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Stimulator of IFN genes (STING) is a critical component of the innate immune system, playing an essential role in defending against DNA virus infections. However, the mechanisms governing basal STING regulation remain poorly understood. In this study, we demonstrate that the basal level of STING is critically maintained by hypoxia-inducible factor 1 (HIF-1)α through transcription. Under normal conditions, HIF-1α binds constitutively to the promoter region of STING, actively promoting its transcription. Knocking down HIF-1α results in a decrease in STING expression in multiple cell lines and zebrafish, which in turn reduces cellular responses to synthetic dsDNAs, including cell signaling and IFN production. Moreover, this decrease in STING levels leads to an increase in cellular susceptibility to DNA viruses HSV-1 and pseudorabies virus. These findings unveil a (to our knowledge) novel role of HIF-1α in maintaining basal STING levels and provide valuable insights into STING-mediated antiviral activities and associated diseases.
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Herpesvirus Humano 1 , Subunidad alfa del Factor 1 Inducible por Hipoxia , Inmunidad Innata , Proteínas de la Membrana , Pez Cebra , Animales , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/inmunología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Pez Cebra/inmunología , Herpesvirus Humano 1/inmunología , Herpesvirus Suido 1/inmunología , Inmunidad Celular , Regulación de la Expresión Génica/inmunología , Transducción de Señal/inmunología , Transcripción Genética/inmunología , Regiones Promotoras Genéticas , Células HEK293 , Línea Celular , Herpes Simple/inmunología , Seudorrabia/inmunologíaRESUMEN
BACKGROUND: Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. RESULTS: Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI. CONCLUSIONS: Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.
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Células Epiteliales Alveolares , Senescencia Celular , Ratones Endogámicos C57BL , Ratones Noqueados , Animales , Ratones , Senescencia Celular/efectos de la radiación , Senescencia Celular/fisiología , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/efectos de la radiación , Células Epiteliales Alveolares/patología , Lesión Pulmonar/metabolismo , Lesión Pulmonar/genética , Lesión Pulmonar/patología , Quinasa del Factor 2 de Elongación/metabolismo , Quinasa del Factor 2 de Elongación/genética , Humanos , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/patología , Traumatismos Experimentales por Radiación/genética , Células Cultivadas , MasculinoRESUMEN
The alkaline hydrolysis reaction of energetic materials is important and complex. With improved performance, AMK_Mountain was used to systematically study the alkaline hydrolysis of the nitrocellulose monomer and hexogen. The reaction pathways showed that the nitrocellulose monomer produces the nitrate anion and nitrite anion differently, while hexogen only produces the nitrite anion. Electronic structure results at the M06-2X/6-311G(d,p)/PCM(Pauling) level showed that the nitrocellulose monomer and hexogen have a similar pathway in their main energy-releasing process (nitrite anion production): with electrostatic attraction effects after proton transfer, the nitrite anion dissociates from the original structure with a low barrier. Moreover, during the alkaline hydrolysis of the nitrocellulose monomer, the metastable intermediates after proton transfer may be directly generated following transition states that, structurally, tend to produce nitrite anions "proximal" to the proton transfer site and produce nitrate anions "distal" to the proton transfer site. Electronic structure analysis showed that representative metastable intermediates revealed that the charge transfer caused by electrostatic attraction may be the direct cause of these reactions.
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Photoinitiators (PIs) are widely used in industrial polymerization processes. It has been reported that PIs are ubiquitous in indoor environments and that humans are exposed to PIs, but the occurrence of PIs in natural environments are rarely known. In the present study, 25 PIs, including 9 benzophenones (BZPs), 8 amine co-initiators (ACIs), 4 thioxanthones (TXs) and 4 phosphine oxides (POs), were analyzed in water and sediment samples collected from eight riverine outlets of the Pearl River Delta (PRD). Eighteen, 14, and 14 of the 25 target PIs were detected in water, suspended particulate matter (SPM) and sediment samples, respectively. The total concentrations of PIs in water, SPM, and sediment were in the ranges of 2.88â96.1 ng/L, 9.25â923 ng/g dry weight (dw), and 3.79â56.9 ng/g dw, with geometric mean concentration (GM) of 10.8 ng/L, 48.6 ng/g dw, and 17.1 ng/g dw, respectively. A significant linear regression was observed between the log partitioning coefficients (Kd) values of PIs and their log octanol water partition coefficient (Kow) values (R2 = 0.535, p < 0.05). The annual riverine input of PIs to the coastal waters of the South China Sea via eight main outlets of the PRD was estimated to be 4.12 × 103 kg/year, and the ∑BZPs, ∑ACIs, ∑TXs and ∑POs contributed to 1.96 × 103, 1.24 × 103, 89.6 and 830 kg/year, respectively. This is the first report of a systematic description of the occurrence characteristics of PIs exposure in water, SPM, and sediment. The environmental fate and risks of PIs in aquatic environments need further investigations.
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Ríos , Contaminantes Químicos del Agua , Humanos , Material Particulado/análisis , Agua , Óxidos , Aminas , Contaminantes Químicos del Agua/análisis , China , Benzofenonas , Monitoreo del Ambiente , Sedimentos GeológicosRESUMEN
An overall carbon-neutral CO2 electroreduction requires enhanced conversion efficiency and intensified functionality of CO2 -derived products to balance the carbon footprint from CO2 electroreduction against fixed CO2 . A liquid Sn cathode is herein introduced into electrochemical reduction of CO2 in molten salts to fabricate core-shell Sn-C spheres (Sn@C). An in situ generated Li2 SnO3 /C directs a self-template formation of Sn@C. Benefitting from the accelerated reaction kinetics from the liquid Sn cathode and the core-shell structure of Sn@C, a CO2 -fixation current efficiency higher than 84 % and a high reversible lithium-storage capacity of Sn@C are achieved. The versatility of this strategy is demonstrated by other low melting point metals, such as Zn and Bi. This process integrates energy-efficient CO2 conversion and template-free fabrication of value-added metal-carbon, achieving an overall carbon-neutral electrochemical reduction of CO2 .
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To improve the transition state (TS) search capability in complex chemical environments, AMK_Mountain is constructed based on the automated reaction mechanisms and kinetics (AutoMeKin) package. AMK_Mountain does not distinguish the reaction type of the TSs, which is beneficial to obtaining a more comprehensive reaction mechanism. In this study, the first step of the alkaline hydrolysis process of nitrocellulose monomer was adopted as the research object, and 730 possible initial configurations are constructed and 22 TSs pass high-level calculations. Energy difference and interaction region indicator reveal that the first step of alkaline hydrolysis is mainly the combination of nitrogen-containing functional groups at the positions α and ß with hydroxide anions, followed by the formation of nitric acid and the further loss of protons to form nitrate. Overall, in combination with GFN2 -xTB and ORCA, the AMK_Mountain technique provides a reliable method for the location of the TSs in complex environments.
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Nitrógeno , Colodión , Hidrólisis , CinéticaRESUMEN
BACKGROUND: Ionizing radiation (IR) can induce pulmonary fibrosis by causing epithelial mesenchymal transition (EMT), but the exact mechanism has not been elucidated. To investigate the molecular mechanism of how radiation induces pulmonary fibrosis by altering miR-486-3p content and thus inducing EMT. METHODS: The changes of miR-486-3p in cells after irradiation were detected by RT-qPCR. Western blot was used to detect the changes of cellular epithelial marker protein E-cadherin, mesenchymal marker N-cadherin, Vimentin and other proteins. The target gene of miR-486-3p was predicted by bioinformatics method and the binding site was verified by dual luciferase reporter system. In vivo experiments, adeno-associated virus (AAV) was used to carry miR-486-3p mimic to lung. Radiation-induced pulmonary fibrosis (RIPF) model was constructed by 25Gy60Co γ-rays. The structural changes of mouse lung were observed by HE and Masson staining. The expression of relevant proteins in mice was detected by immunohistochemistry. RESULTS: IR could decrease the miR-486-3p levels in vitro and in vivo, and that effect was closely correlated to the occurrence of RIPF. The expression of Snail, which induces EMT, was shown to be restrained by miR-486-3p. Therefore, knockdown of Snail blocked the EMT process induced by radiation or knockdown of miR-486-3p. In addition, the molecular mechanism underlying the IR-induced miRNA level reduction was explored. The increased in BCL6 could inhibit the formation of pri-miR-486-3p, thereby reducing the levels of miR-486-3p in the alveolar epithelial cells, which would otherwise promote EMT and contribute to RIPF by targeting Snail. CONCLUSION: IR can exacerbate RIPF in mice by activating the transcription factor BCL6, which inhibits the transcription of miR-486-3p and decreases its content, which in turn increases the content of the target gene slug and triggers EMT.
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Lesión Pulmonar , MicroARNs , Fibrosis Pulmonar , Animales , Transición Epitelial-Mesenquimal/fisiología , Pulmón/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-bcl-6/genética , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismoRESUMEN
Liquid crystal monomers (LCMs) are a class of emerging chemical pollutants; however, their release and gas-particle partitioning remain unknown. This study performed the first comprehensive analysis of a wide range of 93 LCMs in the ambient air of liquid crystal display (LCD) dismantling facilities. A total of 53 of the 93 target LCMs were detected in the air samples. The total atmospheric concentrations (gas and particles) of LCMs (∑LCMs) ranged from 68,800 to 385,000 (median of 204,000) pg/m3. Most LCMs were predominant in the gas phase, implying that their atmospheric transport would be mainly governed by gas rather than particle diffusions. Differential distribution patterns of the LCMs were observed due to their different atmospheric partitioning behaviors. Significant linear correlations were found between the gas-particle partitioning coefficients (KP) and the predicted subcooled vapor pressures (PL) and octanol-air partitioning coefficients (Koa) (p < 0.01). Compared with two equilibrium-state models, the experimentally observed particulate fractions (Ï) fit better with the predicted values based on the Li-Ma-Yang (L-M-Y) steady-state model, and Koa was identified as a key factor determining the atmospheric fate pathways of LCMs. Our study highlights another new class of chemicals significantly contributing to the chemical mixture in the ambient air at e-waste recycling areas.
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Contaminantes Atmosféricos , Residuos Electrónicos , Contaminantes Ambientales , Cristales Líquidos , Contaminantes Atmosféricos/análisis , Polvo/análisis , Residuos Electrónicos/análisis , Monitoreo del Ambiente , Contaminantes Ambientales/análisis , ReciclajeRESUMEN
Eight new aspulvinone analogues, aspulvins A-H (1-8) and aspulvinones D, M, O, and R (9-12), were isolated from cultures of the endophytic fungus Cladosporium sp. 7951. Detailed spectroscopic analyses were conducted to determine the structures of the new compounds. All isolates displayed different degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) at 10 µM. Notably, compounds 9, 10, and 12 showed potential SARS-CoV-2 Mpro inhibition with IC50 values of 10.3 ± 0.6, 9.4 ± 0.6, and 7.7 ± 0.6 µM, respectively. For all compounds except 3 and 4, the anti-inflammatory activity occurred by inhibiting the release of lactate dehydrogenase (LDH) with IC50 values ranging from 0.7 to 7.4 µM. Compound 10 showed the most potent anti-inflammatory activity by inhibiting Casp-1 cleavage, IL-1ß maturation, NLRP3 inflammasome activation, and pyroptosis. The findings reveal that the aspulvinone analogues 9, 10, and 12 could be promising candidates for coronavirus disease 2019 (COVID-19) treatment as they inhibit SARS-CoV-2 infection and reduce inflammatory reactions caused by SARS-CoV-2.
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Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Antiinflamatorios/farmacología , Antivirales/química , Cladosporium , HumanosRESUMEN
Spermidine is an important polyamine that can be used for the synthesis of various bioactive compounds in the food and pharmaceutical fields. In this study, a novel efficient whole-cell biocatalytic method with an NADPH self-sufficient cycle for spermidine biosynthesis was designed and constructed by co-expressing homoserine dehydrogenase (HSD), carboxyspermidine dehydrogenase (CASDH), and carboxyspermidine decarboxylase (CASDC). First, the enzyme-substrate coupled cofactor regeneration system from co-expression of NADP+-dependent ScHSD and NADPH-dependent AfCASDH exactly provides an efficient method for cofactor cycling. Second, we identified and characterized a putative CASDC with high decarboxylase activity from Butyrivibrio crossotus DSM 2876; it showed an optimum temperature of 35 °C and an optimum pH of 7.0, which make it better suited for the designed synthetic route. Subsequently, the protein expression level of each enzyme was optimized through the variation of the gene copy number, and a whole-cell catalyst with high catalytic efficiency was constructed successfully. Finally, a yield of 28.6 mM of spermidine was produced in a 1-L scale of E. coli whole-cell catalytic system with a 95.3% molar conversion rate after optimization of temperature, the ratio of catalyst-to-substrate, and the amount of NADP+, and a productivity of 0.17 g·L-1·h-1 was achieved. In summary, this novel pathway of constructing a whole-cell catalytic system from L-homoserine and putrescine could provide a green alternative method for the efficient synthesis of spermidine. KEY POINTS: ⢠A novel pathway for spermidine biosynthesis was developed in Escherichia coli. ⢠The enzyme-substrate coupled system provides an NADPH self-sufficient cycle. ⢠Spermidine with 28.6 mM was obtained using an optimized whole-cell system.
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Carboxiliasas , Espermidina , Escherichia coli , Homoserina , NADP , PutrescinaRESUMEN
One new ionone glycoside, named centrantheroside F (1), together with 9 known compounds (2-10), were isolated from the roots of Centranthera grandiflora. Their structures were determined by spectroscopic data analyses and comparing with the literature data. The absolute configuration of 1 was confirmed via 2 D NMR and electronic circular dichroism (ECD). All isolated compounds were evaluated for their inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production.
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Glicósidos Cardíacos , Glicósidos , Glicósidos/química , Estructura Molecular , Óxido Nítrico , Norisoprenoides , Raíces de Plantas/químicaRESUMEN
BACKGROUND: Carboxyspermidine (C-Spd) is a potentially valuable polyamine carboxylate compound and an excellent building block for spermidine synthesis, which is a critical polyamine with significant implications for human health and longevity. C-Spd can also be used to prepare multivalent cationic lipids and modify nucleoside probes. Because of these positive effects on human health, C-Spd is of considerable interest as a food additive and pharmaceutical target. RESULTS: A putative gene afcasdh from Agrobacterium fabrum str. C58, encoding carboxyspermidine dehydrogenase with C-Spd biosynthesis activity, was synthesized and transformed into Escherichia coli BL21 (DE3) for overexpression. The recombinant AfCASDH was purified and fully characterized. The optimum temperature and pH for the recombinant enzyme were 30 °C and 7.5, respectively. The coupled catalytic strategy of AfCASDH and various NADPH regeneration systems were developed to enhance the efficient production of C-Spd compound. Finally, the maximum titer of C-Spd production successfully achieved 1.82 mmol L-1 with a yield of 91% by optimizing the catalytic conditions. CONCLUSION: A novel AfCASDH from A. fabrum str. C58 was characterized that could catalyze the formation of C-Spd from putrescine and l-aspartate-ß-semialdehyde (L-Asa). A whole-cell catalytic strategy coupled with NADPH regeneration was established successfully for C-Spd biosynthesis for the first time. The coupled system indicated that AfCASDH might provide a feasible method for the industrial production of C-Spd. © 2021 Society of Chemical Industry.
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Agrobacterium , Poliaminas , Espermidina , Agrobacterium/enzimología , NADP , Oxidorreductasas , Espermidina/análogos & derivadosRESUMEN
Radiation-induced pulmonary ï¬brosis (RIPF) is a major lung complication in using radiotherapy to treat thoracic diseases. MicroRNAs (miRNAs) are reported to be the therapeutic targets for many diseases. However, the miRNAs involved in the pathogenesis of RIPF are rarely studied as potential therapeutic targets. Alveolar epithelial cells participate in RIPF formation by undergoing epithelial-mesenchymal transition (EMT). Here we demonstrated the critical role of miR-155-5p in radiation-induced EMT and RIPF. Using the previously established EMT cell model, we found that miR-155-5p was significantly down-regulated through high-throughput sequencing. Irradiation could decrease the expression of miR-155-5p in intro and in vivo, and it was inversely correlated to RIPF formation. Ectopic miR-155-5p expression inhibited radiation-induced-EMT in vitro and in vivo. Knockdown of glycogen synthase kinase-3ß (GSK-3ß), the functional target of miR-155-5p, reversed the induction of EMT and enhanced the phosphorylation of p65, a subunit of NF-κB, which were mediated by the down-regulation of miR-155-5p. Moreover, our finding demonstrated that ectopic miR-155-5p expression alleviated RIPF in mice by the GSK-3ß/NF-κB pathway. Thus, radiation downregulates miR-155-5p in alveolar epithelial cells that induces EMT, which contributes to RIPF using GSK-3ß/NF-κB pathway. Our observation provides further understanding on the regulation of RIPF and identifies potential therapeutic targets.
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Transición Epitelial-Mesenquimal/efectos de la radiación , Glucógeno Sintasa Quinasa 3 beta/genética , MicroARNs/genética , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/patología , Traumatismos Experimentales por Radiación/genética , Traumatismos Experimentales por Radiación/patología , Animales , Secuencia de Bases , Transición Epitelial-Mesenquimal/genética , Técnicas de Silenciamiento del Gen , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/metabolismo , FN-kappa B/metabolismo , Fibrosis Pulmonar/metabolismo , Traumatismos Experimentales por Radiación/metabolismoRESUMEN
Cellular inflammation is the underlying cause of several diseases and development of a safe and effective anti-inflammatory drug is need-of-the hour for treatment of diseases like lung inflammation. Callicarpa integerrima Champ. is a well-known herbal medicine with hemostatic and anti-inflammatory functions. However, the exact ingredient exhibiting anti-inflammatory activity in C. integerrima Champ. is largely unknown. Here, we first isolated, purified and characterized a novel clerodane-type diterpenoid Cintelactone A (CA) from C. integerrima Champ. We demonstrated that CA could significantly inhibit lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and mediators production both in mouse peritoneal macrophages and THP1 cells. Consistently, CA also relieved inflammation and reduced LPS-induced lung injury in mice. We systematically elucidated the mechanism of action as well. CA interacted with Arg78 of tumor necrosis factor receptor-associated factor 6 (TRAF6) by hydrogen bonding. It further promoted the K48-linked ubiquitination and proteasomal degradation of TRAF6, and suppressed the activation of NF-κB and MAPKs signaling pathways. Collectively, our study reveals that new clerodane-type diterpenoid CA suppresses LPS-induced inflammation by promoting TRAF6 degradation, suggesting that CA as the potential therapeutic candidate for the treatment of inflammation associated diseases.
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Antiinflamatorios/uso terapéutico , Diterpenos de Tipo Clerodano/uso terapéutico , Factor 6 Asociado a Receptor de TNF/metabolismo , Animales , Antiinflamatorios/farmacología , Callicarpa , Células Cultivadas , Citocinas/sangre , Citocinas/genética , Citocinas/metabolismo , Diterpenos de Tipo Clerodano/farmacología , Femenino , Humanos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Lipopolisacáridos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Ratones Endogámicos C57BL , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Hojas de la Planta , Tallos de la Planta , Ubiquitinación/efectos de los fármacosRESUMEN
Our previous study demonstrated massive emissions of liquid crystal monomers (LCMs) from liquid crystal display (LCD)-associated e-waste dismantling; however, the compositions, priority list, and inventory of LCMs in waste LCD panels remain unknown. Herein, we conducted the first comprehensive identification covering a broader range of LCMs, including 21 biphenyls and analogues (BAs), 28 cyanobiphenyls and analogues (CBAs), and 44 fluorinated biphenyls and analogues (FBAs), in waste television/computer LCD panels. A total of 64 of the 93 target LCMs, including 19 BAs, 6 CBAs, and 39 FBAs, were widely detected in collected waste LCD panels. Approximately 10-18 of the 64 detectable LCMs were identified as the main compositions in various waste LCD panels, which contributed to >90% of the total LCMs. Total concentrations of FBAs in the television/computer LCD panel samples were comparable to those of BAs but much higher than those of CBAs, indicating FBAs and BAs being the commonly used LCM categories. The composition distribution of LCMs varied between television/computer LCDs and among different brands of television/computer LCDs. A preliminary estimate of the globally direct release of LCMs from waste television/computer LCD panels into various environmental compartments was about 1.07-107 kg/year, which will increase considerably in the near future.
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Residuos Electrónicos , Cristales Líquidos , Residuos Electrónicos/análisisRESUMEN
Liquid-crystal monomers (LCMs), especially fluorinated biphenyls and analogues (FBAs), are considered to be a new generation of persistent, bioaccumulative, and toxic organic pollutants, but their emissions from liquid-crystal display (LCD)-associated e-waste dismantling remain unknown. To fill this knowledge gap, a broad range of 46 LCMs, including 39 FBAs and 7 biphenyls/bicyclohexyls and analogues (BAs), were investigated by a dedicated target analysis in e-waste dust samples. Of 39 target FBAs, 34 were detected in LCD dismantling-associated dust. Among these 34 detectable FBAs, 9 were detected in 100% of the samples and 25 were frequently detected in >50% of the samples. The total concentrations of these 34 FBAs (∑34FBAs) detected in LCD e-waste dust were in the range of 225-976,000 (median: 18,500) ng/g, significantly higher than those in non-LCD e-waste dust (range: 292-18,500, median: 2300 ng/g). In addition to FBAs, six of seven BAs were also frequently detected in LCD e-waste dust with total concentrations (∑6BAs) of 29.8-269,000 (median: 3470) ng/g. Very strong and significant correlations (P < 0.01) were identified in all frequently detected LCMs, indicating their common applications and similar sources. Our findings demonstrate that e-waste dismantling contributes elevated emissions of FBAs and BAs to the ambient environment.
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Residuos Electrónicos , Contaminantes Ambientales , Cristales Líquidos , Bifenilos Policlorados , China , Polvo/análisis , Residuos Electrónicos/análisis , Monitoreo del Ambiente , Contaminantes Orgánicos PersistentesRESUMEN
Understanding miRNAs regulatory roles in epithelial-mesenchymal transition (EMT) would help establish new avenues for further uncovering the mechanisms underlying radiation-induced pulmonary fibrosis (RIPF) and identifying preventative and therapeutic targets. Here, we demonstrated that miR-541-5p repression by Myeloid Zinc Finger 1 (MZF1) promotes radiation-induced EMT and RIPF. Irradiation could decrease miR-541-5p expression in vitro and in vivo and inversely correlated to RIPF development. Ectopic miR-541-5p expression suppressed radiation-induced-EMT in vitro and in vivo. Knockdown of Slug, the functional target of miR-541-5p, inhibited EMT induction by irradiation. The upregulation of transcription factor MZF1 upon irradiation inhibited the expression of endogenous miR-541-5p and its primary precursor (pri-miR-541-5p), which regulated the effect of the Slug on the EMT process. Our finding showed that ectopic miR-541-5p expression mitigated RIPF in mice by targeting Slug. Thus, irradiation activates MZF1 to downregulate miR-541-5p in alveolar epithelial cells, promoting EMT and contributing to RIPF by targeting Slug. Our observation provides further understanding of the development of RIPF and determines potential preventative and therapeutic targets.
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Transición Epitelial-Mesenquimal/efectos de la radiación , MicroARNs/genética , Fibrosis Pulmonar/genética , Células A549 , Células Epiteliales Alveolares/metabolismo , Animales , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Pulmón/metabolismo , Pulmón/fisiología , Lesión Pulmonar/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Fibrosis Pulmonar/metabolismo , Síndrome de Fibrosis por Radiación/genética , Transducción de Señal/fisiología , Factores de Transcripción de la Familia Snail/genética , Factores de Transcripción de la Familia Snail/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Non-noble electrocatalyst for the oxygen evolution reaction (OER) is essential for water electrolysis and electrochemical conversion of CO2 . Integrating electrochemical fixation of CO2 and electrochemical metallurgy to prepare advanced OER electrocatalyst is a promising solution to promote carbon neutrality and renewable energy. Herein, the electrochemical reduction of CO2 and Fe2 O3 are combined in molten salts to prepare cathodic Fe3 C-based electrocatalyst and anodic oxygen at 600 °C with enhanced current efficiency. The resulting Fe3 C-based electrocatalyst outperforms precious electrocatalyst towards the OER operation in 1â M KOH due to a dynamic structural evolution to form an interface of Fe3 C-FeOOH.
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Sulfur hosts with rationally designed chemistry to confine and convert lithium polysulfides are of prime importance for high-performance lithium-sulfur batteries. A molten salt electrochemical modulation of iron-carbon-nitrogen is herein demonstrated as formation of hollow nitrogen-doped carbon with grafted Fe3 C nanoparticles (Fe3 C@C@Fe3 C), which is rationalized as an excellent sulfur host for lithium-sulfur batteries. Fe3 C over nitrogen-doped carbon contributes to enhanced adsorption and catalytic conversion of lithium polysulfides. The sulfur-loaded Fe3 C@C@Fe3 C electrodes hence show a high capacity, good cyclic stability, and enhanced rate performance. This work highlights the unique chemistry of metal carbides on facilitating adsorption-conversion process of lithium polysulfides, and also extends the scope of molten salt electrolysis to elaboration of energy materials.
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BACKGROUND: Proteus syndrome (PS) is an extremely rare disease characterized by excessive chimeric growth of cells, and progressive and irregular asymmetrical hyperplasia. CASE PRESENTATION: Herein, a PS case with atypical clinical features and syndromes was reported, to improve the understanding of the diagnosis and treatment of the disease. The case was a 3-year-and-11-month-old male child. He was admitted due to a primary diagnosis of McCune-Albright syndrome. After admission, the lesion samples from the milk coffee spots, and nodular thickening skin at hands and feet were subjected to genetic screening. Genetic testing results confirmed the diagnosis of PS. CONCLUSIONS: Based on the clinical manifestations, laboratory tests, imaging data, and literature reviewing, the etiology, diagnosis, treatment and prognosis of PS have been analyzed and discussed.