Targeting Nrf2 signaling pathways in the role of bladder cancer: From signal network to targeted therapy.

Bladder cancer (BC) is the most common malignancy of the urinary system and often recurs after tumor removal and/or is resistant to chemotherapy. In cancer cells, the activity of the signaling pathway changes significantly, affecting a wide range of cell activities from growth and proliferation to apoptosis, invasion and metastasis. Nrf2 is a transcription factor that plays an important role in cellular defense responses to a variety of cellular stresses. There is increasing evidence that Nrf2 acts as a tumor driver and that it is involved in the maintenance of malignant cell phenotypes. Abnormal expression of Nrf2 has been found to be common in a variety of tumors, including bladder cancer. Over-activation of Nrf2 can lead to DNA damage and the development of bladder cancer, and is also associated with various pathological phenomena of bladder cancer, such as metastasis, angiogenesis, and reduced toxicity and efficacy of therapeutic anticancer drugs to provide cell protection for cancer cells. However, the above process can be effectively inhibited or reversed by inhibiting Nrf2. Therefore, Nrf2 signaling may be a potential targeting pathway for bladder cancer. In this review, we will characterize this signaling pathway and summarize the effects of Nrf2 and crosstalk with other signaling pathways on bladder cancer progression. The focus will be on the impact of Nrf2 activation on bladder cancer progression and current therapeutic strategies aimed at blocking the effects of Nrf2. To better determine how to promote new chemotherapy agents, develop new therapeutic agents, and potential therapeutic targets.

Role of Protein Tyrosine Phosphatase 1B Inhibitor in Early Brain Injury of Subarachnoid Hemorrhage in Mice.

Clinically, early brain injury (EBI), which refers to the acute injuries to the whole brain in the phase of the first 72 h following subarachnoid hemorrhage (SAH), is intensely investigated to improve neurological and psychological function. Additionally, it will be meaningful to explore new therapeutic approaches for EBI treatment to improve the prognosis of patients with SAH. To investigate the underlying neuroprotection mechanism in vitro, the Protein tyrosine phosphatase 1B inhibitor (PTP1B-IN-1) was put in primary neurons induced by OxyHb to observe neuroapoptosis, neuroinflammation, and ER stress. Then, one hundred forty male mice were subjected to Experiment two and Experiment three. The mice in the SAH24h + PTP1B-IN-1 group were given an intraperitoneal injection of 5 mg/kg PTP1B-IN-1 30 min before anesthesia. SAH grade, neurological score, brain water content, Western blot, PCR, and Transmission Electron Microscopy (TEM) were performed to observe the underlying neuroprotection mechanism in vivo. Overall, this study suggests that PTP1B-IN-1 could ameliorate neuroapoptosis, neuroinflammation, and ER stress in vitro and in vivo by regulating the IRS-2/AKT signaling pathway, suggesting that PTP1B-IN-1 may be a candidate drug for the treatment of early brain injury after SAH.

Effect of Tempering Temperature on Microstructure and Sulfide Stress Cracking of 125 Ksi Grade Casing Steel.

The influence of tempering temperature on the microstructure of 0.5Cr0.4W steels was investigated by scanning electron microscope, and the roles of grain boundary character, dislocation, and Taylor factor in sulfide stress cracking (SSC) resistance were interpreted using the election backscattered diffraction technique. The 0.5Cr0.4W steels tempered at 690 °C, 700 °C, and 715 °C all showed tempered martensites. The specimen tempered at 715 °C exhibited a higher critical stress intensity factor (KISSC) of 34.58 MPa·m0.5, but the yield strength of 800 MPa did not meet the criterion of 125 ksi (862 MPa) grade. When the specimen was tempered at 690 °C, the yield strength reached 960 MPa and the KISSC was only 21.36 MPa·m0.5, displaying poorer SSC resistance. The 0.5Cr0.4W steel tempered at 700 °C showed a good combination of yield strength (887 MPa) and SSC resistance (KISSC: 31.16 MPa·m0.5). When increasing the tempering temperature, the local average misorientation and Taylor factor of the 0.5Cr0.4W steels were decreased. The reduced dislocation density, and greater number of grains amenable to slippage, produced less hydrogen transport and a lower crack sensitivity. The SSC resistance was, thus, increased, owing to the minor damage to hydrogen aggregation. Therefore, 700 °C is a suitable tempering temperature for 0.5Cr0.4W casing steel.

Traditional soybean (Glycine max) breeding increases seed yield but reduces yield stability under non-phosphorus supply.

Traditional soybean (Glycine max L.) breeding has improved seed yield in high-input agricultural systems, under high nitrogen (N), phosphorus (P) and potassium (K) supply. The seed yield improvements under non-P supply and the seed protein and mineral content dilution by yield improvement were evaluated in 18 soybean cultivars released from 1995 to 2016 in south-east China. Soybean varieties were grown under rainfed conditions in the field under 0 and 35kgPha-1 in four sites: Dafang and Shiqian in the growing season of 2017 and Dafang and Puding in the 2018 season. The seed yield, seed protein content and nine seed nutrition concentration were examined. Soybean seed yield increased with the year of release at rates of 5.5-6.7gm-2 year-1 under 35kgPha-1 and 3.9-4.8gm-2 year-1 under non-P supply in the four experiments. The increase resulted from increases in the number of filled-pods and total seed number rather than from single seed weight and number of seeds per pod. Seed protein content and seed nutrition concentration has not changed with the year of release under 0 and 35kgPha-1 . Grain yield was positively correlated with the seed Fe concentration. The cultivar superiority of seed yield, seed P, Zn and Ca concentration was negatively correlated with their static stability coefficient. Traditional soybean breeding increased yield under both P and non-P supply, without affecting seed protein content and mineral concentrations. A trade-off between high seed yield and seed P, Zn and Ca concentration and their stability under different environments was shown.

Effect of Titanium and Boron Microalloying on Sulfide Stress Cracking in C110 Casing Steel.

The effect of Ti and B microalloying on the hardenability, prior austenite grain size (PAGS), mechanical properties, and sulfide stress cracking (SSC) of C110 grade steel was studied by Jominy testing, static tensile testing, an optical microscope (OM), scanning electron microscopy (SEM) and double cantilever beam (DCB) testing. The results show that the addition of 0.015% Ti and 0.002% B into a medium-carbon Fe-Cr-Mo-Nb-V steel increased the hardenability and refined the PAGS and quenched martensite packets, and the size of carbides was reduced. It is believed that these behaviors are responsible for the improvement in the threshold stress intensity factor KISSC.

[Impact of the freezing-thawing process on human sperm mitochondria].

OBJECTIVE: To study the structure and function of human sperm mitochondria before and after the freezing-thawing process. METHODS: Human sperm from healthy donors were subjected to the slow freezing-thawing process, and the sperm mitochondrion-related indexes compared before and after cryopreservation. The ultrastructural changes of the mitochondria were observed under the projection electron microscope, the mitochondrial membrane potential (MMP) and seminal adenosine triphosphate (ATP) content measured by immunofluorescence labeling and ELISA, respectively, and the sperm oxidative stress related indexes detected before and after sperm cryopreservation. RESULTS: Electron microscopy showed loose structures and widened crests of the sperm mitochondria, some with vacuole-like changes after the freezing-thawing process. The sperm after cryopreservation, compared with those before it, exhibited significantly increased contents of oxygen free radicals (ï¼»11.6 ± 3.8ï¼½% vs ï¼»9.6 ± 4.1ï¼½%, P < 0.05) and malondialdehyde (ï¼»3.2 ± 1.4ï¼½ vs ï¼»2.3 ± 1.2ï¼½ nmol/108, P < 0.05), but decreased antioxidant capacity (ï¼»0.6 ± 0.4ï¼½ vs ï¼»0.9 ± 0.4ï¼½ nmol/108, P < 0.05), superoxide dismutase activity (ï¼»0.9 ± 0.4ï¼½ vs ï¼»9.1 ± 3.9ï¼½ nmol/108, P < 0.05), MMP (ï¼»52.2 ± 6.2ï¼½% vs ï¼»55.7 ± 4.9ï¼½%, P = 0.026) and ATP production (ï¼»56.5 ± 9.0ï¼½ vs ï¼»61.3 ± 10.4ï¼½ pmol/106, P = 0.014). CONCLUSIONS: The freezing-thawing process can cause ultrastructural disorder of human sperm mitochondria, reduce their membrane potential and decrease their ATP production.

Genetic Regulation of Ethylene Dosage for Cucumber Fruit Elongation.

Plant organ growth and development are determined by a subtle balance between growth stimulation and inhibition. Fruit size and shape are important quality traits influencing yield and market value; however, the underlying mechanism regulating the balance of fruit growth to achieve final size and shape is not well understood. Here, we report a mechanistic model that governs cucumber (Cucumis sativus) fruit elongation through fine-tuning of ethylene homeostasis. We identified a cucumber mutant that bears short fruits owing to repressed cell division. SF1 (Short Fruit 1) encodes a cucurbit-specific RING-type E3 ligase, and the mutation resulted in its enhanced self-ubiquitination and degradation, but accumulation of ACS2 (1-aminocyclopropane-1-carboxylate synthase 2), a rate-limiting enzyme for ethylene biosynthesis. The overproduction of ethylene contributes to the short-fruit phenotype of sf1 Dysfunction of ACS2 resulted in reduced ethylene production, but still repressed cell division and shorter fruit, suggesting that ethylene is still required for basal fruit elongation. SF1 ubiquitinates and degrades both itself and ACS2 to control ethylene synthesis for dose-dependent effect on cell division and fruit elongation. Our findings reveal the mechanism by which ethylene dosage is regulated for the control of cell division in developing fruit.

3D thickness distributions of plano lenses as a means of cavity pressure characterization in microinjection molding.

This work presents a novel nondestructive cavity pressure characterization approach in microinjection molding (µIM) through measuring 3D part thickness distributions. For this purpose, a plano lens was designed and experiments based on Taguchi method were conducted. Both overall and local lens thickness distributions under various process conditions were analyzed in terms of their relevance with the cavity pressure during molding. Unexpectedly, a reliable linear regression model was developed fulfilling nondestructive multi-point or even continuous cavity pressure characterization with the overall lens thickness distribution. Furthermore, the topography of the constructed 3D thickness surface was found to depend on both process condition and measuring position. Finally, the process conditions were optimized for obtaining uniform distributions of both 3D thickness and cavity pressure.

Lipopolysaccharide induces autophagy by targeting the AMPK-mTOR pathway in Human Nasal Epithelial Cells.

Chronic rhinosinusitis (CRS) is a well-known disease encountered in the department of otorhinolaryngology, yet little is known about its pathogenesis. Autophagy, a lysosome-dependent degradation process, has been reported to be involved in the process of many chronic inflammatory diseases. Here we tried to evaluate the function of autophagy in CRS as well as explore the related mechanisms. We first stained light chain 3B (LC3B) with immunohistochemistry in uncinate tissues (UT) from patients with and without CRS and found that its expression was up-regulated in CRS patients. Then, Human Nasal Epithelial Cells (HNEpC) were treated with lipopolysaccharide (LPS), one of the most common pathogenic elements in CRS, and we found that autophagy was induced in a dose- and time-dependent manner. This is supported by a rise in the expression of light chain 3B-II (LC3B-II), accumulation of GFP-LC3 vesicles, as well as decreased p62 expression. Furthermore, we found that LPS promoted AMPK phosphorylation and inactived mTOR, while AMPK inhibition by compound C significantly attenuated LPS-induced autophagy. Besides, treatment of HNEpC with LPS increased the amount of Toll-like receptor 4 (TLR4) while inhibiting TLR4 by Polymyxin B (PMB) declined autophagy caused by LPS. Taken together, our study first demonstrated that LPS caused autophagy in HNEpC, and this process was AMPK-mTOR dependent. These data suggested the relationship between LPS and autophagy in the pathogenesis of CRS.

Development of microsatellite markers in Garcinia paucinervis (Clusiaceae), an endangered species of karst habitats.

PREMISE OF THE STUDY: Microsatellite markers were developed for Garcinia paucinervis (Clusiaceae), an endangered and endemic tree species of karst habitats, to analyze its genetic diversity and genetic structure. METHODS AND RESULTS: Using shotgun sequencing on an Illumina MiSeq platform, a total of 22 microsatellite primer sets were characterized, of which 17 were identified as polymorphic. For these polymorphic loci, the total number of alleles per locus ranged from two to 12 across 54 individuals from three populations. The observed and expected heterozygosities ranged from 0.000 to 1.000 and from 0.000 to 0.850, respectively. No pair of loci showed significant linkage disequilibrium. Three loci in one population deviated significantly from Hardy-Weinberg equilibrium (P < 0.05). Seven loci (JSL3, JSL5, JSL22, JSL29, JSL32, JSL39, and JSL43) were successfully amplified in G. bracteata. CONCLUSIONS: These markers will be useful in studies on genetic diversity and population structure of G. paucinervis.

Profiling of ginsenosides in the two medicinal Panax herbs based on ultra-performance liquid chromatography-electrospray ionization-mass spectrometry.

As the king of herb plants, ginseng has been used for nearly 5000 years in medicines in Asia and recently in the West. Ginsenosides, the main active constituents in Panax herbs, have prominent immunoregulatory effects. Although extensively studied in the roots, ginsenosides have not been studied with regard to their profiles and natural variations in the leaf, stem, petiole, lateral root, and main roots during development or among species. In this study, a sensitive ultra-performance liquid chromatography-electrospray ionization-mass spectrometry method with a shorter chromatographic running time was developed and validated for simultaneous quantification of ten ginsenosides. Comparing ginsenoside contents in various parts during different developmental stages revealed part-specific accumulation of most ginsenosides. Further investigation indicated that Rg3 accumulated at significantly higher levels in the petiole of P. ginseng than in that of P. quinquefolius. The relative ratio of ginsenoside Rb2 to Rb1 appears to be a candidate metabolic marker for identifying the ginseng cultivar within a diverse collection of ginseng accessions. In addition, the PCA showed that aboveground parts differed significantly between species and can be considered as species-specific markers rather than roots. This comprehensive survey, providing reliable, affordable and adequate scientific evidence, could be used to differentiate two species and discriminate ginseng cultivar ages.

The Combined Effects of Ethylene and MeJA on Metabolic Profiling of Phenolic Compounds in Catharanthus roseus Revealed by Metabolomics Analysis.

Phenolic compounds belong to a class of secondary metabolites and are implicated in a wide range of responsive mechanisms in plants triggered by both biotic and abiotic elicitors. In this study, we approached the combinational effects of ethylene and MeJA (methyl jasmonate) on phenolic compounds profiles and gene expressions in the medicinal plant Catharanthus roseus. In virtue of a widely non-targeted metabolomics method, we identified a total of 34 kinds of phenolic compounds in the leaves, composed by 7 C6C1-, 11 C6C3-, and 16 C6C3C6 compounds. In addition, 7 kinds of intermediates critical for the biosynthesis of phenolic compounds and alkaloids were identified and discussed with phenolic metabolism. The combinational actions of ethylene and MeJA effectively promoted the total phenolic compounds, especially the C6C1 compounds (such as salicylic acid, benzoic acid) and C6C3 ones (such as cinnamic acid, sinapic acid). In contrast, the C6C3C6 compounds displayed a notably inhibitory trend in this case. Subsequently, the gene-to-metabolite networks were drawn up by searching for correlations between the expression profiles of 5 gene tags and the accumulation profiles of 41 metabolite peaks. Generally, we provide an insight into the controlling mode of ethylene-MeJA combination on phenolic metabolism in C. roseus leaves.

A protocol of homozygous haploid callus induction from endosperm of Taxus chinensis Rehd. var. mairei.

Obtainment and characterization of the novel endosperm callus of Taxus chinensis Rehd. var. mairei are valuable for haploid breeding, genome, and functional genome in Taxus. Callus was obtained by hydropriming with sterile water for 3 days and suitable medium composition. The highest callus induction (70.89 %) and lower browning ratio (7.95 %) were obtained from Gamborg (B5) medium supplemented with 30 g l(-1) of sucrose, 2.5 mg l(-1) of 2,4-dichlorophenoxyacetic (2,4-D), 0.5 mg l(-1) of 6-benzylademine (6-BA) and 7 g l(-1) of agar under dark conditions. The auxin of 2,4-D had a better efficiency of callus induction than naphthylacetic acid, and over 1 mg l(-1) of 6-BA was inhibitory to the callogensis of endosperm. The endosperm callus was haploid which was detectable by the flow cytometry. The genome block of homozygosity of callus was homozygous which was indicated by PCR-based SNP marks. The homozygous haploid of endosperm callus in vitro culture may be useful tools for taxoid-metabolism of gene engineering and bio-fermentation engineering.

[Optimizing Savitzky-Golay Parameters and Its Smoothing Pretreatment for FTIR Gas Spectra].

In the smoothing pretreatment for the quantitative analysis of hydrocarbon mixed gases by Fourier transform infrared analysis (FTIR), the Savitzky- Golay filter is usually used as one of the smoothing preprocessing methods in the Fourier transform infrared spectrum data smoothing pretreatment. However, the parameters of the Savitzky-Golay filter such as the polynomial order and frame size are not easy to decide. There is no one unified choice basis. Users usually adopt multiple sets in the special data set to try, and then select a set of relatively optimal data as the optimizing parameters of the Savitzky-Golay filter. The optimal selection method of the Savitzky-Golay filter parameters was explored, and the concrete calculation equations were deduced according to the relation among the normalized cut-off frequency, the normalized beginning frequency of the stopband, the normalized first side lobe peak frequency of the stopband, the normalized first side lobe peak amplitude with the polynomial order and frame size of the Savitzky-Golay filter parameters. Then when the polynomial order and frame size are set as 8 and 11 respectively according the above conclusion and the characteristics of the actual spectral data, the Savitzky - Golay filter smoothing effect is optimum. Through the acquisition the concentration of 0.1%, 0.2%, 0.5%, 1%, 2%, 5% for the actual CH4 spectra, the relative maximum and minimum error of the raw spectra converted absorbance were 17.230 5% and 0.243 0% respectively, and the relative maximum and minimum error of the smooth spectra converted absorbance were 0.088 0% and 0.088 0% respectively in the second absorption peak. The relative error of converted absorbance was basically stable through the Savitzky-Golay filter after the spectral data preprocessing and it was relatively low, so, it laid a foundation for the late spectral data accurate qualitative and quantitative analysis.

[The spectral characteristic wavelength selection and parameter optimization based on Tikhonov regularization].

In the multicomponent mixture hydrocarbon gases Fourier transform infrared (FTIR) quantitative analysis, especially for light alkane gases, it is not easy to establish the quantitative analysis model because their IR spectra absorption peaks are seriously overlapped. Aiming at this problem, the Tikhonov regularization algorithm was used to select the characteristic wavelengths for seven kinds of light alkane mixture gases FTIR which are composed with methane, ethane, propane, iso-butane, n-butane, iso-pentane and n-pentane. And then the wavelength selection was used to establish the quantitative analysis model. By comparing the analysis characteristics wavelength selection and TR parameters optimization of the mixed gases in the infrared all wave band, the first absorption peak band and the second peak band, the characteristic wavelength of 7 kinds of gases were selected by Tikhonov algorithm. The wavelength selection and Tikhonov regularization parameters were used to test the actual measured methane spectral data, and then we got that with other gas components the max cross sensitivity was 11.153 7%, the minimum cross sensitivity was 1.239 7%, and the root mean square prediction error was 0.004 8. The Tikhonov regularization algorithm effectively enhanced the accuracy in the light alkane mixed gas quantitative analysis. The feasibility of alkane gases mixture Fourier transform infrared spectrum wavelength selection was preliminarily verified by using the Tikhonov regularization algorithm.

[Using 2-DCOS to identify the molecular spectrum peaks for the isomer in the multi-component mixture gases Fourier transform infrared analysis].

The generalized two-dimensional correlation spectroscopy and Fourier transform infrared were used to identify hydrocarbon isomers in the mixed gases for absorption spectra resolution enhancement. The Fourier transform infrared spectrum of n-butane and iso-butane and the two-dimensional correlation infrared spectrum of concentration perturbation were used for analysis as an example. The all band and the main absorption peak wavelengths of Fourier transform infrared spectrum for single component gas showed that the spectra are similar, and if they were mixed together, absorption peaks overlap and peak is difficult to identify. The synchronous and asynchronous spectrum of two-dimensional correlation spectrum can clearly identify the iso-butane and normal butane and their respective characteristic absorption peak intensity. Iso-butane has strong absorption characteristics spectrum lines at 2,893, 2,954 and 2,893 cm(-1), and n-butane at 2,895 and 2,965 cm(-1). The analysis result in this paper preliminary verified that the two-dimensional infrared correlation spectroscopy can be used for resolution enhancement in Fourier transform infrared spectrum quantitative analysis.

[Quantitative analysis of transformer oil dissolved gases using FTIR].

For the defects of requiring carrier gas and regular calibration, and low safety using chromatography to on line monitor transformer dissolved gases, it was attempted to establish a dissolved gas analysis system based on Fourier transform infrared spectroscopy. Taking into account the small amount of characteristic gases, many components, detection limit and safety requirements and the difficulty of degasser to put an end to the presence of interference gas, the quantitative analysis model was established based on sparse partial least squares, piecewise section correction and feature variable extraction algorithm using improvement TR regularization. With the characteristic gas of CH4, C2H6, C2H6, and CO2, the results show that using FTIR meets DGA requirements with the spectrum wave number resolution of 1 cm(-1) and optical path of 10 cm.

Draft Genome Sequence of Lactobacillus plantarum Strain AY01, Isolated from the Raw Material of Fermented Goat Milk Cheese.

Lactobacillus plantarum is an important probiotic that is isolated mostly from fermented foods. Here, we report the first draft genome sequence of L. plantarum strain AY01, isolated from the raw material of fermented goat milk cheese. This bacterium, with optimum growth at 30°C, has a G+C content of 43.68%.

Development of sample preparation method for isoliquiritigenin, liquiritin, and glycyrrhizic acid analysis in licorice by ionic liquids-ultrasound based extraction and high-performance liquid chromatography detection.

An ionic liquid-based ultrasonic-assisted extraction (ILUAE) method had been used for the effective extraction of isoliquiritigenin (IQ), liquiritin (LQ) and glycyrrhizic acid (GA) from licorice. The ionic liquids with different cations and anions were investigated in this work and 0.5 M 1-butyl-3-methylimidazolium bromide solution was selected as solvent. In addition, the technical parameters including soaking time, solid-liquid ratio, ultrasonic power and time were optimized. Compared with the conventional solvent extraction, the proposed approach exhibited higher efficiency, which indicated the ILUAE was an efficient, rapid and simple sample preparation technique. There was no degradation of the target analytes had been observed at the optimum conditions which was evidenced by the stability studies performed with standard of IQ, LQ and GA. The proposed method also showed high reproducibility and was environmental friendly.

Natural populations of lactic acid bacteria in douchi from Yunnan Province, China.

This research was aimed at isolating and identifying the predominant lactic acid bacteria (LAB) in the traditional Chinese salt-fermented soybean food, douchi, from Yunnan, China. The predominant LAB present were isolated and identified by conventional culture-dependent methods combined with molecular biological methods. Two hundred and sixty isolates were obtained from thirty kinds of traditional fermented douchi from six cities and counties in Yunnan, and those strains were divided into twelve groups by their morphological and biochemical characteristics. Based on 16S ribosomal DNA (rDNA) sequencing and analysis, 56 representative strains were identified as belonging to 6 genera and 14 species: Lactobacillus (4 spp.), Weissella (3 spp.), Pediococcus (2 spp.), Staphylococcus (2 spp.), Enterococcus (1 sp.), and Bacillus (2 spp.). The results show that douchi contains a large natural population of LAB of diverse composition from which some strains could be selected as starters for functional fermented foods. This is the first study on the original douchi from Yunnan, and the results suggest that it may be a useful source for the isolation of LAB. This study has also laid a foundation for further research on developing functional douchi products.