Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.511
Filtrar
1.
Sci Rep ; 12(1): 7714, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35545627

RESUMO

Impacts of blending fusel oil with gasoline on fuel combustion have been investigated experimentally in the current research to evaluate engine performance improvement and exhaust emission. Tested fuel include F10, F20 (10% and 20% of fusel oil by volume) and pure gasoline as baseline fuel have been used to operate 4-cylinder SI engine at increasing engine speed and constant throttle valve of 45%. The present results reveal a shorter combustion duration and better engine performance with F10 over engine speeds with maximum value of 33.9% for the engine brake thermal efficiency. The lowest BSFC of 251 g/kW h was recorded at 3500 rpm engine speed also with F10. All blended fuel have almost similar COVIMEP. Less NOx emission was measured with F10 at 4500 engine speed compared to gasoline. However, CO emissions reduced while higher CO2 was observed with introducing fusel oil in the blend. Moreover, HC emission increased an average by 11% over speed range and the highest value was achieved with 10% fusel oil addition compared to 20% and pure gasoline. Accordingly, higher oxygen content of fusel oil and octane number contribute to improve combustion of fuel mixture.

2.
J Clin Invest ; 132(10)2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35575090

RESUMO

In hypertrophied and failing hearts, fuel metabolism is reprogrammed to increase glucose metabolism, especially glycolysis. This metabolic shift favors biosynthetic function at the expense of ATP production. Mechanisms responsible for the switch are poorly understood. We found that inhibitory factor 1 of the mitochondrial FoF1-ATP synthase (ATPIF1), a protein known to inhibit ATP hydrolysis by the reverse function of ATP synthase during ischemia, was significantly upregulated in pathological cardiac hypertrophy induced by pressure overload, myocardial infarction, or α-adrenergic stimulation. Chemical cross-linking mass spectrometry analysis of hearts hypertrophied by pressure overload suggested that increased expression of ATPIF1 promoted the formation of FoF1-ATP synthase nonproductive tetramer. Using ATPIF1 gain- and loss-of-function cell models, we demonstrated that stalled electron flow due to impaired ATP synthase activity triggered mitochondrial ROS generation, which stabilized HIF1α, leading to transcriptional activation of glycolysis. Cardiac-specific deletion of ATPIF1 in mice prevented the metabolic switch and protected against the pathological remodeling during chronic stress. These results uncover a function of ATPIF1 in nonischemic hearts, which gives FoF1-ATP synthase a critical role in metabolic rewiring during the pathological remodeling of the heart.

3.
J Oncol ; 2022: 1934381, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35607327

RESUMO

Pancreatic adenocarcinoma (PAAD) is a major threat to people's health. PRDM1 is a transcription factor with multiple functions, and its functions have been validated in a variety of tumors; however, there are few studies reported on PRDM1 in PAAD. Using the GEPIA2 database, this research found that PRDM1 expression in PAAD was significantly higher than that in normal pancreatic tissue. The Kaplan-Meier Plotter database showed that high expression of PRDM1 in PAAD has a poor prognosis, suggesting that PRDM1 may be a potential prognostic marker in PAAD. The cBioPortal database shows that the expression of PRDM1 in PAAD is significantly correlated with its methylation degree. Further analysis on the coexpressed genes of PRDM1 in PAAD was performed by using LinkedOmics database to explore potential mechanisms. Based on gene enrichment analysis, PRDM1 was implicated in many pathways involved in tumor progression. In the construction of a PPI network of PRDM1 and its coexpressed gene protein via the STRING database, we found that PRDM1 may be involved in the pathogenesis and development of PAAD. TIMER database suggested that a high level of PRDM1 has a significant positive correlation with macrophages, neutrophils, and DCs. Potential methylation sites of PRDM1 were found through DNMIVD database, and MethSurv database explored eight sites which were significantly related with the prognosis of PAAD. In conclusion, PRDM1 may work as a prognostic marker or even provide a potential therapeutic strategy in PAAD.

4.
Asian J Surg ; 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35504778

RESUMO

Autologous lipotransfer is an essential component of soft tissue reconstruction. However, it is not widely applied or accepted by surgeons due to its unstable survival rate and uncertain efficacy. The cell-assisted fat transfer (CAL) is a promising technique that increases the fat survival rate. However, it is controversial based on various clinical studies. Here, we assessed the fat survival and complication rates of CAL, compared to the conventional autologous lipotransfer. To conduct our research, two reviewers independently screened related articles published in Medicine (via PubMed), EMBASE, Cochrane Library, and Web of Science. The combined effect estimates for efficacy evaluation was performed by the Review Manager software (RevMan 5.4.1). In total, 14 articles were included in our analysis (n = 722). Based on our analysis, the survival rate of the fat graft in CAL was significantly higher than the conventional fat grafting group (non-CAL group) (SMD = 2.81, 95%CI [1.54, 4.08], P < 0.01). In the subgroup, the fat retention of CAL in the facial filling was higher than the conventional one (SMD = 3.01, 95%CI [1.68, 4.33], P < 0.01). After breast augmentation, however, the difference between the experimental and control group was not statistically significant (SMD = 1.80, 95%CI [-0.31, 3.91], P = 0.09). Moreover, the CAL group exhibited comparable complications as the non-CAL group. Based on our analysis, the CAL group was significantly better than the conventional lipotransfer in terms of fat survival, particularly, during facial filling. However, it failed to reduce the complication rate, compared to the non-CAL group.

5.
Chem Commun (Camb) ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506638

RESUMO

Multidentate chelation effect can be used to activate the ultralong room-temperature phosphorescence and stabilize the triplet excitons. The as-synthesized cadmium(II) based complexes further exhibit thermo- and excitation-dependent persistent luminescence as potential for optical logic gate.

6.
J Nucl Cardiol ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508796

RESUMO

BACKGROUND: The GE Discovery NM (DNM) 530c/570c are dedicated cardiac SPECT scanners with 19 detector modules designed for stationary imaging. This study aims to incorporate additional projection angular sampling to improve reconstruction quality. A deep learning method is also proposed to generate synthetic dense-view image volumes from few-view counterparts. METHODS: By moving the detector array, a total of four projection angle sets were acquired and combined for image reconstructions. A deep neural network is proposed to generate synthetic four-angle images with 76 ([Formula: see text]) projections from corresponding one-angle images with 19 projections. Simulated data, pig, physical phantom, and human studies were used for network training and evaluation. Reconstruction results were quantitatively evaluated using representative image metrics. The myocardial perfusion defect size of different subjects was quantified using an FDA-cleared clinical software. RESULTS: Multi-angle reconstructions and network results have higher image resolution, improved uniformity on normal myocardium, more accurate defect quantification, and superior quantitative values on all the testing data. As validated against cardiac catheterization and diagnostic results, deep learning results showed improved image quality with better defect contrast on human studies. CONCLUSION: Increasing angular sampling can substantially improve image quality on DNM, and deep learning can be implemented to improve reconstruction quality in case of stationary imaging.

7.
Free Radic Biol Med ; 186: 66-75, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35550920

RESUMO

Developing nuclear factor erythroid-2 related factor 2 (Nrf2)-dependent cytoprotectors against oxidative damage is of concern because they can effectively reduce the risk of oxidative stress-related diseases, such as cancer and inflammation. This work was aimed to develop more active Nrf2-dependent cytoprotectors than curcumin, a well-known dietary Nrf2 activator and cancer chemopreventive agent. Herein we designed a panel of curcumin-inspired mono-carbonyl piperidinone analogs differentiated by placing distinct electron-withdrawing and electron-donating groups on its two aromatic rings in the ortho, meta, or para position to the linker of α, ß-unsaturated piperidinone. Among these, the ortho-fluorine-substituted CN-2F surfaced as a promising lead molecule, which was significantly superior to the parent curcumin in protecting HepG2 cells from oxidative damage induced by tert-butyl hydroperoxide. Mechanically, by virtue of its Michael receptor units and ortho-substituted mode, CN-2F activated Nrf2 signaling by covalently modifying Cys-151 and Cys-288 residues at Keap1, promoting phosphorylation of JNK, ERK and p38, as well as inhibiting Nrf2 degradation. This work reveals the structural determinants and the activity mechanisms of CN-2F as an Nrf2-dependent cytoprotector, and gives useful information on how to design curcumin-inspired Nrf2 activators and cytoprotectors.

8.
Eur J Pharmacol ; 925: 174990, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35500643

RESUMO

Accumulating evidence suggests that ginger and its pungent constituents harbor a wealth of biological activities including cancer chemopreventive activity. However, relatively few researches focus on [6]-dehydroshogaol (6-DHS) compared with other ginger pungent constituents such as [6]-shogaol (6S). In this work, we selected three ginger compounds, 6-DHS, 6S and [6]-paradol (6P) differentiated by the presence and number of the Michael acceptor units, to probe structural basis and mechanism of 6-DHS in inhibiting angiogenesis, a key step for tumor growth and metastasis. It was found that their antiangiogenic activity is significantly dependent on the presence and number of Michael acceptor units. Benefiting from its two Michael acceptor units, 6-DHS is the most potent inhibitor of thioredoxin reductase and depletor of glutathione, thereby being the most active generator of reactive oxygen species, which is responsible for its strongest ability to inhibit angiogenesis. This work highlights 6-DHS being a Michael acceptor-dependent pro-oxidative angiogenesis inhibitor.

9.
Psychoneuroendocrinology ; 142: 105777, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35504198

RESUMO

OBJECTIVE: The purpose of this study was to investigate the role of aberrant DNA methylation of hypothalamic-pituitary-adrenal (HPA) axis-related genes (CRHR1, CRHR2, CRH, FKBP5, HSP90AA1, NR3C1, and POMC) in panic disorder (PD) development. We investigated the correlation among gene methylation levels, adrenocorticotropic hormone (ACTH), cortisol, and PD severity in patients. METHODS: We compared the methylation levels of HPA axis-related genes between 178 patients with PD and 184 healthy controls using MethylTarget. We then measured ACTH and cortisol levels using chemiluminescence. Disease severity was assessed using the Panic Disorder Severity Scale. RESULTS: Compared with healthy controls, patients with PD displayed significantly higher levels of ACTH and cortisol, and significantly reduced methylation levels of CRHR1, FKBP5, HSP90AA1, and NR3C1 after correcting for multiple testing using the false discovery method. A significant positive correlation was observed between the methylation of CRHR1, CRHR2, and NR3C1 and ACTH levels in patients with PD, and methylation levels of CRHR1 and NR3C1 were significantly positively related to cortisol levels. In addition, a negative correlation was observed between PD severity and the methylation of CRH, CRHR1, CRHR2, and HSP90AA1. CONCLUSION: Aberrant methylation of HPA axis-related genes may predict PD development and impact ACTH and cortisol levels.

10.
J Cell Physiol ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35533255

RESUMO

Yes-associated protein (YAP) is a major component of the Hippo pathway involved in development, growth, repair and homeostasis. Nonsense YAP1 mutations in humans result in autosomal dominant coloboma. Here, we generated a conditional knockout mouse model in which Yap1 was specifically deleted in embryonic retinal progenitor cells (RPCs) and in mature Müller cells using a Chx10-Cre driver. Our data demonstrated that the conditional ablation of Yap1 in embryonic RPCs does not prevent normal retinal development and caused no gross changes in retinal structure during embryonic and early postnatal life. Nevertheless, Yap1 deficient in retinal Müller cells in adult mice leads to impaired visual responses and extensive late-onset retinal degeneration, characterized by reduced cell number in all retinal layers. Immunofluorescence data further revealed the degeneration and death of rod and cone photoreceptors, bipolar cells, horizontal cells, amacrine cells and ganglion cells to varying degrees in aged knockout mice. Moreover, alteration of glial homeostasis and reactive gliosis were also observed. Finally, cell proliferation and TUNEL assay revealed that the broad retinal degeneration is mainly caused by enhanced apoptosis in late period. Together, this work uncovers that YAP is essential for the normal vision and retinal maintenance, highlighting the crucial role of YAP in retinal function and homeostasis.

11.
Math Biosci Eng ; 19(6): 5754-5771, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35603377

RESUMO

The study of drug side effects is a significant task in drug discovery. Candidate drugs with unaccepted side effects must be eliminated to prevent risks for both patients and pharmaceutical companies. Thus, all side effects for any candidate drug should be determined. However, this task, which is carried out through traditional experiments, is time-consuming and expensive. Building computational methods has been increasingly used for the identification of drug side effects. In the present study, a new path-based method was proposed to determine drug side effects. A heterogeneous network was built to perform such method, which defined drugs and side effects as nodes. For any drug and side effect, the proposed path-based method determined all paths with limited length that connects them and further evaluated the association between them based on these paths. The strong association indicates that the drug has a side effect with a high probability. By using two types of jackknife test, the method yielded good performance and was superior to some other network-based methods. Furthermore, the effects of one parameter in the method and heterogeneous network was analyzed.


Assuntos
Algoritmos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Descoberta de Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos
12.
Front Cell Dev Biol ; 10: 839583, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433684

RESUMO

Pigs are important biomedical model animals for the study of human neurological diseases. Similar to human aggressive behavior in children and adolescents, weaned pigs also show more aggressive behavior after mixing, which has negative effects on animal welfare and growth performance. The identification of functional single-nucleotide polymorphisms (SNPs) related to the aggressive behavior of pigs would provide valuable molecular markers of the aggressive behavioral trait for genetic improvement program. The Rho GTPase-activating protein 24 (ARHGAP24) gene plays an important role in regulating the process of axon guidance, which may impact the aggressive behavior of pigs. By resequencing the entire coding region, partially adjacent introns and the 5' and 3' flanking regions, six and four SNPs were identified in the 5' flanking region and 5' untranslated region (UTR) of the porcine ARHGAP24 gene, respectively. Association analyses revealed that nine SNPs were significantly associated with aggressive behavioral traits (p = < 1.00 × 10-4-4.51 × 10-2), and their haplotypes were significantly associated with aggressive behavior (p = < 1.00 × 10-4-2.99 × 10-2). The core promoter region of the ARHGAP24 gene has been identified between -670 and -1,113 bp. Furthermore, the luciferase activity of allele A of rs335052970 was significantly less than that of allele G, suggesting that the transcriptional activity of the ARHGAP24 gene was inhibited by allele A of rs335052970. It was identified that the transcription factor p53 bound to the transcription factor binding sites (TFBSs) containing allele A of rs335052970. In porcine primary neural cells, p53 binds to the target promoter region of the ARHGAP24 gene, reduces its promoter transcriptional activity, and then reduces its messenger RNA (mRNA) and protein expression. The results demonstrated that the ARHGAP24 gene had significant genetic effects on aggressive behavioral traits of pigs. Therefore, rs335052970 in the ARHGAP24 gene can be used as a molecular marker to select the less aggressive pigs.

13.
Int J Mol Sci ; 23(8)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35456943

RESUMO

Plant growth and development are greatly affected by the environment. Many genes have been identified to be involved in regulating plant development and adaption of abiotic stress. Apart from protein-coding genes, more and more evidence indicates that non-coding RNAs (ncRNAs), including small RNAs and long ncRNAs (lncRNAs), can target plant developmental and stress-responsive mRNAs, regulatory genes, DNA regulatory regions, and proteins to regulate the transcription of various genes at the transcriptional, posttranscriptional, and epigenetic level. Currently, the molecular regulatory mechanisms of sRNAs and lncRNAs controlling plant development and abiotic response are being deeply explored. In this review, we summarize the recent research progress of small RNAs and lncRNAs in plants, focusing on the signal factors, expression characters, targets functions, and interplay network of ncRNAs and their targets in plant development and abiotic stress responses. The complex molecular regulatory pathways among small RNAs, lncRNAs, and targets in plants are also discussed. Understanding molecular mechanisms and functional implications of ncRNAs in various abiotic stress responses and development will benefit us in regard to the use of ncRNAs as potential character-determining factors in molecular plant breeding.


Assuntos
RNA Longo não Codificante , Regulação da Expressão Gênica de Plantas , Desenvolvimento Vegetal/genética , Plantas/genética , Plantas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA de Plantas/genética , RNA de Plantas/metabolismo , RNA não Traduzido/genética , Estresse Fisiológico/genética
14.
Front Neurosci ; 16: 838942, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401102

RESUMO

Background: Some studies have shown that arginine vasopressin (AVP) can significantly improve the social interaction disorder of autism, but the mechanism remains unclear. Methods: Female Wistar rats were intraperitoneally injected with VPA or normal saline at embryonic day 12.5 to establish an autism model or normal control in their offspring. Male offspring prenatally exposed to VPA were randomly assigned to two groups: the VPA-induced autism model group and the AVP group. The rats in the AVP group were treated with intranasal AVP at postnatal day (PND) 21 and for 3 weeks. The VPA-induced autism model group was given the same dose of normal saline in the same way. Behavioral responses were evaluated in the open field and three-chambered social test apparatus; the expression levels of AVP in serum were detected by enzyme-linked immunosorbent assay kit, and the gene expression levels on the amygdala were measured by RNA-seq at PND42. Results: Intranasal administration of AVP can significantly improve the social interaction disorder and elevate the levels of AVP in serum. Transcriptome sequencing results showed that 518 differently expressed genes (DEGs) were identified in the VPA-induced autism model group compared with the control in this study. Gene Ontology biological process enrichment analysis of DEGs showed that the VPA-induced autism model group had significant nervous system developmental impairments compared with the normal group, particularly in gliogenesis, glial cell differentiation, and oligodendrocyte differentiation. Gene Set Enrichment Analysis (GSEA) enrichment analysis also showed that biological process of oligodendrocyte differentiation, axoneme assembly, and axon ensheathment were inhibited in the VPA-induced autism model group. Pathway enrichment analysis of DEGs between the control and VPA-induced autism model group showed that the PI3K/AKT and Wnt pathways were significantly dysregulated in the VPA-induced autism model group. Few DEGs were found when compared with the transcriptome between the VPA-induced autism model group and the AVP treatment group. GSEA enrichment analysis showed deficits in oligodendrocyte development and function were significantly improved after AVP treatment; the pathways were mainly enriched in the NOTCH, mitogen-activated protein kinase, and focal adhesion signaling pathways, but not in the PI3K/AKT and Wnt pathways. The expression patterns analysis also showed the same results. Conclusion: AVP can significantly improve the social interaction disorder of VPA-induced autism model, and AVP may target behavioral symptoms in autism by modulating the vasopressin pathways, rather than primary disease mechanisms.

15.
PLoS One ; 17(4): e0266981, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35413073

RESUMO

This paper examines the effect of GPA on graduating students' wages using a data set from an elite university in China. Students are homogenous since their majors are closely related to economics and business The OLS regression results indicate that GPA has positive and significant impacts on wages on average. As GPA increases by 1 unit, the starting monthly wage increases by 29.6 percent on average, and the wage in the survey year that is 3-5 years after graduation (current wage) soars by 25 percent. Theoretically, the GPA matters for the wages due to both the human capital or signaling effect. Given that the signaling effect should diminish over time, and the effect on starting wage is a little larger than that on current wage, it is suggested that signaling effect of GPA should be trivial, and high GPA is associated with high wage should be mainly due to the human capital effect. These results are robust to different model specifications. The distributional analysis suggest that the effects are positive for both wages and significant for almost all quantiles. In addition, the effect is basically the same from the 0.05th to 0.80th quantiles, and then rises as the starting wage increases. The effect on current wage is a U shape from the 0.05th to 0.60th quantile, and then becomes an inverse-U shape with peaks at the 0.75th and 0.80th quantiles where the effect is 82.2 percent when GPA increases by one unit.


Assuntos
Salários e Benefícios , Humanos , Universidades
16.
Mov Disord ; 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35426475

RESUMO

BACKGROUND: Spinocerebellar ataxia type 3 (SCA3) is an inherited motor disorder that is characterized by low body mass index (BMI). Considering the role of the hypothalamus in regulating appetitive behaviors and metabolism, low BMI may result from hypothalamic degeneration. OBJECTIVES: To examine hypothalamic volume changes in SCA3 by comparing patients and matched healthy controls and to identify potential mediating effects of hypothalamic pathology on CAG repeats for BMI. METHODS: Magnetic resonance imaging datasets of hypothalamic volumes from 41 SCA3 patients and 49 matched controls were analyzed. Relationships among CAG repeat number, hypothalamic volumes, and BMI were assessed using correlation and mediation analyses. RESULTS: SCA3 patients exhibited significant hypothalamic atrophy. Tubular hypothalamic volume was significantly associated with BMI. Mediation analysis revealed an indirect effect of CAG repeat number on BMI via tubular hypothalamic atrophy. CONCLUSIONS: Low BMI in SCA3 is related to neurodegeneration within the tubular hypothalamus, providing a potential target for energy-based treatment. © 2022 International Parkinson and Movement Disorder Society.

17.
Bioact Mater ; 18: 199-212, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35387162

RESUMO

Although ultra-small nanoclusters (USNCs, < 2 nm) have immense application capabilities in biomedicine, the investigation on body-wide organ responses towards USNCs is scant. Here, applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues, we systematically evaluate the interactions between the host and calcium phosphate (CaP) USNCs at the organism level. Combining single-cell mass cytometry, and magnetic luminex assay results, we identify dynamic immune responses to CaP USNCs at the single cell resolution. The innate immune is initially activated and followed by adaptive immune activation, as evidenced by dynamic immune cells proportions. Furthermore, using Nano Genome Atlas of multi-tissues, we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney. Moreover, based on the immunological response profiles, histological evaluation of major organs and local tissue, and a body-wide transcriptomics, we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection. Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.

18.
J Anim Sci ; 100(5)2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35419600

RESUMO

Variation in genes of the serotonergic system influences aggressive behavior by affecting serotonin levels in the central and cortical nervous system. SLC6A4 (serotonin transporter) is a master regulator of 5-HT signaling and involved in the regulation of aggressive behavior in humans and rodents. To identify potential functional single nucleotide polymorphisms (SNPs) for the porcine SLC6A4 gene associated with aggressive behavior, a total of 500 pigs (268 barrows and 232 gilts) were selected and mixed in 51 pens. Their behavior was recorded and observed for 72 h after mixing. Based on a composite aggressive score (CAS), the most aggressive and the least aggressive pigs within each pen were selected separately (a total of 204 pigs). Ear tissue was sampled to extract genomic DNA. Eight SNPs in the 5'-flanking region, coding region, and 3'-untranslated region (3'-UTR) of SLC6A4 were genotyped, of which 6 SNPs had significant differences (P < 0.05) in allele frequency between the most aggressive and least aggressive pigs. Luciferase activity was greater in plasmids of genotype GG than plasmids of genotype CC of rs345058216 (P < 0.01). Computational analysis nominated MAZ as putative transcription factor (TF) with higher probability to bind the SLC6A4 promoter at the SNP (rs345058216) site. Also, we demonstrated that MAZ overexpression modulates SLC6A4 promoter activity in allele-specific manner with an in vitro assay. In addition, we demonstrated that SLC6A4 was a direct target of miR-671-5p. The dual luciferase reporter gene assay and cell transfection were performed to examine the role of miR-671-5p in regulating SLC6A4 expression. The luciferase assays revealed that the SNP rs332335871 affects regulation of miR-671-5p in SLC6A4 expression. After overexpression of miR-671-5p in porcine primary neural cells, the SLC6A4 mRNA levels can be significantly reduced. In conclusion, we here found that miR-671-5p and MAZ mediated porcine SLC6A4 expression level, which provides the possible molecular mechanism of aggressive behavior.


The current study identified the functional single nucleotide polymorphisms for the porcine SLC6A4 (serotonin transporter) gene associated with aggressive behavior of pigs after mixing. We investigated the underlying molecular regulation mechanism of those functional variations. SNP rs345058216 (c.-1694C > G) affects binding of the transcription factor MAZ (MYC associated zinc finger protein) to the core promoter region of the SLC6A4 gene, whereas SNP rs332335871 (c.*1586G > A) affects the binding of miR-671-5p to the 3ʹ-UTR of SLC6A4 gene. These results suggest that rs345058216 and rs332335871 could be used as candidate molecular markers for aggressive behavior of pigs after mixing.

19.
J Affect Disord ; 308: 98-105, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35427713

RESUMO

BACKGROUND: Generalized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) are both characterized by cognitive and social impairments. Determining disorder-specific neurobiological alterations in GAD and MDD by means of functional magnetic resonance imaging (fMRI) may promote determination of precise diagnostic markers. METHODS: This study aimed to examine disorder-specific behavioral and neural alterations at the intersection of social and cognitive processing in treatment-naïve first-episode GAD (n = 35) and MDD (n = 37) patients compared to healthy controls (n = 35) by employing a social-emotional n-back fMRI paradigm. RESULTS: No behavioral differences between patients and healthy controls were observed. However, GAD patients exhibited decreased bilateral dorsomedial prefrontal cortex (dmPFC) engagement during the 0-back condition yet increased dmPFC engagement during the 1-back condition compared to MDD and healthy participants. In contrast, MDD patients exhibited increased dmPFC-insula coupling during 0-back, yet decreased coupling during 1-back, compared to GAD and healthy participants. Dimensional symptom-load analysis confirmed that increased dmPFC-insula connectivity during 0-back was positively associated with depressive symptom load. LIMITATIONS: The moderate sample size in the present study did not allow us to further explore gender differences. In addition, some patients exhibited GAD and MDD comorbidity according to the M.I.N.I. interview. Finally, the paradigm we used did not allow to further disentangle emotion-specific effects on working memory. CONCLUSIONS: These findings suggest that the dmPFC engaged in integrating affective and cognitive components and self-other processing exhibits GAD-specific neurofunctional dysregulations whereas functional dmPFC communication with the insula, a region involved in salience processing, may represent an MDD-specific neurofunctional deficit.


Assuntos
Transtorno Depressivo Maior , Transtornos de Ansiedade/diagnóstico por imagem , Cognição , Transtorno Depressivo Maior/diagnóstico por imagem , Emoções , Humanos , Imageamento por Ressonância Magnética , Memória de Curto Prazo
20.
Anal Chem ; 94(16): 6216-6224, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35420783

RESUMO

Specific locations of carbon-carbon double bonds (C═C) in lipids often play an essential role in biological processes, and there has been a booming development in C═C composition analysis by mass spectrometry. However, a universal derivatization and fragmentation pattern for the annotation of C═C positions in lipids is still challenging and attractive. To expand this field in lipidomics, a flexible and convenient N-tosylaziridination method was developed, with high derivatization efficiency, sensitivity, and specificity. The derivatization was very fast (15 s), and C═C numbers as well as locations could be pinpointed specifically in tandem mass spectra. By qualitative and quantitative studies of paratumor and tumor thyroid tissues of human beings, the total content of unsaturated fatty acids was suggested to be increased in tumor tissues, and good correlations in and between lysophosphatidylcholines and phosphatidylcholines were revealed by Spearman analysis. Further studies of C═C isomers showed that n-6/n-3 ratios were closely associated with human thyroid tumorigenesis, and high ratios of n-6/n-3 isomers seemed to suffer a high risk of carcinogenesis. Other isomers were not very representative; however, C═C in n-9/n-7 could also be significant for oncology research. Generally, it is supposed that both total amounts and C═C isomer ratios were related to cancer, and N-tosylaziridine derivatization could provide an alternative strategy for the C═C isomer study of disease models.


Assuntos
Fosfatidilcolinas , Glândula Tireoide , Carbono , Cloraminas , Ácidos Graxos Insaturados/análise , Humanos , Espectrometria de Massas em Tandem/métodos , Compostos de Tosil
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...