Orexins are hypothalamic neuropeptides that regulate feeding, reward, wakefulness and energy homeostasis. The present study sought to characterize the involvement of orexin A in glucose metabolism in ...HepG2 human hepatocellular carcinoma cells, and investigated the role of hypoxia-inducible factor-1α (HIF-1α) in the response. HepG2 cells were exposed to different concentrations of orexin A (10-9 to 10-7 M) in vitro, without or with the orexin receptor 1 (OX1R) inhibitor (SB334867), HIF-1α inhibitor (YC-1) or a combination of both inhibitors. Subsequently, OX1R, HIF-1α expression and localization, glucose uptake, glucose transporter 1 (GLUT1) expression and ATP content were measured. We further investigated the intracellular fate of glucose by measuring the gene expression of pyruvate dehydrogenase kinase 1 (PDK1), lactate dehydrogenase (LDHA) and pyruvate dehydrogenase B (PDHB), as well as metabolite levels including lactate generation and mitochondrial pyruvate dehydrogenase (PDH) activity. The activity of phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was also assessed. Our results showed that the expression of OX1R was predominantly located in the nucleus in HepG2 cells. Orexin A oxygen-independently promoted the mRNA and protein expression of HIF-1α as well as its nuclear accumulation in HepG2 cells and the elevated HIF-1α protein was associated, at least partly, with the activation of the PI3K/Akt/mTOR pathway. Orexin A stimulated GLUT1 expression, glucose uptake as well as ATP generation in HepG2 cells via OX1R acting through the HIF-1α pathway. Moreover, orexin A inhibited LDHA, PDK1 expression and lactate production, stimulated PDHB expression and PDH enzyme activity independent of HIF-1α. Our results indicated that orexin signaling facilitated the glucose flux into mitochondrial oxidative metabolism rather than glycolysis in HepG2 cells. These findings provide new insight into the regulation of glucose metabolism by orexin A in hepatocellular carcinoma cells.
Type 2C protein phosphatase (PP2C) plays an essential role in abscisic acid (ABA) signaling transduction processes. In the current study, we identify 719 putative
PP2C
genes in eight Rosaceae ...species, including 118 in Chinese white pear, 110 in European pear, 73 in Japanese apricot, 128 in apple, 74 in peach, 65 in strawberry, 78 in sweet cherry, and 73 in black raspberry. Further, the phylogenetic analysis categorized
PbrPP2C
genes of Chinese white pear into twelve subgroups based on the phylogenic analysis. We observed that whole-genome duplication (WGD) and dispersed gene duplication (DSD) have expanded the Rosaceae
PP2C
family despite simultaneous purifying selection. Expression analysis finds that
PbrPP2C
genes have organ-specific functions. QRT-PCR validation of nine
PbrPP2C
genes of subgroup A indicates a role in ABA-mediated response to abiotic stress. Finally, we find that five
PbrPP2C
genes of subgroup A function in the nucleus. In summary, our research suggests that the
PP2C
family functions to modulate ABA signals and responds to abiotic stress.
Exosomes, a class of extracellular vesicles, are small membrane-bound vesicles derived from almost all cell types that can play important roles in intercellular communication. Exosomes contain ...proteins, lipids, and nucleic acids that are obtained from the parental cells and participate in various pathophysiological processes, including cell growth, migration, inflammation, immune regulation, and tumor pathogenesis. Moreover, exosomes might be applied in clinical settings, such as diagnosis, treatment, and outcome prediction of diseases, including various cancers. The incidence rates of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) have increased in recent decades, and studies have proposed specific factors that may contribute to the development and progression of these diseases. However, how exosomes play a role in this pathological process needs to be clarified. Studies have identified candidate microRNAs (miRNAs) that might be related to BE/EAC. Further studies are needed to ascertain whether circulating exosomal miRNAs are altered before or after disease onset, which could also help understand the pathophysiology of and find potential targets for prevention, diagnosis, and therapy in BE/EAC. This review summarizes recent findings on the features of circulating exosomal miRNAs in BE/EAC, which could be valuable for the early diagnosis, therapeutic approaches, and outcome prediction of BE/EAC.
Background
HIV‐1 Nef regulates several cellular functions in an infected cell which results in viral persistence and AIDS pathogenesis. The currently understood molecular mechanism(s) underlying ...Nef‐dependent cellular function(s) are unable to explain how events are coordinately regulated in the host cell. Intracellular membranous trafficking maintains cellular homeostasis and is regulated by Rab GTPases ‐ a member of the Ras superfamily.
Results
In the current study, we tried to decipher the role of Nef on the Rab GTPases‐dependent complex and vesicular trafficking. Expression profiling of Rabs in Nef‐expressing cells showed that Nef differentially regulates the expression of individual Rabs in a cell‐specific manner. Further analysis of Rabs in HIV‐1NL4‐3 or ΔNef infected cells demonstrated that the Nef protein is responsible for variation in Rabs expression. Using a panel of competitive peptide inhibitors against Nef, we identified the critical domain of HIV‐1 Nef involved in modulation of Rabs expression. The molecular function of Nef‐mediated upregulation of Rab5 and Rab7 and downregulation of Rab11 increased the transport of SERINC5 from the cell surface to the lysosomal compartment. Moreover, the Nef‐dependent increase in Rab27 expression assists exosome release. Reversal of Rabs expression using competitive inhibitors against Nef and manipulation of Rabs expression reduced viral release and infectivity of progeny virions.
Conclusion
This study demonstrates that Nef differentially regulates the expression of Rab proteins in HIV‐1 infected cells to hijack the host intracellular trafficking, which augments viral replication and HIV‐1 pathogenesis.
Significance
Our study emphasized the indispensable role of HIV‐1 protein Nef on various aspects of the intracellular trafficking regulated by Rabs GTPases, which explained how HIV‐1 Nef may hijack membrane trafficking pathways in infected cells.
HIV‐1 Nef hijacks the host intracellular trafficking pathways by manipulating the expression of Rab GTPases in a‐cell specific manner. Nef‐dependent differential regulation of Rab5, Rab11, and Rab7 accelerate endo‐lysosomal trafficking of viral restriction factor SERINC5 and Rab27 upregulation promotes release of exosomes. Reversal of Nef‐induced differential regulation of Rabs expression by competitive inhibitors reduces viral release and infectivity of progeny virions which could be considered as an anti‐retroviral therapeutic agent.
Frost heave has a significant influence on the stability of embankment in seasonally frozen regions, where the active heating embankment has become a new method for preventing and controlling frost ...heave. In this study, a field experiment was conducted based on a solar circulating heating embankment system (SCHES), and the heat collection performance of the SCHES and the heating effect of the soil were analyzed. Additionally, the numerical simulation of the coupled moisture-heat of the embankment under heating conditions was performed, and the heating effects of different buried forms and buried depths of the heat accumulation pipe (HAP) were discussed. The experimental results showed that the SCHES can provide a heating temperature of up to 70 °C and a mean heating flux of 87 W m−2 during the cold season. The heating action of the SCHES makes the temperature of the surrounding soil of HAP above 0 °C in cold season, which significantly reduces the freezing depth. The numerical results also show that the maximum freezing depth of the embankment can be reduced by 70%, the volumetric ice content can be reduced by more than 60%, and the heating embankment can reduce the frost heave deformation by more than 60% compared with the normal embankment. The buried form of the HAP is recommended to be the horizontal insertion on both sides and the horizontal insertion on sunny sides. The optimal buried depth is between 0.5 m ∼ 1.0 m when the HAP burial form is the horizontal insertion on both sides. As a preliminary study, the concept of the active heating embankment utilizing solar energy can provide a reference for the prevention and control of frost heave in seasonally frozen regions.
•A new SCHES was proposed for mitigation of frost heave of the embankment in seasonally frozen regions.•The SCHES has a significant heating effect and can make the surrounding soil of the HAP above 0 °C in cold season.•A coupled moisture-heat model for heating embankment conditions was developed.•The optimal buried forms and buried depths of the HAP were initially given.
In this paper, the photovoltaic performance and charge recombination of the dye-sensitized solar cells (DSCs) based on nitrogen-doped TiO2 electrodes were investigated in detail. A negative shift of ...the flatband potential (V fb) of nitrogen-doped TiO2 film was attributed to the formation of an O−Ti−N bond, and it was indicated that the position of the edge of the V fb is shifted to negative, resulting in the improvement of the open circuit voltage for DSC with nitrogen doping. The UV−vis spectrum of the nitrogen-doped film exhibited a visible absorption in the wavelength range from 400 to 500 nm. The back electron transfer of the nitrogen-doped DSC was studied by measuring the electrochemistry impedance spectra (EIS), and the EIS for DSCs showed that the enhanced electron lifetime for nitrogen-doped TiO2 solar cells could be attributed to the formation of O−Ti−N in the TiO2 electrode to retard the recombination reaction at the TiO2 photoelectrode/electrolyte interface as compared to the undoped TiO2 solar cells. The photovoltaic performance of the DSC under high temperature conditions and one soaking in sun light for more than 1000 h indicated that the nitrogen-doped TiO2 solar cells exhibited better stability. It indicated that the formation of O−Ti−N in the TiO2 electrode influences the performance of the DSC. Especially, the introduction of nitrogen into the DSC can stabilize the DSC system due to the replacement of oxygen-deficient titania by nitrogen-doped TiO2.
The Yellow River Estuary is a typical constructive delta with a complex sedimentary structure. To analyze the physical, mechanical properties, and structural characteristics of the surface sediments ...in the delta, reveal the sedimentary environment and avoid geological hazards, cone penetration test (CPT) is used for nautical in situ testing and evaluating effective internal friction angle (φ'). Four typical areas formed by the diversion of the Yellow River Estuary in different periods are selected as the research objects to perform the in situ CPT, particle size analysis test, scanning electron microscopy, and triaxial test, building calculation model. The main conclusions are as follows: (1) The sediment given priority to are silt and silty clay, where the stratigraphic distribution difference is more significant, accompanied by soft interlayer or alternating layers of hard. (2) Hard soil in the sediments cause abrupt changes and fluctuations in the cone tip resistance and sleeve friction resistance. (3) The empirical formulas proposed by Berezantsev, Khristoforov, and Golubkov, Kulhawy and Mayne, and Mayne are used to predict φ' and the effect of inversion is good. (4) The coefficients of formulas are significantly improved, modified according to site variability.
In recent years, constrained by the challenges associated with expensive data annotation and poor generalization ability in supervised models, domain adaptation has been proposed to effectively ...mitigate domain gaps, which has gained significant attention in the field of remote sensing. However, most existing methods do not consider the inherent characteristics of remote sensing images when formulating adaptive strategies. In addition, there has been limited research on addressing class-imbalanced data situations, leading to undesirable performance in domain adaptation tasks involving long-tailed datasets. To overcome the aforementioned limitations, based on the analysis of intraclass diversity and intradomain style differences of remote sensing images, we propose a novel prototype contrastive learning framework called general-specific prototype contrastive learning (GSPCL). Due to the unreliability of clustering samples in conventional prototype-based clustering methods, the bidirectional weighted prototype strategy is proposed to optimize this loophole. Consequently, more robust prototypes are constructed in both domains, serving as mediators to reduce domain discrepancies bidirectionally. Particularly, often overlooked in most methods, we incorporate low-confidence sample features into the contrastive learning process alongside these prototypes to further guide the model to address feature alignment and long-tail issues effectively. Finally, in order to verify the superiority of our proposed method, we adhere to two existing experimental settings and construct an extra optical remote sensing domain adaptation dataset with class-imbalanced scenarios. In the first two experimental settings, GSPCL outperforms the second-ranked approach by 5.0% and 4.0% in average accuracy. Furthermore, our approach exhibits highly competitive results in handling long-tailed data scenarios.
Spatial segmentation is a critical procedure in mass spectrometry imaging (MSI)-based biochemical analysis. However, the commonly used unsupervised MSI segmentation methods may lead to inappropriate ...segmentation results as the MSI data is characterized by high dimensionality and low signal-to-noise ratio. This process can be improved by the incorporation of precise prior knowledge, which is hard to obtain in most cases. In this study, we show that the incorporation of partial or coarse prior knowledge from different sources such as reference images or biological knowledge may also help to improve MSI segmentation results. Here, we propose a novel interactive segmentation strategy for MSI data called iSegMSI, which incorporates prior information in the form of scribble-regularization of the unsupervised model to fine-tune the segmentation results. By using two typical MSI data sets (including a whole-body mouse fetus and human thyroid cancer), the present results demonstrate the effectiveness of the iSegMSI strategy in improving the MSI segmentations. Specifically, the method can be used to subdivide a region into several subregions specified by the user-defined scribbles or to merge several subregions into a single region. Additionally, these fine-tuned results are highly tolerant to the imprecision of the scribbles. Our results suggest that the proposed iSegMSI method may be an effective preprocessing strategy to facilitate the analysis of MSI data.
A new isocoumarin, penicimarin N (1), along with five known compounds (2-6), were isolated from the mangrove-derived fungus Penicillium sp. TGM112. The structure of 1 was elucidated on the basis of ...extensive spectroscopic data analysis, and the absolute configuration of 1 was determined by comparison of their circular dichroism (CD) spectra with the literature. The structures of known compounds were determined by comparison with the literature data. All the isolated compounds were examined for their antioxidant and α-glucosidase activities. Compound 1 showed strong antioxidant activity with the IC
50
value of 1.0 mM, and 1 also exhibited moderate inhibitory activity against α-glucosidase with the IC
50
value of 620 μM.
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