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1.
J Atten Disord ; : 1087054720964561, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084494

RESUMO

OBJECTIVE: The present study aimed to examine the effects of SNAP25 on the integration ability of intrinsic brain functions in children with ADHD, and whether the integration ability was associated with working memory (WM). METHODS: A sliding time window method was used to calculate the spatial and temporal concordance among five rs-fMRI regional indices in 55 children with ADHD and 20 healthy controls. RESULTS: The SNAP25 exhibited significant interaction effects with ADHD diagnosis on the voxel-wise concordance in the right posterior central gyrus, fusiform gyrus and lingual gyrus. Specifically, for children with ADHD, G-carriers showed increased voxel-wise concordance in comparison to TT homozygotes in the right precentral gyrus, superior frontal gyrus, postcentral gyrus, and middle frontal gyrus. The voxel-wise concordance was also found to be related to WM. CONCLUSION: Our findings provided a new insight into the neural mechanisms of the brain function of ADHD children.

2.
Neurosci Lett ; : 135429, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33069813

RESUMO

BACKGROUND: Bone fracture may subsequently cause chronic postoperative pain after orthopedic surgery, but mechanisms remain elusive. The necessity of caspase-3 in neuroinflammation and synaptic plasticity has been summarized in pathological pain. Leucine-rich repeat transmembrane protein 1 (LRRTM1) mediates synaptic delivery of AMPA receptor and synaptogenesis. This study evaluated whether caspase-3 and LRRTM1 are required for fracture-associated postoperative allodynia. METHODS: A model of tibial fracture with intramedullary pinning in mice was established for the induction of postoperative pain, verified by measurement of mechanical paw withdrawal threshold and cold scores response to acetone. The caspase-3 specific inhibitor, recombinant caspase-3 and LRRTM1 knockdown by shRNA were utilized for the investigation of pathogenesis as well as the prevention of allodynia. Also, the activity of caspase-3 and the expression of LRRTM1 in the spinal dorsal horn were examined by Western blot and RT-qPCR. RESULTS: This study reported that tibial fracture and orthopedic surgery produced long-lasting mechanical allodynia and cold allodynia, along with the up-modulation of spinal caspase-3 activity (but not caspase-3 expression) and LRRTM1 expression. Spinal caspase-3 inhibition prevented fracture-associated behavioral allodynia in a dose-dependent manner. Caspase-3 inhibitor also reduced the spinal increased LRRTM1 level after tibial fracture with pinning. Spinal LRRTM1 deficiency impaired fracture-caused postoperative pain. Intrathecal recombinant caspase-3 facilitated acute pain hypersensitivity and spinal LRRTM1 expression in naïve mice, reversing by LRRTM1 knockdown. CONCLUSION: Our current results demonstrate the spinal up-regulation of LRRTM1 by caspase-3 activation in the development of tibial fracture-associated postoperative pain in mice.

3.
Ann Intensive Care ; 10(1): 144, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074406

RESUMO

BACKGROUND: Patient-ventilator asynchrony is common in mechanically ventilated patients and may be related to adverse outcomes. Few studies have reported the occurrence of asynchrony in brain-injured patients. We aimed to investigate the prevalence, type and severity of patient-ventilator asynchrony in mechanically ventilated patients with brain injury. METHODS: This prospective observational study enrolled acute brain-injured patients undergoing mechanical ventilation. Esophageal pressure monitoring was established after enrollment. Flow, airway pressure, and esophageal pressure-time waveforms were recorded for a 15-min interval, four times daily for 3 days, for visually detecting asynchrony by offline analysis. At the end of each dataset recording, the respiratory drive was determined by the airway occlusion maneuver. The asynchrony index was calculated to represent the severity. The relationship between the prevalence and the severity of asynchrony with ventilatory modes and settings, respiratory drive, and analgesia and sedation were determined. Association of severe patient-ventilator asynchrony, which was defined as an asynchrony index ≥ 10%, with clinical outcomes was analyzed. RESULTS: In 100 enrolled patients, a total of 1076 15-min waveform datasets covering 330,292 breaths were collected, in which 70,156 (38%) asynchronous breaths were detected. Asynchrony occurred in 96% of patients with the median (interquartile range) asynchrony index of 12.4% (4.3%-26.4%). The most prevalent type was ineffective triggering. No significant difference was found in either prevalence or asynchrony index among different classifications of brain injury (p > 0.05). The prevalence of asynchrony was significantly lower during pressure control/assist ventilation than during other ventilatory modes (p < 0.05). Compared to the datasets without asynchrony, the airway occlusion pressure was significantly lower in datasets with ineffective triggering (p < 0.001). The asynchrony index was significantly higher during the combined use of opioids and sedatives (p < 0.001). Significantly longer duration of ventilation and hospital length of stay after the inclusion were found in patients with severe ineffective triggering (p < 0.05). CONCLUSIONS: Patient-ventilator asynchrony is common in brain-injured patients. The most prevalent type is ineffective triggering and its severity is likely related to a long duration of ventilation and hospital stay. Prevalence and severity of asynchrony are associated with ventilatory modes, respiratory drive and analgesia/sedation strategy, suggesting treatment adjustment in this particular population. Trial registration The study has been registered on 4 July 2017 in ClinicalTrials.gov (NCT03212482) ( https://clinicaltrials.gov/ct2/show/NCT03212482 ).

4.
J Anim Sci ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32954430

RESUMO

Immature Sertoli cell proliferation determines the final number of mature Sertoli cells and further regulates spermatogenesis. Accumulating evidence demonstrated that microRNAs (miRNA) play an important role in Sertoli cell proliferation, differentiation, and apoptosis. However, the effect and molecular mechanism of miRNA on bovine immature Sertoli cells remains to be poorly understood. In this study, miRNA sequencing of testes collected in mature (24-month-old) and immature (neonatal) bulls was conducted to determine the miRNA expression profiles. MicroRNA-34b was one of the differentially expressed miRNA and was selected for in-depth functional studies pertaining to Sertoli cell growth. The results showed that miR-34b mimic transfection in primary Sertoli cells (PSC) inhibited cell proliferation and induced cell cycle arrested at G2 phase and decreased the expression of cell cycle-related genes CCNB1, CDK1, CDC25C, and C-MYC. MicroRNA-34b overexpression also lead to increased cell apoptosis, with pro-apoptotic genes P53 and BAX upregulated, while anti-apoptotic gene BCL2 decreased. However, miR-34b knockdown had the opposite effects. Through a combination of transcriptome sequencing, bioinformatics analysis, dual luciferase reporter assay, and western blotting, mitogen-activated protein kinase kinase1 (MAP2K1), also known as MEK1, was identified as a target of miR-34b. In addition, PSC proliferation inhibition was mediated by cell cycle arrest and apoptosis with MAP2K1 interference. Overexpression of MAP2K1 effectively reversed the miR-34b-repressed PSC cell growth. Moreover, both miR-34b overexpression and MAP2K1 knock-down decreased the protein levels of P-ERK1/2, while MAP2K1 overexpression showed opposite effects. In summary, data suggest that miR-34b regulates PSC proliferation and apoptosis through MEK/ERK signaling pathway. These data provide a theoretical and experimental framework for further clarifying the regulation of cell growth in PSC of bovine.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32963566

RESUMO

Background: This study aims to systematically evaluate the effect of moxibustion on the level of inflammatory cytokines in animal models with rheumatoid arthritis (RA) and to provide evidence for the clinical application of moxibustion to the treatment of RA and related basic researches. Methods: The databases employed in this study include PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), SinoMed, and Wanfang Data Information Site. The retrieval time was from the establishment of these databases to March 2020. The reviewers made use of the CAMARADES 10-item checklist to evaluate the quality of each included study. The inflammatory cytokines were considered as the outcome measure. The Revman 5.3 software was used to conduct meta-analysis on the outcome indicators of the studies included. Results: A total of 648 articles were retrieved and 18 animal experiments were included in this study. The quality scores of the studies ranged from two to eight with a mean of 5.8. Compared with the effect of the control group, moxibustion reduced the expression of TNF-α (SMD 2.95, 95% CI: 1.99-3.92, P < 0.00001), IL-1ß (SMD 4.10, 95% CI: 2.37-5.84, P < 0.00001), IFN-γ (MD 25, 95% CI: 16.17-33.82, P < 0.00001), IL-6 (MD 11.83, 95% CI: 6.22-17.44, P < 0.0001), and IL-17 (MD 99.3, 95% CI: 86.83-111.76, P < 0.00001). At the same time, the level of IL-2 (SMD 8.89, 95% CI: 0.93-16.86, P=0.03), IL-4 (MD 1.79, 95% CI: 0.26-3.32, P=0.02), and IL-10 (MD 5.93, 95% CI: 1.37-10.49, P=0.01) increased after moxibustion treatment. Asymmetric funnel plots indicated that there was publication bias. Conclusion: The findings of the present review indicate that moxibustion can protect the synovium of joint in animal models with RA by upregulation of the level of anti-inflammatory cytokines and downregulation of the level of proinflammatory cytokines. Moxibustion has the potential to relieve inflammation of RA.

6.
Ann Rheum Dis ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868391

RESUMO

OBJECTIVES: The present study aimed to discover novel susceptibility loci associated with risk of rheumatoid arthritis (RA). METHODS: We performed a new genome-wide association study (GWAS) in Chinese subjects (1027 RA cases and 2879 controls) and further conducted an expanded meta-analysis with previous GWAS summary data and replication studies. The functional roles of the associated loci were interrogated using publicly available databases. Dual-luciferase reporter and cytokine assay were also used for exploring variant function. RESULTS: We identified five new susceptibility loci (IL12RB2, BOLL-PLCL1, CCR2, TCF7 and IQGAP1; pmeta <5.00E-08) with same effect direction in each study cohort. The sensitivity analyses showed that the genetic association of at least three loci was reliable and robust. All these lead variants are expression quantitative trait loci and overlapped with epigenetic marks in immune cells. Furthermore, genes within the five loci are genetically associated with risk of other autoimmune diseases, and genes within four loci are known functional players in autoimmunity, which supports the validity of our findings. The reporter assay showed that the risk allele of rs8030390 in IQGAP1 have significantly increased reporter activity in HEK293T cells. In addition, the cytokine assay found that the risk allele of rs244672 in TCF7 was most significantly associated with increased plasma IL-17A levels in healthy controls. Finally, identified likely causal genes in these loci significantly interacted with RA drug targets. CONCLUSION: This study identified novel RA risk loci and highlighted that comprehensive genetic study can provide important information for RA pathogenesis and drug therapy.

7.
Hypertens Res ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908237

RESUMO

Our recent work demonstrates that infusion of sodium butyrate (NaBu) into the renal medulla blunts angiotensin II-induced hypertension and improves renal injury. The present study aimed to test whether oral administration of NaBu attenuates salt-sensitive hypertension in deoxycorticosterone acetate (DOCA)/salt-treated rats. Uninephrectomized male Sprague-Dawley (SD) rats were treated with DOCA pellets (150 mg/rat) plus 1% NaCl drinking water for 2 weeks. Animals received oral administration of NaBu (1 g/kg) or vehicle once per day. Our results showed that NaBu administration significantly attenuated DOCA/salt-increased mean arterial pressure from 156 ± 4 mmHg to 136 ± 1 mmHg. DOCA/salt treatment markedly enhanced renal damage as indicated by an increased ratio of kidney weight/body weight, elevated urinary albumin, extensive fibrosis, and inflammation, whereas kidneys from NaBu-treated rats exhibited a significant reduction in these renal damage responses. Compared to the DOCA/salt group, the DOCA/salt-NaBu group had ~30% less salt water intake and decreased Na+ and Cl- excretion in urine but no alteration in 24-h urine excretion. Mechanistically, NaBu inhibited the protein levels of several sodium transporters stimulated by DOCA/salt in vivo, such as ßENaC, γENaC, NCC, and NKCC-2. Further examination showed that NaBu downregulated the expression of mineralocorticoid receptor (MR) and serum and glucocorticoid-dependent protein kinase 1 (SGK1) in DOCA/salt-treated rats or aldosterone-treated human renal tubular duct epithelial cells. These results provide evidence that NaBu may attenuate DOCA/salt-induced hypertension and renal damage by inhibiting the MR/SGK1 pathway.

8.
Adv Ther ; 37(11): 4660-4674, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32970315

RESUMO

INTRODUCTION: Simultaneous administration of acetylsalicylic acid (ASA) and clopidogrel has demonstrated efficacy in the treatment of acute coronary syndrome. Clopidogrel + ASA in a fixed-dose combination (FDC) provides a pharmaceutical option to enhance adherence to the coadministration of dual antiplatelet therapy (DAPT). Herein, we evaluate the bioequivalence of enteric ASA and clopidogrel in an FDC compared with simultaneous administration of the individual formulations. METHODS: This study is a randomized, single-center, open-label, three-sequence, three-period, two-treatment, crossover study conducted in healthy Chinese male and female subjects under fed conditions. Subjects were randomized to receive, in each period, a single dose of (1) a combination tablet containing 75-mg clopidogrel and 100-mg enteric ASA (test formulation) or (2) coadministration of one 75-mg clopidogrel tablet and one 100-mg enteric-coated ASA tablet (reference formulations) under fed conditions. Plasma samples were analyzed for ASA, salicylic acid, clopidogrel, and the clopidogrel metabolite SR26334. For ASA, the reference-scaled average bioequivalence (RSABE) analysis was conducted for Cmax of ASA because within-subject standard deviation (SDW) was ≥ 0.294 for log-transformed Cmax. RESULTS: The point estimate (test/reference geometric mean ratio) was between 0.80 and 1.25, and the upper one-sided 95% confidence interval (CI) for the scaled average bioequivalence metric was ≤ 0 (-0.08). AUC of ASA as SDW was < 0.294 for log-transformed AUClast and AUC. Estimates of 90% CIs for log-transformed AUClast and AUC ratios were within the bioequivalence range of 0.80 to 1.25 (0.98-1.08 and 1.00-1.10, respectively). For clopidogrel, the 90% CIs for the ratios comparing log-transformed Cmax, AUClast, and AUC ratios of clopidogrel following administration of test versus reference formulation were calculated using the ABE method and were well within the acceptable range of 0.80 to 1.25 (1.02-1.12, 0.92-0.99, and 0.92-0.98, respectively). CONCLUSION: FDC of ASA and clopidogrel was bioequivalent to the simultaneous administration of the individual formulations in healthy Chinese subjects under fed conditions. TRIAL REGISTRATION: CTR20190376.

11.
Cell Death Dis ; 11(9): 745, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917859

RESUMO

The histone acetyltransferases CREB-binding protein (CBP) and its paralogue p300 are transcriptional coactivators which are essential for a multitude of signaling pathways and energy homeostasis. However, the role of CBP/p300 HAT domain in regulating energy balance is still unclear. Here, C57BL/6 mice fed with either normal chow diet (NCD) or high-fat diet (HFD) were administrated with A-485, a recently reported selective inhibitor of CBP/p300 HAT activity for 1 week and the metabolic change was analyzed. The white adipose tissue (WAT) weight and adipocyte size were reduced in A-485-administrated mice, with decreased expressions of lipogenic genes and transcriptional factors. In the liver of A-485-treated mice, the lipid content and lipogenic gene expressions were lowered while the binding of forkhead box O1 (FOXO1) to glucose-6-phosphatase (G6Pc) promoter was reduced, leading to decreased expression of G6Pc. In primary mouse hepatocytes, A-485 abolished cAMP-elicited mRNA expressions of key gluconeogenic enzymes and promoted FOXO1 protein degradation via increasing its ubiquitination. Thus, A-485 inhibits lipogenesis in WAT and liver as well as decreases hepatic glucose production via preventing FOXO1 acetylation, leading to its protein degradation through a proteasome-dependent pathway. The specific inhibition of CBP/p300 HAT will provide a novel therapeutic approach for metabolic diseases.

12.
Life Sci ; 261: 118484, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32976885

RESUMO

AIM: Chloride channel 7 (CLC-7), broadly expressed in kidney tissues, affects the lysosome degradation pathway. And redox status impairment contributes to cell apoptosis and activates autophagy flux. This study mainly investigates the role and molecular mechanism of CLC-7 in redox status impairment-induced autophagic flux and apoptosis. MAIN METHODS: When NRK52E cells, rat renal tubular epithelial cells, were exposed to H2O2 treatment, apoptosis, autophagy flux, and CLC-7 expression were detected. Further investigation was done to observe the change of apoptosis and autophagy flux in renal cells under overexpression or knocking down of CLC-7. The lysosomes acidity, lysosome enzyme Cathepsin D activity and phosphorylation of Ampk/mTOR were also examined when CLC-7 was overexpressed or knocked down. KEY FINDINGS: Redox status impairment induced apoptosis and autophagy flux in NRK52E cells and upregulated CLC-7. Overexpression of CLC-7 increased lysosome acidity and Cathepsin D activity. In cells with CLC-7 overexpression, we observed a significant increase of autophagy flux and decline of apoptosis, as well as an apparent increase of p-Ampk and decrease of p-mTOR. On the contrary, cells with knocking down CLC-7 led to opposite results. SIGNIFICANCES: CLC-7 is essential to maintain and enhance acidity and enzyme activity in lysosome. Through activating autophagy flux, it exerts survival against renal tubular epithelial cell apoptosis induced by redox status impairment. Its function to modulate Ampk/mTOR pathway is the possible reason why CLC-7 can trigger autophagy flux.

13.
Cancer Biomark ; 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32831194

RESUMO

Previous studies have suggested potential signature genes for lung cancer, however, due to factors such as sequencing platform, control, data selection and filtration conditions, the results of lung cancer-related gene expression analysis are quite different. Here, we performed a meta-analysis on existing lung cancer gene expression results to identify Meta-signature genes without noise. In this study, functional enrichment, protein-protein interaction network, the DAVID, String, TfactS, and transcription factor binding were performed based on the gene expression profiles of lung adenocarcinoma and non-small cell lung cancer deposited in the GEO database. As a result, a total of 574 differentially expressed genes (DEGs) affecting the pathogenesis of lung cancer were identified (207 up-regulated expression and 367 down-regulated expression in lung cancer tissues). A total of 5,093 interactions existed among the 507 (88.3%) proteins, and 10 Meta-signatures were identified: AURKA, CCNB1, KIF11, CCNA2, TOP2A, CENPF, KIF2C, TPX2, HMMR, and MAD2L1. The potential biological functions of Meta-signature DEGs were revealed. In summary, this study identified key genes involved in the process of lung cancer. Our results would help the developing of novel biomarkers for lung cancer.

14.
Monogr Soc Res Child Dev ; 85(3): 7-99, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32779237

RESUMO

Respect is an integral part of everyday life. It is a virtue central to the aim of living an ethically good life. Despite its importance, little is known about its emergence, development, correlates, and consequences. In this monograph, we aim to fill this gap by presenting empirical work on children's and adolescents' thinking and feelings about respect. Specifically, we examined the development of respect in ethnically diverse samples of children between the ages of 5 and 15 years (N = 476). Using a narrative and semi-structured interview, as well as self-, caregiver- and teacher-reports, and peer-nominations, we collected information on children's respect conceptions and reasoning, as well as on the social-emotional correlates and prosocial and aggressive behavioral outcomes of respect. We begin with a review of theoretical accounts on respect. This includes a selective overview of the history of respect in philosophy and psychology in Chapter I. Here, we discuss early writings and conceptualizations of respect across the seminal works of Kant and others. We then provide an account of the various ways in which respect is conceptualized across the psychological literature. In Chapter II, we review extant developmental theory and research on respect and its development, correlates, and behavioral consequences. In this chapter, as part of our developmental framework, we discuss how respect is related and distinct from other emotions such as sympathy and admiration. Next, we describe our methodology (Chapter III). This includes a summary of our research aims, samples, and measures used for exploring this novel area of research. Our primary goals were to examine how children and adolescents conceptualize respect, how their conceptualizations differ by age, whether and to what degree children feel respect toward others' "good" behavior (i.e., respect evaluations for behavior rooted in ethical norms of kindness, fairness, and personal achievement goals), and how children's respect is related to other ethical emotions and behaviors. The next three chapters provide a summary of our empirical findings. Chapter IV showcases our prominent results on the development of children's conceptions of respect. Results revealed that children, across age, considered prosociality to be the most important component involved in conceptualizations of respect. We also found age-related increases in children's beliefs about fairness as a core component of respect. Children and adolescents also reported feeling higher levels of respect for behavior in the ethical domain (e.g., sharing fairly and inclusion) than behavior in the personal domain (i.e., achieving high grades in school). Chapter V investigates how sympathy and feelings of sadness over wrongdoing relate to respect conceptions and respect for behavior. Our findings show that sadness over wrongdoing was positively associated with adolescents' fairness conceptions of respect. Sympathy was positively related to children's feelings of respect toward others' ethical behavior. In Chapter VI, we present links between respect and social behavior. Our findings provide some evidence that children's feelings of respect are positively linked with prosocial behavior and children's conceptions of respect (particularly those reflecting themes of fairness and equality) are negatively related to physical aggression. In the last two chapters, we discuss the empirical findings and their implications for practice and policy. In Chapter VII, we draw upon recent work in the field of social-emotional development to interpret our results and provide insight into how our findings extend previous seminal work on the development of respect from early childhood to adolescence. Finally, in Chapter VIII, we conclude by discussing implications for educational and clinical practice with children and adolescents, as well as social policies aimed at reducing discrimination and nurturing children's well-being and positive peer relationships.

15.
Chem Commun (Camb) ; 56(77): 11477-11480, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32856638

RESUMO

Electrochemical reduction of nitrogen to ammonia under ambient conditions is regarded as a potential approach to tackle the energy-intensive Haber-Bosch process. However, it usually suffers from extremely low ammonia yield and faradaic efficiency due to the lack of highly active and selective electrocatalysts. Herein, fusiform-like ruthenium-copper alloy nanosheets (RuCu-FNs) were prepared by alloy engineering and utilized for the electrocatalytic NRR under ambient conditions. A high FE of 7.2% and an NH3 yield rate of 53.6 µg h-1 mgcat-1 were achieved at -0.1 V vs. RHE, which were better than those of the corresponding non-metallic catalyst and most alloy catalysts. The superior performance was ascribed to the differentiated second catalytic site for achieving both effectively adsorptive activation of chemically inert N2 and intermediate desorption from the catalyst surface. The source of NH3 was also identified with isotopic labeling via a self-developed simple and economic pathway. We provided a feasible pathway for the rational design of electrocatalysts for artificial N2 fixation.

16.
J Org Chem ; 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32786223

RESUMO

A highly efficient electrophilic oxyselenation of propargylic amines with diselenides and CO2 under atmospheric pressure promoted by copper/DTBP is reported. Various biologically important selenyl 2-oxazolidinones were produced in moderate to excellent yields. The developed method features a broad substrate scope, easy scalability, and mild reaction conditions.

17.
Chem Commun (Camb) ; 56(72): 10497-10500, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32776053

RESUMO

A robust thermo-responsive polymeric Janus cage with a PNIPAM-cPVBC-PEO sandwiched shell is synthesized. The Janus cage provides a general method of thermally triggered separation of oil/water emulsions independent of the type of surfactant and emulsion. It can selectively capture organic compounds at a higher temperature and release them at a lower temperature.

18.
J Int Med Res ; 48(8): 300060520949037, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32816562

RESUMO

OBJECTIVE: To investigate the accuracy of derecruitment volume (VDER) assessed by pressure-impedance (P-I) curves derived from electrical impedance tomography (EIT). METHODS: Six pigs with acute lung injury received decremental positive end-expiratory pressure (PEEP) from 15 to 0 in steps of 5 cmH2O. At the end of each PEEP level, the pressure-volume (P-V) curves were plotted using the low constant flow method and release maneuvers to calculate the VDER between the PEEP of setting levels and 0 cmH2O (VDER-PV). The VDER derived from P-I curves that were recorded simultaneously using EIT was the difference in impedance at the same pressure multiplied by the ratio of tidal volume and corresponding tidal impedance (VDER-PI). The regional P-I curves obtained by EIT were used to estimate VDER in the dependent and nondependent lung. RESULTS: The global lung VDER-PV and VDER-PI showed close correlations (r = 0.948, P<0.001); the mean difference was 48 mL with limits of agreement of -133 to 229 mL. Lung derecruitment extended into the whole process of decremental PEEP levels but was unevenly distributed in different lung regions. CONCLUSIONS: P-I curves derived from EIT can assess VDER and provide a promising method to estimate regional lung derecruitment at the bedside.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32785185

RESUMO

The concentrations, chemical availability, distribution, and sources of potentially toxic elements (PTEs) in the soil of Xiangjiang Basin in Hunan Province, China were investigated at 85 sites. The highest mean concentrations of Cd, Cu, Zn, As, and Pb were observed in Hengyang, whereas those for Mn, Co, and Hg were observed in Changde. The pollution index values followed the order: Cd > Hg > Cu > Zn > As > Pb; the mean geo-accumulation index values were in the order: Cd > Hg > Pb > Cu > Zn > As > Co > Mn. Cd was associated with moderate contaminated level, Hg and Pb were associated with moderate contaminated to uncontaminated level, and Cu, Zn, As, Co, and Mn were associated with uncontaminated level of pollution. Furthermore, 64.5% of Cd was water-soluble and exhibited exchangeable fractions; its chemical availability posed a risk to the ecosystem. Spatial analysis, principal component analysis, and a positive matrix factorization model were used to assess the PTE sources. Four principal components contributed to 88.8% of the 8 PTEs concentrations. Mining, smelting, industrial, and agricultural activities, alongside sewage irrigation, the use of agrochemicals, and vehicular emissions are the possible anthropogenic sources that pollute agricultural products and threaten human health in the Xiangjiang Basin.

20.
J Biol Chem ; 295(42): 14343-14351, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-32796032

RESUMO

Tripartite motif-containing protein 21 (TRIM21) is a cytosolic antibody receptor that targets the internalized virus-antibody complex to the proteasome for degradation. However, the precise mechanism regulating TRIM21 activity is unknown. Here we show that TRIM21 is a substrate of histone deacetylase 6 (HDAC6) and that its function is regulated by acetylation. HDAC6 interacts with TRIM21 through its PRYSPRY motif and deacetylates TRIM21 at lysine 385 and lysine 387, thus promoting its homodimerization. Inhibiting HDAC6 activity increases TRIM21 acetylation, and hyperacetylation blocks TRIM21 dimerization and ubiquitination, preventing its binding to the virus-antibody complex and its degradation via the ubiquitin-proteasome pathway. HDAC6 depletion or inhibition increases virus accumulation in cells, indicative of an impaired capacity for antibody-dependent intracellular neutralization of viruses, whereas TRIM21 acetylation-deficient K385/387R mutant rescues HDAC6 depletion-caused ADIN impairment. These findings provide evidence for HDAC6 as a novel regulator of TRIM21-mediated intracellular innate immunity.

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