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The antioxidant defense system is essential for animals to cope with homeostasis disruption and overcome oxidative stress caused by adverse environmental conditions such as hypoxia. However, our understanding of how this system works in subterranean rodents remains limited. In this study, Brandt's vole Lasiopodomys brandtii was exposed to normoxia (21% O2 ) or hypoxia (mild or severe hypoxia: 10% or 5% O2 ) for 6 h. Changes in key enzymes of the classic enzymatic antioxidant system at both mRNA and enzyme activity levels, and tissue antioxidant levels of the low-molecular-weight antioxidant system were determined in brain, liver, and kidney. Transcript levels of the upstream regulator NF-E2-related factor 2 (Nrf2) were also measured. We found that the mRNA expression of Nrf2 and its downstream antioxidant enzyme genes in L. brandtii were relatively conserved in response to hypoxia in most tissues and genes tested, except in the liver. Hepatic Nrf2, Cu/Zn SOD, GPx1, and GPx3 levels were significantly upregulated in response to mild hypoxia, whereas Mn SOD level decreased significantly in severe hypoxia. Unmatched with changes at the RNA level, constitutively high and relatively stable antioxidant enzyme activities were maintained throughout. For the low-molecular-weight antioxidant system, an abrupt increase of cerebral ascorbic acid (AA) levels in hypoxia indicated a tissue-specific antioxidant response. Although hypoxia did not cause significant oxidative damage in most tissues tested, the significant decrease in antioxidant enzyme activities (GPX and GR) and increase in lipid peroxidation in the kidney suggest that prolonged hypoxia may pose a critical threat to this species. This article is protected by copyright. All rights reserved.

The response mechanism and interaction patterns of HIF-1α and p53 in animals in an hypoxic environment are crucial for their hypoxic tolerance and adaptation. Many studies have shown that underground rodents have better hypoxic adaptation characteristics. However, the mechanism by which HIF-1α and p53 in underground rodents respond to hypoxic environments compared with in ground rodents remains unclear. Further, whether a synergy between HIF-1α and p53 enables animals tolerate extremely hypoxic environments is unclear. We studied HIF-1α and p53 expression in the brain tissue and cell apoptosis in the hippocampal CA1 region during 6 hours of acute hypoxia (5% oxygen) in Lasiopodomys mandarinus (Milne-Edwards, 1871) and Lasiopodomys brandtii (Radde, 1861), two closely related small rodents with different life characteristics (underground and aboveground, respectively), using a comparative biology method to determine the mechanisms underlying their adaptation to this environment. Our results indicate that HIF-1α and p53 expression is more rapid in L. mandarinus than in L. brandtii under acute hypoxic environments, resulting in a significant synergistic effect in L. mandarinus. Correlation analysis revealed that HIF-1α expression and the apoptotic index of the hippocampal CA1 regions of the brain tissues of L. mandarinus and L. brandtii, both under hypoxia, were significantly negatively and positively correlated, respectively. Long-term existence in underground burrow systems could enable better adaptation to hypoxia in L. mandarinus than in L. brandtii. We speculate that L. mandarinus can quickly eliminate resulting damage via the synergistic effect of p53 and HIF-1α in response to acute hypoxic environments, helping the organism quickly return to a normal state after the stress.

With the increasing emphasis on remote electrocardiogram (ECG) monitoring, a variety of wearable remote ECG monitoring systems have been developed. However, most of these systems need improvement in terms of efficiency, stability, and accuracy. In this study, the performance of an ECG monitoring system is optimized by improving various aspects of the system. These aspects include the following: the judgment, marking, and annotation of ECG reports using artificial intelligence (AI) technology; the use of Internet of Things (IoT) to connect all the devices of the system and transmit data and information; and the use of a cloud platform for the uploading, storage, calculation, and analysis of patient data. The use of AI improves the accuracy and efficiency of ECG reports and solves the problem of the shortage and uneven distribution of high-quality medical resources. IoT technology ensures the good performance of remote ECG monitoring systems in terms of instantaneity and rapidity and, thus, guarantees the maximum utilization efficiency of high-quality medical resources. Through the optimization of remote ECG monitoring systems with AI and IoT technology, the operating efficiency, accuracy of signal detection, and system stability have been greatly improved, thereby establishing an excellent health monitoring and auxiliary diagnostic platform for medical workers and patients.

High energy pulsed High-order Mode (HOM) beams has great potential in materials processing and particle acceleration. We experimentally demonstrate a high energy mode-locking Raman all-fiber laser with switchable HOM state. A home-made fiber mode-selective coupler (MSC) is used as the mode converter with a wide bandwidth of 60 nm. By combining advantages of MSC and stimulated Raman scattering, 1.1 μJ pulsed HOM beams directly emitting from the all-fiber cavity can be achieved. After controlling the category and phase delay of vector modal superposition, different pulsed HOM beams including cylindrical vector beams (CVBs) (radial and angular) and optical vortex beams (OVBs) are reasonably obtained with high purity (all over 95%), as well as arbitrary switching. Furtherly, the slope efficiency of HOM beams in the mode-locking and continuous wave operations are as much as 20.3% and 31.8%, respectively. It may provide an effective way to achieve high energy pulsed HOM beams.

MicroRNAs are emerging as important endogenous regulators of gene function and they are playing an important role in the occurrence and development of cancer. They are also regarded as robust biomarkers of cancer diagnosis and prognosis. Hepatocellular carcinoma (HCC) is a common and complex human malignancy with high mortality and morbidity in the world. MicroRNA-122 (miR-122) is a liver-specific microRNA and is closely associated with HCC metastasis, which makes miR-122 a promising target for drug design and development. In this study, we performed a cell-based screening method for discovering miR-122 activators and found that oleanolic acid (OA), a natural pentacyclic triterpene, specifically increased miR-122 expression in a concentration-dependent manner. Two HCC cell lines (HepG2 and Sk-hep-1 cells) were used to evaluate the effect of OA on cell migration and invasion abilities. The results indicated that OA attenuated the migration and invasion abilities of HCC cells by upregulating miR-122 expression. In addition, OA increased the expression of E-cadherin and decreased the expression of β-catenin, N-cadherin and vimentin. After knocking down miR-122 with miR-122 inhibitor, we found that the effect of OA on these epithelial-to-mesenchymal transition (EMT) related molecules was significantly weakened, indicating OA exhibited anti-EMT effect by increasing the expression of miR-122. These finding may help to better understand the molecular mechanism of OA's anti-metastasis activity.

Within the stirred-tank flocculating system under equivalent shear-rate (Gave) cases, the effects of both reactor shape (cylindrical or square) and baffles on floc morphological evolution during flocculation were investigated by applying flocculation tests with the aid of computational fluid dynamics (CFD) simulations. At a constant Gave, the recirculating times for those floc aggregates existing in water flow to the impeller region and the intensity of turbulence occurring within this region, together with the non-uniform nature of turbulence for water flow above the rotating impeller, were found to be distinct in the various stirred-tank reactors investigated, thereby affecting the development of floc size and structure. Besides, the importance of reactor shape and baffles to floc morphological evolution seemed to be largely determined by predominant growth behavior(s). For aggregation-dominated circumstances, the baffled square stirred tank formed the largest and most compact floc aggregates among all reactors, due to the most visiting times for pre-formed micro-floc aggregates to the highest turbulent-intensity impeller region; while for breakage-dominated circumstances, the most non-uniform distributions of turbulent water flow were generated via impeller-baffle interactions in this reactor, thereby giving the highest breakage rate and producing the smallest floc aggregates with the smoothest and most compact structures.

The impeller clearance (C) and shear rate (Gave) effects on aggregation and breakage behaviors in the whole process of floc growth were investigated by applying lab-scale flocculation tests with the aid of computational fluid dynamics (CFD) simulations. For a baffled square stirred-tank flocculating reactor, the recirculating times for water flow to the impeller region and intensity of turbulence occurring within this region, together with the non-uniform nature of turbulence for water flow above the rotating impeller, were found to be more or less different in all C-value cases at a constant Gave, thereby affecting the development of floc morphology. Besides, the importance of impeller clearance (C) to floc morphological evolution seemed to be largely determined by predominant growth behavior(s), likely as a result of distinct occurring degrees of either aggregation or breakage for each combination of C and Gave; and interestingly, a certain compaction for the above effect took place at a relatively high shear, possibly attributed to increasingly pronounced occurrence of floc breakage and irreversibility of this behavior. To produce fractal flocs with favorable morphological characteristics, the impeller should be placed at an appropriate distance from the reactor bottom within the flocculating system, under whether aggregation-dominated or breakage-dominated circumstances, for weakening the role of reactor bottom and water surface on floc growth behaviors during flocculation. This research would be beneficial for thoroughly understanding floc formation mechanisms and optimally designing impeller-based flocculating reactors.

For enhancing the understanding of ballasted flocculation (BF) mechanisms, a series of BF tests were performed to explore the coagulant dosage and mixing intensity effects on floc growth behaviors and corresponding particle settling by using coagulants of aluminum sulphate (AS) or polyaluminum chloride (PACl). As expected, different coagulant dosages brought about distinct surface charge characteristics of micro-floc aggregates after either Al-based coagulant addition, thereby affecting the development of ballasted floc size. More specifically, the higher the coagulant dosage was, the more the cationic hydrolyzed-Al species were produced, leading to a requirement of more binding sites on the injected polymer for bridging between micro-flocs and ballasting agent (BA) particles, and accordingly, the degree to which BA particles had been incorporated into the aggregate matrix seemed to largely account for ballasted floc formation. Besides, floc aggregates formed after breakage appeared larger than those after maturation, especially at higher coagulant dosages, possibly caused by a stretched conformation of long polymer chains providing more binding sites available within a higher-shear suspension. In an operational sense, poor incorporation should be maximally eliminated, since this undesirable behavior could produce a greater number of resultant flocs with fewer or even no BA particles, thus worsening the settling performance. This research would be helpful for thoroughly understanding ballasted floc formation mechanisms in either water or wastewater treatment operations.

Asymmetric supercapacitors have potential applications in renewable-energy technology owing to their remarkable electrochemical properties. A high-voltage asymmetric supercapacitor was developed based on a core–shell-structured MnO2@carbon sphere composite (MnO2@CS) as the cathode, nitrogen-doped activated carbon as the anode and a neutral aqueous Na2SO4 solution as the electrolyte. MnO2@CS was successfully fabricated by hydrothermally growing MnO2 on the surface of carbon spheres. A nitrogen-containing benzoxazine resin was adopted as a precursor to produce in situ nitrogen-doped activated carbon. Such an aqueous electrolyte-based asymmetric supercapacitor can be cycled reversibly in the high-voltage region of 0–1.9 V and exhibits a superior energy density of 8 Wh kg−1 at an ultrahigh power density of 9627 W kg−1 owing to the matching of MnO2@CS and porous nitrogen-doped activated carbon. Moreover, the asymmetric supercapacitor presents acceptable cycling performance, with 74.4% retention after 1000 cycles at 1 A g−1, and a charge–discharge efficiency of the electrode of almost 100%. A high-voltage asymmetric supercapacitor was developed based on a core–shell-structured MnO2@carbon sphere composite as the cathode, and in situ nitrogen-doped activated carbon as the anode. It exhibits a superior energy density of 8 Wh kg−1 at an ultrahigh power density of 9627 W kg−1.

Through regulating the in-band absorption of used gain fiber, we demonstrate an ultra-broadband tunable and switchable multi-wavelength mode-locking Tm-doped all-fiber laser. The tuning range can be enlarged as much as 153 nm (from 1828.45 to 1981.35 nm, the largest tuning range so far) by employing different lengths of used gain fiber with different in-band absorption and birefringent filtering mechanism. In addition, benefiting from four in-line polarization controllers and broadband gain profile of Tm-doped fiber, switchable quad-wavelength mode locking with part binary control can be observed clearly, even penta-wavelength. Such kind of ultra-broadband tunable and switchable mode-locking laser provide simpler and elastic way for practical application, such as optical signal processing, spectroscopy, optical communications, and so on.

The effects of global warming and anthropogenic disturbance force animals to migrate from lower to higher elevations to find suitable new habitats. As such migrations increase hypoxic stress on the animals, it is important to understand how plateau- and plain-dwelling animals respond to low-oxygen environments. We used comparative transcriptomics to explore the response of Neodon fuscus, Lasiopodomys brandtii, and Mus musculus skeletal muscle tissues to hypoxic conditions. Results indicate that these species have adopted different oxygen transport and energy metabolism strategies for dealing with a hypoxic environment. N. fuscus promotes oxygen transport by increasing hemoglobin synthesis and reduces the risk of thrombosis through cooperative regulation of genes, including Fga, Fgb, Alb, and Ttr; genes such as Acs16, Gpat4, and Ndufb7 are involved in regulating lipid synthesis, fatty acid β-oxidation, hemoglobin synthesis, and electron-linked transmission, thereby maintaining a normal energy supply in hypoxic conditions. In contrast, the oxygen-carrying capacity and angiogenesis of red blood cells in L. brandtii are promoted by genes in the CYP and COL families; this species maintains its bodily energy supply by enhancing the pentose phosphate pathway and mitochondrial fatty acid synthesis pathway. However, under hypoxia, M. musculus cannot effectively transport additional oxygen; thus, its cell cycle, proliferation, and migration are somewhat affected. Given its lack of hypoxic tolerance experience, M. musculus also shows significantly reduced oxidative phosphorylation levels under hypoxic conditions. Our results suggest that the glucose capacity of M. musculus skeletal muscle does not provide sufficient energy during hypoxia; thus, we hypothesize that it supplements its bodily energy by synthesizing ketone bodies. For the first time, we describe the energy metabolism pathways of N. fuscus and L. brandtii skeletal muscle tissues under hypoxic conditions. Our findings, therefore, improve our understanding of how vertebrates thrive in high altitude and plain habitats when faced with hypoxic conditions.

MicroRNAs are emerging as critical endogenous regulators of gene function. Aberrant regulation of microRNAs is associated with various human diseases, most importantly cancer. MicroRNA-122 (miR-122), a liver-specific microRNA, has been implicated in the control of hepatitis C virus (HCV) RNA replication and its response to interferon (IFN) in human hepatoma cells. Here, we report that daidzein, a naturally occurring plant isoflavone, inhibits HCV replication and enhances the antiviral effect of IFN-α on HCV therapy by decreasing microRNA-122 levels in vitro without significantly affecting cell growth. Moreover, daidzein was found to inhibit the expression of miR-122 and miR-21 by down-regulating the expression of TRBP, indicating that daidzein is possibly a general inhibitor of the miRNA pathway. Thus, daidzein provides new insights for drug discovery and HCV prevention.

Concise stereoselective syntheses of (−)-clavaminol A and deacetyl (+)-clavaminol H have been achieved from simple starting materials. Highlights of the synthesis for (−)-clavaminol A include a highly diastereoselective chelation-controlled hydride reduction of an amino ketone to give the anti amino alcohol directly, and NaBH 4 -mediated dehalogenation. The main synthetic approach for deacetyl (+)-clavaminol H features a highly diastereoselective chelation-controlled hydride reduction of the amino ketone to construct the anti amino alcohol and a palladium catalyzed hydrogenation reaction at the final step.

Several glutathione derivatives bearing the S-(N-aryl-N-hydroxycarbamoyl) or S-(C-aryl-N-hydroxycarbamoyl) moieties (10, 10', 13-15) were synthesized, characterized, and their human glyoxalase I (hGLO1) inhibitory activity was evaluated. Compound 10 was proved to be the effective hGLO1 inhibitor with a Ki value of 1.0 nM and the inhibition effect of compound 10 on hGLO1 was nearly ten-fold higher than that of the strongest inhibitor 2 (Ki=10.0 nM) which has been reported in the field of glutathione-type hGLO1 inhibitors. Its diethyl ester prodrug 10' was able to penetrate cell membrane and had good inhibitory effect on the growth of NCI-H522 cell xenograft tumor model.

Rh@UIO-66, prepared by using the double-solvent host–guest strategy and excess reduction methods, exhibited a higher catalytic activity in AB hydrolysis compared with Rh/UIO-66 because the ultrafine Rh nanoparticles were confined to UIO-66 channels. This confinement effect played a key role in enhancing the catalytic activity for AB hydrolysis.

The glyoxalase system is a ubiquitous enzymatic network which plays important roles in biological life. It consists of glyoxalase 1 (GLO1), glyoxalase 2 (GLO2), and reduced glutathione (GSH), which perform an essential metabolic function in cells by detoxifying methylglyoxal (MG) and other endogenous harmful metabolites into non-toxic d-lactate. MG and MG-derived advanced glycation endproducts (AGEs) are associated with various diseases, such as diabetes, cardiovascular disease, neurodegenerative disorders and cancer, and GLO1 is a key rate-limiting enzyme in the anti-glycation defense. The abnormal activity and expression of GLO1 in various diseases make this enzyme a promising target for drug design and development. This review focuses on the regulatory mechanism of GLO1 in diverse pathogenic conditions with a thorough discussion of GLO1 regulators since their discovery, including GLO1 activators and inhibitors. The different classes, chemical structure and structure-activity relationship are embraced. Moreover, assays for the discovery of small molecule regulators of the glyoxalase system are also introduced in this article. Compared with spectrophotometer-based assay, microplate-based assay is a more simple, rapid and quantitative high-throughput method. This review will be useful to design novel and potent GLO1 regulators and hopefully provide a convenient reference for researchers.

Nanostructure of catalysts plays a critical role in catalytic activity and durability. Herein, a ceria nanorod catalyst, CeO2(NR), was designed and synthesized, and the relationships between nanostructure and catalytic activity as well as aging resistibility were investigated. Scanning electron microscopy, transmission electron microscopy and X-ray diffraction results indicate that the nanorod structure of CeO2(NR) can be well maintained after aging at 900 °C for 8 h and can prevent the excessive expansion of crystals during high-temperature aging. X-ray photoelectron spectroscopy and hydrogen temperature-programmed reduction results suggest that the CeO2(NR) nanorod has distinctly more oxygen vacancies than the CeO2 nanoparticle; moreover the nanorod structure of CeO2(NR) and CeO2(NR)-A can enhance the lattice oxygen mobility and contribute to the spillover of lattice oxygen to form surface active oxygen during high temperature reaction. Finally, the catalytic activity tests indicate that the synthesized CeO2(NR) nanorod catalyst displays significantly better soot purification efficiency and intrinsic activity for soot oxidation; more than that, this superior catalytic activity of CeO2(NR) is well maintained after high-temperature thermal aging. Thus, this work suggests that the nanorod structure of ceria-based catalysts plays a key role in enhancing aging resistibility and catalytic soot oxidation activity.

Glyoxalase I (GLO1) is a homodimeric Zn2+-metalloenzyme that catalyses the transformation of methylglyoxal (MG) to d-lacate through the intermediate S-d-lactoylglutathione. Growing evidence indicates that GLO1 has been identified as a potential target for the treatment cancer and other diseases. Various inhibitors of GLO1 have been discovered or developed over the past several decades including natural or natural product-based inhibitors, GSH-based inhibitors, non-GSH-based inhibitors, etc. The aim of this review is to summarize recent achievements of concerning discovery, design strategies, as well as pharmacological aspects of GLO1 inhibitors with the target of promoting their development toward clinical application.

An optimal approach for process tolerance balancing is presented. The new approach is based on process capabilities and is to be used in the stage of process planning. A nonlinear programming model is used to simultaneously optimise process tolerances of required operations. In the optimisation model, the objective function is to minimise the total manufacturing cost with different weighting factors. Using the estimated standard deviations of the dimensions and the manufacturing cost-tolerance functions, the constraint equations for the process tolerance chains and the manufacturing capability indices are established, together with a model for the economical tolerance bounds of machine tools. A practical example was used to verify the usefulness of the proposed approach. The results of the comparative study show that the proposed approach is more advantageous in relaxing tolerance requirements and in reducing scrap rates generally, compared with the existing methods.

Dimension synthesis for higher-order kinematic parameters is a method to realize higher motion accuracy and to control the motion characteristics of planar linkage mechanisms. In this paper, taking a two-output impulse generator as an example, the construction of dimension synthesis equations for higher-order kinematic parameters and their solutions were carried out in four steps. In addition, to realize the self-adjustability of planar linkage mechanisms, a novel non-overconstraint basic bar group method was established to eliminate the overconstraint present in the mechanisms, which forms obstacles to planar motions. A prototype of a two-output impulse generator was produced based on the synthesis and self-adjustability design. Experimental results showed that fluctuation range of the output velocity of the two-output impulse generator was reduced by 10.3 % in comparison with a conventional impulse generator and a more steady motion was achieved, indicating the reliable motion accuracy and self-adjustability.Copyright © 2005 by ASME

This paper reports an empirical study that explores the problem of finding a highly-efficient, user-friendly interface design method on small display devices. We compared three models using our PDA interface simulator: presentation optimization method, semantic conversion method, and zooming method. A controlled experiment has been carried out to identify the pros and cons of each method. The results show that of the three interface methods, the zooming method is slightly better than the semantic conversion method, while they both outperform the optimizing presentation method. © 2004 IEEE.