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1.
Dalton Trans ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34642725

RESUMO

Confinement of LiBH4 in porous materials is an efficient route to enhance the ionic conductivity of lithium, which seems to be associated with various types of scaffolding and its mixture ratios. In the present work, we reveal the effect of supports on ionic conductivity improvements based on a comparison of different silica supports, including micro-SiO2 (SM), porous nano-SiO2 (MSN), and nano-SiO2 with nanochannels (SBA-15). All LiBH4/silica composites exhibited higher lithium ionic conductivity, where LiBH4/SBA-15 (47% weight ratio) exhibited the highest conductivity of 3 × 10-5 S cm-1 at 35 °C, nearly three orders of magnitude higher than that of pure LiBH4. In addition, the LiBH4/SBA-15 composite has a wider electrochemical stability window of -0.2 to 5 V, satisfactory compatibility with the Li anode, and no occurrence of side reactions. These ionic conductivity enhancements can be attributed to the support effects of distinct SiO2, i.e., the increase in surface area for superior interfacial ionic conductivity and/or the increased disorder of LiBH4 for faster matrix ionic conductivity. The present study offers useful insights for designing a new hydride solid electrolyte for all-solid-state lithium ion batteries.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34625799

RESUMO

The pandemic influenza A (H1N1) virus spread globally and posed one of the most serious global public health challenges. The traditional Chinese medicine is served as a complementary treatment strategy with vaccine immunization. Here, we demonstrated the mixed polysaccharides (MPs) derived from shiitake mushroom, poriacocos, ginger and tyangerine peel prevent the H1N1 virus infections in mice. MPs pretreatment attenuated H1N1 virus-induced weight loss, clinical symptoms and death. The lymphocytes detection results showed the CD3+, CD19+ and CD25+ cell proportions were up-regulated in thymus under MPs pretreatment. Besides, MPs pretreatment reduced the inflammatory cell infiltration and increased the cell proportions of CD19+, CD25+ and CD278+ in lung. However, MPs treatment have no effective therapeutic effect after H1N1 virus challenge. The current study suggested that pretreatment with MPs could attenuate H1N1 virus-induced lung injury and up-regulate humoral and cellular immune responses in non- immunized mice.

3.
J Hazard Mater ; 423(Pt B): 127042, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34536850

RESUMO

Livestock manure is a main source of heavy metals, antibiotics and antibiotic resistance genes (ARGs) in agricultural soils. The co-existence of heavy metals and ARGs needs to be systematically studied, since manure application is greatly encouraged. In this study, we examined soils for alterations in antibiotic resistance where doxycycline, Cu, and Zn were added equivalent to those found in typical pig manure applications. The results indicated that high levels of Cu inhibited soil respiration and urease for the first 10 days. Metagenomic analysis demonstrated that Cu and Zn additions caused profound alterations in bacterial community, metal resistance genes (MRGs) and mobile genetic elements. Among the differential ARGs, efflux pump genes took a significantly high ratio compared with control for the first 5 days, emphasizing their important roles in the profile of antibiotic resistance. Moreover, the number of differential MRGs was < 30 for doxycycline treatment, but 66-87 for Cu and Zn treatments. The number of differential integrative and conjugative elements was 3 for doxycycline treatment, and 6-13 for Cu and Zn treatments. Overall, high Cu and Zn levels caused a greater influence than did doxycycline on bacterial communities and transfer of antibiotic resistance in soil.

5.
Waste Manag Res ; : 734242X211032031, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34407708

RESUMO

While the construction industry has brought substantial economic benefits to society, it has also generated substantial construction and demolition waste (CDW). Illegal dumping, which refers to dumping CDW in an unauthorized non-filling location, has become widespread in many countries and regions. Illegally dumping CDW destroys the environment, causing groundwater pollution and forest fires and causing significant economic impacts. However, there is a lack of research on the decision-making behaviours and logical rules of the main participants, construction contractors and the government in the illegal CDW dumping process. This paper constructs an evolutionary game model on a small-world network considering government supervision to portray the decision-making behaviours of illegal dumping participants and conducts a numerical simulation based on empirical equations to propose an effective supervision strategy for the government to manage illegal CDW dumping efficiently. It is found that the illegal dumping behaviours of contractors are mainly affected by the intensity of government supervision, the cost of fines and the income of illegal dumping; while for government, a supervision strategy is found to be necessary, and a supervision intensity of approximately 0.7 is the optimal supervision probability given supervision efficiency. Notably, under a low-level supervision probability, increasing the penalty alone does not curb illegal dumping, and a certain degree of supervision must be maintained. The results show that in addition to setting fines for illegal dumping, the government must enforce a certain level of supervision and purify the market environment to steadily reduce illegal dumping.

6.
Platelets ; : 1-11, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34346853

RESUMO

Several clinical trials exploring the effect of platelet-rich plasma (PRP) on Achilles tendon rupture (ATR) or Achilles tendinopathy (AT) have been published. However, current evidence is limited to small-sized trials. This study aims to evaluate whether PRP improves the outcomes of ATR or AT. PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched to identify randomized controlled trials comparing PRP injection versus placebo for ATR or AT. Eleven studies with 574 patients were included. Quantitative synthesis suggested that compared with placebo, AT patients in PRP group had higher VISA-A score improvement at six-week follow-up (mean difference (MD) = 2.64; 95% CI) = 1.12 to 4.15). However, there was no significant difference between two groups for VISA-A score improvement at three-month follow-up (MD = 0.93; 95% CI = -2.75 to 4.62), or 6-month follow-up (MD = 5.46; 95% CI = -1.19 to 12.11). In ATR patients, quantitative synthesis suggested that no significant difference was seen between PRP and control group at 3-month, 6-month, and 1-year follow-up. In addition, no significant difference was detected between the two groups in improving tendon thickness and pain for AT patients, and no significant difference was seen in improving heel-rise work, maximum heel-rise height, dorsal and plantar flexion, rate of returning to sports activities, and complication for ATR patients. To conclude, no evidence indicates that PRP injection can improve the patient-reported/clinical/functional outcomes of AT or ATR. The increasing times of PRP injection could improve the outcomes, and further clinical randomized controlled trials are expected to be conducted to verify this hypothesis.

7.
J Gen Virol ; 102(8)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34424158

RESUMO

Bovine astrovirus (BoAstV) belongs to genus Mamastravirus (MAstV). It can be detected in the faeces of both diarrhoeal and healthy calves. However, its prevalence, genetic diversity, and association with cattle diarrhoea are poorly understood. In this study, faecal samples of 87 diarrhoeal and 77 asymptomatic calves from 20 farms in 12 provinces were collected, and BoAstV was detected with reverse transcription-polymerase chain reaction (RT-PCR). The overall prevalence rate of this virus in diarrhoeal and asymptomatic calves was 55.17 % (95 % CI: 44.13, 65.85 %) and 36.36 % (95 % CI: 25.70, 48.12 %), respectively, indicating a correlation between BoAstV infection and calf diarrhoea (OR=2.15, P=0.024). BoAstV existed mainly in the form of co-infection (85.53 %) with one to five of nine viruses, and there was a strong positive correlation between BoAstV co-infection and calf diarrhoea (OR=2.83, P=0.004). Binary logistic regression analysis confirmed this correlation between BoAstV co-infection and calf diarrhoea (OR=2.41, P=0.038). The co-infection of BoAstV and bovine rotavirus (BRV) with or without other viruses accounted for 70.77 % of all the co-infection cases. The diarrhoea risk for the calves co-infected with BoAstV and BRV was 8.14-fold higher than that for the calves co-infected with BoAstV and other viruses (OR=8.14, P=0.001). Further, the co-infection of BoAstV/BRV/bovine kobuvirus (BKoV) might increase the risk of calf diarrhoea by 14.82-fold, compared with that of BoAstV and other viruses (OR=14.82, P <0.001). Then, nearly complete genomic sequences of nine BoAstV strains were assembled by using next-generation sequencing (NGS) method. Sequence alignment against known astrovirus (AstV) strains at the levels of both amino acids and nucleotides showed a high genetic diversity. Four genotypes were identified, including two known genotypes MAstV-28 (n=3) and MAstV-33 (n=2) and two novel genotypes designated tentatively as MAstV-34 (n=1) and MAstV-35 (n=3). In addition, seven out of nine BoAstV strains showed possible inter-genotype recombination and cross-species recombination. Therefore, our results increase the knowledge about the prevalence and the genetic evolution of BoAstV and provide evidence for the association between BoAstV infection and calf diarrhoea.


Assuntos
Infecções por Astroviridae , Doenças dos Bovinos , Coinfecção , Diarreia , Animais , Animais Recém-Nascidos/virologia , Infecções por Astroviridae/epidemiologia , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/virologia , China/epidemiologia , Coinfecção/epidemiologia , Coinfecção/veterinária , Coinfecção/virologia , Diarreia/epidemiologia , Diarreia/veterinária , Diarreia/virologia , Fezes/virologia , Prevalência
8.
Waste Manag ; 131: 491-502, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34274861

RESUMO

The market power and competition scenario of recycling enterprises and landfills may change in the future due to the environmental pressure caused by landfills and the environmental potential of construction and demolition waste (C&DW) recycling. In this context, how these changes will affect the economic performance of enterprises and the environmental performance of the whole society remains unclear, along with how the willingness to pay and the environmental awareness of contractors will affect the pricing decisions of recycling enterprises and landfills. This study investigates the charging and recycling problem under different power structures in the reverse supply chain of C&DW, which is composed of waste generators (construction contractors) and two disposers (recycling enterprises and landfills). The interactive decisions of three stakeholders are discussed and the optimal charge fee, profit, and recycling ratio are obtained. Results indicate the following (i) The environmental preference of contractors directly increases the charge fee of recycling enterprises, and indirectly increases the charge fee of landfills. (ii) An increase in contractors' environmental preference will reduce the recycling ratio of C&DW and increase landfill and illegal dumping ratios. (iii) From the perspective of environmental benefits, illegal dumping and recycling ratios experience the worst scenario in the Recycling-Stackelberg game model and the best scenario in Nash game model because recycling enterprises take advantage of their dominant market position and set higher charges than those that contractors can afford. This theoretical study bridges the research gap on the effects of the market power on the environmental and economic performance of stakeholders in the field of C&DW management. The findings also help policy makers understand the behavior of stakeholders under different power structures to formulate the most effective intervention strategies.


Assuntos
Indústria da Construção , Gerenciamento de Resíduos , Materiais de Construção , Custos e Análise de Custo , Humanos , Resíduos Industriais , Reciclagem , Instalações de Eliminação de Resíduos
9.
Nat Commun ; 12(1): 4358, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272367

RESUMO

Premature termination codons (PTCs) prevent translation of a full-length protein and trigger nonsense-mediated mRNA decay (NMD). Nonsense suppression (also termed readthrough) therapy restores protein function by selectively suppressing translation termination at PTCs. Poor efficacy of current readthrough agents prompted us to search for better compounds. An NMD-sensitive NanoLuc readthrough reporter was used to screen 771,345 compounds. Among the 180 compounds identified with readthrough activity, SRI-37240 and its more potent derivative SRI-41315, induce a prolonged pause at stop codons and suppress PTCs associated with cystic fibrosis in immortalized and primary human bronchial epithelial cells, restoring CFTR expression and function. SRI-41315 suppresses PTCs by reducing the abundance of the termination factor eRF1. SRI-41315 also potentiates aminoglycoside-mediated readthrough, leading to synergistic increases in CFTR activity. Combining readthrough agents that target distinct components of the translation machinery is a promising treatment strategy for diseases caused by PTCs.


Assuntos
Códon sem Sentido/antagonistas & inibidores , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Células Epiteliais/efeitos dos fármacos , Degradação do RNAm Mediada por Códon sem Sentido , Terminação Traducional da Cadeia Peptídica/efeitos dos fármacos , Fatores de Terminação de Peptídeos/metabolismo , Aminoglicosídeos/metabolismo , Códon sem Sentido/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Células Epiteliais/metabolismo , Genes Reporter , Gentamicinas/farmacologia , Células HEK293 , Humanos , Microssomos Hepáticos/efeitos dos fármacos , Fatores de Terminação de Peptídeos/genética , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Interferência de RNA , Ribossomos/metabolismo , Relação Estrutura-Atividade
10.
Neurochem Int ; 149: 105122, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34284076

RESUMO

As a double-stranded DNA (dsDNA) sensor, the PYHIN family member absent in melanoma 2 (AIM2) is an essential component of the inflammasome families. Activation of AIM2 by dsDNA leads to the assembly of cytosolic multimolecular complexes termed the AIM2 inflammasome, resulting in activation of caspase-1, the maturation and secretion of pro-inflammatory cytokines interleukin (IL)-1ß and IL-18, and pyroptosis. Multiple central nervous system (CNS) diseases are accompanied by immune responses and inflammatory cascade. As the resident macrophage cells, microglia cells act as the first and main form of active immune defense in the CNS. AIM2 is highly expressed in microglia as well as astrocytes and neurons and is essential in neurodevelopment. In this review, we highlight the recent progress on the role of AIM2 inflammasome in CNS disorders, including cerebral stroke, brain injury, neuropsychiatric disease, neurodegenerative diseases, and glioblastoma.

11.
Nat Plants ; 7(7): 893-898, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34168319

RESUMO

Resource allocation to reproduction is a critical trait for plant fitness1,2. This trait, called harvest index in the agricultural context3-5, determines how plant biomass is converted to seed yield and consequently financial revenue from numerous major staple crops. While plant diversity has been demonstrated to increase plant biomass6-8, plant diversity effects on seed yield of crops are ambiguous9 and dependent on the production syndrome10. This discrepancy might be explained through changes in the proportion of resources invested in reproduction in response to changes in plant diversity, namely through changes in species interactions and microenvironmental conditions11-14. Here, we show that increasing crop plant diversity from monocultures over two- to four-species mixtures increased annual primary productivity, resulting in overall higher plant biomass and, to a lesser extent, higher seed yield in mixtures compared with monocultures. The difference between the two responses to diversity was due to a reduced harvest index of the eight tested crop species in mixtures, possibly because their common cultivars have been bred for maximum performance in monoculture. While crop diversification provides a sustainable measure of agricultural intensification15, the use of currently available cultivars may compromise larger gains in seed yield. We therefore advocate regional breeding programmes for crop varieties to be used in mixtures that should exploit complementarity16 among crop species.


Assuntos
Biodiversidade , Biomassa , Produção Agrícola/métodos , Produção Agrícola/estatística & dados numéricos , Produtos Agrícolas/crescimento & desenvolvimento , Espanha , Suíça
12.
Nat Metab ; 3(7): 983-1000, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34183849

RESUMO

Acetyl-CoA is a central node in carbon metabolism and plays critical roles in regulatory and biosynthetic processes. The acetyl-CoA synthetase Acs2, which catalyses acetyl-CoA production from acetate, is an integral subunit of the serine-responsive SAM-containing metabolic enzyme (SESAME) complex, but the precise function of Acs2 within the SESAME complex remains unclear. Here, using budding yeast, we show that Acs2 within the SESAME complex is required for the regulation of telomere silencing and cellular senescence. Mechanistically, the SESAME complex interacts with the histone acetyltransferase SAS protein complex to promote histone H4K16 acetylation (H4K16ac) enrichment and the occupancy of bromodomain-containing protein, Bdf1, at subtelomeric regions. This interaction maintains telomere silencing by antagonizing the spreading of Sir2 along the telomeres, which is enhanced by acetate. Consequently, dissociation of Sir2 from telomeres by acetate leads to compromised telomere silencing and accelerated chronological ageing. In human endothelial cells, ACSS2, the ortholog of yeast Acs2, also interacts with H4K16 acetyltransferase hMOF and are required for acetate to increase H4K16ac, reduce telomere silencing and induce cell senescence. Altogether, our results reveal a conserved mechanism to connect cell metabolism with telomere silencing and cellular senescence.


Assuntos
Acetilcoenzima A/metabolismo , Carbono/metabolismo , Senescência Celular/fisiologia , Complexos Multienzimáticos/metabolismo , Células Endoteliais/metabolismo , Inativação Gênica , Histonas/metabolismo , Humanos , Saccharomycetales/fisiologia , Telômero/genética , Telômero/metabolismo
13.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070207

RESUMO

In domestic ruminants, endometrial receptivity is related to successful pregnancy and economic efficiency. Despite several molecules having been reported in the past regarding endometrial receptivity regulation, much regarding the mechanism of endometrial receptivity regulation remains unknown due to the complex nature of the trait. In this work, we demonstrated that the cysteine-rich transmembrane bone morphogenetic protein (BMP) regulator 1 (CRIM1) served as a novel regulator in the regulation of goat endometrial receptivity in vitro. Our results showed that hormones and IFN-τ increased the expression of CRIM1 in goat endometrial epithelial cells (EECs). Knockdown of CRIM1 via specific shRNA hindered cell proliferation, cell adhesion and prostaglandins (PGs) secretion and thus derailed normal endometrial receptivity. We further confirmed that receptivity defect phenotypes due to CRIM1 interference were restored by ATG7 overexpression in EECs while a loss of ATG7 further impaired receptivity phenotypes. Moreover, our results showed that changing the expression of ATG7 affected the reactive oxygen species (ROS) production. Moreover, mR-143-5p was shown to be a potential upstream factor of CRIM1-regulated endometrial receptivity in EECs. Overall, these results suggest that CRIM1, as the downstream target of miR-143-5p, has effects on ATG7-dependent autophagy, regulating cell proliferation, cell adhesion and PG secretion, and provides a new target for the diagnosis and treatment of early pregnancy failure and for improving the success rates of artificial reproduction.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas/fisiologia , Implantação do Embrião/genética , Endométrio/fisiologia , Cabras/fisiologia , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Autofagia/fisiologia , Proteína 7 Relacionada à Autofagia/deficiência , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/fisiologia , Receptores de Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Receptores de Proteínas Morfogenéticas Ósseas/genética , Adesão Celular , Proliferação de Células , Células Cultivadas , Implantação do Embrião/fisiologia , Endométrio/citologia , Endométrio/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Estradiol/farmacologia , Feminino , Técnicas de Silenciamento de Genes , Cabras/genética , Interferon Tipo I/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos , Gravidez , Proteínas da Gravidez/farmacologia , Progesterona/farmacologia , Prostaglandinas/metabolismo , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima
14.
J Cell Biol ; 220(7)2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33978709

RESUMO

The ER tethers tightly to mitochondria and the mitochondrial protein FUNDC1 recruits Drp1 to ER-mitochondria contact sites, subsequently facilitating mitochondrial fission and preventing mitochondria from undergoing hypoxic stress. However, the mechanisms by which the ER modulates hypoxia-induced mitochondrial fission are poorly understood. Here, we show that USP19, an ER-resident deubiquitinase, accumulates at ER-mitochondria contact sites under hypoxia and promotes hypoxia-induced mitochondrial division. In response to hypoxia, USP19 binds to and deubiquitinates FUNDC1 at ER-mitochondria contact sites, which facilitates Drp1 oligomerization and Drp1 GTP-binding and hydrolysis activities, thereby promoting mitochondrial division. Our findings reveal a unique hypoxia response pathway mediated by an ER protein that regulates mitochondrial dynamics.


Assuntos
Dinaminas/genética , Endopeptidases/genética , Proteínas de Membrana/genética , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Retículo Endoplasmático/genética , Humanos , Hipóxia/genética , Dinâmica Mitocondrial/genética , Mitofagia/genética , Fosforilação/genética , Transdução de Sinais/genética
15.
BMJ Open ; 11(5): e044039, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33980521

RESUMO

OBJECTIVE: The association between ABO blood group and risk of liver cancer is unclear, although few studies have reported positive results. This study examined the relationship between ABO blood group and liver cancer in hepatitis B surface antigen (HBsAg)-positive individuals. DESIGN: A high-risk population-based cohort study. SETTING: The study was started in 2007 and closed in 2019; the number of observed person-years as obtained by ABO blood group. PARTICIPANTS: The study included 3663 individuals with positive HBsAg, including men aged 30-70 and women aged 40-70. OUTCOME MEASURES: The frequencies of ABO group in the cohort population and patients with liver cancer were calculated, respectively. χ2 test was used to compare differences, and the relative risk (95% CI) for development of liver cancer was evaluated. RESULTS: The frequency distribution of blood types A, B, O and AB was 1118 (30.52%), 1073 (29.29%), 1104 (30.14%) and 368 (10.05%), respectively, among 3663 cohort individuals. In the cohort, patients with liver cancer (n=336) were of the following frequencies: type A: 104 (30.95%); type B: 97 (28.87%); type O: 95 (28.27%); and type AB: 40 (11.90%). No significant difference was found between patients with liver cancer and other individuals. The annual incidence rate of liver cancer was 906.34 per 100 000 person-years, and for blood type A, B, O and AB the rates were 917.76, 893.78, 846.02 and 1093.43 per 100 000 person-years, respectively. The relative risk (95% CI) was 0.97 (0.74 to 1.29), 0.92 (0.70 to 1.22) and 1.19 (0.82 to 1.72) for blood types B, O and AB, respectively, compared with blood type A. CONCLUSION: There were no significant differences in the frequency distribution of ABO blood groups in patients with liver cancer within this high-risk cohort, which demonstrates lack of positive association between ABO blood group and risk of liver cancer.


Assuntos
Sistema ABO de Grupos Sanguíneos , Neoplasias Hepáticas , Estudos de Coortes , Feminino , Antígenos de Superfície da Hepatite B , Humanos , Neoplasias Hepáticas/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco
16.
Chem Res Toxicol ; 34(4): 1183-1196, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33793228

RESUMO

Outdoor air pollution, a spatially and temporally complex mixture, is a human carcinogen. However, ambient measurements may not reflect subject-level exposures, personal monitors do not assess internal dose, and spot assessments of urinary biomarkers may not recapitulate chronic exposures. Nucleophilic sites in serum albumin-particularly the free thiol at Cys34-form adducts with electrophiles. Due to the 4-week lifetime of albumin in circulation, accumulating adducts can serve as intermediate- to long-residence biomarkers of chronic exposure and implicate potential biological effects. Employing nanoflow liquid chromatography-high-resolution mass spectrometry (nLC-HRMS) and parallel reaction monitoring (PRM), we have developed and validated a novel targeted albumin adductomics platform capable of simultaneously monitoring dozens of Cys34 adducts per sample in only 2.5 µL of serum, with on-column limits of detection in the low-femtomolar range. Using this platform, we characterized the magnitude and impact of ambient outdoor air pollution exposures with three repeated measurements over 84 days in n = 26 nonsmoking women (n = 78 total samples) from Qidong, China, an area with a rising burden of lung cancer incidence. In concordance with seasonally rising ambient concentrations of NO2, SO2, and PM10 measured at stationary monitors, we observed elevations in concentrations of Cys34 adducts of benzoquinone (p < 0.05), benzene diol epoxide (BDE; p < 0.05), crotonaldehyde (p < 0.01), and oxidation (p < 0.001). Regression analysis revealed significant elevations in oxidation and BDE adduct concentrations of 300% to nearly 700% per doubling of ambient airborne pollutant levels (p < 0.05). Notably, the ratio of irreversibly oxidized to reduced Cys34 rose more than 3-fold during the 84-day period, revealing a dramatic perturbation of serum redox balance and potentially serving as a portent of increased pollution-related mortality risk. Our targeted albumin adductomics assay represents a novel and flexible approach for sensitive and multiplexed internal dosimetry of environmental exposures, providing a new strategy for personalized biomonitoring and prevention.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Biológico , Carcinógenos/análise , Albumina Sérica/análise , Humanos , Estrutura Molecular
17.
Biomed Res Int ; 2021: 5529431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33898623

RESUMO

Purpose: Postischemic inflammation induces angiogenesis, while platelet P2Y12 inhibitors can alleviate this inflammation. Therefore, we studied the potential effects of P2Y12 inhibitor, ticagrelor, on angiogenesis in a mouse model of hindlimb ischemia. Methods: Laser Doppler perfusion imaging and capillary density measurement were used for angiogenesis quantified. Immunofluorescence was used to detect the level of CD31. The mice muscle was harvested for enzyme-linked immunosorbent (ELISA) assay of interleukin- (IL) 10 activity and Western blot determination of vascular endothelial growth factor (VEGF) production. Results: Ischemic hindlimb angiogenesis was sharply decreased in IL-10+/+ mice than IL-10-/- mice. Ticagrelor inhibited angiogenesis and blood reperfusion recovery significantly elevated the levels of IL-10 and decreased the expression of VEGF in the IL-10+/+ mouse ischemic hindlimb, which were abolished in IL-10-deficient (IL-10-/-) C57BL/6J mice. Conclusion: The study underscores that the effect of ticagrelor antiangiogenic function is related with the higher IL-10 expression.


Assuntos
Indutores da Angiogênese/farmacologia , Membro Posterior/irrigação sanguínea , Isquemia/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Receptores Purinérgicos P2Y12/metabolismo , Animais , Capilares/patologia , Interleucina-10/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Músculos/metabolismo , Perfusão , Ticagrelor/farmacologia , Fatores de Crescimento do Endotélio Vascular/metabolismo
18.
Acta Pharmacol Sin ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33927360

RESUMO

Individual differences in the development of uncontrollable fear in response to traumatic stressors have been observed in clinic, but the underlying mechanisms remain unknown. In the present study we first conducted a meta-analysis of published clinical data and found that malondialdehyde, an oxidative stress biomarker, was significantly elevated in the blood of patients with fear-related anxiety disorders. We then carried out experimental study in rats subjected to fear conditioning. We showed that reestablishing redox homeostasis in basolateral amygdale (BLA) after exposure to fear stressors determined the capacity of learned fear inhibition. Intra-BLA infusion of buthionine sulfoximine (BSO) to deplete the most important endogenous antioxidant glutathione (GSH) blocked fear extinction, whereas intra-BLA infusion of dithiothreitol or N-acetylcysteine (a precursor of GSH) facilitated extinction. In electrophysiological studies conducted on transverse slices, we showed that fear stressors induced redox-dependent inhibition of NMDAR-mediated synaptic function, which was rescued by extinction learning or reducing agents. Our results reveal a novel pharmacological strategy for reversing impaired fear inhibition and highlight the role of GSH in the treatment of psychiatric disorders.

19.
Sensors (Basel) ; 21(7)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805537

RESUMO

Acoustic emission (AE) monitoring has become an optional technology to quantify slope deformation. However, there are still challenges in developing generic AE interpretation strategies. Dynamics and kinematics models are two physical methods for analysing slope stability, which appear to improve the interpretability of AE monitoring data. The aim of this study is to explore the change patterns and interrelations of dynamics, kinematics, and AE measurements using a model test and physical analysis, to further understand the development process of a progressive landslide. A model test is designed based on the kinematics model of landslide three-stage deformation. An equation between factor of safety (FoS) and thrust is proposed based on the mechanical model of a landslide test. There is a clear correspondence between the displacement and inverse velocity during the deformation-controlled process. Relationships are uncovered between the thrust and FoS as well as the thrust and acceleration. As a characteristic parameter of AE, ring down count (RDC) is able to quantify the deformation process of the soil slope. Moreover, acceleration and RDC can reflect the sudden change of the slope state and, hence, can be effective indicators for the early warning in a progressive landslide.

20.
ESC Heart Fail ; 8(3): 2070-2078, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33689236

RESUMO

AIMS: There is paucity of clinical data comparing continuous infusion (CI) with bolus injection (BI) of intravenous loop diuretics in patients with acute decompensated heart failure (ADHF) and chronic renal dysfunction. This study aimed to compare the efficacy and safety of CI versus BI intravenous furosemide administration in patients with ADHF and moderate chronic renal insufficiency. METHODS AND RESULTS: Acute decompensated heart failure and moderate chronic renal insufficiency [with estimated glomerular filtration rate (eGFR) 15.0-44.9 mL/min/1.73 m2 ] were randomized to start intravenous furosemide by BI or by a 6 h CI. End points included freedom from congestion at 72 h, the degree of dyspnoea assessed using the 0-10 Borg's category ratio scale, net daily urine output, weight loss during the study, length of hospital stay, total urinary sodium excretion, and development of acute kidney injury or electrolyte disturbance. After 72 h of treatment, the rate of the primary endpoint of freedom from congestion in the CI group was significantly higher than that in the BI group (69.05% vs. 43.59%, P = 0.02). The modified Borg scale indicated patients in the CI group had lower dyspnoea score than those in the BI group at 48 h (4.29 ± 1.23 vs. 5.97 ± 1.56; P = 0.02) and 72 h (1.15 ± 0.35 vs. 2.66 ± 0.83; P = 0.003). There were other significant differences favouring the CI group with regard to net urine output at 72 h (5145.98 ± 621.37 mL vs. 3755.95 ± 456.93 mL; P = 0.007), the mean body weight loss (4.72 ± 1.01 kg vs. 3.53 ± 0.73 kg; P = 0.02) and the total urinary sodium excretion (385.05 ± 38.15 vs. 320.33 ± 37.67; P = 0.02). The length of hospitalization in the CI group was significantly shorter than that in the BI group (10.36 ± 4.20 days vs. 15.68 ± 6.15 days; P = 0.02). No significant differences were observed between groups in the frequency of acute kidney injury, tinnitus, electrolyte disturbance or mortality. CONCLUSIONS: Continuous intravenous infusion of furosemide resulted in significantly greater diuresis than bolus administration of an equal dose in patients with moderate chronic renal insufficiency and ADHF, while no differences emerged in terms of side effects or mortality.


Assuntos
Injúria Renal Aguda , Insuficiência Cardíaca , Diuréticos , Furosemida , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Inibidores de Simportadores de Cloreto de Sódio e Potássio
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