MicroRNA miR-31 is implicated in the neoplastic process of various malignancies including oral squamous cell carcinoma (OSCC). Silent information regulator 3 (Sirtuin3 or SIRT3) is a NAD-dependent ...deacetylase that regulates metabolic process. Suppressor role of SIRT3 has been found in neoplasms. This study investigates the disruptions of miR-31-SIRT3 cascade to explore their potential association with metabolic change in OSCC. We identified that miR-31 directly targeted SIRT3 in OSCC cells, and a reverse correlation between miR-31 expression and SIRT3 expression was noted in OSCC tumors. SIRT3 expression attenuated the miR-31 enhanced tumor cell migration and invasion. It also reduced the tumorigenic potential of FaDu cell line. miR-31-SIRT3 impaired the mitochondrial membrane potential and structural integrity. The dis-regulation of this axis also contributed to the genesis of oxidative stress. In addition, miR-31 switched tumor cells from aerobic metabolism to glycolytic metabolism. This study provides novel evidences demonstrating the presence of miR-31-mediated post-transcriptional regulation of SIRT3 in OSCC. The disruption of miR-31-SIRT3 cascade and the consequential metabolic aberrances are involved in OSCC progression.
•miR-31 targets SIRT3 to drive OSCC invasion.•OSCC tumors exhibit miR-31 upregulation and SIRT3 downregulation.•miR-31-SIRT3 disruption underlies the mitochondrial disturbance.•miR-31-SIRT3 cascade induces ROS, glycolytic metabolism and lactate production.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Layered oxide cathodes usually exhibit high compositional diversity, thus providing controllable electrochemical performance for Na‐ion batteries. These abundant components lead to complicated ...structural chemistry, closely affecting the stacking preference, phase transition and Na+ kinetics. With this perspective, we explore the thermodynamically stable phase diagram of various P2/O3 composites based on a rational biphasic tailoring strategy. Then a specific P2/O3 composite is investigated and compared with its monophasic counterparts. A highly reversible structural evolution of P2/O3–P2/O3/P3–P2/P3–P2/Z/O3′–Z/O3′ based on the Ni2+/Ni3.5+, Fe3+/Fe4+ and Mn3.8+/Mn4+ redox couples upon sequential Na extraction/insertion is revealed. The reduced structural strain at the phase boundary alleviates the phase transition and decreases the lattice mismatch during cycling, endowing the biphasic electrode a large reversible capacity of 144 mAh g−1 with the energy density approaching 514 Wh kg−1.
A rational biphasic tailoring strategy to prepare layered composite cathodes with the desired phase ratio is proposed. Benefiting from the reversible phase transition within transition metal slabs and the decreased structure strain at the phase boundary of the intergrowth structure during Na extraction and insertion, the Com‐NaNMFT composite material demonstrates excellent electrochemical performance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
With the development of functional genomics studies, a mass of long non‐coding RNAs (LncRNA) were discovered from the human genome. Long non‐coding RNAs serve as pivotal regulators of genes that are ...able to generate LncRNA–binding protein complexes to modulate a great number of genes. Recently, the LncRNA urothelial carcinoma‐associated 1 (UCA1) has been revealed to be dysregulated, which plays a critical role in the development of a few cancers. However, the role of the biology and clinical significance of UCA1 in the tumorigenesis of oral squamous cell carcinoma (OSCC) remain unknown. We found that UCA1 expression levels were upregulated aberrantly in tongue squamous cell carcinoma tissues and associated with lymph node metastasis and TNM stage. We explored the expression, function, and molecular mechanism of LncRNA UCA1 in OSCC. In the present work, we revealed that UCA1 silencing suppressed proliferation and metastasis and induced apoptosis of OSCC cell lines in vitro and in vivo, which might be related to the activation level of the WNT/β‐catenin signaling pathway. Our research results emphasize the pivotal role of UCA1 in the oncogenesis of OSCC and reveal a novel LncRNA UCA1–β‐catenin–WNT signaling pathway regulatory network that could contribute to our understanding in the pathogenesis of OSCC and assist in the discovery of a viable LncRNA‐directed diagnostic and therapeutic strategy for this fatal disease.
Our data highlighted the pivotal role of UCA1 in the tumorigenesis of oral squamous cell carcinoma, and revealed a novel LncRNA UCA1‐β‐catenin‐Wnt signaling pathway regulatory network, which may contribute to understand the pathogenesis of oral squamous cell carcinoma.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Liver transplantation is the only definitive treatment for end‐stage cirrhosis and fulminant liver failure, but the lack of available donor livers is a major obstacle to liver transplantation. ...Recently, induced pluripotent stem cells (iPSCs) derived from the reprogramming of somatic fibroblasts, have been shown to resemble embryonic stem (ES) cells in that they have pluripotent properties and the potential to differentiate into all cell lineages in vitro, including hepatocytes. Thus, iPSCs could serve as a favorable cell source for a wide range of applications, including drug toxicity testing, cell transplantation, and patient‐specific disease modeling. Here, we describe an efficient and rapid three‐step protocol that is able to rapidly generate hepatocyte‐like cells from human iPSCs. This occurs because the endodermal induction step allows for more efficient and definitive endoderm cell formation. We show that hepatocyte growth factor (HGF), which synergizes with activin A and Wnt3a, elevates the expression of the endodermal marker Foxa2 (forkhead box a2) by 39.3% compared to when HGF is absent (14.2%) during the endodermal induction step. In addition, iPSC‐derived hepatocytes had a similar gene expression profile to mature hepatocytes. Importantly, the hepatocyte‐like cells exhibited cytochrome P450 3A4 (CYP3A4) enzyme activity, secreted urea, uptake of low‐density lipoprotein (LDL), and possessed the ability to store glycogen. Moreover, the hepatocyte‐like cells rescued lethal fulminant hepatic failure in a nonobese diabetic severe combined immunodeficient mouse model. Conclusion: We have established a rapid and efficient differentiation protocol that is able to generate functional hepatocyte‐like cells from human iPSCs. This may offer an alternative option for treatment of liver diseases. (Hepatology 2012)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In mammals, maternal-to-zygotic transition (MZT), or oocyte-to-embryo transition, begins with oocyte meiotic resumption due to the sequential translational activation and destabilization of dormant ...maternal transcripts stored in the ooplasm. It then continues with the elimination of maternal transcripts during oocyte maturation and fertilization and ends with the full transcriptional activation of the zygotic genome during embryonic development. A hallmark of MZT in mammals is its reliance on translation and the utilization of stored RNAs and proteins, rather than de novo transcription of genes, to sustain meiotic maturation and early development. Impaired maternal mRNA clearance at the onset of MZT prevents zygotic genome activation and causes early arrest of developing embryos. In this review, we discuss recent advances in our knowledge of the mechanisms whereby mRNA translation and degradation are controlled by cytoplasmic polyadenylation and deadenylation which set up the competence of maturing oocyte to accomplish MZT. The emphasis of this review is on the mouse as a model organism for mammals and BTG4 as a licensing factor of MZT under the translational control of the MAPK cascade. Summary Sentence This review highlights the new mechanisms that regulate maternal mRNA translation and degradation during oocyte meiotic cell cycle progression and oocyte-to-embryo transition.
Background/Purpose
This over 7‐year case study is the first to compare the results of laparoscopic Glissonian pedicle approach hemihepatectomy (LGAH) and laparoscopic hilar dissection approach ...hemihepatectomy (LHAH) in a randomized controlled trial (RCT).
Methods
Patients who had undergone laparoscopic hemihepatectomy, either LGAH or LHAH, between March 2012 and December 2019 at our center were prospectively enrolled and assigned to the LGAH or LHAH group. Both groups were stratified and compared, and the preoperative and follow‐up outcomes were analyzed. The primary endpoint was total operative time.
Results
The groups were equally matched for age, sex, HBsAg, Child‐Pugh class, benign disease, malignancy, liver cirrhosis, tumor diameter and type of resection. Ninety‐six patients had undergone LGAH and 94 had undergone LHAH. No preoperative death occurred in the two groups. LGAH did not enhance the postoperative overall complication rates (P = .465) or intraoperative blood loss (P = .535) compared with LHAH. However, the overall operative time (P = .014) and hilar dissection time (P = .000) were significantly shorter in the LGAH group than in the LHAH group. No significant differences were found between the groups regarding the 1‐year (P = .384), 3‐year (P = .332), and 5‐year overall survival rates (P = .662) or 1‐year (P = .856), 3‐year (P = .348), and 5‐year disease‐free survival rates (P = .573).
Conclusions
LGAH and LHAH are both effective procedures for treating the hilar structures in selected patients. LGAH has advantages over LHAH in reducing total operation time under the condition where both procedures can be used. LGAH for selected patients is worthy of promotion owing to its simplicity and convenience.
Registration number: NCT01567631 (http://www.clinicaltrials.gov).
HighlightLiao and colleagues report on the first randomized controlled trial to evaluate the potential advantages of laparoscopic Glissonian pedicle approach hemihepatectomy (LGAH) over laparoscopic hilar dissection approach hemihepatectomy. LGAH may reduce total operative time and may be the procedure of choice in selected patients owing to its simplicity and convenience.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) is one of the major concerns reflecting the higher mortality of HCC. This study aimed to explore the ...impact of circulating exosomes on HCC development and recurrence. One‐shot transfusion of hepatoma serum to naïve rats induced liver cancer development with gradual elevation of alpha‐fetoprotein (AFP), but exosome‐free hepatoma serum failed to induce AFP elevation. The microarray analysis revealed miR‐92b as one of the highly expressing microribonucleic acids in hepatoma serum exosomes. Overexpression of miR‐92b enhanced the migration ability of liver cancer cell lines with active release of exosomal miR‐92b. The hepatoma‐derived exosomal miR‐92b transferred to natural killer (NK) cells, resulting in the downregulation of CD69 and NK cell‐mediated cytotoxicity. Furthermore, higher expression of miR‐92b in serum exosomes was confirmed in HCC patients before LDLT, and its value at 1 month after LDLT was maintained at a higher level in the patients with posttransplant HCC recurrence. In summary, we demonstrated the impact of circulating exosomes on liver cancer development, partly through the suppression of CD69 on NK cells by hepatoma‐derived exosomal miR‐92b. The value of circulating exosomal miR‐92b may predict the risk of posttransplant HCC recurrence.
This study demonstrates the impact of circulating exosomes on liver cancer development in rats, explores functional roles of exosomal miR‐92b in the tumor microenvironment, and verifies its clinical value for early prediction of posttransplant hepatocellular carcinoma recurrence.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The formation of social memory between individuals of the opposite sex is crucial for expanding mating options or establishing monogamous pair bonding. A specialized neuronal circuit that regulates ...social memory could enhance an individual's mating opportunities and provide a parallel pathway for computing social behaviors. While the influence of light exposure on various forms of memory, such as fear and object memory, has been studied, its modulation of social recognition memory remains unclear. Here, we demonstrate that acute exposure to light impairs social recognition memory (SRM) in mice. Unlike sound and touch stimuli, light inhibits oxytocin neurons in the supraoptic nucleus (SON) via M1 SON-projecting intrinsically photosensitive retinal ganglion cells (ipRGCs) and GABAergic neurons in the perinuclear zone of the SON (pSON). We further show that optogenetic activation of SON oxytocin neurons using channelrhodopsin is sufficient to enhance SRM performance, even under light conditions. Our findings unveil a dedicated neuronal circuit through which luminance affects SRM, utilizing a non-image-forming visual pathway, distinct from the canonical modulatory role of the oxytocin system.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The support vector regression (SVR) has been employed to deal with stock price forecasting problems. However, the selection of appropriate kernel parameters is crucial to obtaining satisfactory ...forecasting performance. This paper proposes a novel approach for forecasting stock prices by combining the SVR with the firefly algorithm (FA). The proposed forecasting model has two stages. In the first stage, to enhance the global convergence speed, a modified version of the FA, which is termed the MFA, is developed in which the dynamic adjustment strategy and the opposition-based chaotic strategy are introduced. In the second stage, a hybrid SVR model is proposed and combined with the MFA for stock price forecasting, in which the MFA is used to optimize the SVR parameters. Finally, comparative experiments are conducted to show the applicability and superiority of the proposed methods. Experimental results show the following: (1) Compared with other algorithms, the proposed MFA algorithm possesses superior performance, and (2) The proposed MFA-SVR prediction procedure can be considered as a feasible and effective tool for forecasting stock prices.
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