USP11 promotes glycolysis by regulating HIF-1α stability in hepatocellular carcinoma.

Understanding the mechanisms underlying metastasis in hepatocellular carcinoma (HCC) is crucial for developing new therapies against this fatal disease. Deubiquitinase ubiquitin-specific protease 11 (USP11) belongs to the deubiquitinating family and has previously been reported to play a critical role in cancer pathogenesis. Although it has been established that USP11 can facilitate the metastasis and proliferation ability of HCC, the underlying regulatory mechanisms are poorly understood. The primary objective of this research was to reveal hitherto undocumented functions of USP11 during HCC progression, especially those related to metabolism. Under hypoxic conditions, USP11 was found to significantly impact the glycolysis of HCC cells, as demonstrated through various techniques, including RNA-Seq, migration and colony formation assays, EdU and co-immunoprecipitation. Interestingly, we found that USP11 interacted with the HIF-1α complex and maintained HIF-1α protein stability by removing ubiquitin. Moreover, USP11/HIF-1α could promote glycolysis through the PDK1 and LDHA pathways. In general, our results demonstrate that USP11 promotes HCC proliferation and metastasis through HIF-1α/LDHA-induced glycolysis, providing new insights and the experimental basis for developing new treatments for this patient population.

Tanshinone IIA ameliorates Aß transendothelial transportation through SIRT1-mediated endoplasmic reticulum stress.

BACKGROUND: The disruption of blood-brain barrier (BBB), predominantly made up by brain microvascular endothelial cells (BMECs), is one of the characteristics of Alzheimer's disease (AD). Thus, improving BMEC function may be beneficial for AD treatment. Tanshinone IIA (Tan IIA) has been proved to ameliorate the cognitive dysfunction of AD. Herein, we explored how Tan IIA affected the function of BMECs in AD. METHODS: Aß1-42-treated brain-derived endothelium cells.3 (bEnd.3 cells) was employed for in vitro experiments. And we performed molecular docking and qPCR to determine the targeting molecule of Tan IIA on Sirtuins family. The APPswe/PSdE9 (APP/PS1) mice were applied to perform the in vivo experiments. Following the behavioral tests, protein expression was determined through western blot and immunofluorescence. The activities of oxidative stress-related enzymes were analyzed by biochemically kits. Nissl staining and thioflavin T staining were conducted to reflect the neurodegeneration and Aß deposition respectively. RESULTS: Molecular docking and qPCR results showed that Tan IIA mainly acted on Sirtuin1 (SIRT1) in Sirtuins family. The inhibitor of SIRT1 (EX527) was employed to further substantiate that Tan IIA could attenuate SIRT1-mediated endoplasmic reticulum stress (ER stress) in BMECs. Behavioral tests suggested that Tan IIA could improve the cognitive deficits in APP/PS1 mice. Tan IIA administration increased SIRT1 expression and alleviated ER stress in APP/PS1 mice. In addition, LRP1 expression was increased and RAGE expression was decreased after Tan IIA administration in both animals and cells. CONCLUSION: Tan IIA could promote Aß transportation by alleviating SIRT1-mediated ER stress in BMECs, which ameliorated cognitive deficits in APP/PS1 mice.

Evolution of the time delay signature of chaos generated in three types of optical injection systems.

The time delay signature (TDS) of chaos generated in three schemes of optical injection has been investigated, and the mechanism of TDS suppression (TDSS) is revealed. The first scheme is a continuous-wave (CW) laser unidirectionally injecting into a chaotic laser, and the TDS of the chaotic laser is suppressed below 0.08 in this structure. The second scheme is a chaotic laser unidirectionally injecting into a CW laser, where the parameter range of TDSS lower than 0.06 of this structure is the largest among the three schemes. The third scheme is two CW lasers coupling to each other, and two chaotic lasers with TDS (T D S<0.1) suppression can be obtained simultaneously. For the further analysis of the mechanism of TDSS, the quasi-linear relationship between the synchronization coefficient and TDS is revealed. This study will provide insight into the generation of chaotic lasers by optical injection and promote the application of chaotic lasers.

Broadband chaos generation utilizing a wavelength-tunable monolithically integrated chaotic semiconductor laser subject to optical feedback.

We demonstrate a broadband and wavelength-tunable chaotic laser by using a monolithically integrated wavelength-tunable chaotic semiconductor laser subject to optical feedback. The chip consists of a gain section, a distributed Bragg reflection grating section, a semiconductor optical amplifier section, and a phase section. By applying an optical feedback loop to the chaotic semiconductor laser chip, a nonlinear frequency mixing is stimulated in the laser cavity, and the chaos bandwidth is expanded to 33.6 GHz, which is 4.4 times larger than the bandwidth without optical feedback. Furthermore, the effect of feedback optical power on the bandwidth is investigated. The results show that the wide power spectrum of chaotic laser is available in a large wavelength range from 1556.44 nm to 1566.42 nm. This work explores a broadband and wavelength-tunable chaotic semiconductor laser for the wavelength division multiplexing to enlarge the capacity in chaotic secure optical communications.

Effect of resolution bandwidth and video bandwidth on the characterization of chaos in a radio-frequency spectrum analyzer.

The effect of resolution bandwidth (RBW) and video bandwidth (VBW) of a radio-frequency spectrum analyzer on the characteristics of a power spectrum for chaos generated by a semiconductor laser with external optical feedback is investigated experimentally and numerically. We describe the spectral characteristics with effective bandwidth and time-delay signature (TDS) quantificationally. The experimental results demonstrate that the ratio of VBW to RBW has a significant impact on the smoothness of the power spectrum and effective bandwidth of chaos. Meanwhile, the RBW affects the resolution of periodical peaks of the power spectrum and the TDS of chaos, which is obtained by the power spectrum. The incorrect characterization of chaos can be avoided by setting the RBW to no more than 0.1 times as much as the resonance frequency of the external cavity of chaos and setting the VBW/RBW to no more than 0.01. The simulation results qualitatively agree with the analysis of the experiment.

Ligustilide ameliorates cognitive impairment via AMPK/SIRT1 pathway in vascular dementia rat.

Vascular dementia (VaD) is the second cause of dementia after Alzheimer's disease. Ligustilide (LIG) is one of the main active ingredients of traditional Chinese medicines, such as Angelica. Studies have reported that LIG could protect against VaD. However, the mechanism is still confused. In this study, we employed a bilateral common carotid artery occlusion rat model to study. LIG (20 or 40 mg/kg/day) and Nimodipine (20 mg/kg) were orally administered to the VaD rats for four weeks. Morris water maze test showed that LIG effectively ameliorated learning and memory impairment in VaD rats. LIG obviously reduced neuronal oxidative stress damage and the level of homocysteine in the brain of VaD rats. Western blot results showed that pro-apoptotic protein Bax and cleaved caspase 3 increased and anti-apoptotic protein Bcl-2 decreased in the hippocampi of VaD rats. But after LIG treatment, these changes were reversed. Moreover, Nissl staining result showed that LIG could reduce neuronal degeneration in VaD rats. Furthermore, LIG enhanced the expressions of P-AMPK and Sirtuin1(SIRT1) in VaD rats. In conclusion, these studies indicated that LIG could ameliorate cognitive impairment in VaD rats, which might be related to AMPK/SIRT1 pathway activation.

Sodium tanshinone IIA sulfonate improves cognitive impairment via regulating Aß transportation in AD transgenic mouse model.

Alzheimer's disease (AD) is a most common neurodegenerative disease. Sodium Tanshinone IIA Sulfonate (STS) has been reported to ameliorate AD pathology. However, the underlying mechanism is still unclear. In this study, AD transgenic mouse model (APP/PS1) was used to explore the potential mechanism of STS against AD. Morris water maze and Y-maze tests showed that administration of STS improved learning and memory abilities of APP/PS1 mice. STS reduced the levels of reactive oxygen species and malondialdehyde, while improved the activity of superoxide dismutase in both hippocampus and cortex in APP/PS1 mice. STS inhibited the activity of acetylcholinesterase, while improved the activity of choline acetyltransferase in APP/PS1 mice. In addition, STS elevated the protein expressions of neurotrophic factors and synapse-related proteins in both the hippocampus and cortex in APP/PS1 mice. At last, STS improved the protein expressions of glucose transporter 1 (GLUT1) and low-density lipoprotein receptor-related protein 1 (LRP1). These results indicated that the potential mechanism of STS on AD might be related to Aß transportation function via GLUT1/LRP1 pathway. HIGHLIGHTS: STS improves cognitive impairment of APP/PS1 mice. STS ameliorates the oxidative stress damage and improves the cholinergic system. STS protects against neuronal dysfunction and enhances the synaptic plasticity. STS mediates the Aß transportation of BMECs.

An Optimized Probabilistic Roadmap Algorithm for Path Planning of Mobile Robots in Complex Environments with Narrow Channels.

In this paper, we propose a new path planning algorithm based on the probabilistic roadmaps method (PRM), in order to effectively solve the autonomous path planning of mobile robots in complex environments with multiple narrow channels. The improved PRM algorithm mainly improves the density and distribution of sampling points in the narrow channel, through a combination of the learning process of the PRM algorithm and the APF algorithm. We also shortened the required time and path length by optimizing the query process. The first key technology to improve the PRM algorithm involves optimizing the number and distribution of free points and collision-free lines in the free workspace. To ensure full visibility of the narrow channel, we extend the obstacles through the diagonal distance of the mobile robot while ignoring the safety distance. Considering the safety distance during movement, we re-classify the all sampling points obtained by the quasi-random sampling principle into three categories: free points, obstacle points, and adjacent points. Next, we transform obstacle points into the free points of the narrow channel by combining the APF algorithm and the characteristics of the narrow channel, increasing the density of sampling points in the narrow space. Then, we include potential energy judgment into the construction process of collision-free lines shortening the required time and reduce collisions with obstacles. Optimizing the query process of the PRM algorithm is the second key technology. To reduce the required time in the query process, we adapt the bidirectional A* algorithm to query these local paths and obtain an effective path to the target point. We also combine the path pruning technology with the potential energy function to obtain a short path without collisions. Finally, the experimental results demonstrate that the new PRM path planning technology can improve the density of free points in narrow spaces and achieve an optimized, collision-free path in complex environments with multiple narrow channels.

Phenotypic Characterization and Fine Mapping of a Major-Effect Fruit Shape QTL FS5.2 in Cucumber, Cucumis sativus L., with Near-Isogenic Line-Derived Segregating Populations.

Cucumber (Cucumis sativus L.) fruit size/shape (FS) is an important yield and quality trait that is quantitatively inherited. Many quantitative trait loci (QTLs) for fruit size/shape have been identified, but very few have been fine-mapped or cloned. In this study, through marker-assisted foreground and background selections, we developed near-isogenic lines (NILs) for a major-effect fruit size/shape QTL FS5.2 in cucumber. Morphological and microscopic characterization of NILs suggests that the allele of fs5.2 from the semi-wild Xishuangbanna (XIS) cucumber (C. s. var. xishuangbannesis) reduces fruit elongation but promotes radial growth resulting in shorter but wider fruit, which seems to be due to reduced cell length, but increased cellular layers. Consistent with this, the NIL carrying the homozygous XIS allele (fs5.2) had lower auxin/IAA contents in both the ovary and the developing fruit. Fine genetic mapping with NIL-derived segregating populations placed FS5.2 into a 95.5 kb region with 15 predicted genes, and a homolog of the Arabidopsis CRABS CLAW (CsCRC) appeared to be the most possible candidate for FS5.2. Transcriptome profiling of NIL fruits at anthesis identified differentially expressed genes enriched in the auxin biosynthesis and signaling pathways, as well as genes involved in cell cycle, division, and cell wall processes. We conclude that the major-effect QTL FS5.2 controls cucumber fruit size/shape through regulating auxin-mediated cell division and expansion for the lateral and longitudinal fruit growth, respectively. The gibberellic acid (GA) signaling pathway also plays a role in FS5.2-mediated fruit elongation.

A novel hypoxia gene signature indicates prognosis and immune microenvironments characters in patients with hepatocellular carcinoma.

Due to the lack of a suitable gene signature, it is difficult to assess the hypoxic exposure of HCC tissues. The clinical value of assessing hypoxia in HCC is short of tissue-level evidence. We tried to establish a robust and HCC-suitable hypoxia signature using microarray analysis and a robust rank aggregation algorithm. Based on the hypoxia signature, we obtained a hypoxia-associated HCC subtypes system using unsupervised hierarchical clustering and a hypoxia score system was provided using gene set variation analysis. A novel signature containing 21 stable hypoxia-related genes was constructed to effectively indicate the exposure of hypoxia in HCC tissues. The signature was validated by qRT-PCR and compared with other published hypoxia signatures in multiple large-size HCC cohorts. The subtype of HCC derived from this signature had different prognosis and other clinical characteristics. The hypoxia score obtained from the signature could be used to indicate clinical characteristics and predict prognoses of HCC patients. Moreover, we reveal a landscape of immune microenvironments in patients with different hypoxia score. In conclusion, we identified a novel HCC-suitable 21-gene hypoxia signature that could be used to estimate the hypoxia exposure in HCC tissues and indicated prognosis and a series of important clinical features in HCCs. It may enable the development of personalized counselling or treatment strategies for HCC patients with different levels of hypoxia exposure.

Rapid noise removal based dual adversarial network for the Brillouin optical time domain analyzer.

We propose a dual adversarial network (DANet) to improve the signal-to-noise ratio (SNR) of the Brillouin optical time domain analyzer. Rather than inferring the conditional posteriori distribution in the conventional maximum a posteriori (MAP) framework, DANet constructs a joint distribution from two different factorizations corresponding to the noise removal and generation tasks. This method utilizes all the information between the clean-noisy image pairs to preserve data completely without requiring traditional image priors and noise distribution assumptions. Additionally, the clean-noisy image pairs produced by the generator can expand the original dataset to retrain and enhance the denoising effect. The performance of DANet is verified using the simulated and experimental data. Without spatial resolution deterioration, an SNR improvement of 35.51 dB is observed in the simulation, and the Brillouin frequency shift (BFS) uncertainty along the fiber is reduced by 3.56 MHz. Experiments yield a maximum SNR improvement of 19.08 dB, with the BFS uncertainty along the fiber reduced by 0.93 MHz. Significantly, DANet has a processing time of 1.26 s, which is considerably faster than conventional methods, demonstrating its potential for rapid noise removal tasks.

Experimental observation of chaotic Brillouin dynamic grating.

We experimentally observe the local Brillouin dynamic grating (BDG) based on a chaotic laser in a polarization-maintaining fiber for the first time, to the best of our knowledge. The grating length of the chaotic BDG can be adjusted by changing the optical spectral width of the chaotic laser. The characteristics of the reflection spectrum versus the grating length are further analyzed, which agrees with the theory of fiber Bragg grating. Temperature distributed measurements based on the chaotic BDG have been demonstrated with a spatial resolution of an order of centimeter.

Garlic Volatile Diallyl Disulfide Induced Cucumber Resistance to Downy Mildew.

Allicin compositions in garlic are used widely as fungicides in modern agriculture, in which diallyl disulfide (DADS) is a major compound. Downy mildew, caused by Pseudoperonospora cubensis (P. cubensis), is one of the most destructive diseases and causes severe yield losses in cucumbers. To explore the potential mechanism of DADS-induced cucumber resistance to downy mildew, cucumber seedlings were treated with DADS and then inoculated with P. cubensis at a 10-day interval. Symptom observation showed that DADS significantly induced cucumber resistance to downy mildew. Furthermore, both lignin and H2O2 were significantly increased by DADS treatment to responding P. cubensis infection. Simultaneously, the enzyme activities of peroxidase (POD) in DADS-treated seedlings were significantly promoted. Meanwhile, both the auxin (IAA) and salicylic acid (SA) contents were increased, and their related differentially expressed genes (DEGs) were up-regulated when treated with DADS. Transcriptome profiling showed that many DEGs were involved in the biological processes of defense responses, in which DEGs on the pathways of 'phenylpropanoid biosynthesis', 'phenylalanine metabolism', 'MAPK signaling', and 'plant hormone signal transduction' were significantly up-regulated in DADS-treated cucumbers uninoculated with the pathogen. Based on the results of several physiological indices and transcriptomes, a potential molecular mechanism of DADS-induced cucumber resistance to downy mildew was proposed and discussed. The results of this study might give new insight into the exploration of the induced resistance mechanism of cucumber to downy mildew and provide useful information for the subsequent mining of resistance genes in cucumber.

Effect of chaotic time delay signature on Brillouin gain spectrum in the slope-assisted chaotic BOCDA.

In the chaotic Brillouin optical correlation domain analysis (CBOCDA) system, the broadband chaotic laser naturally widens the Brillouin gain spectrum (BGS), which provides an enhanced range for dynamic strain measurement via slope-assisted technology. However, inherent off-peak amplification at the time delay signature (TDS) position results in a deteriorated gain envelope. The mechanism behind the sub-peak of chaotic BGS is first analyzed and the negative correlated relationship between the value of main-sub-peak ratio (MSPR) and magnitude of TDS has been experimentally demonstrated. The limitation of sub-peak on the dynamic range is investigated, where the range is not greater than 400 µÎµ at MSPR < 0 dB, and 600 µÎµ at MSPR > 0 dB. Meanwhile, by eliminating the TDS, the BGS without sub-peak is obtained and a dynamic strain of 1200 µÎµ is successfully identified. Moreover, the application of optimized chaotic BGS in a multi-slope assisted system to realize the enlargement of dynamic strain range is also discussed.

Generation of a broadband chaotic laser by active optical feedback loop combined with a high nonlinear fiber.

We propose and demonstrate a method to generate a flat broadband chaotic laser by using an active optical feedback loop combined with a high nonlinear fiber. The feedback strength and nonlinear effect, especially the four-wave mixing effect of high nonlinear fiber, are studied to improve the bandwidth and flatness of chaos. When the feedback strength is 6.6 and injected fiber power is 1.0 W, a chaotic signal with a frequency range over 50 GHz, 80% bandwidth of 38.9 GHz, and flatness of 4.2 dB are experimentally achieved.

Dynamic strain measurement by a single-slope-assisted chaotic Brillouin optical correlation-domain analysis.

We propose a novel, to the best of our knowledge, method to enhance the measurement range of dynamic strain using a single-slope-assisted chaotic Brillouin optical correlation-domain analysis. The broadband chaos provides a Gaussian-shape pump-probe beat spectrum so that not only the centimeter-level spatial resolution is achieved but also the linewidth of the chaotic Brillouin gain spectrum is naturally broadened. Thus, the enlarged linear region could be employed to dynamically measure a large-range stretched strain. This experiment is the first to accurately identify the maximal strain of 1200 $\unicode{x00B5}\unicode{x03B5}$µÎµ with a high spatial resolution of 3.45 cm using the single-slope-assisted technology. The dynamic frequency is 4.67 Hz in the highest but limited by the practical devices.

Temperature accuracy and resolution improvement for a Raman distributed fiber-optics sensor by using the Rayleigh noise suppression method.

A novel Rayleigh noise suppression method is proposed to improve temperature accuracy and resolution for Raman distributed fiber-optics sensors. The proposed temperature demodulation method can eliminate temperature measurement inaccuracy caused by Rayleigh noise. The experimental results indicate that the temperature accuracy is optimized from 6.2°C to 1.7°C at a sensing distance of 9.1 km by using the proposed method, and the temperature resolution leads to about 1.5°C improvement compared with the tradition demodulation method at a sensing distance of 10.0 km. The proposed method provides a robust and reliable high performance for long sensing ranges.

Signal-to-noise ratio improvement of Brillouin optical time domain analysis system based on empirical mode decomposition and finite impulse response.

We propose a denoising algorithm based on empirical mode decomposition (EMD) and finite impulse response (FIR) to improve the signal-to-noise ratio (SNR) of Brillouin optical time domain analysis. Denoising results indicate EMD-FIR can effectively reduce noise, and the maximum SNR improvement is 11.69 dB, which is 4.98 dB and 4.26 dB larger than the maximum SNR improvement of wavelet and Butterworth. The temperature uncertainty along the heated section is reduced to 0.62°C by EMD-FIR. The improvement of SNR opens opportunities to apply high measurement accuracy to Brillouin optical time domain analysis and other distributed sensing fields.

Temperature Resolution Improvement in Raman-Based Fiber-Optic Distributed Sensor Using Dynamic Difference Attenuation Recognition.

There is an optical interference noise in the conventional Raman-based fiber-optics distributed sensing, which results in a poor temperature resolution performance. In addition, the traditional whole-fiber demodulation principle complicates the operation steps of the system. In this paper, a novel dynamic difference attenuation recognition (DDAR) principle is operated in the DDP scheme (dual demodulation principle) and the SDP scheme (self-demodulation principle) respectively. It not only helps to eliminate the optical interference noise, but also omits the whole-fiber calibration process. In this experiment, a temperature resolution of 0.30 °C (17.0 km) is achieved through using the DDP scheme based on the DDAR principle, and the measurement time can be shortened to 1.5 s. Meanwhile, a temperature resolution of 0.18 °C (17.0 km) is obtained for the SDP scheme under the DDAR principle. The SNR of DDP and DSP schemes can be optimized to 12.82 dB and 13.32 dB by the proposed DDAR technology. Furthermore, the temperature resolution performance under a large temperature measurement range (0-1000 °C) is theoretically analyzed. The results indicate that the temperature responsivity for DDP and SDP schemes are parabolic and linear type respectively, which causes the temperature resolution of the two schemes to show a different trend with the change of temperature. The proposed DDAR method also can improve the temperature resolution in such a large temperature measurement range.

Advances in Random Fiber Lasers and Their Sensing Application.

Compared with conventional laser, random laser (RL) has no resonant cavity, reducing the requirement of cavity design. In recent years, the random fiber laser (RFL), a novel kind of RL, has made great progress in theories and experiments. The RFL has a simpler structure, a more flexible design, and higher reliability. It has valuable applications for earth sciences, biological life sciences, and national defense security, due to these unique properties. This paper reviews the development of RFLs in the last decade, including their configurations based on various optical fibers and their output properties, especially the method of control. Moreover, we also introduce their applications in the optical fiber sensing system, which is a very important and practical orientation to study. Finally, this paper presents the prospects of RFLs.