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The quest for nonmagnetic Weyl semimetals with high tunability of phase has remained a demanding challenge. As the symmetry-breaking control parameter, the ferroelectric order can be steered to turn on/off the Weyl semimetals phase, adjust the band structures around the Fermi level, and enlarge/shrink the momentum separation of Weyl nodes which generate the Berry curvature as the emergent magnetic field. Here, we report the realization of a ferroelectric nonmagnetic Weyl semimetal based on indium-doped Pb1- x Sn x Te alloy in which the underlying inversion symmetry as well as mirror symmetry are broken with the strength of ferroelectricity adjustable via tuning the indium doping level and Sn/Pb ratio. The transverse thermoelectric effect (i.e., Nernst effect), both for out-of-plane and in-plane magnetic field geometry, is exploited as a Berry curvature-sensitive experimental probe to manifest the generation of Berry curvature via the redistribution of Weyl nodes under magnetic fields. The results demonstrate a clean, nonmagnetic Weyl semimetal coupled with highly tunable ferroelectric order, providing an ideal platform for manipulating the Weyl fermions in nonmagnetic systems.
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Increasing the number of teats in sheep helps to improve the survival rate of sheep lambs after birth. In order to analyze the candidate genes related to the formation of multiple teats in Hu sheep, the present study was conducted to investigate the genetic pattern of multiple teats in Hu sheep. In this study, based on genome-wide data from 157 Hu sheep, Fst, xp-EHH, Pi and iHS signaling were performed, and the top 5% signal regions of each analyzed result were annotated based on the Oar_v4.0 for sheep. The results show that a total of 142 SNP loci were selected. We found that PTPRG, TMEM117 and LRP1B genes were closely associated with polypodium formation in Hu sheep, in addition, among the candidate genes related to polypodium we found genes such as TMEM117, SLC25A21 and NCKAP5 related to milk traits. The present study screened out candidate genes for the formation of multiple teats at the genomic level in Hu sheep.
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Polimorfismo de Nucleotídeo Único , Animais , Ovinos/genética , Polimorfismo de Nucleotídeo Único/genética , Feminino , Estudo de Associação Genômica Ampla/veterináriaRESUMO
Cardiovascular diseases are considered the leading cause of death worldwide. Myocardial ischaemia/reperfusion (I/R) injury is recognized as a critical risk factor for cardiovascular diseases. Although increasing advances have been made recently in understanding the mechanisms of I/R injury, they remain largely unknown. In this study, we found that the expression of circPAN3 (circular RNA PAN3) was decreased in a mouse model of myocardial I/R. Overexpression of circPAN3 significantly inhibited autophagy and alleviated cell apoptosis of cardiomyocytes, which was further verified in vivo by decreased autophagic vacuoles and reduced myocardial infarct sizes. Moreover, miR-421 (microRNA-421) was identified as a downstream target involved in circPAN3-mediated myocardial I/R injury. Additionally, miR-421 could negatively regulate Pink1 (phosphatase and tensin homologue-induced putative kinase 1) via a direct binding relationship. Furthermore, the mitigating effects of circPAN3 overexpression on myocardial I/R injury by suppressing autophagy and apoptosis were abolished by knockdown of Pink1. Our findings reveal a novel role for circPAN3 in modulating autophagy and apoptosis in myocardial I/R injury and the circPAN3-miR-421-Pink1 axis as a regulatory network, which might provide potential therapeutic targets for cardiovascular diseases.
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Autofagia , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Proteínas Quinases/metabolismo , Animais , Regulação para Baixo , Masculino , Camundongos Endogâmicos C57BL , RNA Circular/metabolismoRESUMO
MicroRNAs are small non-coding RNA molecules that are important regulators of gene expression at the post-transcriptional level. miRNAs impact the processes of cell proliferation, differentiation and apoptosis. Thus, the regulation of miRNA expression profiles associated with mastitis will be conducive for its control. In this study, Staphylococcus aureus (S. aureus) was administered to the mammary gland of Chinese Holstein cows to construct a bacteria-type mastitis model. Total RNA was isolated from bovine mammary gland tissue samples from the S. aureus-induced mastitis group and controls. miRNAs were analyzed using Solexa sequencing and bioinformatics processing for the experimental group and control group. Two miRNA libraries were constructed respectively. A total of 370 known bovine miRNAs and 341 novel mi RNAs were detected for the S. aureus and 358 known bovine miRNAs and 232 novel miRNAs for control groups. A total of 77 miRNAs in the S. aureus group showed significant differences compared to the control group. GO (Gene Ontology) analysis showed these target genes were involved in the regulation of cells, binding, etc., while KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that these genes were enriched in endocytosis, and olfactory transduction pathways involved in cancer. These results provide an experimental basis to reveal the cause and regulatory mechanism of mastitis and also suggest the potential of miRNAs to serve as biomarkers for the diagnosis of mastitis in dairy cows.
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Perfilação da Expressão Gênica , Glândulas Mamárias Animais/metabolismo , MicroRNAs/metabolismo , Staphylococcus aureus/genética , Animais , Biomarcadores/metabolismo , Bovinos , DNA Bacteriano/química , DNA Bacteriano/metabolismo , Feminino , Biblioteca Gênica , Mastite Bovina/diagnóstico , Mastite Bovina/genética , Mastite Bovina/microbiologia , Modelos Biológicos , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA , Staphylococcus aureus/isolamento & purificaçãoRESUMO
OBJECTIVE: To determine the impact of Traditional Chinese Medicine on patients with chronic kidney disease (CKD). METHODS: A total of 225 CKD patients in an outpatient department were recruited for this study, among whom 170 received regular Western and Chinese medicine treatments (control group) and 55 received treatments guided by the theory of Traditional Chinese Medicine (experimental group). The effectiveness of the treatments was determined through a pre-post comparison. RESULTS: Significant pre-intervention differences in age (P < 0.01), stage of glomerular filtration rate (GFR) (P = 0.007) and urine protein (P < 0.01) were found between the two groups of patients. But age, gender and proteinuria were not significant predictors on clinical outcomes of the patients in the multivariate regression models. The experimental group had a greater level of decrease in blood urea nitrogen (P < 0.01) and serum creatine (P < 0. 01) than the control group. No significant differences between the groups were found in changes of uric acid (P = 0.475), urine protein (P = 0.058), urine red cells (P = 0.577), and urine white cells (P = 0.01). A greater level of increase in estimated glomerular filtration rate was found in the experimental group compared with the control (P < 0.001). The multivariate linear regression analysis identified group (B = 0.395, P < 0.001) and stage of GFR (B = 0.165, P = 0.008) as significant predictors on the outcomes of treatment. CONCLUSION: The treatment of CKD patients guided by the theory of Traditional Chinese Medicine can improve renal function through influencing glomerular filtration rate. The effect is more prominent than the regular treatment regime.
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Medicina Tradicional Chinesa , Insuficiência Renal Crônica/terapia , Nitrogênio da Ureia Sanguínea , Taxa de Filtração Glomerular , Humanos , ProteinúriaRESUMO
Topological flat bands - where the kinetic energy of electrons is quenched - provide a platform for investigating the topological properties of correlated systems. Here, we report the observation of a topological flat band formed by polar-distortion-assisted Rashba splitting in the three-dimensional Dirac material ZrTe5. The polar distortion and resulting Rashba splitting on the band are directly detected by torque magnetometry and the anomalous Hall effect, respectively. The local symmetry breaking further flattens the band, on which we observe resistance oscillations beyond the quantum limit. These oscillations follow the temperature dependence of the Lifshitz-Kosevich formula but are evenly distributed in B instead of 1/B at high magnetic fields. Furthermore, the cyclotron mass gets anomalously enhanced about 102 times at fields ~ 20 T. Our results provide an intrinsic platform without invoking moiré or order-stacking engineering, which opens the door for studying topologically correlated phenomena beyond two dimensions.
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Extreme environmental conditions are a major challenge for livestock production. Changes in climate conditions, especially those that lead to extreme weather, can reduce livestock production. The screening of genes and molecular markers is of great significance to explore the genetic mechanism of sheep prolificacy traits in Taklimakan Desert environment. We selected healthy adult Pishan Red Sheep (PRS) and Qira Black Sheep (QR) which live in Taklimakan Desert environment, collected blood from jugular vein, extracted DNA, and prepared Illumina Ovine SNP50 chip. For PRS, linkage disequilibrium (LD) was calculated using the ovine SNP50 Beadchip and the effective population size (Ne) was estimated using SMC++. The genetic characteristics of PRS were analyzed by integrated haplotype score (iHS) and fixation index (F ST ). The result showed that r 2 of PRS was 0.233 ± 0.280 in the range of 0-10 Kb and decreased with increasing distances. SMC++ tested that the Ne of PRS remained at 236.99 in recent generations. 184 genes were screened out under iHS 1% threshold, and 1148 genes were screened out with F ST under the 5% threshold, and 29 genes were obtained from the intersection of the two gene sets. In this study, the genetic characteristics of PRS and QR were compared by ovine genome chip, and the related excellent genes were searched, providing reference for the protection of sheep germplasm resources and molecular breeding in a desert environment.
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Growth traits are quantitative traits controlled by multiple micro-effect genes. we identified molecular markers related to sheep growth traits, which formed the basis of molecular breeding. In this study, we randomly selected 100 Qira Black sheep and 84 German Merino sheep for the blood collection the jugular vein to genotype by using the Illumina Ovine SNP 50K Bead Chip. quality control criteria for statistical analysis were: rejection detection rate < 90% and minimum allele frequency (MAF) < 5%. Then, we performed Genome-wide association studies (GWAS) on sheep body weight, body height, body length, and chest circumference using mixed linear models. After getting 55 SNPs with significant correlation, they were annotated by reference genome of Ovis aries genome (Oar_v4.0) and We obtained a total of 84 candidate genes associated with production traits (BMPR1B, HSD17B3, TMEM63C, etc.). We selected BMPR1B for population validation and found a correlation between the FecB locus and body weight traits. Therefore, this study not only supplements the existing knowledge of molecular markers of sheep growth traits, but also has important theoretical significance and reference value for the mining of functional genes of sheep growth traits.
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Estudo de Associação Genômica Ampla , Genoma , Animais , Ovinos/genética , Estudo de Associação Genômica Ampla/veterinária , Fenótipo , Genótipo , Peso Corporal/genética , Polimorfismo de Nucleotídeo Único , Carneiro Doméstico/genéticaRESUMO
BACKGROUND: Preoperative anemia is associated with increased postoperative morbidity and mortality and increased perioperative transfusion risk. For surgical patients, this affects physical and cognitive ability and quality of life, but it is an important and modifiable risk factor. AIM: To determine the effect of preoperative anemia on the prognosis of gastric cancer (GC) patients and generate a prognostic nomogram to predict the postoperative overall survival (OS) of GC patients with preoperative anemia. METHODS: Clinicopathological and follow-up data of GC patients treated at Zhejiang Provincial People's Hospital (China) from 2010 to 2015 were collected. Independent prognostic factors were screened by univariate and multivariate Cox regression analyses. Then, these factors were used to construct a nomogram to predict 1-, 3-, and 5-year postoperative OS in preoperative anemic GC patients. The nomogram was assessed by calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). RESULTS: Nine hundred and sixty GC patients were divided into two groups (preoperatively anemic and nonanemic), and postoperative survival analysis was performed on both groups, yielding a shorter postoperative survival for preoperatively anemic patients than for nonanemic patients. A total of 347 GC patients with preoperative anemia were included. Age, preoperative alpha-fetoprotein level, monocyte count, lymphocyte count, clinicopathological stage, liver metastasis, and GC type were identified as independent prognostic factors for OS. The area under the ROC curve (AUC) of the nomogram for predicting 1-, 3-, and 5-year OS was 0.831, 0.845, and 0.840, respectively, for the training cohort, and the corresponding AUC values in the validation cohort were 0.827, 0.829, and 0.812, respectively. Calibration curves and DCA indicated good performance of the nomogram. CONCLUSION: In all, we have successfully produced and verified a useful nomogram for predicting OS in GC patients with preoperative anemia. This nomogram based on a variety of clinicopathological indices can provide an effective prognostic assessment and help clinicians choose an appropriate treatment strategy for GC patients with preoperative anemia.
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Sheep are important livestock animals that have evolved under various ecological pressures. Xinjiang is a region with diverse and harsh environments that have shaped many local sheep breeds with unique characteristics and environmental adaptability. However, these breeds are losing ecological flexibility due to the promotion of intensive farming practices. Here we sequenced 14 local sheep breeds from Xinjiang and analyzed their genetic structure and gene flow with other sheep breeds from neighboring regions. The Tibetan Plateau was the geographic origin of Xinjiang native sheep evolution. We performed genome-environment association analysis and identified Bio9: Mean Temperature of Driest Quarter and Bio15: Precipitation Seasonality as the key environmental factors affecting Xinjiang local sheep and the key genes involved in their survival and adaptation. We classified Xinjiang native sheep breeds into six groups based on their differential genes by pairwise selective sweep analysis and Community Network Analysis. We analyzed transcriptome expression data of 832 sheep tissues and detected tissue-specific enrichment of six group-specific genes in different biological systems. Our results revealed the genetic basis of year-round estrus, drought tolerance, hypoxia resistance, and cold tolerance traits of Xinjiang sheep breeds. Moreover, we proposed conservation strategies for Xinjiang local sheep breeds and provided theoretical guidance for breeding new sheep breeds under global extreme environments.
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Meio Ambiente , Carneiro Doméstico , Feminino , Ovinos/genética , Animais , Carneiro Doméstico/genética , Genômica , China , Polimorfismo de Nucleotídeo ÚnicoRESUMO
PURPOSE: To prepare PEGS/ß-TCP modified magnesium alloy (PEGS/ß-TCP/MZG) membranes by forming a glycolated poly(sebacate)/ß-tricalcium phosphate (PEGS/ß-TCP) coating on the surface of magnesium-zinc-gadolinium alloy (MZG) membranes, and to evaluate the osteogenic induction activity and immunomodulatory properties of PEGS/ß-TCP/MZG using the material extract medium. METHODS: PEGS/ß-TCP coating was prepared on the surface of MZG by solvent method, and the PEGS/ß-TCP/MZG membrane was fabricated and compared with PEGS/ß-TCP and MZG to examine the morphology, composition, and hydrophilicity. The amount of magnesium ions released and the pH value of the materials were tested after 3 days of immersion. The cell viability and osteogenic differentiation of MC3T3 cells induced by extract medium were investigated by CCK-8 assay, ALP and mineralized nodule staining. The cell viability and polarization of RAW cells induced by extract medium were then investigated. The expression of macrophage-secreted cytokines was examined by PCR analysis. GraphPad Prism 9.0 software package was used for statistical analysis. RESULTS: PEGS/ß-TCP/MZG membranes with PEGS/ß-TCP coating tightly embedded with MZG were successfully fabricated, and the material had good hydrophilicity. The results of degradation experiments indicated that the PEGS/ß-TCP coating effectively slowed down the degradation rate of MZG, leading to a lower pH value and concentration of Mg2+ ion in the extract medium of PEGS/ß-TCP/MZG group. The results of in vitro cell experiments showed that PEGS/ß-TCP/MZG had no significant effect on the proliferation activity of both MC3T3-E1 and macrophages. PEGS/ß-TCP/MZG significantly enhanced the expression of ALP and mineralized nodule staining in MC3T3-E1. Although there was no significant difference in macrophage polarization pattern between PEGS/ß-TCP and PEGS/ß-TCP/MZG groups, PEGS/ß-TCP/MZG further reduced inflammation based on the immunomodulation of PEGS/ß-TCP coating related TNF-α expression and increased osteogenesis related TGF-ß expression. CONCLUSIONS: MZG membrane modified by PEGS/ß-TCP may provide a new material option for the development of bone tissue engineering.
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Magnésio , Osteogênese , Magnésio/farmacologia , Magnésio/química , Ligas/farmacologia , Ligas/química , Fosfatos de Cálcio/farmacologia , Diferenciação Celular , Polietilenoglicóis/farmacologiaRESUMO
[This corrects the article DOI: 10.3389/fgene.2023.1281601.].
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Local sheep in the northeastern Tarim Basin can adapt to dry and low-rainfall regional environments. In this study, three local sheep breeds in the northeastern Tarim Basin, LOP (LOP) sheep, Bayinbuluke (BYK) sheep, and Kunlun (KUN, also known as the Qiemo sheep) sheep, and three introduced sheep breeds, Suffolk (SUF) sheep, Dorset (APD) sheep, and Texel (TEX) sheep, were analyzed for genetic diversity, population structure, and selective signature using the Illumina OvineSNP50K BeadChip. We found that LOP, BYK, and KUN had lower observed heterozygosity and expected heterozygosity than TEX, SUF, and ADP, which were differentiated based on geographic distribution. We performed fixation index (FST) analysis on three local sheep breeds in the northeastern Tarim Basin (LOP, BYK, and KUN) and introduced sheep breeds (TEX, SUF, and ADP) to measure genetic differentiation. Nucleotide diversity (PI) analysis was performed on single-nucleotide polymorphism (SNP) data of LOP, BYK, and KUN. A total of 493 candidate genes were obtained by taking the intersection at a threshold of 5%. Among them, SMAD2, ESR2, and HAS2 were related to reproductive traits. PCDH15, TLE4, and TFAP2B were related to growth traits. SOD1, TSHR, and DNAJB5 were related to desert environmental adaptation. Analyzing the genetic patterns of local sheep in the northeastern Tarim Basin can protect the germplasm resources of local sheep and promote the development and utilization of sheep genetic resources.
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OBJECTIVE: Investigate the effects of compound Radix Notoginseng on renal interstitial fibrosis and kidney-targeting treatment. METHODS: 100 healthy Sprague-Dawley rats were randomly divided into 5 groups: Unilateral ureteral obstruction (UUO) group, sham-operation (SOR) group, Radix Notoginseng (RN) group, compound Radix Notoginseng (CRN) group and Losartan (ARB) group. After operation, RN, CRN and ARB groups were intragastric administrated with RN (3 mL/d), CRN (3 mL/d) and ARB [20 mg/(kg x d)] respectively. Each group randomly included 18 rats for statistical analysis. The histological changes of renal interstitial tissues were observed by HE, Masson and PAS staining. Total kidney collagen content was determined by measuring the amount of hydroxyproline. The mRNA of alpha-SMA, collagen I and fibronectin were reverse transcribed and quantified by real-time PCR. The expression of alpha-SMA protein was assessed by immunohistochemistry and Western blot analysis. RESULTS: In UUO model, the obstructed kidney showed typical features of renal tubulointerstitial fibrosis, such as severe tubular loss, dilation, atrophy, infiltration of inflammatory cells, interstitial matrix deposition (P < 0.05). Partial correlation assay showed that the expression of alpha-SMA was related to the renal tubular injury (r = 0.55; P < 0.05). Administration of RN, CRN and ARB improved tubulointerstitial damage and collagen matrix accumulation induced by UUO in different degree. The expression of the alpha-SMA at mRNA and protein levels were significantly increased in the UUO group (P < 0.05), which was also suppressed by treatment with RN, CRN and ARB in different degree. Moreover, more effective role in preventing fibrosis was observed in CRN group than when compared with that of RN group. CONCLUSION: RN and CRN can inhibit UUO-induced renal interstitial fibrosis in rats, and CRN treatment is more effective than RN in reducing interstitial fibrosis.
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Medicamentos de Ervas Chinesas/uso terapêutico , Rim/patologia , Nefrite Intersticial/prevenção & controle , Panax notoginseng/química , Fitoterapia , Actinas/genética , Actinas/metabolismo , Animais , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Fibronectinas/genética , Fibronectinas/metabolismo , Fibrose/etiologia , Fibrose/prevenção & controle , Losartan/uso terapêutico , Masculino , Nefrite Intersticial/etiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Obstrução Ureteral/complicaçõesRESUMO
The southern margin of the Taklimakan Desert is characterized by low rainfall, heavy sandstorms, sparse vegetation and harsh ecological environment. The indigenous sheep in this area are rich in resources, with the advantages of perennial estrus and good resistance to stress in most sheep. Exploring the molecular markers of livestock adaptability in this environment will provide the molecular basis for breeding research to cope with extreme future changes in the desert environment. In this study, we analyzed the population genetic structure and linkage imbalance of five sheep breeds with three different agricultural geographic characteristics using four complementary genomic selection signals: fixation index (FST), cross-population extended haplotype homozygosity (xp-EHH), Rsb (extended haplotype homozygosity between-populations) and iHS (integrated haplotype homozygosity score). We used Illumina Ovine SNP 50K Genotyping BeadChip Array, and gene annotation and enrichment analysis were performed on selected regions of the obtained genome. The ovary of Qira Black sheep (Follicular phase, Luteal phase, 30th day of pregnancy, 45th day of pregnancy) was collected, and the differentially expressed genes were screened by transcriptomic sequencing. Genome-wide selective sweep results and transcriptome data were combined for association analysis to obtain candidate genes associated with perennial estrus and stable reproduction. In order to verify the significance of the results, 15 resulting genes were randomly selected for fluorescence quantitative analysis. The results showed that Dolang sheep and Qira Black sheep evolved from Kazak sheep. Linkage disequilibrium analysis showed that the decay rate of sheep breeds in the Taklimakan Desert was higher than that in Yili grassland. The signals of FST, xp-EHH, Rsb and iHS detected 526, 332, 308 and 408 genes, respectively, under the threshold of 1% and 17 overlapping genes under the threshold of 5%. A total of 29 genes were detected in association analysis of whole-genome and transcriptome data. This study reveals the genetic mechanism of perennial estrus and environmental adaptability of indigenous sheep breeds in the Taklimakan Desert. It provides a theoretical basis for the conservation and exploitation of genetic resources of indigenous sheep breeds in extreme desert environment. This provides a new perspective for the quick adaptation of sheep and other mammals to extreme environments and future climate changes.
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Genômica , Polimorfismo de Nucleotídeo Único , Animais , Feminino , Haplótipos , Homozigoto , Desequilíbrio de Ligação , Mamíferos , Ovinos/genéticaRESUMO
Renal interstitial fibrosis is the major histopathological change seen in a variety of renal disorders and is closely related to renal dysfunction. Progressive interstitial fibrosis accompanied by the loss of renal tubules and interstitial capillaries typifies all progressive renal disease. Thrombospondin-1 (TSP-1) is a major angiogenic inhibitor. It is demonstrated that TSP-1 levels were correlated with the loss of glomerular and peritubular capillaries and TSP-1 could promote renal scarring by effects on the endothelium. It has been reported that ginsenoside Rg1 inhibited renal interstitial fibrosis in rats via suppressing the expression of TSP-1. The present study was designed to examine whether ginsenoside Rg1 could modulate the integrity of the microvasculature and hence affect the progression of renal fibrosis in a rat unilateral ureteral obstruction (UUO) model. In UUO control kidneys, associated with interstitial fibrosis, lower peritubular capillary densities were prominent. These changes were all improved by ginsenoside Rg1 treatment. Interestingly, ginsenoside Rg1 decreased the expression of TSP-1 and enhanced vascular endothelial growth factor (VEGF) expression. The results show for the first time that ginsenoside Rg1 can evidently inhibit renal interstitial fibrosis in rats with UUO. The mechanism might be related to suppression of the expression of TSP-1 and to repair of the peritubular capillary.
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Ginsenosídeos/farmacologia , Nefrite Intersticial/tratamento farmacológico , Trombospondina 1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Fibrose , Túbulos Renais/irrigação sanguínea , Túbulos Renais/patologia , Masculino , Nefrite Intersticial/patologia , Ratos , Ratos Sprague-Dawley , Obstrução Ureteral/patologiaRESUMO
BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Cardiac fibrosis is the scarring process occurs commonly with CVDs impairing the function and structure of heart. Herein, we investigated the role of circPAN3 in the pathogenesis of cardiac fibrosis. METHODS: A rat myocardial infarction (MI) model was constructed to evaluate the role of circPAN3. Expression of circPAN3 in MI was determined, and si-circPAN3 was applied to verify its profibrotic effects. With an in vitro model, cardiac fibroblasts were stimulated by transforming growth factor beta 1 (TGFß1). Immunofluorescent staining was employed to assess the fibrosis-related markers, as well as autophagy activity. CCK-8 and transwell assays were performed to determine cell proliferation and migration. Luciferase reporter assay and RNA pull-down were subjected to verify the interaction of circPAN3/miR-221. The enrichment of FoxO3 on the promoter region of ATG7 was detected using CHIP assay. RESULTS: Elevated circPAN3 was found in rat MI heart tissue, of which knockdown attenuated cardiac fibrosis after MI. In an in vitro model exposing with TGFß1, increasing cell proliferation and migration were observed, whereas these effects were abolished by circPAN3 knockdown, as well as autophagy activity. miR-221 was identified as a target to be involved in circPAN3-mediated cardiac fibrosis after MI. miR-221 negatively regulated FoxO3, thus causing the inhibition of ATG7 transcription. The regulatory network of circPAN3/miR-221/FoxO3/ATG7 in cardiac fibrosis was further determined in vivo. CONCLUSION: circPAN3 exhibited profibrotic effects during autophagy-mediated cardiac fibrosis via miR-221/FoxO3/ATG7 axis, which may serve as potential biomarkers for cardiac fibrosis therapeutics.
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Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , RNA Circular/genética , Animais , Autofagia/genética , Autofagia/fisiologia , Proteína 7 Relacionada à Autofagia/metabolismo , Proliferação de Células/genética , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibrose/metabolismo , Proteína Forkhead Box O3/metabolismo , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Miocárdio/metabolismo , RNA Circular/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/genéticaRESUMO
Phenotypic transformation of vascular smooth muscle cells (VSMCs) contributes to vascular remodeling in hypertension. High mobility group box-1 (HMGB1) has been reported to be involved in several pathogenic processes including VSMC proliferation and migration. The present study was designed to determine the role of HMGB1 in VSMC phenotypic transformation in hypertension. First, we demonstrated that HMGB1 was elevated in a model of Ang II-induced VSMC phenotypic transformation, which showed down-regulation of contractile proteins and up-regulation of synthetic proteins. Knockdown of HMGB1 and losartan could block the phenotypic transformation. Next, we identified three potential miRNAs for upstream regulation of HMGB1 by bioinformatic analysis; only miR-181b-5p was significantly down-regulated in Ang II-treated cells. Co-treating the cells with miR-181b-5p mimics suppressed HMGB1 expression as well as the phenotypic transformation, migration, and proliferation. Furthermore, the luciferase reporter gene assay confirmed the direct interaction between miR-181b-5p and HMGB1. Finally, to extend these cell-based studies to clinical patients, we demonstrated that plasma miR-181b-5p levels were decreased, while Ang II and HMGB1 levels, as well as the intima-media thickness (IMT) were increased in hypertensive patients; these effects were reversed following the administration of angiotensin receptor blockers. Based on these observations, we conclude that the down-regulation of miR-181b-5p leads to the elevation of HMGB1 levels in hypertensive patients, which accounts, at least partially, for VSMCs phenotypic transformation and vascular remodeling. Our findings also highlight that the plasma levels of miR-181b-5p and HMGB1 may serve as novel biomarkers for vascular remodeling in the hypertensive patients.
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Detecting the spectroscopic signatures of relativistic quasiparticles in emergent topological materials is crucial for searching their potential applications. Magnetometry is a powerful tool for fathoming electrons in solids, by which a clear method for discerning relativistic quasiparticles has not yet been established. Adopting the probes of magnetic torque and parallel magnetization for the archetype Weyl semimetal TaAs in strong magnetic field, we observed a quasi-linear field dependent effective transverse magnetization and a non-saturating parallel magnetization when the system enters the quantum limit. Distinct from the saturating magnetic responses for non-relativistic quasiparticles, the non-saturating signals of TaAs in strong field is consistent with our newly developed magnetization calculation for a Weyl fermion system in an arbitrary angle. Our results establish a high-field thermodynamic method for detecting the magnetic response of relativistic quasiparticles in topological materials.