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In language comprehension, listeners expect a speaker to be consistent in their word choice for labeling the same object. For instance, if a speaker previously refers to a piece of furniture as a "couch," in subsequent references, listeners would expect the speaker to repeat this label instead of switching to an alternative label such as "sofa." Moreover, it has been found that speakers' demographic backgrounds, often inferred from their voice, influence how listeners process their language. The question in focus, therefore, is whether speaker demographics influence how listeners expect the speaker to repeat or switch labels. In this study, we used ERPs to investigate whether listeners expect a child speaker to be less likely to switch labels compared to an adult speaker, given the common belief that children are less flexible in language use. In the experiment, we used 80 pictures with alternative labels in Mandarin Chinese (e.g., yi1sheng1 vs. dai4fu, "doctor"). Each picture was presented twice over two experimental phases: In the establishment phase, participants listened to an adult or a child naming a picture with one of the labels and decided whether the label matched the picture they saw; in the test phase, participants listened to the same speaker naming the same picture by either repeating the original label or switching to an alternative label and, again, decided whether the label matched the picture they saw. ERP results in the test phase revealed that, compared to repeated labels, switched labels elicited an N400 effect (300-600 msec after label onset) and a P600 effect (600-1000 msec after label onset). Critically, the N400 effect was larger when listeners were exposed to the child speaker than to the adult speaker, suggesting that listeners found a switched label harder to comprehend when it was produced by a child speaker than an adult speaker. Our study shows that the perceived speaker demographic backgrounds influence listeners' neural responses to spoken words, particularly in relation to their expectations regarding the speaker's label switching behavior. This finding contributes to a broader understanding of the relationship between social cognition and language processing.
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In this work, we report multiple-intercalation stages and universal Tc enhancement of superconductivity in 1T-SnSe2 through Li and organic molecule co-intercalation. We observe significantly increased lattice parameters of up to 40 Å and a dramatically enlarged interlayer distance of up to â¼11 Å in Li and N,N-dimethylformamide (DMF) co-intercalated SnSe2. Well-separated co-intercalation stages with different stacking patterns have been discovered by carefully controlled reaction times and concentrations of solutions. These co-intercalation stages are superconductors showing different superconducting signals. In addition, Li and various organic species such as acetone, dimethyl sulfoxide (DMSO), and tetrahydrofuran (THF) have been co-intercalated into SnSe2 crystals; all of which show an enhanced superconducting Tc compared to solely Li-intercalated SnSe2. Our findings may provide more insight into effectively tuning the electronic structure of the lamellar structure through organic molecule co-regulation and open a new strategy to engineer the physical properties of these layered materials by controlling their different intercalation stages.
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BACKGROUND: The secretion of Muc5ac is closely related to the pathogenesis, treatment and prognosis of bronchial asthma. Atmospheric PM2.5 entered the airway can irritate and corrode the bronchial wall, affecting the expression and secretion of Muc5ac. However, the underlying mechanism is not clear. In this study, we investigated the role of the Notch signaling pathway in mucin section induced by atmospheric PM2.5 in rats. METHODS: Fifty rats were divided randomly into five groups: the control received physiological saline; the health, health Notch signaling pathway inhibition and asthma, asthma Notch signaling pathway inhibition groups received 7.5 mg/kg PM2.5. PM2.5 or saline was instilled into the trachea at 2-day intervals for two doses. IL-1ß, TNF-α and Muc5ac levels were detected by ELISA. The mRNA expression levels of Notch signaling pathway genes were detected by real time PCR. The levels of Notch signaling pathway protein were detected by western blot. RESULTS: The levels of Muc5ac in the lungs and TNF-α in serum of asthmatic rats exposed to PM2.5 was the highest, and when Notch signaling pathway was inhibited, the levels of Muc5ac in the lungs and tracheas and TNF-α in serum of asthmatic rats exposed to PM2.5 was significantly decreased. Hes1 mRNA expression level in trachea was the lowest in the asthma inhibition group; and inhibiting the Notch signaling pathway could decrease the mRNA and protein levels of Hes1 in rats' lung. The mRNA relative levels of Notch3 and Notch4 in rats' trachea, the protein levels of Notch3 in rats' lung, and the mRNA relative levels of Jagged1 and Jaggeed2 in rats' lung were more consist with the changes of Muc5ac, TNF-α and Hes1. CONCLUSION: Notch signaling pathway played an important role in Muc5ac secretion induced by atmospheric PM2.5 of the asthmatic rats' airways. Jagged1 and Jagged2 interacting with Notch3 and Notch4 regulated the expression of Hes1, further regulated TNF-α in the process of PM2.5 inducing the secretion of Muc5ac.
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Asma , Transdução de Sinais , Animais , Asma/induzido quimicamente , Brônquios , Pulmão , Mucina-5AC/genética , Material Particulado/toxicidade , RatosRESUMO
A new ternary nonstoichiometric Zr6.5Pt6Se19 has been discovered as a part of effort to dope Zr into the layered transitional metal chalcogenide PtSe2. With a new structure type (oC68), it is the first Pt-based ternary chalcogenide with group 4 elements (Ti, Zr, and Hf). The crystal structure adopts the orthorhombic space group Cmmm with lattice parameters of a = 15.637(6) Å, b = 26.541(10) Å, c = 3.6581(12) Å, and V = 1518.2(9) Å3. This unusual structure consists of several building units: chains of edge-sharing selenium trigonal prisms and octahedra centered by zirconium atoms, chains of corner-shared square pyramid, and square planar centered by Pt atoms. The condensation of these building blocks forms a unique structure with bilayered Zr5.54Pt6Se19 slabs stacking along the b direction and large channels parallel to the c direction within the bilayered slabs. Band structure calculations suggest that partial occupancy of Zr atoms creates a pseudo gap at the Fermi level and is likely the main cause for the stability of this new phase.
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Pomfret fishes of the genus Pampus are commercially important in the Indo-Pacific region, yet the phylogenetic relationships and taxonomy of Pampus remain contentious. Here, we sampled 151 specimens, representing all known species of the genus, as well as two outgroup species (two families). We collected sequences from 17,292 single-copy nuclear coding loci using target-gene enrichment and Illumina sequencing for a subset samples of P. echinogaster, P. argenteus, P. cinereus, P. liuorum, P. chinensis, P. minor, and P. punctatissimus, which were carefully examined according to their species descriptions. Concatenated gene tree and species tree analyses resulted in identical and highly supported phylogenies, in which P. argenteus was sister to P. minor in one clade and P. cinereus sister to P. chinensis and P. punctatissimus in the other clade. Phylogenetic reconstruction using sequences of cytochrome c oxidase subunit I (COI) collected by us and those retrieved from NCBI suggests extensive misidentification of Pampus species in the NCBI database. We also measured morphological characters of each species as well as observed their osteological structure using micro-CT. Both molecular and morphological results suggest that P. echinogaster is a synonym of P. argenteus, and P. liuorum is a synonym of P. cinereus. Pampus cinereus from China, Bangladesh and an uncertain origin were grouped into three clades according to their sampling localities, but we could not find decisive morphological characters to describe the "cryptic species" of P. cinereus. Finally, based on the results of the molecular analyses and morphological reexamination, we created an identification key for the genus of Pampus.
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Núcleo Celular/genética , Loci Gênicos , Perciformes/classificação , Perciformes/genética , Animais , China , Complexo IV da Cadeia de Transporte de Elétrons/genética , Genoma , Sequenciamento de Nucleotídeos em Larga Escala , Perciformes/anatomia & histologia , FilogeniaRESUMO
A nonstoichiometric ternary antimonide, Zr3.55Pt4Sb4, with a new structure type (hP24), has been synthesized via arc-melting. Its crystal structure was determined by single-crystal X-ray diffraction with hexagonal space group P63/mmc and lattice parameters a = 4.391(3) Å, c = 30.53(2) Å, and V = 509.7(8) Å3. It features the unique Pt4Sb4 slab with Pt-Pt bonds and is reminiscent to hexagonal diamond substructures. Three different Zr atoms, occupying three different sites, aid in the close-packing of the Pt and Sb atoms. Electronic structure calculations show the half occupancy of one Zr site creates a pseudogap at the Fermi level and optimizes the Pt-Sb bonding interactions. This enhances the electronic stability and accounts for the very narrow phase width observed for this nonstoichiometric compound. Furthermore, strong Zr-Pt and Zr-Sb interactions play a crucial role in the chemical bonding of the title compound. Electrical transport measurements show metallic behavior of this compound down to 2 K, consistent with the band structure calculations.
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OBJECTIVE: To assess whether functional activity, perceived health, and depressive symptoms differ between individuals with traumatic paraplegia with and without shoulder pain. DESIGN: Cross sectional and comparative investigation using the unified questionnaire. SETTING: Neural Regeneration and Repair Division unit of Taipei Veterans General Hospital in Taiwan. PARTICIPANTS: Seventy-six patients with paraplegia (23 with and 53 without shoulder pain) who had experienced spinal cord injury at American Spinal Injury Association Impairment Scale T2 to T12 neurologic level (at least 6 months previously). OUTCOME MEASURES: Spinal Cord Independence Measure (SCIM), a single item from the Medical Outcomes Study 36-Item Short-Form Health Survey, and Patient Health Questionnaire-9 (PHQ-9) depression scale. RESULTS: Shoulder pain was prevalent in 30% patients. Patients with shoulder pain had significantly worse perceived health and greater depressive symptoms than those without. No significant difference was found in functional ability between groups. Greater shoulder pain intensity was related to higher depressive scores (r=0.278, P=0.017) and lower self-perceived health scores (r=-0.433, P<0.001) but not SCIM scores (P=0.342). CONCLUSION: Although shoulder pain was unrelated to functional limitation, it was associated with lower perceived health and higher depressive mood levels.
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Depressão/etiologia , Paraplegia/complicações , Dor de Ombro/complicações , Traumatismos da Medula Espinal/complicações , Adulto , Idoso , Depressão/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/etiologia , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paraplegia/epidemiologia , Paraplegia/etiologia , Prevalência , Qualidade de Vida , Dor de Ombro/epidemiologia , Dor de Ombro/etiologia , Traumatismos da Medula Espinal/epidemiologia , Adulto JovemRESUMO
BACKGROUND: This work aimed to synthesize a cathepsin B (CTSB)-cleavable tumor-targeting prodrug peptide doxorubicin (PDOX) and study the in vivo efficacy and toxicities on an animal model of gastric peritoneal carcinomatosis (PC). METHODS: PDOX was synthesized using doxorubicin (DOX) attaching to a CTSB-cleavable dipeptide Ac-Phe-Lys and a para-amino-benzyloxycarbonyl (PABC) spacer. PC model was established by injecting VX2 tumor cells into the gastric sub-mucosa of 40 rabbits, which then were randomized into 4 groups: the Control (n = 10) without treatment, the HIPEC (n = 10) receiving cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the PDOX (n = 10) and the DOX (n = 10) receiving systemic chemotherapy with PDOX 50.0 mg/kg or DOX 5.0 mg/kg, respectively, after CRS + HIPEC. RESULTS: The median overall survivals (OS) were 23.0 d (95% CI: 19.9 d - 26.1 d) in the Control, 41.0 d (36.9 d - 45.1 d) in the HIPEC, 65.0 d (44.1 d - 71.9 d) in the PDOX, and 58.0 d (39.6 d - 54.4 d) in the DOX. Compared with the Control, the OS was extended by 70% in the HIPEC (p < 0.001) and further extended by 40% in the DOX (p = 0.029) and by 58% in the PDOX (p = 0.021), and the PC severity was decreased in the HIPEC and further decreased in the PDOX and DOX. Animals receiving DOX treatment showed hematological toxicities with marked reduction of white blood cells and platelets, as well as cardiac toxicities with significant increases in creatine kinase mb isoenzyme, evident myocardium coagulation necrosis, significant nuclear degeneration, peri-nucleus mitochondria deletion, mitochondria-pyknosis, and abnormal intercalated discs. But these toxicities were not evident in the PDOX. CONCLUSIONS: PDOX is a newly synthesized tumor-targeting prodrug of DOX. Compared with DOX, PDOX has similar efficacy but reduced hematological and cardiac toxicities in treating rabbit model of gastric PC.
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Carcinoma/tratamento farmacológico , Doxorrubicina/análogos & derivados , Oligopeptídeos/síntese química , Oligopeptídeos/farmacologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/patologia , Animais , Carcinoma/secundário , Modelos Animais de Doenças , Doxorrubicina/síntese química , Doxorrubicina/farmacologia , Masculino , Neoplasias Peritoneais/secundário , Pró-Fármacos/farmacologia , Coelhos , Neoplasias Gástricas/tratamento farmacológicoRESUMO
In the context of carbon emission reduction in the shipping industry, CCUS technology can modify ships to reduce carbon emissions, providing a new direction for the green development of the shipping industry. Based on this, this paper investigates the technology related to carbon capture on ships, firstly puts forward the applicable requirements of carbon capture technology; and analyses the adaptability of the existing carbon capture solutions to the shipping industry; and discusses the development prospect of carbon capture on ships through the three challenges of space utilisation, safety, and economy; and finally analyses the related policies. After analysis and discussion, this paper concludes that the alcohol-amine method is the most suitable carbon capture solution for ships, but there are challenges in economics and space utilisation. The future research direction lies in optimising the performance of the absorber, improving the energy efficiency of the system and solving the CO2 storage problem.
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OBJECTIVE: Our aim is to explore the value of intraoperative facial motor evoked potentials (FMEP) for facial outcomes in cerebellopontine angle (CPA) tumor surgery to provide an evidence-based consensus standard for future clinical practice and prospective studies. METHODS: Electronic databases were searched from inception to June 2023. Study quality was assessed with the QUADAS-2 tool. Bivariate and random-effects models for meta-analysis and meta-regression generated summary receiver operating characteristic curves (ROC) and forest plots for estimates of sensitivity and specificity. RESULTS: We included 17 studies (1,206 participants). Sensitivity was lower in the immediate (IM) post-operative (0.76, 95% CI 0.65-0.84) compared to follow-up (FU) period (0.82, 95% CI 0.74-0.88) while specificity was similar in both groups (IM, 0.94, 95% CI 0.89-0.97; FU, 0.93, 95% CI 0.87-0.96). Data driven estimates improved FMEP performance but require confirmation from future studies. Amplitude cutoff criteria and studies that scored new deficits as worse than House-Brackmann (HB) grade 2 yielded best sensitivities. CONCLUSIONS: FMEP demonstrated statistically significant accuracy for facial function monitoring. Implementation of FMEPs varied widely across studies. SIGNIFICANCE: Our study is the first systematic review with meta-analysis to demonstrate that intraoperative FMEP is valuable in CPA tumor surgery for facial outcomes. Meta-regression identified the methods that were most useful in the application of FMEPs.
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During bottom trawl surveys carried out between 20132021, 52 specimens (33.854.0 mm SL) of Egglestones bumblebee goby Egglestonichthys bombylios were collected at a depth of 1.515 m from Dongshan Bay, Sanmen Bay, and Niushan Island, China. They represent the first records of this species from China. A full description, including fresh colouration of the species is provided as it is poorly known. The individuals collected in China agree with most morphological features of the holotype, except for the pelvic fin fraenum that was not observed or appears to be absent in most specimens. A strong relationship between E. bombylios, Larsonella pumilus, and the genus Priolepis is herein demonstrated by the mitochondrial genome sequences of E. bombylios and twenty closely related species. This study enriches the existing genetic data of the so-called Priolepis lineage and provides useful insights into the phylogenetic relationships across species of the genera Egglestonichthys, Priolepis, and Larsonella.
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Genoma Mitocondrial , Perciformes , Humanos , Animais , Filogenia , Peixes , ChinaRESUMO
Psoriasis, a chronic inflammatory skin disorder, is associated with comorbidities such as acute myocardial infarction (AMI). However, the molecular mechanisms connecting these conditions are unclear. In this study, we conducted bioinformatics analyses using gene expression datasets to identify differentially expressed genes and hub genes associated with both psoriasis and AMI. Our findings emphasize the involvement of immune-related pathways in the pathogenesis of both conditions. Furthermore, we investigated the expression levels of hub genes in AMI patients and myocardial infarction (MI) mice. ELISA measurements revealed significantly higher levels of CXCL8, IL1B, S100A9, and S100A12 in the serum of AMI patients compared to normal individuals. Immunohistochemical staining of heart tissue from MI mice showed a progressive increase in the expression of CXCL8 and IL-1B as MI advanced, while S100A9 exhibited high expression at day 3 post-MI. mRNA expression analysis validated these findings. Additionally, we explored the skin lesions of psoriasis patients and found significantly higher expression of CXCL8, IL-1B, S100A9, and S100A12 in the affected skin areas compared to unaffected regions. These results highlight the consistent upregulation of hub genes in both AMI and psoriasis patients, as well as in myocardial infarction mice, underscoring their potential as reliable markers for disease diagnosis. Moreover, molecular docking simulations revealed potential interactions between simvastatin and key target proteins, suggesting a potential therapeutic avenue. Overall, our study uncovers shared molecular signatures and potential therapeutic targets, providing a foundation for future investigations targeting common pathways in psoriasis and AMI.
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Calgranulina B , Infarto do Miocárdio , Psoríase , Psoríase/genética , Psoríase/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Animais , Humanos , Camundongos , Calgranulina B/genética , Calgranulina B/metabolismo , Interleucina-8/metabolismo , Interleucina-8/genética , Simulação de Acoplamento Molecular , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico , Proteína S100A12/genética , Proteína S100A12/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Masculino , Modelos Animais de Doenças , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Feminino , BiomarcadoresRESUMO
Advanced diabetic cardiomyopathy (DCM) patients are often accompanied by severe peripheral artery disease. For patients with DCM combined with diabetic foot ulcer (DFU), there are currently no good therapeutic targets and drugs. Here, we investigated the underlying network of molecular actions associated with the occurrence of these two complications. The datasets were downloaded from the Gene Expression Omnibus (GEO) database. We performed enrichment and protein-protein interaction analyses, and screened for hub genes. Construct transcription factors (TFs) and microRNAs regulatory networks for validated hub genes. Finally, drug prediction and molecular docking verification were performed. We identified 299 common differentially expressed genes (DEGs), many of which were involved in inflammation and lipid metabolism. 6 DEGs were identified as hub genes (PPARG, JUN, SLC2A1, CD4, SCARB1 and SERPINE1). These 6 hub genes were associated with inflammation and immune response. We identified 31 common TFs and 2 key miRNAs closely related to hub genes. Interestingly, our study suggested that fenofibrate, a lipid-lowering medication, holds promise as a potential treatment for DCM combined with DFU due to its stable binding to the identified hub genes. Here, we revealed a network involves a common target for DCM and DFU. Understanding these networks and hub genes is pivotal for advancing our comprehension of the multifaceted complications of diabetes and facilitating the development of future therapeutic interventions.
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Diabetes Mellitus , Cardiomiopatias Diabéticas , Pé Diabético , MicroRNAs , Humanos , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/genética , Pé Diabético/tratamento farmacológico , Pé Diabético/genética , Simulação de Acoplamento Molecular , MicroRNAs/genética , Biologia Computacional , Inflamação/genética , Redes Reguladoras de Genes , Perfilação da Expressão GênicaRESUMO
BACKGROUND: Pentamethylquercetin (PMQ) is a natural polymethyl flavonoid that possesses anti-apoptotic and other biological properties. Abdominal aortic aneurysm (AAA), a fatal vascular disease with a high risk of rupture, is associated with phenotypic switching and apoptosis of medial vascular smooth muscle cells (VSMCs). This study aimed to investigate the protective effects of PMQ on the development of AAA and the underlying mechanism. METHODS: ApoE-/- mice were continuously infused with angiotensin II (Ang II) for 4 weeks to develop the AAA model. Intragastric administration of PMQ was initiated 5 days before Ang II infusion and continued for 4 weeks. In vitro, VSMCs were cultured and pretreated with PMQ, stimulated with Ang II. Real-time PCR, western blotting, and immunofluorescence staining were used to examine the roles and mechanisms of PMQ on the phenotypic switching and apoptosis of VSMCs. RESULTS: PMQ dose-dependently reduced the incidence of Ang II-induced AAA, aneurysm diameter enlargement, elastin degradation, VSMCs phenotypic switching and apoptosis. Furthermore, PMQ also inhibited phenotypic switching and apoptosis in Ang II-stimulated VSMCs. PMQ exerted protective effects by regulating the C/EBPß/PTEN/AKT/GSK-3ß axis. AAV-mediated overexpression of PTEN reduced the therapeutic effects of PMQ in the AAA model mice, suggesting that the effects of PMQ on Ang II-mediated AAA formation were related to the PTEN/AKT/GSK-3ß axis. PMQ inhibited VSMCs phenotypic switching and apoptosis by bounding to C/EBPß at Lys253 with hydrogen bond to regulate C/EBPß nuclear translocation and PTEN/AKT/GSK-3ß axis, thereby inhibiting Ang II-induced AAA formation. CONCLUSIONS: Pentamethylquercetin inhibits angiotensin II-induced abdominal aortic aneurysm formation by bounding to C/EBPß at Lys253. Therefore, PMQ prevents the formation of AAA and reduces the incidence of AAA.
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Angiotensina II , Aneurisma da Aorta Abdominal , Apoptose , Músculo Liso Vascular , Quercetina , Animais , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/prevenção & controle , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/tratamento farmacológico , Angiotensina II/farmacologia , Camundongos , Quercetina/análogos & derivados , Quercetina/farmacologia , Apoptose/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Masculino , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Modelos Animais de Doenças , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos Endogâmicos C57BL , Glicogênio Sintase Quinase 3 beta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Cultivadas , Núcleo Celular/metabolismo , Núcleo Celular/efeitos dos fármacosRESUMO
OBJECTIVE: Doxorubicin (DOX)-induced cardiotoxicity limits the application of DOX in cancer patients. Currently, there is no effective prevention or treatment for DOX-induced cardiotoxicity. The cellular repressor of E1A-stimulated genes (CREG1) is a cardioprotective factor that plays an important role in the maintenance of cardiomyocytes differentiation and homeostasis. However, the role and mechanism of CREG1 in DOX-induced cardiotoxicity has not yet been elucidated. METHODS: In vivo, C57BL/6J mice, CREG1 transgenic and cardiac-specific CREG1 knockout mice were used to establish a DOX-induced cardiotoxicity model. H&E staining, Masson's trichrome, WGA staining, real-time PCR, and western blotting were performed to examine fibrosis and ferroptosis in the myocardium. In vitro, neonatal mouse cardiomyocytes (NMCMs) were cultured and stimulated with DOX, CREG1-overexpressed adenovirus, and small interfering RNA was used to establish CREG1 overexpression or knockdown cardiomyocytes. Transcriptomics, real-time PCR, western blotting, and immunoprecipitation were used to examine the roles and mechanisms of CREG1 in cardiomyocytes ferroptosis. RESULTS: The mRNA and protein levels of CREG1 were reduced in the hearts and NMCMs after DOX treatment. CREG1 overexpression alleviated myocardial damage and inhibited DOX-induced ferroptosis in the myocardium. CREG1 deficiency in the heart aggravated DOX-induced cardiotoxicity and ferroptosis. In vitro, CREG1 overexpression inhibited cardiomyocytes ferroptosis induced by DOX, and CREG1 knockdown aggravated DOX-induced cardiotoxicity. Mechanistically, CREG1 inhibited the mRNA and protein expression of pyruvate dehydrogenase kinase 4 (PDK4) by regulating the F-box and WD repeat domain containing 7 (FBXW7)-forkhead box O1 (FOXO1) pathway. PDK4 deficiency reversed the effects of CREG1 knockdown on cardiomyocytes ferroptosis following DOX treatment. CONCLUSION: CREG1 alleviated DOX-induced cardiotoxicity by inhibiting ferroptosis in cardiomyocytes. Our findings may help clarify the new roles of CREG1 in the development of DOX-induced cardiotoxicity.
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Cardiotoxicidade , Doxorrubicina , Ferroptose , Miócitos Cardíacos , Animais , Doxorrubicina/efeitos adversos , Ferroptose/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Camundongos , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Cardiotoxicidade/patologia , Cardiotoxicidade/genética , Camundongos Endogâmicos C57BL , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Camundongos Knockout , Modelos Animais de Doenças , Proteínas de Homeodomínio , Fatores de Transcrição Hélice-Alça-Hélice BásicosRESUMO
Phenotypic switching of vascular smooth muscle cells is a central process in abdominal aortic aneurysm (AAA) pathology. We found that knockdown TCF7L1 (transcription factor 7-like 1), a member of the TCF/LEF (T cell factor/lymphoid enhancer factor) family of transcription factors, inhibits vascular smooth muscle cell differentiation. This study hints at potential interventions to maintain a normal, differentiated smooth muscle cell state, thereby eliminating the pathogenesis of AAA. In addition, our study provides insights into the potential use of TCF7L1 as a biomarker for AAA.
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Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone secreted primarily by the liver and is considered a major regulator of energy homeostasis. Recent research has revealed that FGF21 could play an important role in cardiac pathological remodeling effects and prevention of cardiomyopathy; however, the underlying mechanism remains largely unknown. This study aimed to determine the mechanism underlying the cardioprotective effects of FGF21. We engineered FGF21 knock out mice and subsequently elucidated the effects of FGF21 and its downstream mediators using western blotting, qRT-PCR, and mitochondrial morphological and functional analyses. FGF21 knockout mice showed cardiac dysfunction, accompanied by a decline in global longitudinal strain (GLS) and ejection fraction (EF), independent of metabolic disorders. Mitochondrial quality, quantity, and function were abnormal, accompanied by decreased levels of optic atrophy-1 (OPA1) in FGF21 KO mice. In contrast to FGF21 knockout, cardiac-specific overexpression of FGF21 alleviated the cardiac dysfunction caused by FGF21 deficiency. In an in vitro study, FGF21 siRNA deteriorated mitochondrial dynamics and impaired function induced by cobalt chloride (CoCl2). Both recombinant FGF21 and adenovirus-mediated FGF21 overexpression could alleviate CoCl2-induced mitochondrial impairment by restoring mitochondrial dynamics. FGF21 was essential for maintaining mitochondrial dynamics and function of the cardiomyocytes. As a regulator of cardiomyocyte mitochondrial homeostasis under oxidative stress, FGF21 could be an important new target for therapeutic options for patients with heart failure.
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Cardiopatias , Miócitos Cardíacos , Animais , Camundongos , Fatores de Crescimento de Fibroblastos/metabolismo , Cardiopatias/tratamento farmacológico , Homeostase , Camundongos Knockout , Miócitos Cardíacos/metabolismoRESUMO
BACKGROUND AND OBJECTIVES: Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease with abnormal vascular hyperplasia, which causes cerebrovascular accidents like intracranial arteriosclerosis. This study aimed to explore whether plasma apelin levels are related to good collateral circulation in ischemic diseases, which may be higher in patients with MMD than middle cerebral artery (MCA) occlusion or healthy controls, and may have a connection with the MMD grades. METHODS: We recruited 68 MMD patients and 25 MCA occlusion patients diagnosed by angiography, including 29 patients without cerebrovascular problems as controls. We examined the plasma apelin, serum nitric oxide (NO), and vascular endothelial growth factor (VEGF) levels of all subjects by ELISA kit. We compared the relationship between apelin, NO, and VEGF in the blood of three groups, to explore the relationship. We also investigated whether the plasma apelin-13, apelin-17, and apelin-36 levels correlate with the MMD classification. RESULTS: Univariate analyses indicated that the MMD group had the higher plasma apelin-13, apelin-17, apelin-36, and serum NO levels than the MCA occlusion and healthy control groups. Binary logistic regression analyses further showed that the apelin-13 level was substantially higher in MMD patients than in MCA occlusion patients. Patients with MMD were significantly younger than patients with MCA occlusion by their mean ages. Linear regression analyses were performed to compare apelin levels between different grades of the patients with MMD. Apelin-13, apelin-17, and apelin-36 levels increased with the gradual increase of compensation grades level independent of NO and VEGF. Apelin-13 and apelin-36 showed a positive effect on the compensation scores in MMD. CONCLUSION: Our study demonstrated that apelin-13 was significantly increased in patients with MMD than patients with MCA occlusion independent of NO and VEGF. Moreover, plasma apelin-13, apelin-17, and apelin-36 levels increase with the grades of MMD.
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A Ce0.8Gd0.2O1.95-based mixed potential type sensor attached with a commercially available Au paste sensing electrode material was fabricated to detect methanol. The optimum working temperature of the sensor was 545 °C, and the response value to 100 ppm methanol was -53 mV. The selectivity of the sensor was poor. The addition of a 4A molecular sieve filter layer and the method of pattern recognition were combined to improve it. Only gas molecules smaller than the pore diameter of the 4A molecular sieve were able to pass through the zeolite channel, and the selectivity coefficient of the sensor to methanol was improved by adding the filter layer. Meanwhile, there was an obvious distinction between the response and recovery times of the sensor toward methanol, ethanol, acetone, n-butanol, and n-pentanol. Next, the pattern recognition method was adopted. The relationship between the response value and the logarithm of gas concentration and the relationship between the maximum rate of the response process and the gas concentration were plotted separately. By comprehensively considering the two characteristic parameters of the response value and the maximum value of the differential response signal, the purpose of qualitative identification of gas types and quantitative analysis of gas concentrations was hopefully achieved.
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Eletrólitos , Metanol , Eletrodos , TemperaturaRESUMO
This study investigated cross-cultural differences in individual pride and collective pride between Chinese and Americans using data from text corpora. We found higher absolute frequencies of pride items in the American corpus than in the Chinese corpus. Cross-cultural differences were found for relative frequencies of different types of pride, and some of them depended on the genre of the text corpora. For both blogs and news genres, Americans showed higher frequencies of individual pride items and lower frequencies of relational pride items than did their Chinese counterparts. Cross-cultural differences in national pride, however, depended on the genre: Chinese news genre included more national pride items than its American counterpart, but the opposite was true for the blog genre. We discuss the implications of these results in relation to the existing literature (based on surveys and laboratory-based experiments) on cultural differences in individual pride and collective pride.