Highlights • Seven PI3K isoforms were isolated and characterized. • mRNA levels of PI3Ks were widely distributed in tissues, but the highest in ovary. • Insulin significantly influenced hepatic ...protein metabolism and the effects were time-dependent. • PI3KCb and PI3KC2a mediated the insulin-induced changes of protein metabolism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•The regions of grp78, perk, ire-1α and atf-6α promoters were cloned.•Multiple CREB binding sites were identified in their promoter regions.•These CREB binding sites played crucial role in ...transcriptional regulation of UPR.•perk, ire-1α and atf-6α were involved in Cu-induced changes of lipid metabolism.•Cu induced UPR via activation of CREB binding sites in their promoter regions.
The present study was conducted to explore the underlying mechanism of unfolded protein response (UPR) mediating the Cu-induced changes of hepatic lipogenic metabolism in a low vertebrate, freshwater teleost yellow catfish Pelteobagrus fulvidraco. To this end, three experiments were conducted. In Exp. 1, we cloned the regions of grp78, perk, ire-1α and atf-6α promoters, and found that multiple cAMP-response element binding protein (CREB) binding sites were identified in their promoter regions. Furthermore, these CREB binding sites played crucial role in transcriptional regulation of UPR. In Exp. 2, the involvement of perk, ire-1α and atf-6α in Cu-induced changes of hepatic lipid metabolism was confirmed by specific miRNA. In Exp. 3, the regulatory mechanism of CREB underlying UPR mediating Cu-induced hepatic lipogenic metabolism were investigated. Cu induced UPR via the activation of CREB binding sites in the promoter regions of grp78, perk, ire-1α and atf-6α. In addition, the inhibition of CREB markedly attenuated the Cu-induced up-regulation of hepatic lipogenic metabolism in hepatocytes. This conclusion was further supported by the results from the trial of CREB over-expression. Taken together, the present study indicated that CREB was essential for UPR mediating Cu-induced lipogenic metabolism, supporting a mechanistic link among CREB, UPR and Cu-induced changes of lipid metabolism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that plays critical roles in the regulation of many important physiological processes. In the present ...study, the 1686-bp PPARα promoter for yellow catfish Pelteobagrus fulvidraco was first cloned and characterized. The transcription start site (TSS) of PPARα gene was mapped using RLM-5′RACE method. The luciferase vectors were constructed and transiently transfected into HepG2 cells and HEK293 cells, respectively, for functional analysis of promoters. Bioinformatics analysis revealed the putative core promoter regions including a TATA-box and a CAAT-box located at −35bp and −75bp upstream of the TSS, respectively. A cluster of putative binding sites of several transcription factors, such as AP1, C2H2ZFP, E-box, HNF4α, NF-κB, PPAR, Sp1 and STAT1, were identified. Deletion analysis indicated that these transcriptional factor binding sites were essential to the basal promoter activity. Subsequent mutation analysis showed that the PPARα promoter activity was down-regulated following mutation of the TFBSs including NF-κB, PPAR and HNF4α, indicating that these TFBSs were responsible for PPARα activation. Furthermore, the transcription activity of the PPARα promoter was increased and PPARα mRNA expression was up-regulated after fenofibrate treatment. Overall, the present study provided new insights into the mechanisms for transcriptional regulation of PPARα in fish.
•The 1686-bp PPARα promoter for yellow catfish was first cloned and characterized.•The putative core promoter regions included a TATA-box and a CAAT-box located at -35 bp and -75 bp upstream of the TSS, respectively.•A cluster of putative binding sites of transcription factors, such as AP1, C2H2ZFP, E-box, HNF4α, NF-κb, were identified.•Deletion analysis and the mutations of the TFBSs were used to analyze PPARα promoter activity.•The transcription activity of PPARα promoter and PPARα mRNA expression was up-regulated after fenofibrate treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Highlights • Full-length cDNA sequences of five JAKs and seven STAT members were obtained from yellow catfish. • All of these members were widely expressed across the eleven tissues but at the ...variable levels. • Leptin changed TG content and mRNA expression of several JAKs and STATs members, and genes involved in lipid metabolism. • JAK2a/b–STAT3 pathway exerts main actions in leptin influencing lipid metabolism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We characterized the promoters of target genes of the signal transducer and activator of transcription 3, STAT3 (carnitine palmitoyltransferase I,
, acetyl-CoA carboxylase alpha,
; fatty acid ...synthase,
; and peroxisome proliferator-activated receptor gamma,
) in a teleost
. Binding sites of STAT3 were predicted on these promoters, indicating that STAT3 probably mediated their transcriptional activities. Leptin had no effect on the activity of
and
promoters, but increased
promoter activity and decreased
promoter activity. The −979/−997 STAT3 binding site of
and the −794/−812 STAT3 binding site of
were functional binding loci responsible for leptin-induced transcriptional activation. The study provided direct evidence that STAT3 regulated the expression of
and
at the transcription level, and determined the STAT3 response element on promoters of
and
under leptin signal.
Firefly algorithm (FA) is a swarm-intelligence-based, meta-heuristic algorithm and has been widely applied since its establishment in 2009. In this paper, a modified FA based on light intensity ...difference (LFA) is proposed. The light intensity of a firefly is determined by the landscape of the objective function in FA. The modifications are established in consideration of the variation trend of light intensity differences. As the light intensity differences vary with movements of fireflies, the parameter settings could be adjusted pertinently and self-adaptively at any moment for different problems. The applications to numeric experiments show that, LFA is well adaptive and efficient for different problems, and can make a trade-off between global exploration and local exploitation so as to decrease the risk of premature convergence effectively.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The prognosis prediction of locally advanced rectal cancer (LARC) was important to individualized treatment, we aimed to investigate the performance of ultra-high b-value DWI (UHBV-DWI) in ...progression risk prediction of LARC and compare with routine DWI.
This retrospective study collected patients with rectal cancer from 2016 to 2019. Routine DWI (b = 0, 1000 s/mm
) and UHBV-DWI (b = 0, 1700 ~ 3500 s/mm
) were processed with mono-exponential model to generate ADC and ADCuh, respectively. The performance of the ADCuh was compared with ADC in 3-year progression free survival (PFS) assessment using time-dependent ROC and Kaplan-Meier curve. Prognosis model was constructed with ADCuh, ADC and clinicopathologic factors using multivariate COX proportional hazard regression analysis. The prognosis model was assessed with time-dependent ROC, decision curve analysis (DCA) and calibration curve.
A total of 112 patients with LARC (TNM-stage II-III) were evaluated. ADCuh performed better than ADC for 3-year PFS assessment (AUC = 0.754 and 0.586, respectively). Multivariate COX analysis showed that ADCuh and ADC were independent factors for 3-year PFS (P < 0.05). Prognostic model 3 (TNM-stage + extramural venous invasion (EMVI) + ADCuh) was superior than model 2 (TNM-stage + EMVI + ADC) and model 1 (TNM-stage + EMVI) for 3-year PFS prediction (AUC = 0.805, 0.719 and 0.688, respectively). DCA showed that model 3 had higher net benefit than model 2 and model 1. Calibration curve demonstrated better agreement of model 1 than model 2 and model 1.
ADCuh from UHBV-DWI performed better than ADC from routine DWI in predicting prognosis of LARC. The model based on combination of ADCuh, TNM-stage and EMVI could help to indicate progression risk before treatment.
Our study cloned cDNA sequences of ar, sf-1 and star in P. fulvidraco.30μg Cu/l on 28-day exposure was beneficial on the secretion of sex-steroid hormone.60μg Cu/l on 56-day exposure had toxic ...effect on the secretion of sex-steroid hormone.The present study demonstrated the mechanism of waterborne Cu exposure influencing hormones secretion and synthesis.
The present study was conducted to determine the effects and mechanism of waterborne copper (Cu) exposure influencing ovary development and related hormones secretion in yellow catfish Pelteobagrus fulvidraco. To this end, two experiments were conducted. In Exp. 1, the partial cDNA sequences of three steroidogenesis-related genes (androgen receptor (ar), steroidogenic factor 1 (sf-1) and steroidogenic acute regulatory protein (star)) were firstly characterized from P. fulvidraco. The predicted amino acid sequences for the P. fulvidraco ar, sf-1 and star contained the main structural features characteristic in other species. In Exp. 2, P. fulvidraco were exposed to three waterborne Cu concentrations (control, 30μg/l and 60μg/l, respectively) for 56days. Sampling occurred on day 28 and day 56, respectively. On day 28, the levels of serum sex-steroid hormones (FSH and LH) and the mRNA levels of steroidogenesis-related genes (3β-hsd, cyp11a1, cyp17, cyp19a, sf-1 and star) were significantly increased in ovary of P. fulvidraco exposed to 30μg Cu/l. The immunohistochemical analysis showed the positive reaction of ER, VTG and aromatase in low dose exposure group. These indicated that in low dose and relative short-term exposure, Cu was beneficial. In contrast, 60μg Cu/l exposure significantly reduced the levels of serum FSH, LH, E2 and P, and the mRNA levels of ovarian 20β-hsd, cyp19a and erα in P. fulvidraco. On day 56, waterborne Cu concentration exposure reduced the levels of serum gonadotropins and sex hormones, and down-regulated the mRNA levels of steroidogenesis-related genes, indicating long-term Cu exposure had toxic effect on the secretion of sex-steroid hormone in P. fulvidraco. For the first time, our study cloned cDNA sequences of ar, sf-1 and star in P. fulvidraco, and demonstrated the effects and mechanism of waterborne Cu exposure influencing hormones secretion and synthesis in dose- and time-dependent manner in P. fulvidraco, which will help to understand the Cu-induced reproductive toxicity at both protein and transcriptional levels in fish.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This paper developed a judging principle of crucial vibrational transmission path (VTP) in plates. Novel generalized definitions of VTPs are given referred to the meaning of streamlines. And by ...comparing governing equations, the similarity between energy flow and fluid motion is firstly found so that an analytic method of VTPs in plates is proposed by analogy with fluid motion. Hereafter, the crucial VTP is defined for energy flows at objective points and relative judging criteria is given. Finally, based on two numerical experiments of passive control, the judging principle is indirectly verified by comparing the reduction effects of energy flows at focused points and relative judgment results of crucial VTPs. This paper is meaningful for analyzing and applying the VTPs in plates to guide the control design in future.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objective
To investigate the prognostic significance of and risk factors for solitary lymph node metastasis (SLNM) of patients with cervical carcinoma.
Methods
Clinical data from patients with ...International Federation of Gynecology and Obstetrics (FIGO) stages IA2 to IIA cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy between January 2003 and December 2010 were analysed retrospectively. Histopathological analysis was used to identify SLNM. Long-term survival and risk factors associated with SLNM were analysed.
Results
The study enrolled 302 patients with cervical cancer: 48 with SLNM (SLNM group) and 254 patients with no lymph node metastases (nLNM group). FIGO stage, tumour grade, depth of tumour invasion, uterine body involvement, parametrial involvement and lymphovascular invasion differed significantly between the two groups. Logistic regression analysis revealed that FIGO stage, depth of tumour invasion and lymphovascular invasion were independent factors associated with SLNM. The 5-year survival rates of the SLNM and nLNM groups were 54.2% and 87.8%, respectively. Multivariate analysis identified SLNM as an independent factor affecting survival.
Conclusions
The occurrence of just one solitary lymph node metastasis significantly worsened the prognosis in patients with cervical carcinoma compared with patients without lymph node metastases.
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