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1.
Bioresour Technol ; 343: 126062, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34601025

RESUMO

This study evaluated the performance of spent coffee biochar (SCBC)/granular activated carbon (GAC) activating peroxymonosulfate (PMS) and peroxydisulfate (PDS) for urea degradation in reclaimed water used for ultrapure water production. Results showed that catalyst and oxidant wielded a great influence on urea removal. Of them, the GAC-PMS system could completely remove urea at the least oxidant (1 g/L) and catalyst dosage (0.2 g/L). GAC activating PMS mainly depended on graphite C structure and minor oxygen functional groups. However, the amounts of urea removed by 600BC-PMS and 900BC-PMS were 57% and 70%, respectively. In the PDS system, the urea removal through GAC-PDS could reach 90%, which mainly depends on the graphite C structure of GAC. Using the same conditions, the urea removal of 900BC-PDS was similar to GAC-PDS, so it has some potential as an alternative to commercial GAC.


Assuntos
Carvão Vegetal , Poluentes Químicos da Água , Café , Peróxidos , Ureia , Água , Poluentes Químicos da Água/análise
2.
Chemosphere ; 288(Pt 1): 132459, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34619254

RESUMO

The demand for ultrapure water (UPW) in the semiconductor industry has increased in recent years, while the idea to use reclaimed water instead of tap water for UPW production has also attracted more attention. However, since urea concentration in reclaimed water is higher than that in tap water, UPW production has not been efficient. To resolve this problem, this study aims to develop a new spent coffee grounds based biochar (SCG-BC)/persulfate catalytic system as a pretreatment unit. The objective is to enhance urea removal from reclaimed water so that UPW production is more effective. In this study, the biochar used was prepared from spent coffee grounds with detailed characterization. Results strongly suggested that the urea removed by SCG-BC/persulfate catalytic system was very encouraging (up to 73%). The best possible dosages for SCG-BC and persulfate for urea removal were 0.2 and 2.0 g L-1, respectively. Furthermore, this system could remove urea effectively in a wide range of pH (3-10). Moreover, the characterizations of SCG-BC (graphite C, defective edges and functional groups, i.e. -OH, CO, carboxyl C-O) helped to activate persulfate in the catalytic process. OH• and SO4• - were all involved in this process, while the SO4• - was the main radical for urea degradation.


Assuntos
Café , Poluentes Químicos da Água , Carvão Vegetal , Ureia , Água , Poluentes Químicos da Água/análise
3.
Sci Total Environ ; : 152123, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34864031

RESUMO

To tackle membrane fouling and limited removals of pollutants (nutrients and emerging pollutants) that hinder the wide applications of membrane bioreactor (MBR), attached growth MBR (AGMBR) combining MBR and attached growth process has been developed. This review comprehensively presents the up-to-date developments of media used in both aerobic and anaerobic AGMBRs for treating wastewaters containing conventional and emerging pollutants. It also elaborates the properties of different media, characteristics of attached biomass, and their contributions to AGMBR performance. Conventional media, such as biological activated carbon and polymeric carriers, induce formation of aerobic, anoxic and/or anaerobic microenvironment, increase specific surface area or porous space for biomass retention, improve microbial activities, and enrich diverse microorganisms, thereby enhancing pollutants removal. Meanwhile, new media (i.e. biochar, bioaugmented carriers with selected strain/mixed cultures) do not only eliminate conventional pollutants (i.e. high concentration of nitrogen, etc.), but also effectively remove emerging pollutants (i.e. micropollutants, nonylphenol, adsorbable organic halogens, etc.) by forming thick and dense biofilm, creating anoxic/anaerobic microenvironments inside the media, enriching special functional microorganisms and increasing activity of microorganisms. Additionally, media can improve sludge characteristics (i.e. less extracellular polymeric substances and soluble microbial products, larger floc size, better sludge settleability, etc.), alleviating membrane fouling. Future studies need to focus on the development and applications of more new functional media in removing wider spectrum of emerging pollutants and enhancing biogas generation, as well as scale-up of lab-scale AGMBRs to pilot or full-scale AGMBRs.

4.
Biology (Basel) ; 10(11)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34827119

RESUMO

The development of crop cultivars with high nitrogen use efficiency (NUE) under low-N fertilizer inputs is imperative for sustainable agriculture. However, there has been little research on the molecular mechanisms underlying enhanced resilience to low N in high-NUE plants. The comparison of the transcriptional responses of genotypes contrasting for NUE will facilitate an understanding of the key molecular mechanism of wheat resilience to low-N stress. In the current study, the RNA sequencing (RNA-seq) technique was employed to investigate the genotypic difference in response to N deficiency between two wheat NILs (1Y, high-NUE, and 1W, low-NUE). In our research, high- and low-NUE wheat NILs showed different patterns of gene expression under N-deficient conditions, and these N-responsive genes were classified into two major classes, including "frontloaded genes" and "relatively upregulated genes". In total, 103 and 45 genes were identified as frontloaded genes in high-NUE and low-NUE wheat, respectively. In summary, our study might provide potential directions for further understanding the molecular mechanism of high-NUE genotypes adapting to low-N stress.

5.
Proc Natl Acad Sci U S A ; 118(47)2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34782454

RESUMO

Cholesterol biosynthetic intermediates, such as lanosterol and desmosterol, are emergent immune regulators of macrophages in response to inflammatory stimuli or lipid overloading, respectively. However, the participation of these sterols in regulating macrophage functions in the physiological context of atherosclerosis, an inflammatory disease driven by the accumulation of cholesterol-laden macrophages in the artery wall, has remained elusive. Here, we report that desmosterol, the most abundant cholesterol biosynthetic intermediate in human coronary artery lesions, plays an essential role during atherogenesis, serving as a key molecule integrating cholesterol homeostasis and immune responses in macrophages. Depletion of desmosterol in myeloid cells by overexpression of 3ß-hydroxysterol Δ24-reductase (DHCR24), the enzyme that catalyzes conversion of desmosterol to cholesterol, promotes the progression of atherosclerosis. Single-cell transcriptomics in isolated CD45+CD11b+ cells from atherosclerotic plaques demonstrate that depletion of desmosterol increases interferon responses and attenuates the expression of antiinflammatory macrophage markers. Lipidomic and transcriptomic analysis of in vivo macrophage foam cells demonstrate that desmosterol is a major endogenous liver X receptor (LXR) ligand involved in LXR/retinoid X receptor (RXR) activation and thus macrophage foam cell formation. Decreased desmosterol accumulation in mitochondria promotes macrophage mitochondrial reactive oxygen species production and NLR family pyrin domain containing 3 (NLRP3)-dependent inflammasome activation. Deficiency of NLRP3 or apoptosis-associated speck-like protein containing a CARD (ASC) rescues the increased inflammasome activity and atherogenesis observed in desmosterol-depleted macrophages. Altogether, these findings underscore the critical function of desmosterol in the atherosclerotic plaque to dampen inflammation by integrating with macrophage cholesterol metabolism and inflammatory activation and protecting from disease progression.

6.
Natl Sci Rev ; 8(2): nwaa150, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34691570

RESUMO

The dendrite growth of Li anodes severely degrades the performance of lithium-oxygen (Li-O2) batteries. Recently, hybrid solid electrolyte (HSE) has been regarded as one of the most promising routes to tackle this problem. However, before this is realized, the HSE needs to simultaneously satisfy contradictory requirements of high modulus and even, flexible contact with Li anode, while ensuring uniform Li+ distribution. To tackle this complex dilemma, here, an HSE with rigid Li1.5Al0.5Ge1.5(PO4)3 (LAGP) core@ultrathin flexible poly (vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) shell interface has been developed. The introduced large amount of nanometer-sized LAGP cores can not only act as structural enhancer to achieve high Young's modulus but can also construct Li+ diffusion network to homogenize Li+ distribution. The ultrathin flexible PVDF-HFP shell provides soft and stable contact between the rigid core and Li metal without affecting the Li+ distribution, meanwhile suppressing the reduction of LAGP induced by direct contact with Li metal. Thanks to these advantages, this ingenious HSE with ultra-high Young's modulus of 25 GPa endows dendrite-free Li deposition even at a deposition capacity of 23.6 mAh. Moreover, with the successful inhibition of Li dendrites, the HSE-based quasi-solid-state Li-O2 battery delivers a long cycling stability of 146 cycles, which is more than three times that of gel polymer electrolyte-based Li-O2 battery. This new insight may serve as a starting point for further designing of HSE in Li-O2 batteries, and can also be extended to various battery systems such as sodium-oxygen batteries.

7.
Angew Chem Int Ed Engl ; 60(51): 26806-26812, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34582084

RESUMO

The performance of electrode material is correlated with the choice of electrolyte, however, how the solvation has significant impact on electrochemical behavior is underdeveloped. Herein, N-heteropentacenequinone (TAPQ) is investigated to reveal the solvation effect on the performance of sodium-ion batteries in different electrolyte environment. TAPQ cycled in diglyme-based electrolyte exhibits superior electrochemical performance, but experiences a rapid capacity fading in carbonate-based electrolyte. The function of solvation effect is mainly embodied in two aspects: one is the stabilization of anion intermediate via the compatibility of electrode and electrolyte, the other is the interfacial electrochemical characteristics influenced by solvation sheath structure. By revealing the failure mechanism, this work presents an avenue for better understanding electrochemical behavior and enhancing performance from the angle of solvation effect.

8.
J Pharm Pharmacol ; 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34387671

RESUMO

OBJECTIVES: Platycarya strobilacea Sieb. et Zucc. is the dry infructescence of P. strobilacea, a Juglandaceae plant and is a traditional Chinese medicine with great development potential and utilization value. This study summarizes the research progress on the traditional uses, botany, phytochemistry, extraction methods, pharmacology and toxicology of Platycarya strobilacea Sieb. et Zucc., and provides potential therapeutic uses and drug development prospects for this plant. KEY FINDINGS: Phytochemical studies showed that this plant mainly contains volatile constituents, phenols, terpenoids and a carbohydrate. The pharmacological activity of Platycarya strobilacea Sieb. et Zucc. includes antibacterial and anti-inflammatory effects, anti-tumour effects and antioxidant effects. This plant is especially effective in the treatment of allergic rhinitis and chronic sinusitis. SUMMARY: In this review, the phytochemistry and pharmacological effects of Platycarya strobilacea Sieb. et Zucc. are described in detail, which will have guiding significance for the future development of this drug.

9.
Medicine (Baltimore) ; 100(32): e26923, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397935

RESUMO

BACKGROUND: The function of Angipoietin-2 (Agn2) in osteosarcoma has not been fully explored and exists controversial. Therefore, we conducted a meta-analysis to investigate the role of Agn2 in the prognosis of osteosarcoma. In addition, bioinformatics analysis was carried out to reveal the mechanism and related pathways of Agn2 in osteosarcoma. METHODS: Literature search was operated on databases up to July 2021, including PubMed, Web of Science, China National Knowledge Infrastructure, China Biology Medicine disc, and Wan Fang Data. The relation between Agn2 expression and survival outcome was estimated by hazard ratio and 95% confidence interval. Meta-analysis was performed on the Stata 16.0. Being obtained from The Cancer Genome Atlas, the original data were used to further verify the prognostic role of Agn2 in osteosarcoma. Gene set enrichment analysis was applied to predict the potential mechanism of Agn2. The correlation between Agn2 and osteosarcoma immune infiltration was analyzed by TIMER database. RESULTS: The results of this meta-analysis would be submitted to peer-reviewed journals for publication. CONCLUSION: This study will provide evidence for the exploration of the relationship between Agn2 and the prognosis of osteosarcoma and its mechanism. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results will be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/GWQ53.


Assuntos
Angiopoietina-2/genética , Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica , Osteossarcoma/genética , Angiopoietina-2/biossíntese , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Neoplasias Ósseas/metabolismo , Humanos , Osteossarcoma/metabolismo
10.
Biology (Basel) ; 10(8)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34440020

RESUMO

Nitrogen (N) is an essential nutrient element for crop productivity. Unfortunately, the nitrogen use efficiency (NUE) of crop plants gradually decreases with the increase of the N application rate. Nevertheless, little has been known about the molecular mechanisms of differences in NUE among genotypes of wheat. In this study, we used RNA-Sequencing (RNA-Seq) to compare the transcriptome profiling of flag leaves at the stage of anthesis in wheat NILs (1Y, high-NUE, and 1W, low-NUE) under normal nitrogen conditions (300 kg N ha-1, corresponding to 1.6 g N pot-1). We identified 7023 DEGs (4738 upregulated and 2285 downregulated) in the comparison between lines 1Y and 1W. The responses of 1Y and 1W to normal N differed in the transcriptional regulatory mechanisms. Several genes belonging to the GS and GOGAT gene families were upregulated in 1Y compared with 1W, and the enhanced carbon metabolism might lead 1Y to produce more C skeletons, metabolic energy, and reductants for nitrogen metabolism. A subset of transcription factors (TFs) family members, such as ERF, WRKY, NAC, and MYB, were also identified. Collectively, these identified candidate genes provided new information for a further understanding of the genotypic difference in NUE.

11.
Sci Total Environ ; 793: 148598, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34328983

RESUMO

This study investigated the effect of CaO2 pretreatment on sulfonamide antibiotics (SMs) remediation by Chlorella sp. Results showed that a CaO2 dose ranging from 0.05 to 0.1 g/g biomass was the best and led to higher SMs removal efficacy 5-10% higher than the control. The contributions made by cometabolism and CaO2 in SMs remediation were very similar. Bioassimilation could remove 24% of sulfadiazine (SDZ) and sulfamethazine (SMZ), and accounted for 38% of sulfamethoxazole (SMX) remediation. Pretreatment by CaO2 wielded a positive effect on microalgae. The extracellular polymeric substances (EPS) level of the CaO2 pretreatment microalgae was three times higher when subjected to non-pretreatment. For the long-term, pretreatment microalgae removed SMs 10-20% more than the non-pretreatment microalgae. Protein fractions of EPS in continuous operation produced up to 90 mg/L for cometabolism. For bioassimilation, SMX intensity of the pretreatment samples was 160-fold less than the non-treatment one. It indicated the CaO2 pretreatment has enhanced the biochemical function of the intracellular environment of microalgae. Peroxidase enzyme involved positively in the cometabolism and degradation of SMs to several metabolites including ring cleavage, hydroxylation and pterin-related conjugation.


Assuntos
Chlorella , Microalgas , Antibacterianos , Peróxidos , Sulfonamidas
12.
J Clin Invest ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255741

RESUMO

Hepatic uptake and biosynthesis of fatty acids (FA), as well as the partitioning of FA into oxidative, storage, and secretory pathways are tightly regulated processes. Dysregulation of one or more of these processes can promote excess hepatic lipid accumulation, ultimately leading to systemic metabolic dysfunction. Angiopoietin-like-4 (ANGPTL4) is a secretory protein that inhibits lipoprotein lipase (LPL) and modulates triacylglycerol (TAG) homeostasis. To understand the role of ANGPTL4 in liver lipid metabolism under normal and high-fat fed conditions, we generated hepatocyte specific Angptl4 mutant mice (Hmut). Using metabolic turnover studies, we demonstrate that hepatic Angptl4 deficiency facilitates catabolism of TAG-rich lipoprotein (TRL) remnants in the liver via increased hepatic lipase (HL) activity, which results in a significant reduction in circulating TAG and cholesterol levels. Consequently, depletion of hepatocyte Angptl4 protects against diet-induce obesity, glucose intolerance, liver steatosis, and atherogenesis. Mechanistically, we demonstrate that loss of Angptl4 in hepatocytes promotes FA uptake which results in increased FA oxidation, ROS production, and AMPK activation. Finally, we demonstrate the utility of a targeted pharmacologic therapy that specifically inhibits Angptl4 gene expression in the liver and protects against diet-induced obesity, dyslipidemia, glucose intolerance, and liver damage, which likely occurs via increased HL activity. Notably, this novel inhibition strategy does not cause any of the deleterious effects previously observed with neutralizing antibodies.

13.
Sci Total Environ ; 795: 148755, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34246151

RESUMO

This study investigates the performance of microbial fuel cells (MFC) for on-line monitoring ammonium (NH4+-N) in municipal wastewater. A double chamber microbial fuel cell (MFC) was established in a continuous mode under different influent ammonium concentrations ranging from 5 to 40 mg L-1. Results indicated that excess ammonium would inhibit the activity of electrogenic bacteria in the anode chamber and consequently affect electricity production. An inversely linear relationship between concentration and voltage generation was obtained with coefficient R2 0.99 and the MFC could detect up to 40 mg L-1 of NH4+-N. Notably, no further decline was observed in voltage output and there was in fact a further increase in ammonia concentration (>40 mg L-1). The stability and high accuracy of ammonium-based MFC biosensors exposed competitive results compared to traditional analytical tools, confirming the biosensor's reliability. Furthermore, pH 7.0; R 1000 Ω and HRT of 24 h are the best possible conditions for the MFC biosensor for monitoring ammonium. The simplicity in design and operation makes the biosensor more realistic for practical application.


Assuntos
Compostos de Amônio , Fontes de Energia Bioelétrica , Técnicas Biossensoriais , Eletricidade , Eletrodos , Nitrogênio , Reprodutibilidade dos Testes , Águas Residuárias
14.
Elife ; 102021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34151773

RESUMO

Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome, and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.


Assuntos
Infecções por Coronavirus/dietoterapia , Dieta Cetogênica/métodos , Vírus da Hepatite Murina/patogenicidade , Fatores Etários , Envelhecimento , Animais , COVID-19/dietoterapia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/mortalidade , Modelos Animais de Doenças , Glicólise , Humanos , Inflamassomos/metabolismo , Corpos Cetônicos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vírus da Hepatite Murina/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , SARS-CoV-2
15.
Sci Total Environ ; 785: 147254, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933770

RESUMO

The recent and vigorous developments in semiconductor technology strictly request better quality and large quantity of ultrapure water (UPW) for their production. It is crucial to secure a large amount of raw water for the future development of UPW production. Using reclaimed water as alternative raw water source to produce UPW is therefore considered the feasible trend and solution for sustainable use of water resources towards a common future practice in UPW production. The challenge of using reclaimed water is due to its higher content of organic pollutants, especially small molecule organic pollutants such as urea, which are difficult to remove through traditional UPW production process. Consequently, improving the existing UPW production process to meet the water standard desired in the semiconductor industry is essential. This paper reviewed the current traditional processes for removing organic matters in UPW production, including ion-exchange (IX) adsorption, granular activated carbon (GAC) adsorption, reverse osmosis (RO) and ultraviolet (UV) irradiation. The potential problems in the actual UPW production process were identified when using reclaimed water as raw water source. A new strategy of applying the advanced oxidation process (AOPs) to UPW production as a supplementary unit to guarantee UPW quality was proposed. Its feasibility and research focus were then analyzed and discussed in obtaining a new solution for a future development of the UPW production process.

16.
J Hepatol ; 75(3): 647-658, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33991637

RESUMO

BACKGROUND AND AIMS: COVID-19 is associated with liver injury and elevated interleukin-6 (IL-6). We hypothesized that IL-6 trans-signaling in liver sinusoidal endothelial cells (LSECs) leads to endotheliopathy (a proinflammatory and procoagulant state) and liver injury in COVID-19. METHODS: Coagulopathy, endotheliopathy, and alanine aminotransferase (ALT) were retrospectively analyzed in a subset (n = 68), followed by a larger cohort (n = 3,780) of patients with COVID-19. Liver histology from 43 patients with COVID-19 was analyzed for endotheliopathy and its relationship to liver injury. Primary human LSECs were used to establish the IL-6 trans-signaling mechanism. RESULTS: Factor VIII, fibrinogen, D-dimer, von Willebrand factor (vWF) activity/antigen (biomarkers of coagulopathy/endotheliopathy) were significantly elevated in patients with COVID-19 and liver injury (elevated ALT). IL-6 positively correlated with vWF antigen (p = 0.02), factor VIII activity (p = 0.02), and D-dimer (p <0.0001). On liver histology, patients with COVID-19 and elevated ALT had significantly increased vWF and platelet staining, supporting a link between liver injury, coagulopathy, and endotheliopathy. Intralobular neutrophils positively correlated with platelet (p <0.0001) and vWF (p <0.01) staining, and IL-6 levels positively correlated with vWF staining (p <0.01). IL-6 trans-signaling leads to increased expression of procoagulant (factor VIII, vWF) and proinflammatory factors, increased cell surface vWF (p <0.01), and increased platelet attachment in LSECs. These effects were blocked by soluble glycoprotein 130 (IL-6 trans-signaling inhibitor), the JAK inhibitor ruxolitinib, and STAT1/3 small-interfering RNA knockdown. Hepatocyte fibrinogen expression was increased by the supernatant of LSECs subjected to IL-6 trans-signaling. CONCLUSION: IL-6 trans-signaling drives the coagulopathy and hepatic endotheliopathy associated with COVID-19 and could be a possible mechanism behind liver injury in these patients. LAY SUMMARY: Patients with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection often have liver injury, but why this occurs remains unknown. High levels of interleukin-6 (IL-6) and its circulating receptor, which form a complex to induce inflammatory signals, have been observed in patients with COVID-19. This paper demonstrates that the IL-6 signaling complex causes harmful changes to liver sinusoidal endothelial cells and may promote blood clotting and contribute to liver injury.


Assuntos
COVID-19/complicações , Células Endoteliais/patologia , Interleucina-6/fisiologia , Hepatopatias/etiologia , SARS-CoV-2 , Adulto , Transtornos da Coagulação Sanguínea/etiologia , Fibrinogênio/análise , Humanos , Interleucina-6/sangue , Janus Quinase 1/metabolismo , Nitrilas , Pirazóis/farmacologia , Pirimidinas , Estudos Retrospectivos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/fisiologia , Fator de von Willebrand/análise
17.
JCI Insight ; 6(12)2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34003795

RESUMO

Epigenetic modifications of the genome, including DNA methylation, histone methylation/acetylation, and noncoding RNAs, have been reported to play a fundamental role in regulating immune response during the progression of atherosclerosis. SETDB2 is a member of the KMT1 family of lysine methyltransferases, and members of this family typically methylate histone H3 Lys9 (H3K9), an epigenetic mark associated with gene silencing. Previous studies have shown that SETDB2 is involved in innate and adaptive immunity, the proinflammatory response, and hepatic lipid metabolism. Here, we report that expression of SETDB2 is markedly upregulated in human and murine atherosclerotic lesions. Upregulation of SETDB2 was observed in proinflammatory M1 but not antiinflammatory M2 macrophages. Notably, we found that genetic deletion of SETDB2 in hematopoietic cells promoted vascular inflammation and enhanced the progression of atherosclerosis in BM transfer studies in Ldlr-knockout mice. Single-cell RNA-Seq analysis in isolated CD45+ cells from atherosclerotic plaques from mice transplanted with SETDB2-deficient BM revealed a significant increase in monocyte population and enhanced expression of genes involved in inflammation and myeloid cell recruitment. Additionally, we found that loss of SETDB2 in hematopoietic cells was associated with macrophage accumulation in atherosclerotic lesions and attenuated efferocytosis. Overall, these studies identify SETDB2 as an important inflammatory cell regulator that controls macrophage activation in atherosclerotic plaques.

18.
Proc Natl Acad Sci U S A ; 118(22)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34035164

RESUMO

Inducible regulatory T (iTreg) cells play a crucial role in immune suppression and are important for the maintenance of immune homeostasis. Mounting evidence has demonstrated connections between iTreg differentiation and metabolic reprogramming, especially rewiring in fatty acid oxidation (FAO). Previous work showed that butyrate, a specific type of short-chain fatty acid (SCFA) readily produced from fiber-rich diets through microbial fermentation, was critical for the maintenance of intestinal homeostasis and capable of promoting iTreg generation by up-regulating histone acetylation for gene expression as an HDAC inhibitor. Here, we revealed that butyrate could also accelerate FAO to facilitate iTreg differentiation. Moreover, butyrate was converted, by acyl-CoA synthetase short-chain family member 2 (ACSS2), into butyryl-CoA (BCoA), which up-regulated CPT1A activity through antagonizing the association of malonyl-CoA (MCoA), the best known metabolic intermediate inhibiting CPT1A, to promote FAO and thereby iTreg differentiation. Mutation of CPT1A at Arg243, a reported amino acid required for MCoA association, impaired both MCoA and BCoA binding, indicating that Arg243 is probably the responsible site for MCoA and BCoA association. Furthermore, blocking BCoA formation by ACSS2 inhibitor compromised butyrate-mediated iTreg generation and mitigation of mouse colitis. Together, we unveil a previously unappreciated role for butyrate in iTreg differentiation and illustrate butyrate-BCoA-CPT1A axis for the regulation of immune homeostasis.


Assuntos
Butiratos/imunologia , Carnitina O-Palmitoiltransferase/imunologia , Diferenciação Celular/imunologia , Ácidos Graxos/imunologia , Microbioma Gastrointestinal/imunologia , Linfócitos T Reguladores/imunologia , Acetato-CoA Ligase/imunologia , Animais , Regulação Enzimológica da Expressão Gênica/imunologia , Camundongos , Oxirredução , Regulação para Cima/imunologia
19.
Acc Chem Res ; 54(3): 632-641, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33449629

RESUMO

ConspectusIt is a permanent issue for modern society to develop high-energy-density, low-cost, and safe batteries to promote technological innovation and revolutionize the human lifestyle. However, the current popular Li-ion batteries are approaching their ceiling in energy density, and thus other battery systems with more power need to be proposed and studied to guide this revolution. Lithium-air batteries are among the candidates for next-generation batteries because of their high energy density (3500 Wh/kg). The past 20 years have witnessed rapid developments of lithium-air batteries in electrochemistry and material engineering with scientists' collaboration from all over the world. Despite these advances, the investigation on Li-air batteries is still in its infancy, and many bottleneck problems, including fundamental and application difficulties, are waiting to be resolved. For the electrolyte, it is prone to be attacked by intermediates (LiO2, O2-, 1O2, O22-) and decomposed at high voltage, accompanying side reactions that will induce cathode passivation. For the lithium anode, it can be corroded severely by H2O and the side products, thus protection methods are urgently needed. As an integrated system, the realization of high-performance Li-air batteries requires the three components to be optimized simultaneously.In this Account, we are going to summarize our progress for optimizing Li-air batteries in the past decade, including air-electrochemistry and anode optimization. Air-electrochemistry involves the interactions among electrolytes, cathodes, and air, which is a complex issue to understand. The search for stable electrolytes is first introduced because at the early age of its development, the use of incompatible Li-ion battery electrolytes leads to some misunderstandings and troubles in the advances of Li-air batteries. After finding suitable electrolytes for Li-air batteries, the fundamental research in the reaction mechanism starts to boom, and the performance has achieved great improvement. Then, air electrode engineering is introduced to give a general design principle. Examples of carbon-based cathodes and all-metal cathodes are discussed. In addition, to understand the influence of air components on Li-air batteries, the electro-activity of N2 has been tested and the role of CO2 in Li-O2/CO2 has been refreshed. Following this, the strategies for anode optimization, including constructing artificial films, introducing hydrophobic polymer electrolytes, adding electrolyte additives, and designing alloy anodes, have been discussed. Finally, we advocate researchers in this field to conduct cell level optimizations and consider their application scenarios to promote the commercialization of Li-air batteries in the near future.

20.
Proc Natl Acad Sci U S A ; 118(5)2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33495342

RESUMO

miR-33 is an intronic microRNA within the gene encoding the SREBP2 transcription factor. Like its host gene, miR-33 has been shown to be an important regulator of lipid metabolism. Inhibition of miR-33 has been shown to promote cholesterol efflux in macrophages by targeting the cholesterol transporter ABCA1, thus reducing atherosclerotic plaque burden. Inhibition of miR-33 has also been shown to improve high-density lipoprotein (HDL) biogenesis in the liver and increase circulating HDL-C levels in both rodents and nonhuman primates. However, evaluating the extent to which these changes in HDL metabolism contribute to atherogenesis has been hindered by the obesity and metabolic dysfunction observed in whole-body miR-33-knockout mice. To determine the impact of hepatic miR-33 deficiency on obesity, metabolic function, and atherosclerosis, we have generated a conditional knockout mouse model that lacks miR-33 only in the liver. Characterization of this model demonstrates that loss of miR-33 in the liver does not lead to increased body weight or adiposity. Hepatic miR-33 deficiency actually improves regulation of glucose homeostasis and impedes the development of fibrosis and inflammation. We further demonstrate that hepatic miR-33 deficiency increases circulating HDL-C levels and reverse cholesterol transport capacity in mice fed a chow diet, but these changes are not sufficient to reduce atherosclerotic plaque size under hyperlipidemic conditions. By elucidating the role of miR-33 in the liver and the impact of hepatic miR-33 deficiency on obesity and atherosclerosis, this work will help inform ongoing efforts to develop novel targeted therapies against cardiometabolic diseases.


Assuntos
Aterosclerose/genética , Aterosclerose/fisiopatologia , Peso Corporal , Homeostase , Fígado/metabolismo , Fígado/fisiopatologia , MicroRNAs/metabolismo , Animais , Aterosclerose/sangue , Transporte Biológico , Tetracloreto de Carbono , Colesterol/metabolismo , Dieta Hiperlipídica , Comportamento Alimentar , Regulação da Expressão Gênica , Lipoproteínas HDL/sangue , Camundongos , MicroRNAs/genética , Obesidade/genética , Placa Aterosclerótica/genética , Placa Aterosclerótica/fisiopatologia
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