, the number of observed OTUs first slightly decreased from the treatment plant to the transportation network and then sharply increased from the transportation network to the distribution network. The SourceTracker2 results revealed that the contribution of particle-associated bacteria from the treatment plant decreased along the distribution distance. The spatial results indicate the dominant role of sedimentation of particles from the treatment plant, while the observed increases in particles and the associated bacteria mainly originated from the distribution network, which were confirmed directly by the increased contributions of loose deposits and biofilm. Temporally, the daily peaks of particle-associated bacterial quantity, observed OTU number, and contributions of loose deposits and biofilms were captured during water demand peaks (e.g., 18-21 h). The temporal results reveal clear linkages between the distribution system harboring bacteria (e.g., within loose deposits and biofilms) and the planktonic and particle-associated bacteria flowing through the distribution system, which are dynamically connected and interact. This study highlights that the spatiotemporal variations in planktonic and particle-associated bacteria are valuable and unneglectable for the widely on-going sampling campaigns required by water quality regulations and/or drinking water microbiological studies.

12.
Artigo em Inglês | MEDLINE | ID: mdl-35548977

RESUMO

In recent years, thin layered indium selenide (In2Se3) has attracted rapidly increasing attention due to its fascinating properties and promising applications. Here, we report the temperature-driven α-ß phase transformation and the enhanced electronic property of 2H α-In2Se3. We find that 2H α-In2Se3 transforms to ß-In2Se3 when it is heated to a high temperature, and the transformation temperature increases from 550 to 650 K with the thickness decreasing from 67 to 17 nm. Additionally, annealing the sample below the phase transformation temperature can effectively improve the electronic property of a 2H α-In2Se3 field-effect transistor, including increasing the on-state current, decreasing the off-state current, and improving the subthreshold swing. After annealing, not only the contact resistance decreases significantly but also the mobility at 300 K increases more than 2 times to 45.83 cm2 V-1 s-1, which is the highest among the reported values. Our results provide an effective method to improve the electrical property and the stability of the In2Se3 nanodevices.

13.
Proc Natl Acad Sci U S A ; 119(20): e2201113119, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35533275

RESUMO

SignificanceWhy do unrelated poisonous mushrooms (Amanita, Galerina, and Lepiota) make the same deadly toxin, α-amanitin? One of the most effective and fast strategies for organisms to acquire new abilities is through horizontal gene transfer (HGT). With the help of genome sequencing and the finding of two genes for the amanitin biosynthetic pathway, we demonstrate that the pathway distribution resulted from HGT probably through an unknown ancestral fungal donor. In Amanita mushrooms, the pathway evolved, through a series of gene manipulations, to produce very high levels of toxins, generating "the deadliest mushroom known to mankind."


Assuntos
Amanitinas , Toxinas Biológicas , Amanita/genética , Amanitinas/genética , Evolução Biológica , Vias Biossintéticas/genética , Transferência Genética Horizontal
14.
Neural Regen Res ; 17(11): 2427-2428, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35535885
15.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35560460

RESUMO

The prevalence of obesity has increased dramatically in the United States during the past three decades. This increase has occurred in children, adolescents and adults of both sexes and all ethnic groups. In addition, the proportion of women and men of reproductive age who are overweight and obese has been increasing considerably, and maternal obesity and excessive gestational weight gain may predispose their offspring to health-related consequences during childhood and adulthood, and increase cardiovascular responses to stress. Therefore, we examined the impact of parental (maternal + paternal) obesity on offspring blood pressure (BP) regulation and cardiovascular responses to stress. Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN, n=5 per sex) or a high fat (H) diet (NH, n=5-7 per sex) from weaning until adulthood. Offspring from obese H diet-fed parents were also fed N (HN, n=5-6 per sex) or H diet (HH, n=5-8 per sex). Body weight, calorie intake and fat mass were measured at 22 weeks of age when cardiovascular phenotyping was performed. Male and female HH offspring were 15% heavier than NH and 70% heavier than NN offspring. Male HH and HN offspring had elevated BP (121±2 and 115±1 mmHg, by telemetry) compared to male NH and NN offspring (108±6 and 107±3 mmHg, respectively) and augmented BP response to angiotensin II, losartan and hexamethonium. Male HH and HN offspring also showed increased BP response to acute air-jet stress (37±2 and 38±2 mmHg) compared to only 24±3 and 25±3 mmHg in NH and NN offspring. Baseline heart rate (HR) and HR responses to air-jet stress were similar among groups. In females, BP and cardiovascular responses to stress were similar among all offspring. Male H diet-fed offspring from obese H diet-fed purinoreceptor 7 deficient (HH-P2X7R-KO) parents had normal BP that was similar to control NN-P2X7R-KO offspring from lean parents. These results indicate that parental obesity leads to increased BP and augmented BP response to stress in their offspring in a sex-dependent manner and that the impact of parental obesity on male offspring BP regulation is markedly attenuated in P2X7R-KO mice.

16.
Front Pharmacol ; 13: 872085, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600860

RESUMO

Breast cancer is one of the most deadly malignancies in women worldwide. Salvia miltiorrhiza, a perennial plant that belongs to the genus Salvia, has long been used in the management of cardiovascular and cerebrovascular diseases. The main anti-breast cancer constituents in S. miltiorrhiza are liposoluble tanshinones including dihydrotanshinone I, tanshinone I, tanshinone IIA, and cryptotanshinone, and water-soluble phenolic acids represented by salvianolic acid A, salvianolic acid B, salvianolic acid C, and rosmarinic acid. These active components have potent efficacy on breast cancer in vitro and in vivo. The mechanisms mainly include induction of apoptosis, autophagy and cell cycle arrest, anti-metastasis, formation of cancer stem cells, and potentiation of antitumor immunity. This review summarized the main bioactive constituents of S. miltiorrhiza and their derivatives or nanoparticles that possess anti-breast cancer activity. Besides, the synergistic combination with other drugs and the underlying molecular mechanisms were also summarized to provide a reference for future research on S. miltiorrhiza for breast cancer treatment.

17.
Artigo em Inglês | MEDLINE | ID: mdl-35537311

RESUMO

Monocrotaline (MCT), derived from most flowering plants, showed significant hepatotoxicity and carcinogenicity. Humans are easily exposed to MCT by eating traditional herbs or contaminated foods, posing a huge threat to human health. In order to selectively and conveniently separate and enrich MCT from these complex samples, we fabricated three-dimensional porous and homogeneous molecularly imprinted polymer foams (MIPFs) by using considerably inexpensive polyurethane foam (PU) as the carrier. The morphology, stability, adsorption properties and extraction parameters of MIPFs were investigated. The results indicated that an imprinted layer was coated on the surface of the carrier; the stability of MIPFs was excellent; In addition to hydrogen bonding and spatial complementarity, the electrostatic interactions were crucial for the recognition between MCT and MIPFs; MIPFs exhibited high adsorption capacity of 22.78 mg g-1, fast mass transfer rate, and satisfactory selectivity for MCT. Subsequently, MIPFs were applied as the solid phase extraction (SPE) absorbents and combined with high performance liquid chromatography (HPLC) to enrich and detect MCT in herbal plants. The results showed that MCT could be efficiently enriched, and the impurities could be dramatically reduced. MIPFs hold great potential for selective separation and detection of MCT in complex matrices, such as traditional Chinese medicine samples and food samples.


Assuntos
Impressão Molecular , Adsorção , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Impressão Molecular/métodos , Polímeros Molecularmente Impressos , Monocrotalina , Polímeros/química , Extração em Fase Sólida/métodos
18.
Radiology ; : 212361, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35471109

RESUMO

Background The diagnostic value of screening the contralateral breast with MRI in patients with newly diagnosed breast cancer is poorly understood. Purpose To assess the impact of MRI for screening the contralateral breast on long-term outcomes in patients with newly diagnosed breast cancer and to determine whether subgroups with unfavorable prognoses would benefit from MRI in terms of survival. Materials and Methods Data on consecutive patients with newly diagnosed breast cancer seen from January 2008 to December 2010 were reviewed retrospectively. Patients with neoadjuvant chemotherapy, previous breast cancer, distant metastasis, absence of contralateral mammography at diagnosis, and no planned surgical treatment were excluded. Groups that did and did not undergo preoperative MRI were compared. Survival analysis was performed using the Kaplan-Meier method for propensity score-matched groups to estimate cause-specific survival (CSS) and overall survival (OS). A marginal Cox proportional hazards model was used to evaluate association of MRI and clinicopathologic variables with OS. Results Of 1846 patients, 1199 fulfilled the inclusion criteria. Median follow-up time was 10 years (range, 0-14 years). The 2:1 matched sample comprised 705 patients (470 in the MRI group and 235 in the no-MRI group); median ages at surgery were 59 years (range, 31-87 years) and 64 years (range, 37-92 years), respectively. MRI depicted contralateral synchronous disease more frequently (27 of 470 patients [5.7%] vs five of 235 patients [2.1%]; P = .047) and was associated with a higher OS (hazard ratio [HR], 2.51; 95% CI: 1.25, 5.06; P = .01). No differences were observed between groups in metachronous disease rate (MRI group: 21 of 470 patients [4.5%]; no-MRI group: 10 of 235 patients [4.3%]; P > .99) or CSS (HR, 1.34; 95% CI: 0.56, 3.21; P = .51). MRI benefit was greater in patients with larger tumor sizes (>2 cm) (HR, 2.58; 95% CI: 1.11, 5.99; P = .03) and histologic grade III tumors (HR, 2.94; 95% CI: 1.18, 7.32; P = .02). Conclusion Routine MRI screening of the contralateral breast after first diagnosis of breast cancer improved overall survival; the most pronounced benefit was found in patients with larger primary tumor size and primary tumors of histologic grade III. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Taourel in this issue.

19.
Nano Lett ; 22(9): 3532-3538, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35451845

RESUMO

The use of nonlinear elements with memory as photonic computing components has seen a huge surge in interest in recent years with the rise of artificial intelligence and machine learning. A key component is the nonlinear element itself. A class of materials known as phase change materials has been extensively used to demonstrate the viability of such computing. However, such materials continue to have relatively slow switching speeds, and issues with cyclability related to phase segregation of phase change alloys. Here, using antimony (Sb) thin films with thicknesses less than 5 nm we demonstrate reversible, ultrafast switching on an integrated photonic platform with retention time of tens of seconds. We use subpicosecond pulses, the shortest used to switch such elements, to program seven distinct memory levels. This portends their use in ultrafast nanophotonic applications ranging from nanophotonic beam steerers to nanoscale integrated elements for photonic computing.


Assuntos
Antimônio , Inteligência Artificial , Ligas , Óptica e Fotônica , Fótons
20.
Adv Sci (Weinh) ; : e2200383, 2022 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-35434939

RESUMO

The ever-increasing demands for data processing and storage will require seamless monolithic co-integration of electronics and photonics. Phase-change materials are uniquely suited to fulfill this function due to their dual electro-optical sensitivity, nonvolatile retention properties, and fast switching dynamics. The extreme size disparity however between CMOS electronics and dielectric photonics inhibits the realization of efficient and compact electrically driven photonic switches, logic and routing elements. Here, the authors achieve an important milestone in harmonizing the two domains by demonstrating an electrically reconfigurable, ultra-compact and nonvolatile memory that is optically accessible. The platform relies on localized heat, generated within a plasmonic structure; this uniquely allows for both optical and electrical readout signals to be interlocked with the material state of the PCM while still ensuring that the writing operation is electrically decoupled. Importantly, by miniaturization and effective thermal engineering, the authors achieve unprecedented energy efficiency, opening up a path towards low-energy optoelectronic hardware for neuromorphic and in-memory computing.

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