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Toll-like receptor (TLR) activation contributes to premalignant hematologic conditions, such as myelodysplastic syndromes (MDS). TRAF6, a TLR effector with ubiquitin (Ub) ligase activity, is overexpressed in MDS hematopoietic stem/progenitor cells (HSPCs). We found that TRAF6 overexpression in mouse HSPC results in impaired hematopoiesis and bone marrow failure. Using a global Ub screen, we identified hnRNPA1, an RNA-binding protein and auxiliary splicing factor, as a substrate of TRAF6. TRAF6 ubiquitination of hnRNPA1 regulated alternative splicing of Arhgap1, which resulted in activation of the GTP-binding Rho family protein Cdc42 and accounted for hematopoietic defects in TRAF6-expressing HSPCs. These results implicate Ub signaling in coordinating RNA processing by TLR pathways during an immune response and in premalignant hematologic diseases, such as MDS.
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Células-Tronco Hematopoéticas/fisiologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Síndromes Mielodisplásicas/imunologia , Lesões Pré-Cancerosas/imunologia , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/metabolismo , Ubiquitinação , Animais , Autoimunidade , Células Cultivadas , Hematopoese/genética , Ribonucleoproteína Nuclear Heterogênea A1 , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transdução de Sinais/genética , Fator 6 Associado a Receptor de TNF/genética , Receptores Toll-Like/metabolismo , Ubiquitinação/genética , Proteína cdc42 de Ligação ao GTP/metabolismoRESUMO
We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C terminus and is associated with autism. Expressed as a single copy [Shank3(+/ΔC) mice], Shank3ΔC protein interacts with the wild-type (WT) gene product and results in >90% reduction of Shank3 at synapses. This "gain-of-function" phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of postsynaptic density proteins, spine morphology, and synapse number are unchanged in Shank3(+/ΔC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/ΔC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder.
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Transtorno Autístico/genética , Proteínas de Transporte/metabolismo , Modelos Animais de Doenças , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Transtorno Autístico/metabolismo , Transtorno Autístico/fisiopatologia , Proteínas de Transporte/genética , Hipocampo/metabolismo , Humanos , Relações Interpessoais , Potenciação de Longa Duração , Depressão Sináptica de Longo Prazo , Camundongos , Proteínas dos Microfilamentos , Proteínas do Tecido Nervoso , Receptores de Glutamato Metabotrópico/metabolismo , Sinapses/metabolismo , UbiquitinaçãoRESUMO
Leptin is a hormone that secreted by adipocytes and may promote energy expenditure by increasing thermogenesis. Our previous studies have shown that thermo-transient receptor potentials (thermo-TRPs) and gut microbiota are associated with thermoregulation in Mongolian gerbils, which are characterized by relative high serum leptin concentrations. Here, we test whether leptin can stimulate non-shivering thermogenesis (NST) in Mongolian gerbils, and whether thermo-TRPs and gut microbiota are involved in leptin-induced thermogenesis. First, gerbils were given acute leptin treatment (ALT) with different doses. Results showed that ALT significantly increased the body temperature of gerbils and change the composition of gut microbiota. Moreover, ALT groups showed a trend towards increased expression of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). Then, we investigated the effect of chronic leptin treatment (CLT) on gerbils. Surprisingly, CLT did not affect gerbils' food intake and body weight, but it significantly increased the body temperature at the end. Besides, CLT did not affect the expression of thermogenic markers in BAT, white adipose tissue (WAT) and skeletal muscle. However, CLT increased the expression of leptin receptors and TRPV2 in the small intestine and affected the composition of gut microbiota. Together, our data suggest leptin may increase body temperature by regulating gut microbiota. In conclusion, the Mongolian gerbils with serum hyperleptin is beneficial for adapting the cold living environments, and TRPV2 and gut microbiota are involved.
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BACKGROUND: Accompanied by the growing prevalence of nonalcoholic fatty liver disease (NAFLD), the coexistence of chronic hepatitis B (CHB) and NAFLD has increased. In the context of CHB, there is limited understanding of the factors that influence the development of NASH. METHODS: We enrolled CHB combined NAFLD patients who had liver biopsy and divided them to NASH vs. non-NASH groups. A whole transcriptome chip was used to examine the expression profiles of long noncoding RNAs (lncRNAs) and mRNA in biopsied liver tissues. The function analysis of HIGD1A were performed. We knocked down or overexpressed HIGD1A in HepG2.2.15 cells by transient transfection of siRNA-HIGD1A or pcDNA-HIGD1A. In vivo investigations were conducted using hepatitis B virus (HBV) transgenic mice. RESULTS: In 65 patients with CHB and NAFLD, 28 were patients with NASH, and 37 were those without NASH. After screening 582 differentially expressed mRNAs, GO analysis revealed differentially expressed mRNAs acting on nicotinamide adenine dinucleotide phosphate (NADPH), which influenced redox enzyme activity. KEGG analysis also shown that they were involved in the NAFLD signaling pathway. The function analysis revealed that HIGD1A was associated with the mitochondrion. Then, both in vivo and in vitro CHB model, HIGD1A was significantly higher in the NASH group than in the non-NASH group. HIGD1A knockdown impaired mitochondrial transmembrane potential and induced cell apoptosis in HepG2.2.15 cells added oleic acid and palmitate. On the contrary, hepatic HIGD1A overexpression ameliorated free fatty acids-induced apoptosis and oxidative stress. Furthermore, HIGD1A reduced reactive oxygen species (ROS) level by increasing glutathione (GSH) expression, but Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/Acetyl-CoA carboxylase (ACC) pathway was not involved. CONCLUSION: Both in vivo and in vitro CHB model, an upward trend of HIGD1A was observed in the NASH-related inflammatory response. HIGDIA played a protective role in cells against oxidative stress. Our data suggested that HIGD1A may be a positive regulator of NASH within the CHB context.
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Hepatite B Crônica , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Humanos , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatite B Crônica/complicações , Fígado/patologia , Vírus da Hepatite B/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
The Qinghai-Tibetan Plateau, with low precipitation, low oxygen partial pressure, and temperatures routinely dropping below -30 °C in winter, presents several physiological challenges to its fauna. Yet it is home to many endemic mammalian species, including the plateau pika (Ochotona curzoniae). How these small animals that are incapable of hibernation survive the winter is an enigma. Measurements of daily energy expenditure (DEE) using the doubly labeled water method show that pikas suppress their DEE during winter. At the same body weight, pikas in winter expend 29.7% less than in summer, despite ambient temperatures being approximately 25 °C lower. Combined with resting metabolic rates (RMRs), this gives them an exceptionally low metabolic scope in winter (DEE/RMRt = 1.60 ± 0.30; RMRt is resting metabolic rate at thermoneutrality). Using implanted body temperature loggers and filming in the wild, we show that this is achieved by reducing body temperature and physical activity. Thyroid hormone (T3 and T4) measurements indicate this metabolic suppression is probably mediated via the thyroid axis. Winter activity was lower at sites where domestic yak (Bos grunniens) densities were higher. Pikas supplement their food intake at these sites by eating yak feces, demonstrated by direct observation, identification of yak DNA in pika stomach contents, and greater convergence in the yak/pika microbiotas in winter. This interspecific coprophagy allows pikas to thrive where yak are abundant and partially explains why pika densities are higher where domestic yak, their supposed direct competitors for food, are more abundant.
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Aclimatação , Altitude , Metabolismo Basal , Metabolismo Energético , Fezes/química , Lagomorpha/fisiologia , Estações do Ano , Animais , TibetRESUMO
Ambient temperatures have great impacts on thermoregulation of small mammals. Brown adipose tissue (BAT), an obligative thermogenic tissue for small mammals, is localized not only in the interscapular depot (iBAT), but also in supraclavicular, infra/subscapular, cervical, paravertebral, and periaortic depots. The iBAT is known for its cold-induced thermogenesis, however, less has been paid attention to the function of BAT at other sites. Here, we investigated the function of BAT at different sites of the body during cold acclimation in a small rodent species. As expected, Brandt's voles (Lasiopodomys brandtii) consumed more food and reduced the body mass gain when they were exposed to cold. The voles increased resting metabolic rate and maintained a relatively lower body temperature in the cold (36.5 ± 0.27 °C) compared to those in the warm condition (37.1 ± 0.36 °C). During cold acclimation, the uncoupling protein 1 (UCP1) increased in aBAT (axillary), cBAT (anterior cervical), iBAT (interscapular), nBAT (supraclavicular), and sBAT (suprascapular). The levels of proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, were higher in cBAT and iBAT in the cold than in the warm group. The pAMPK/AMPK and pCREB/CREB were increased in cBAT and iBAT during cold acclimation, respectively. These data indicate that these different sites of BAT play the cold-induced thermogenic function for small mammals.
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Aclimatação , Tecido Adiposo Marrom , Arvicolinae , Temperatura Baixa , Termogênese , Proteína Desacopladora 1 , Animais , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Marrom/metabolismo , Arvicolinae/fisiologia , Aclimatação/fisiologia , Proteína Desacopladora 1/metabolismo , Termogênese/fisiologia , Masculino , Regulação da Temperatura Corporal/fisiologia , Metabolismo BasalRESUMO
Temporal niche partitioning is a crucial strategy for sympatric species to avoid predation and competition for habitat space and food resources. This study investigated the effect of the gut microbiota on the metabolic rhythms of two sympatric gerbil species (Meriones unguiculatus and Meriones meridianus) to test the hypothesis that the oscillatory patterns of microbiota may not fully mirror those of the host's metabolism. Experiment 1 compared the circadian metabolic and gut microbiota rhythms of M. unguiculatus (n = 12) and M. meridianus (n = 12) and measured the subjects' body temperatures and environmental temperature preferences. In Experiment 2.1, six M. meridianus gerbils were treated with antibiotics, and in Experiment 2.2, 21 M. unguiculatus gerbils (seven per treatment) were randomly gavaged with saline or a gut microbiota suspension from either M. unguiculatus or M. meridianus; their metabolic rhythms were subsequently measured. The results showed that the two gerbils had different metabolic phenotypes that determined activity heterogeneity and contributed to their coexistence. The relative abundances of Bacteroidetes, Actinobacteria, and Cyanobacteria in M. meridianus varied rhythmically in parallel with the daily metabolic rate, which was significantly higher at night than during the day. The rhythm of the metabolic rate was not noticeable in M. unguiculatus. However, in M.unguiculatus, the relative abundances of Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia were significantly higher during the day than at night, while Cyanobacteria exhibited the opposite pattern. Antibiotic treatment significantly weakened the metabolic rhythms of M. meridianus, and the circadian rhythms slowly recovered after stopping antibiotic gavage. However, after transplanting M. meridianus' gut microbiota into M. unguiculatus, the metabolic rate of M. unguiculatus was not significantly different from that of the control groups. Our hypothesis was partly supported: the microbiota was only partially involved in regulating the metabolic rhythms of gerbils, and other factors could compensate for the effect of the gut microbiota on host metabolic rhythms. This finding underscores the complexity of host-microbiota interactions and highlights the need for further exploration into the multifaceted mechanisms governing host metabolic regulation.
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Ritmo Circadiano , Microbioma Gastrointestinal , Gerbillinae , Animais , Fenótipo , Masculino , Simpatria , Temperatura Corporal , Antibacterianos/farmacologiaRESUMO
AIM: This study assessed the myocardial infarction (MI) using a novel fusion approach (multi-flavored or tensor-based) of multi-parametric cardiac magnetic resonance imaging (CMRI) at four sequences; T1-weighted (T1W) in the axial plane, sense-balanced turbo field echo (sBTFE) in the axial plane, late gadolinium enhancement of heart short axis (LGE-SA) in the sagittal plane, and four-chamber views of LGE (LGE-4CH) in the axial plane. METHODS: After considering the inclusion and exclusion criteria, 115 patients (83 with MI diagnosis and 32 as healthy control patients), were included in the present study. Radiomic features were extracted from the whole left ventricular myocardium (LVM). Feature selection methods were Least Absolute Shrinkage and Selection Operator (Lasso), Minimum Redundancy Maximum Relevance (MRMR), Chi-Square (Chi2), Analysis of Variance (Anova), Recursive Feature Elimination (RFE), and SelectPersentile. The classification methods were Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF). Different metrics, including receiver operating characteristic curve (AUC), accuracy, F1- score, precision, sensitivity, and specificity were calculated for radiomic features extracted from CMR images using stratified five-fold cross-validation. RESULTS: For the MI detection, Lasso (as the feature selection) and RF/LR (as the classifiers) in sBTFE sequences had the best performance (AUC: 0.97). All features and classifiers of T1 + sBTFE sequences with the weighted method (as the fused image), had a good performance (AUC: 0.97). In addition, the results of the evaluated metrics, especially mean AUC and accuracy for all models, determined that the T1 + sBTFE-weighted fused method had strong predictive performance (AUC: 0.93±0.05; accuracy: 0.93±0.04), followed by T1 + sBTFE-PCA fused method (AUC: 0.85±0.06; accuracy: 0.84±0.06). CONCLUSION: Our selected CMRI sequences demonstrated that radiomics analysis enables to detection of MI accurately. Among the investigated sequences, the T1 + sBTFE-weighted fused method with the highest AUC and accuracy values was chosen as the best technique for MI detection.
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Imageamento por Ressonância Magnética , Infarto do Miocárdio , Humanos , Infarto do Miocárdio/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Idoso , Adulto , Interpretação de Imagem Assistida por Computador/métodos , Máquina de Vetores de Suporte , Coração/diagnóstico por imagem , Curva ROC , RadiômicaRESUMO
Bone is a preferred metastatic site of prostate cancer (PCa), and most patients with PCa metastases develop osteogenic bone metastasis, which manifests as disturbed bone structure and poor bone quality. However, the underlying mechanisms of PCa bone metastasis remain unclear. In recent years, increasing evidence has implicated extracellular vesicles, especially exosomes, in PCa bone metastasis. Exosomes are 30-150 nm in diameter, enclosing a cargo of biomolecules, such as DNA, RNA, and proteins. Exosomes play a functional role in intercellular communication, modulate the functions of recipient cells, and potentially modulate bone microenvironment changes, thereby influencing the development of PCa bone metastasis. This review summarizes the involvement of exosomes in the imbalance between bone resorption and formation, and establishing a pre-metastatic niche in bone marrow, as well as potential clinical applications of exosomes in therapeutic strategies for treating patients with advanced PCa with bone metastasis.
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Neoplasias Ósseas , Exossomos , Vesículas Extracelulares , Neoplasias da Próstata , Masculino , Humanos , Exossomos/metabolismo , Neoplasias da Próstata/patologia , Neoplasias Ósseas/patologia , Comunicação Celular , Vesículas Extracelulares/metabolismo , Microambiente Tumoral , Metástase NeoplásicaRESUMO
Using fully ab initio molecular dynamics simulations based on the SCAN functional, we study the inherent structure of water and its temperature dependence. Our results show three types of translational ordering of the second oxygen coordination shell. With this as a criterion, the local structures in water are classified into three types, here named structures I, II, and III. In structure I, the second shell loses its translational ordering, while in structures II and III it presents a translational ordering similar to that in ice II (or ice V) and ice III, respectively. However, the tetrahedral orientational ordering distribution and bond-angle distribution in structures II and III are different from those in ice II (or ice V) and ice III. This indicates that the local atomic structures of liquid water and crystalline ice are not identical, although they have similar translational ordering. The temperature dependence of the inherent structure suggests that the density maximum of water originates from the competition not only between structures I and III, but also between structures II and III. These results provide fully ab initio evidence for the mixture model of water.
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AIM: To determine whether continuous venovenous hemodiafiltration (CVVHDF) plus standard medical therapy (SMT) vs. SMT alone prevents rhabdomyolysis (RM)-induced acute kidney injury (AKI) and analyze the related health economics. METHODS: This retrospective cohort study involved 9 RM patients without AKI, coronary heart disease, or chronic kidney disease treated with CVVHDF plus SMT (CVVHDF + SMT group). Nine matched RM patients without AKI treated with SMT only served as controls (SMT group). Baseline characteristics, biochemical indexes, renal survival data, and health economic data were compared between groups. In the CVVHDF + SMT group, biochemical data were compared at different time points. RESULTS: At 2 and 7 days after admission, serum biochemical indices (e.g., myoglobin, creatine kinase, creatinine, and blood urea nitrogen) did not differ between the groups. Total (P = 0.011) and daily hospitalization costs (P = 0.002) were higher in the CVVHDF + SMT group than in the SMT group. After 53 months of follow-up, no patient developed increased serum creatinine, except for 1 CVVHDF + SMT-group patient who died of acute myocardial infarction. In the CVVHDF + SMT group, myoglobin levels significantly differed before and after the first CVVHDF treatment (P = 0.008), and serum myoglobin, serum creatinine, and blood urea nitrogen decreased significantly at different time points after CVVHDF. CONCLUSIONS: Although CVVHDF facilitated myoglobin elimination, its addition to SMT did not improve biochemical indices like serum myoglobin, serum creatine kinase, creatinine, blood urea nitrogen, and lactate dehydrogenase or the long-term renal prognosis. Despite similar hospitalization durations, both total and daily hospitalization costs were higher in the CVVHDF + SMT group.
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Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Hemodiafiltração , Rabdomiólise , Humanos , Creatinina , Estudos Retrospectivos , Mioglobina , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Rabdomiólise/complicações , Creatina QuinaseRESUMO
BACKGROUND: Lumbar spinal stenosis (LSS) is a prevalent and disabling cause of low back and leg pain in elderly people and nerve root sedimentation sign (NRSS) has been demonstrated to have high sensitivity and specificity in diagnosing LSS in selected patients. The purpose of this study was to investigate the diagnosis of LSS and the predictive value of NRSS. METHODS: The clinical and imaging data of 176 patients diagnosed with LSS and 156 patients with non-specific low back pain (LBP) were analyzed retrospectively. Transverse magnetic resonance images (MRI) of the narrowest spinal canal in all patients were acquired and graded by two experienced doctors using the Braz classification, Schizas classification and Chen Jia classification. Receiver operating curve (ROC) was used to compare the diagnostic efficacy of the three classifications. Univariate and multivariate logistic regression models were established to predict the surgical indications of LSS patients. RESULT: The diagnostic efficacy of Schizas classification (AUC:0.943; 95%CI:0.918,0.969) and Chen Jia classification (AUC:0.942; 95%CI:0.918,0.966) was significantly higher than that of Braz classification (AUC:0.853; 95%CI:0.808,0.898). Chen Jia classification had the highest correlation with the degree of dural sac cross-sectional area (DCSA) stenosis. In the multivariate analysis of LSS surgical indications, Chen Jia classification (odds ratio [OR], 2.127; 95%CI:1.596,2.835), DCSA (OR,0.398; 95%CI:0.169,0.802) and intermittent claudication (OR,9.481; 95%CI:3.439,26.142) were associated with surgical indications. CONCLUSION: Among the three types, it is found that Chen Jia classification has better diagnostic efficacy in differentiating LSS from LBP. In addition, Chen Jia classification is simple to be implemented in clinical practice and has high clinical application value. Hence, Chen Jia classification can be used as an effective surgical treatment indicator for LSS patients.
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Estenose Espinal , Humanos , Idoso , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/patologia , Dor/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
In recent years, Fusarium head blight (FHB) has developed into a global disease that seriously affects the yield and quality of wheat. Effective measures to solve this problem include exploring disease-resistant genes and breeding disease-resistant varieties. In this study, we conducted a comparative transcriptome analysis to identify the important genes that are differentially expressed in FHB medium-resistant (Nankang 1) and FHB medium-susceptible (Shannong 102) wheat varieties for various periods after Fusarium graminearum infection using RNA-seq technology. In total, 96,628 differentially expressed genes (DEGs) were identified, 42,767 from Shannong 102 and 53,861 from Nankang 1 (FDR < 0.05 and |log2FC| > 1). Of these, 5754 and 6841 genes were found to be shared among the three time points in Shannong 102 and Nankang 1, respectively. After inoculation for 48 h, the number of upregulated genes in Nankang 1 was significantly lower than that of Shannong 102, but at 96 h, the number of DEGs in Nankang 1 was higher than that in Shannong 102. This indicated that Shannong 102 and Nankang 1 had different defensive responses to F. graminearum in the early stages of infection. By comparing the DEGs, there were 2282 genes shared at the three time points between the two strains. GO and KEGG analyses of these DEGs showed that the following pathways were associated with disease resistance genes: response to stimulus pathway in GO, glutathione metabolism, phenylpropanoid biosynthesis, plant hormone signal transduction, and plant-pathogen interaction in KEGG. Among them, 16 upregulated genes were identified in the plant-pathogen interaction pathway. There were five upregulated genes, TraesCS5A02G439700, TraesCS5B02G442900, TraesCS5B02G443300, TraesCS5B02G443400, and TraesCS5D02G446900, with significantly higher expression levels in Nankang 1 than in Shannong 102, and these genes may have an important role in regulating the resistance of Nankang 1 to F. graminearum infection. The PR proteins they encode are PR protein 1-9, PR protein 1-6, PR protein 1-7, PR protein 1-7, and PR protein 1-like. In addition, the number of DEGs in Nankang 1 was higher than that in Shannong 102 on almost all chromosomes, except chromosomes 1A and 3D, but especially on chromosomes 6B, 4B, 3B, and 5A. These results indicate that gene expression and the genetic background must be considered for FHB resistance in wheat breeding.
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Fusarium , Transcriptoma , Resistência à Doença/genética , Fusarium/genética , Perfilação da Expressão Gênica , Genótipo , Melhoramento Vegetal , Doenças das Plantas/genética , Triticum/genéticaRESUMO
Polyoxometalates have emerged as promising bactericidal agents. In the current study, the bactericidal activity of polyoxometalate K6[P2Mo18O62] against Escherichia coli (E. coli) O157:H7 and its possible underlying mechanisms were explored. The obtained results demonstrated that K6[P2Mo18O62] could effectively kill E. coli O157:H7 at millimolar levels. Moreover, K6[P2Mo18O62] treatment also induced significant increases in recA protein expression and further triggered characteristic apoptosis-like bacterial death events such as DNA fragmentation and phosphatidylserine exposure. In conclusion, polyoxometalate K6[P2Mo18O62] possesses a desirable antibacterial activity, and induction of bacterial apoptosis-like death might be involved in its underlying bactericidal mechanisms.
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Escherichia coli O157 , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Fragmentação do DNA , ApoptoseRESUMO
Heat sensation and tolerance are crucial for determining species' survival and distribution range of small mammals. As a member of the transmembrane proteins, transient receptor potential vanniloid 1 (TRPV1) is involved in the sensation and thermoregulation of heat stimuli; however, the associations between animal's heat sensitivity and TRPV1 in wild rodents are less studied. Here, we found that Mongolian gerbils (Meriones unguiculatus), a rodent species living in Mongolia grassland, showed an attenuated sensitivity to heat compared with sympatrically distributed mid-day gerbils (M. meridianus) based on a temperature preference test. To explain this phenotypical difference, we measured the TRPV1 mRNA expression of two gerbil species in the hypothalamus, brown adipose tissue, and liver, and no statistical difference was detected between two species. However, according to the bioinformatics analysis of TRPV1 gene, we identified two single amino acid mutations on two TRPV1 orthologs in these two species. Further Swiss-model analyses of two TRPV1 protein sequences indicated the disparate conformations at amino acid mutation sites. Additionally, we confirmed the haplotype diversity of TRPV1 in both species by expressing TRPV1 genes ectopicly in Escherichia coli system. Taken together, our findings supplemented genetic cues to the association between the discrepancy of heat sensitivity and the functional differentiation of TRPV1 using two wild congener gerbils, promoting the comprehension of the evolutionary mechanisms of the TRPV1 gene for heat sensitivity in small mammals.
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Regulação da Temperatura Corporal , Temperatura Alta , Animais , Gerbillinae/metabolismo , Regulação da Temperatura Corporal/genética , Aminoácidos/metabolismo , Variação GenéticaRESUMO
BACKGROUND: Some coronary artery angiography (CAG) scores are associated with the no-reflow phenomenon after percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). However, quality evidence regarding the association between the CAG scores and microvascular injury is still needed. Our study aimed to validate the ability of the CAG scores in predicting microvascular obstruction (MVO) detected by cardiac magnetic resonance (CMR) imaging. METHODS: From October 2020 to October 2021, 141 consecutive patients with acute STEMI who underwent primary PCI and CMR were retrospectively reviewed. CMR imaging was performed between 3 and 7 days after PCI. The patients were divided into MVO and non-MVO group based on the CMR results. Three CAG scores (SYNTAX score, SYNTAX II score and Gensini score) were used to assess the severity of coronary artery atherosclerotic burden. RESULTS: A total of 122 patients were included (mean age 60.6 ± 12.8 years). MVO occurred in 51 patients (41.8%). Patients with MVO had higher SYNTAX scores, SYNTAX II scores and Gensini scores than those without MVO (all p < 0.001). The Gensini score (r = 0.567, p < 0.001) showed the strongest correlation with infarction size than SYNTAX score (r = 0.521, p < 0.001) and SYNTAX II score (r = 0.509, p < 0.001). The areas under the receiver operator characteristic curves of SYNTAX score, SYNTAX II score and Gensini score for predicting MVO patients were 0.726, 0.774 and 0.807. In multivariable regression analysis, peak troponin I (odd ratio [OR] = 1.236, p = 0.001) and SYNTAX II score (OR = 11.636, p = 0.010) were identified as independent predictors of MVO. CONCLUSIONS: In patients with acute STEMI undergoing primary PCI treatment, the peak troponin I and SYNTAX II score may be an independent predictor of MVO.
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Infarto Miocárdico de Parede Anterior , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Idoso , Arritmias Cardíacas , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Humanos , Microcirculação , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Troponina IRESUMO
BACKGROUND: In the past, the diagnosis of hourglass-like fascicular constriction(s) of the anterior interosseous nerve mostly depended on electrophysiological examination, by which the location could not be diagnosed. There are few studies on the evaluation of hourglass-like fascicular constriction(s) by ultrasonography. PURPOSE: To evaluate the role of ultrasonography in the diagnosis of hourglass-like fascicular constriction(s) of the anterior interosseous nerve. MATERIAL AND METHODS: A retrospective analysis of 12 patients with hourglass-like fascicular constriction(s) of the anterior interosseous nerve was carried out, and the characteristics of the high-frequency ultrasonographic images were summarized and compared with surgical exploration. RESULTS: The 12 cases of hourglass-like fascicular constriction(s) of the anterior interosseous nerve were all located in the median nerve of the distal upper arm, including nine cases of single hourglass-like fascicular constriction and three cases of multiple hourglass-like fascicular constrictions. High-frequency ultrasonography can accurately locate the hourglass-like fascicular constriction(s) of the anterior interosseous nerve and the extent of neuropathy. The ultrasonographic images of hourglass-like fascicular constriction(s) of the anterior interosseous nerve showed single or multiple hourglass-like change(s) in the median nerve of the distal upper arm. The nerve fascicles on both sides of the affected nerve with hourglass-like change thickened. CONCLUSIONS: High-frequency ultrasonography could be a reliable, convenient, and non-invasive diagnostic imaging method for hourglass-like fascicular constriction(s) of the anterior interosseous nerve.
Assuntos
Nervo Mediano , Doenças do Sistema Nervoso Periférico , Constrição , Constrição Patológica/cirurgia , Humanos , Estudos Retrospectivos , UltrassonografiaRESUMO
Skeletal muscle-based nonshivering thermogenesis (NST) plays an important role in the regulation and maintenance of body temperature in birds and large mammals, which do not contain brown adipose tissue (BAT). However, the relative contribution of muscle-based NST to thermoregulation is not clearly elucidated in wild small mammals, which have evolved an obligate thermogenic organ of BAT. In this study, we investigated whether muscle would become an important site of NST when BAT function is conditionally minimized in Brandt's voles (Lasiopodomys brandtii). We surgically removed interscapular BAT (iBAT, which constitutes 52%~56% of total BAT) and exposed the voles to prolonged cold (4 °C) for 28 days. The iBAT-ablated voles were able to maintain the same levels of NST and body temperature (~37.9 °C) during the entire period of cold acclimation as sham voles. The expression of uncoupling protein 1 (UCP1) and its transcriptional regulators at both protein and mRNA levels in the iBAT of cold-acclimated voles was higher than that in the warm group. However, no difference was observed in the protein or mRNA levels of these thermogenesis-related markers except for PGC-1α in other sites of BAT (including infrascapular region, neck, and axilla) between warm and cold groups either in sham or iBAT-ablated voles. The iBAT-ablated voles showed higher UCP1 expression in white adipose tissue (WAT) than sham voles during cold acclimation. The expression of sarcolipin (SLN) and sarcoplasmic endoplasmic reticulum Ca2+-dependent adenosine triphosphatase (SERCA) in skeletal muscles was higher in cold than in warm, but no alteration in phospholamban (PLB) and phosphorylated-PLB (P-PLB) was observed. Additionally, there was increased in iBAT-ablated voles compared to that in the sham group in cold. Moreover, these iBAT-ablated voles underwent extensive remodeling of mitochondria and genes of key components related with mitochondrial metabolism. These data collectively indicate that recruitment of skeletal muscle-based thermogenesis may compensate for BAT impairment and suggest a functional interaction between the two forms of thermogenic processes of iBAT and skeletal muscle in wild small mammals for coping cold stress.
Assuntos
Tecido Adiposo Marrom , Temperatura Baixa , Animais , Aclimatação/fisiologia , Tecido Adiposo Marrom/metabolismo , Arvicolinae/genética , Músculo Esquelético/metabolismo , RNA Mensageiro/metabolismo , Termogênese/genética , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
We theoretically investigate the photodissociation dynamics of H2+ using the methodology of ultrafast X-ray photoelectron diffraction (UXPD). We use a femtosecond infrared pulse to prompt a coherent excitation from the molecular vibrational state (v = 9) of the electronic ground state (1sσg) and then adopt another time-delayed attosecond X-ray pulse to probe the dynamical properties. We have calculated photoionization momentum distributions by solving the non-Born-Oppenheimer time-dependent Schrödinger equation (TDSE). We unambiguously identify the phenomena associated with the g - u symmetry breakdown in the time-resolved photoelectron diffraction spectra. Using the two-center interference model, we can determine the variation in nuclear spacing with high accuracy. In addition, we use a strong field approximation (SFA) model to interpret the UXPD profile, and the SFA simulations can reproduce the TDSE results in a quantitative way.