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1.
Nephrology (Carlton) ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034833

RESUMO

AIM: The aim of the present study was to characterize the role of Smad3 signaling on high glucose-induced podocyte injury. METHODS: Synchronized MPC5 cells were treated either with D-glucose alone or D-glucose plus the Smad3 inhibitor SIS3. The distribution of F-actin and transgelin in a high glucose-induced model of podocyte injury were examined by immunofluorescence. Levels of transgelin and Smad3 signaling proteins in MPC5 cells were determined by western blot. RESULTS: A disordered distribution of F-actin, as well as colocalization of F-actin and transgelin, were observed in podocytes exposed to high glucose. Increased levels of transgelin were first observed 10 min after treatment with glucose, suggesting that this protein is sensitive to hyperglycemic injury. Levels of phosphorylated Smad3 and cleaved caspase 3 increased significantly with glucose stimulation. Moreover, expression of the downstream protein c-Myc, but not JAK1/STAT3, was induced in conditions of high glucose. The Smad3-specific inhibitor SIS3 prevented the effects of high glucose on Smad3 phosphorylation, expression of transgelin and c-Myc, caspase 3 cleavage, and cytoskeletal organization. Expression of the tumor suppressor protein p15INK4B increased after podocyte injury but was unaffected by Smad3 inhibition, suggesting that Smad3 regulation of high glucose-induced podocyte injury occurs through a p15INK4B -independent mechanism. CONCLUSION: Smad3 signaling plays a critical role in the modulation of hyperglycemic injury. Targeted inhibition of the Smad3 pathway may offer a novel route for treatment of podocyte damage, especially in cases of diabetic nephropathy. This article is protected by copyright. All rights reserved.

2.
Medicine (Baltimore) ; 99(6): e19047, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028419

RESUMO

BACKGROUND: Although evidence from animal and observational studies has supported the beneficial effects of green tea intake for lowering blood pressure (BP), randomized placebo-controlled trials (RCTs) have yielded conflicting results. In this meta-analysis of RCTs, we aimed to assess the effects of green tea supplementation on measures of BP control. METHODS: The PubMed, Embase, and Cochrane Library databases were electronically searched from inception to August 2019 for all relevant studies. The results were pooled using the generic inverse-variance method with random-effects weighting and expressed as mean differences (MDs) with 95% confidence intervals (CIs). The quality of studies was assessed using the Jadad score. Publication bias was evaluated using funnel plots, Egger test, and Begg test. RESULTS: Twenty-four trials with 1697 subjects were included in the meta-analysis. The pooled results showed that green tea significantly lowered systolic BP (SBP; MD: -1.17 mm Hg; 95%CI: -2.18 to -0.16mm Hg; P = .02) and diastolic BP (DBP; MD: -1.24 mm Hg; 95%CI:-2.07 to -0.40mm Hg; P = .004). Significant heterogeneity was found for both SBP (I = 43%) and DBP (I = 57%). In addition, no evidence of significant publication bias was found from funnel plots or Egger test (P = .674 and P = .270 for SBP and DBP, respectively). CONCLUSION: Overall, green tea significantly reduced SBP and DBP over the duration of the short-term trials. Larger and longer-term trials are needed to further investigate the effects of green tea supplementation on BP control and clinical events.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Chá , Suplementos Nutricionais , Humanos , Hipertensão/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Water Res ; 173: 115596, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32062228

RESUMO

Selective reduction of nitrate to N2 is attractive but still a difficult challenge in the water treatment field. Herein, we established a flow-through electrochemical system packed with polymeric beads supported nZVI (nZVI@D201) for selective nitrate reduction. Consequently, efficient nitrate reduction in the flow mode was achieved on nZVI@D201 under electrochemical regulation with N2 selectivity of up to 95% for at least 60 h. Otherwise, nZVI was gradually exhausted after 20 h, and the product was mainly the undesired NH4+. Through a series of comparative experiments, we clarified that the enhanced nitrate reduction on nZVI under electrochemical regulation was mainly attributed to electrons (from cathode) and active hydrogen ([H]) rather than the previously speculated H2. Combining the characterizations of nZVI during nitrate reduction by X-ray diffraction and X-ray photoelectron spectrometry, we found that nitrate reduction under electrochemical regulation was mediated by nZVI along with the resultant Fe0@FexOy-Fe(II) structure and was sustained by electrons (from cathode) and [H] via the in situ reduction of Fe(III) back to Fe(II). Meanwhile, the undesirable product NH4+ was efficiently oxidized to N2 by the active chlorine generated on the anode. This study not only clarifies the mechanism of enhanced nitrate reduction on nZVI via electrochemical regulation but also advances the technological coupling of nZVI reduction with electrochemistry.

4.
Hepatology ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32083756

RESUMO

NF-κB signaling pathway is important for linking inflammation and tumorigenesis. Here, we characterized a NF-κB-signaling-activation induced long intergenic non-coding RNA in hepatocellular carcinoma (HCC), LINC00665 that contributes to the enhanced cell proliferation of HCC cells both in vitro and in vivo. LINC00665 physically interacts with the double-stranded RNA (dsRNA)-activated protein kinase (PKR) and enhances its activation, and maintains PKR protein stability by blocking ubiquitin/proteasome-dependent degradation, thus resulting in a positive feedback regulation of NF-κB signaling in HCC cells. Notably, HCC patients with higher LINC00665 have poorer outcomes in clinic CONCLUSION: Our findings indicate that LINC00665 is involved in the NF-κB signaling activation in HCC cells and inflammatory LINC00665/PKR/NF-κB loop plays important oncogenic roles in hepatic cancer progression and may be a potential therapeutic target.

5.
Autophagy ; : 1-19, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31983283

RESUMO

Macroautophagy/autophagy is indispensable for testosterone synthesis in Leydig cells (LCs), and here we report a negative association between m6A modification and autophagy in LCs during testosterone synthesis. A gradual decrease of METTL14 (methyltransferase like 14) and an increase of ALKBH5 (alkB homolog 5, RNA demethylase) were observed in LCs during their differentiation from stem LCs to adult LCs. These events led to reduced mRNA methylation levels of N6-methyladenosine (m6A) and enhanced autophagy in LCs. Similar regulation of METTL14, ALKBH5, and m6A was also observed in LCs upon treatment with human chorionic gonadotropin (HsCG). Mechanistically, m6A modification promoted translation of PPM1A (protein phosphatase 1A, magnesium dependent, alpha isoform), a negative AMP-activated protein kinase (AMPK) regulator, but decreased expression of CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, beta), a positive AMPK regulator, by reducing its RNA stability. Thus, m6A modification resulted in reduced AMPK activity and subsequent autophagy inhibition. We further demonstrated that ALKBH5 upregulation by HsCG was dependent on enhanced binding of the transcriptional factor CEBPB (CCAAT/enhancer binding protein [C/EBP], beta) and the TFEB (transcription factor EB) to its gene promoter. Moreover, HsCG treatment decreased METTL14 by reducing its stability. Collectively, this study highlights a vital role of m6A RNA methylation in the modulation of testosterone synthesis in LCs, providing insight into novel therapeutic strategies by exploiting m6A RNA methylation as targets for treating azoospermatism and oligospermatism patients with reduction in serum testosterone.Abbreviations: 3-MA: 3-methyladenine; ACTB: Actin, beta; ALKBH5: alkB homolog 5, RNA demethylase; AMPK: AMP-activated protein kinase; BafA1: bafilomycin A1; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2, beta; CEBPB: CCAAT/enhancer-binding protein (C/EBP), beta; ChIP: chromatin immunoprecipitation; FTO: fat mass and obesity associated; HsCG: human chorionic gonadotropin; HSD3B: 3ß-hydroxysteroid dehydrogenase; LCs: Leydig cells; m6A: N6-methyladenosine; METTL14: methyltransferase like 14; METTL3: methyltransferase like 3; MTOR: mechanistic target of rapamycin kinase; PPM1A: protein phosphatase 1A, magnesium dependent, alpha isoform; PRKAA: 5'-AMP-activated protein kinase catalytic subunit alpha; SQSTM1: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TFEB: transcription factor EB; ULK1: unc-51-like kinase 1; WTAP: Wilms tumor 1-associating protein; YTHDF: YTH N6-methyladenosine RNA binding protein.

6.
Biomaterials ; 232: 119726, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31901502

RESUMO

Reactive oxygen species (ROS) play an important role in the pathogenesis of numerous diseases including atherosclerosis, diabetes, inflammation and myocardial infarction (MI). In this study, a ROS-responsive biodegradable elastomeric polyurethane containing thioketal (PUTK) linkages was synthesized from polycaprolactone diol (PCL-diol ), 1,6-hexamethylene diisocyanate (HDI), and ROS-cleavable chain extender. The PUTK was electrospun into fibrous patches with the option to load glucocorticoid methylprednisolone (MP), which were then used to treat MI of rats in vivo. The fibrous patches exhibited suitable mechanical properties and high elasticity. The molecular weight of PUTK was decreased significantly after incubation in 1 mM H2O2 solution for 2 weeks due to the degradation of thioketal bonds on the polymer backbone. Both the PUTK and PUTK/MP fibrous patches showed good antioxidant property in an oxidative environment in vitro. Implantation of the ROS-responsive polyurethane patches in MI of rats in vivo could better protect cardiomyocytes from death in the earlier stage (24 h) than the non ROS-responsive ones. Implantation of the PUTK/MP fibrous patches for 28 days could effectively improve the reconstruction of cardiac functions including increased ejection fraction, decreased infarction size, and enhanced revascularization of the infarct myocardium.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31947763

RESUMO

Rice water-saving irrigation technology can remarkably reduce irrigation water input and maintain high yield; however, this technology can also accelerate the decomposition of soil organic matter in paddy fields. The spatial and temporal distributions of soil organic carbon (SOC), water-soluble organic carbon (WSOC), and soil microbial biomass carbon (SMBC) under different water-carbon regulation scenarios were analyzed on the basis of field experiments in the Taihu Lake region in China to explore the effects of biochar application on SOC and its components in water-saving irrigation paddy fields. The response of soil catalase (CAT) and invertase (INV) to biochar application in water-saving irrigated rice fields was clarified. The results showed that water-saving irrigation reduced the SOC content by 5.7% to 13.3% but increased WSOC and SMBC contents by 13.8% to 26.1% and 0.9% to 11.1%, respectively, as compared with flooding irrigation. Nonflooding management promoted the oxidative decomposition of soil organic matter. Two years after straw biochar was added, paddy soil SOC content under water-saving irrigation was increased by 4.0% to 26.7%. The WSOC and SMBC contents were also increased by 4.0% to 52.4% and 7.0% to 40.8%, respectively. The high straw biochar addition rate exhibited great impact on SOC. Remarkable correlations among SOC, WSOC, and SMBC were observed, indicating that the addition of straw biochar improved soil labile C, such as WSOC and SMBC, which promoted SOC transformation and stability in paddy soil under water-saving irrigation. Soil CAT and INV were related to SOC conversion. In conclusion, the combination of water-saving irrigation and straw biochar addition was beneficial to the improvement of soil properties and fertility of paddy fields.

8.
Talanta ; 209: 120508, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892057

RESUMO

A custom-tailored design was proposed for the fabrication of carbon dots coupled with restricted access materials and molecularly imprinted polymers (CDs@RAM-MIPs) to detect metronidazole (MNZ). Biomass carbon dots (CDs) were derived from longan peels assisted with high pressure microwave, and had the merits of eco-friendly, excellent photostability and low toxicity. In this work, glycidyl methacrylate was used as a co-polymeric monomer to increase hydroxyl groups on the surface of synthetic materials, which eliminated the interference of biological macromolecules. The specific binding cavities of CDs@RAM-MIPs were formed after removing the template molecule (MNZ). The obtained CDs@RAM-MIPs can selectively capture MNZ through the specific interaction between recognition sites and MNZ, and obey photoinduced electron transfer fluorescence quenching mechanism. The highly sensitive and selective fluorescent sensor based CDs@RAM-MIPs had a wide linear range (50-1200 ng mL-1) and a low detection limit (17.4 ng mL-1) for MNZ. It has been utilized to detect MNZ in serum with recoveries of 93.5%-102.7%, and the relative standards (RSDs) were 1.9%-3.6%, respectively. This work provides a thoughtful strategy for preparation and application of CDs@RAM-MIPs, which presages its great potential for detecting trace compounds in real samples.

9.
J Gerontol A Biol Sci Med Sci ; 75(2): 380-386, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-30796828

RESUMO

BACKGROUND: We investigated whether carotid intima-media thickness is associated with measures of cerebral blood flow (CBF), white matter hyperintensities, and brain volume in a biracial cohort of middle-aged individuals. METHODS: We performed a cross-sectional cohort study based on data from a multicenter, population-based study Coronary Artery Risk Development in Young Adults. Using linear and logistic regression, we estimated the association of the composite intima-media thickness measured in three segments of carotid arteries (common carotid artery, carotid artery bulb, and internal carotid artery) with volume (cm3) and CBF (mL/100 g/min) in the total brain and gray matter as well as volume of white matter hyperintensities (cm3). RESULTS: In the analysis, 461 participants (54% women, 34% African Americans) were included. Greater intima-media thickness was associated with lower CBF in gray matter (ß=-1.36; p = .04) and total brain (ß=-1.26; p = .04), adjusting for age, sex, race, education, and total brain volume. The associations became statistically nonsignificant after further controlling for cardiovascular risk factors. Intima-media thickness was not associated with volumes of total brain, gray matter, and white matter hyperintensities. CONCLUSIONS: This study suggests that lower CBF in middle age is associated with markers of atherosclerosis in the carotid arteries. This association may reflect early long-term exposure to traditional cardiovascular risk factors. Early intervention on atherosclerotic risk factors may modulate the trajectory of CBF as people age and develop brain pathology.

10.
Ecotoxicol Environ Saf ; 189: 109957, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31759744

RESUMO

The large yellow croaker (Larimichthys crocea) is one of the most important marine economic fish in the southeast coast of China. However, hypoxia stress become a major obstacle to the benign development of L. crocea industry. To understand the energy metabolism mechanism adapted to hypoxia, we analyzed the transcriptome and physiology of L. crocea liver in response to hypoxia stress for different durations. We obtained 243,756,080 clean reads, of which 83.38% were successfully mapped to the reference genome of L. crocea. The heat map analysis showed that genes encoding enzymes involved in glycolysis/gluconeogenesis were significantly upregulated at various time points. Moreover, genes encoding enzymes related to the citrate cycle, oxidative phosphorylation, and amino acid metabolism were significantly downregulated at 6 and 24 h, but upregulated at 48 and 96 h. The change of liver in physiology processes, including respiratory metabolism, and activities of the carbohydrate metabolism enzymes showed a similar trend. The results revealed that the respiratory metabolism of L. crocea was mainly anaerobic within 24 h of hypoxia stress, and aerobic metabolism was dominant after 24 h. Carbohydrate metabolism plays a crucial role in energy supply and amino acid metabolism is an important supporting character to cope with acute hypoxia stress. There was no significant change in lipid utilization under short-term acute stress. This study increases our understanding of the energy metabolism mechanism of the hypoxia response in fish and provides a useful resource for L. crocea genetics and breeding.

11.
Anal Chem ; 92(1): 975-982, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31808334

RESUMO

As a representative transition metal, iron plays a key role in chemical activities of atmospheric particulate matter (PM), being involved in particle-related free radical generation and adverse health effects. However, limited understanding of the structure and properties of individual micrometer-sized particulates obscures investigating the contributions of iron toward chemical activities. Here, we describe multidimensional analytical strategies to characterize the mass, spatial distribution, and chemical forms of iron in single haze particles using synchrotron radiation techniques. We first used X-ray fluorescence imaging to quantify the masses of multiple metals and yielded distribution maps of transition metals, which revealed the types of elements that tend to occur together. Additionally, we employed nanocomputed tomography to assess the spatial distribution of iron and observed that iron exists as small aggregates and is concentrated primarily in subsurface regions. We also combined X-ray absorption near structures with scanning transmission X-ray microscopy to quantify the ferrous and ferric forms and mapped their distributions in individual particles, which probably attribute chemical activity of iron. In conclusion, we demonstrated the power of synchrotron radiation-based techniques to study heretofore inaccessible chemical information in single haze particles, which may provide important clues about iron chemistry as a source of Fenton reactions and health effects. The multifaceted analytical approaches exhibit high sensitivity (subfemtogram per particle or ∼0.2 fg/µm2) toward multiple elements and are promising to be used for studying other concepts such as the solubility of aerosol iron, the heterogeneous oxidation of organic matters and SO2, and the formation and the aging of haze particles.

12.
Angew Chem Int Ed Engl ; 59(2): 798-803, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31657106

RESUMO

Designing effective electrocatalysts for the carbon dioxide reduction reaction (CO2 RR) is an appealing approach to tackling the challenges posed by rising CO2 levels and realizing a closed carbon cycle. However, fundamental understanding of the complicated CO2 RR mechanism in CO2 electrocatalysis is still lacking because model systems are limited. We have designed a model nickel single-atom catalyst (Ni SAC) with a uniform structure and well-defined Ni-N4 moiety on a conductive carbon support with which to explore the electrochemical CO2 RR. Operando X-ray absorption near-edge structure spectroscopy, Raman spectroscopy, and near-ambient X-ray photoelectron spectroscopy, revealed that Ni+ in the Ni SAC was highly active for CO2 activation, and functioned as an authentic catalytically active site for the CO2 RR. Furthermore, through combination with a kinetics study, the rate-determining step of the CO2 RR was determined to be *CO2 - +H+ →*COOH. This study tackles the four challenges faced by the CO2 RR; namely, activity, selectivity, stability, and dynamics.

13.
Mol Genet Genomic Med ; 8(1): e1025, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31701656

RESUMO

BACKGROUND: Preeclampsia (PE) is a common pregnancy-related syndrome characterized by hypertension and proteinuria, and a major cause of maternal mortality. Therefore, there is an urgent need to identify early biomarkers of PE. The aim of the present study was to identify the functions of miR-576-5p in PE. METHODS: Effects of miR-576-5p and transcription factor AP-2α (TFAP2A) on invasion of human trophoblast HTR8/SVneo cells were investigated. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to assess the expression of miR-576-5p, TFAP2A, E-cad, and Vimentin in PE tissues and cells. Additionally, immunofluorescence was used to detect the expression of TFAP2A in PE trophoblastic tissue. Subsequently, constructed miR-576-5p mimics, miR-576-5p inhibitor, and siRNA-TFAP2A plasmids were transfected into HTR8/SVneo cells for further experiments, including a CCK-8 assay for cell proliferation, Transwell assay for cell invasion and the luciferase reporter gene system was employed for target verification. RESULTS: A lower expression of miR-576-5p and a higher expression of TFAP2A were identified in PE rats. E-cadherin was highly expressed while Vimentin was downregulated. Further statistical analysis indicated that cell proliferation of HTR8/SVneo cells decreased in the miR-576-5p inhibitor group and increased in the miR-576-5p mimics and siRNA-TFAP2A groups. miR-576-5p inhibitor suppressed cell invasion, and miR-576-5p mimics and siRNA-TFAP2A improved cell invasion. The analysis of luciferase reporter demonstrated a decreased luciferase activity in miR-576-5p mimics group compared with control group, which indicates that TFAP2A may be a target of miR-576-5p. Interference of TFAP2A could downregulate E-cadherin and upregulate Vimentin expression. CONCLUSION: Overexpression of miR-576-5p and knockdown of TFAP2A may elevate cell proliferation and invasion of human trophoblast cells in vitro. Therefore, miR-576-5p may be used as a notable biomarker for the diagnosis, prevention, and treatment of PE. miR-576-5p targeting TFAP2A deserve further investigation in order to explore their potential role in PE.

14.
Eur J Hum Genet ; 28(2): 244-252, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31576025

RESUMO

X-linked Alport syndrome (XLAS) is an inherited renal disease caused by mutations in COL4A5 gene. The c.2858G>T(p.(G953V)) in COL4A5 gene (rs78972735) has been considered pathogenic previously. However, there are conflicting interpretations of its pathogenicity recently. Here we presented 19 Chinese families, out of which 36 individuals (18 probands and 18 family members) carried the c.2858G>T(p.(G953V)) in COL4A5 gene. The clinical manifestations and genetic findings of them were analyzed. We found there were no clinical features of Alport syndrome not only in six probands with c.2858G>T(p.(G953V)) in COL4A5 plus pathogenic variants in other genes (e.g., WT1, ADCK4, NPHP1, TRPC6, COL4A4, and PAX2) but also in another six probands with only the c.2858G>T(p.(G953V)) variant. The other six probands with a combination of c.2858G>T(p.(G953V)) and another pathogenic variant in COL4A5 had XLAS. Eleven family members (11/18, nine females and two males) who had only the c.2858G>T(p.(G953V)) variant were asymptomatic. These two males (at age of 42 and 35 years) had normal result of urine analysis and no more clinical traits of Alport syndrome. We conclude c.2858G>T(p.(G953V)) in COL4A5 gene is not a pathogenic variant for XLAS. Individuals should not be diagnosed as XLAS only based on the detection of c.2858G>T(p.(G953V)) in COL4A5 gene.

15.
CNS Neurosci Ther ; 26(2): 251-259, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31342670

RESUMO

AIMS: The exact pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) remains unclear. A variety of cytokines are involved, but few studies have been performed to explore the novel roles of interleukin-22 (IL-22) and interleukin-35 (IL-35) in NMOSD. Therefore, this study was designed to investigate serum levels of IL-22 and IL-35, and their correlations with clinical and laboratory characteristics in NMOSD. METHODS: We performed a cross-section study, 18 patients with acute NMOSD, 23 patients with remission NMOSD, and 36 healthy controls were consecutively enrolled. Serum levels of IL-22 and IL-35 were measured by enzyme-linked immunosorbent assay (ELISA). The correlations between serum IL-22 and IL-35 levels and clinical and laboratory characteristics were evaluated by Spearman's rank or Pearson's correlation coefficient. RESULTS: The serum levels of IL-22 and IL-35 were significantly lower in patients with acute NMOSD and remission NMOSD than in healthy controls (IL-22: 76.96 ± 13.62 pg/mL, 87.30 ± 12.79 pg/mL, and 94.02 ± 8.52 pg/mL, respectively, P < .0001; IL-35: 45.52 ± 7.04 pg/mL, 57.07 ± 7.68 pg/mL, and 60.05 ± 20.181 pg/mL, respectively, P < .0001). Serum levels of IL-35 were negatively correlated with EDSS scores and cerebrospinal fluid protein levels (r = -.5438, P = .0002 and r = -.3523, P = .0258, respectively) in all patients. CONCLUSIONS: Lower serum levels of IL-22 and IL-35 are associated with disease status in NMOSD. Additionally, lower serum levels of IL-35 are associated with disease severity in NMOSD.

16.
Sci Total Environ ; 707: 136139, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31863983

RESUMO

Di-n-butyl phthalate (DBP), as one of the environmental chemicals, can cause male reproductive decline including testicular hypoplasia and impairments of spermatogenesis. Testicular inflammation is positively related to decline in male reproductive function. However, whether exposure to DBP in utero can cause testicular inflammation in progeny has not been studied. In this study, we established an animal model and observed that DBP exposure during gestation induced testicular inflammation in progeny with the increased expression of pro-inflammatory cytokines and chemokines including tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1) and CXC chemokine ligand-10 (CXCL-10), representing the activation of the nuclear factor kappa B (NF-κB). However, NF-κB was activated within 1 h in Sertoli cells (SCs) when exposed to MBP (a metabolite of DBP) in vitro. Meanwhile, we detected increased expression of inflammatory NLR family pyrin domain containing 3 (NLRP3), resulting from Pellino2-mediated NLRP3 inflammasome priming. Further, we confirmed that the activation of the NLRP3/caspase-1/IL-1ß canonical inflammasome pathway induced secretion of inflammatory factors of SCs and immune response, and INF39 (an inhibitor of NLRP3) could inhibit the inflammation in vitro. Collectively, these findings indicated that NLRP3 inflammasomes played key roles in DBP-induced inflammation in testicular SCs.

17.
Nanoscale ; 12(3): 1356-1365, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31854411

RESUMO

High-density growth nanotwins enable high-strength and good ductility in metallic materials. However, twinning propensity is greatly reduced in metals with high stacking fault energy. Here we adopted a hybrid technique coupled with template-directed heteroepitaxial growth method to fabricate single-crystal-like, nanotwinned (nt) Ni. The nt Ni primarily contains hierarchical twin structures that consist of coherent and incoherent twin boundary segments with few conventional grain boundaries. In situ compression studies show the nt Ni has a high flow strength of ∼2 GPa and good deformability. Moreover, the nt Ni has superb corrosion behavior due to the unique twin structure in comparison to coarse grained and nanocrystalline counterparts. The hybrid technique opens the door for the fabrication of a wide variety of single-crystal-like nt metals with unique mechanical and chemical properties.

18.
J Clin Neurosci ; 71: 9-14, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31864829

RESUMO

Natural killer (NK) cells are involved in the pathogenesis of inflammatory demyelinating diseases of the central nervous system. However, the differential expressions of NK cells in the peripheral blood of patients with neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) are unknown. This study aimed to explore the differential expressions of NK cells in NMOSD and MS and evaluate the clinical implications of this difference. We performed a cross-sectional study to investigate the expression of NK cells in the peripheral blood of patients with NMOSD (n = 78) and MS (n = 24) and of healthy controls (HC, n = 27). Furthermore, we investigated the relationship between NK cell level and disease phase in 102 patients with NMOSD and MS through Spearman correlation analysis and receiver operating characteristic (ROC) analysis. Our results showed that the median (interquartile range) NK cell levels in acute-phase NMOSD patients, remission-phase NMOSD patients, acute-phase MS patients, and HC subjects were 114.10 (64.75-153.38) cells/µL, 167.60 (116.35-266.15) cells/µL, 282.55 (140.57-368.20) cells/µL, and 221.00 (170.40-269.55) cells/µL, respectively (p < 0.001). The Spearman correlation coefficient (95%) for the relationship between NK level and disease phase in NMOSD patients was 0.366 (0.150-0.550) (p < 0.001). Furthermore, ROC analysis revealed that patients with NK cell values lower than 172.200 cells/µL were more prone to have acute-phase NMOSD than MS. In conclusion, the expression of NK cells in peripheral blood was lower in patients with NMOSD than in patients with MS in the acute phase, and a low expression of NK cells may suggest having acute-phase NMOSD rather than MS.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31881514

RESUMO

Peptide mapping by liquid chromatography-mass spectrometry (LC-MS) is a common method for characterizing primary sequences of monoclonal antibodies (mAbs) and their post-translational modifications (PTMs). Most methods prepare digests by incubating samples with proteases from several hours to overnight. This often induces artifacts of some modifications such as deamidation and isomerization, resulting in overestimated product-related modifications levels. Hour-long-digestion can generate complicate chromatographic profiles due to semi-cleavages or other unnecessary reactions, interfering with the quantitation of peaks of interest. On the other hand, shortening digestion-time can cause incomplete peptide cleavages, thus low sequence coverage and poor repeatability. This study applied pressure cycling technology (PCT) to tryptic digestion and PNGase F deglycosyaltion. A 0.5-h PCT assistant tryptic digestion, by alternating cycles of 10-s atmospheric pressure and 50-s high pressure (30 kpsi) at 37 °C, was evaluated and compared with two conventional digestions, 4-h and 18-h (i.e., overnight) incubations at 37 °C under atmospheric pressure. The 0.5-h PCT assistant deglycosylation was also assessed using the same conditions as those by PCT tryptic digestion. The results demonstrated the application of a 0.5-h PCT to tryptic digestion minimized modification artifacts and reduced interference with quantitation by providing a clean chromatographic profile. The 0.5-h PCT assistant deglycosylation completely removed the N-glycans from the Asn301 in the heavy chains of monoclonal antibody with no impact on the chromatographic profile of the tryptic digests.

20.
Chemosphere ; 240: 124940, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31574446

RESUMO

Charged ultrafiltration (UF) membranes can repel electrically charged molecules that are smaller than the size of the membrane pores and display high rejection of solutes, high flux, and low operation pressures compared to uncharged UF, nanofiltration (NF) and reverse osmosis (RO). Here, a charged UF membrane composite (PANI/PVDF) was prepared and regulated via electrochemically reversible control in portions of amine/imine functional groups of PANI. As a result, the permeability and rejection ratios of CR2- on charged PANI/PVDF, with PVDF as a control, increased from 19.6 to a maximum of 183.3 L m-2 h-1 bar-1 and from 3.4% to 74%, which expands the trade-off confine benefited from surface potential change from -12.21 mV to -25.26 mV, furtherly, the rejection ratio of CR2- on PANI/PVDF reached up to 93% via the electrochemical regulation. Finally, a fixed-charge model was built that well describes the steric and electric repulsion effects on membrane performance and the important roles of the electrochemically controllable surface charge. Moreover, the contour map of rejection ratios containing the ratio of molecular size vs the average pore size of the membrane (r/R = 0.2-1.0) and the zeta potential (-10 to -60 mV) were taken into account, which can be used to visually understand the rejection performance of membranes. This model is also appropriate for varying molecular sizes and for molecules with different charges. Our work opens a new horizon for the design of electrochemically controllable charged membranes to remove charged compounds.


Assuntos
Corantes/análise , Técnicas Eletroquímicas/métodos , Ultrafiltração/métodos , Purificação da Água/métodos , Eletricidade , Membranas Artificiais , Propriedades de Superfície
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