Building adjustment capacity to cope with running water in cultured grass carp through flow stimulation conditions.

The adaptability of cultured fish to complex flow conditions is crucial for their survival after being released into the wild. Running water in natural environments poses significant challenges for the proliferation and release of cultured fish. This study aimed to investigate the effects of flow stimulation on the adjustment capacity of cultured fish to cope with running water. The target fish were cultured grass carp. An annular flume was used to conduct tests on training and control groups. The results demonstrated an enhancement in the adjustment capacity of cultured fish following appropriate flow stimulation training. (1) The trained fish exhibited a heightened preference for low-velocity areas. (2) The trained fish displayed the ability to select a route characterized by low energy consumption, predominantly following the periphery of the low-velocity area. This suggested that an appropriate flow velocity could improve the sensitivity of training fish to water flow information, and their adjustment capacity to cope with running water improved to a certain extent. A higher adjustment capacity allowed them to process flow rate information rapidly and identify a migration strategy with lower energy consumption. This study provides a useful reference for enhancing the survival rate of grass carp through stock enhancement initiatives and contributes to the sustainability of freshwater ecosystems.

Self-Concept Clarity and Loneliness among College Students: The Chain-Mediating Effect of Fear of Negative Evaluation and Self-Disclosure.

Self-concept clarity is considered a crucial indicator of mental health. Although several studies have examined the correlation between self-concept clarity and loneliness, few studies have investigated the underlying mechanism. Based on the evolutionary theory of loneliness and social penetration theory, this cross-sectional study focused on cognitive and behavioral factors in interpersonal communication situations, aiming to explore the relationship between self-concept clarity and loneliness as well as its internal mechanism. An online questionnaire survey comprised 1145 college students in China to assess their self-concept clarity, fear of negative evaluation, self-disclosure, and loneliness. After controlling for demographic variables, the results showed that self-concept clarity was not only able to directly and negatively predict loneliness but also indirectly predict loneliness through the independent mediating effects of fear of negative evaluation and self-disclosure, as well as the chain-mediating effect of fear of negative evaluation to self-disclosure. This study provides important implications for cognitive and behavioral intervention strategies to alleviate people's loneliness and improve their mental health.

BRD4 inhibitor MZ1 exerts anti-cancer effects by targeting MYCN and MAPK signaling in neuroblastoma.

Neuroblastoma(NB) is a common childhood solid tumor, and most patients in the high-risk group with MYCN gene amplification have a poor prognosis. Inhibition of bromodomain and extra terminal (BET) proteins has shown considerable promise in the investigation of MYCN-driven malignancies in recent years. MZ1 is a novel BET inhibitor that employs proteolytic-targeting chimera (PROTAC) technology for proteasomal degradation of target proteins and has shown excellent effects in some tumors, but its role in neuroblastoma remains poorly understood. Herein, we observed that MZ1 suppressed MYC-amplified NB cell proliferation and normal cell cycle, while simultaneously boosting cell apoptosis. MZ1 also provides a significant therapeutic impact in vivo. Mechanistically, MZ1 exhibits anti-tumor effect in NB cells by suppressing the expression of N-Myc or C-Myc as well as the MAPK signaling pathway. Overall, our data imply that MZ1 might be exploited as a possible therapeutic method for NB therapy.

Effect of Metal Ions on Oxidation of Micropollutants by Ferrate(VI): Enhancing Role of FeIV Species.

This paper investigated the oxidation of recalcitrant micropollutants [i.e., atenolol (ATL), flumequine, aspartame, and diatrizoic acid] by combining ferrate(VI) (FeVIO42-, FeVI) with a series of metal ions [i.e., Fe(III), Ca(II), Al(III), Sc(III), Co(II), and Ni(II)]. An addition of Fe(III) to FeVI enhanced the oxidation of micropollutants compared solely to FeVI. The enhanced oxidation of studied micropollutants increased with increasing [Fe(III)]/[FeVI] to 2.0. The complete conversion of phenyl methyl sulfoxide (PMSO), as a probe agent, to phenyl methyl sulfone (PMSO2) by the FeVI-Fe(III) system suggested that the highly reactive intermediate FeIV/FeV species causes the increased oxidation of all four micropollutants. A kinetic modeling of the oxidation of ATL demonstrated that the major species causing the increase in ATL removal was FeIV, which had an estimated rate constant as (6.3 ± 0.2) × 104 M-1 s-1, much higher than that of FeVI [(5.0 ± 0.4) × 10-1 M-1 s-1]. Mechanisms of the formed oxidation products of ATL by FeIV, which included aromatic and/or benzylic oxidation, are delineated. The presence of natural organic matter significantly inhibited the removal of four pollutants by the FeVI-Fe(III) system. The enhanced effect of the FeVI-Fe(III) system was also seen in the oxidation of the micropollutants in river water and lake water.

PROTAC Bromodomain Inhibitor ARV-825 Displays Anti-Tumor Activity in Neuroblastoma by Repressing Expression of MYCN or c-Myc.

Neuroblastoma (NB) is one of the most common solid tumors in childhood. To date, targeting MYCN, a well-established driver gene in high-risk neuroblastoma, is still challenging. In recent years, inhibition of bromodomain and extra terminal (BET) proteins shows great potential in multiple of Myc-driven tumors. ARV-825 is a novel BET inhibitor using proteolysis-targeting chimera (PROTAC) technology which degrades target proteins by the proteasome. In this study, we investigated the effect of ARV-825 in neuroblastoma in vitro and in vivo. Our results showed that ARV-825 treatment robustly induced proliferative suppression, cell cycle arrest, and apoptosis in NB cells. Moreover, ARV-825 efficiently depleted BET protein expression, subsequently repressing the expression of MYCN or c-Myc. In the NB xenograft model, ARV-825 profoundly reduced tumor growth and led to the downregulation of BRD4 and MYCN expression in mice. Taken together, these findings provide evidence that PROTAC BET inhibitor is an efficient way to achieve MYCN/c-Myc manipulation, and ARV-825 can be used as a potential therapeutic strategy for the treatment of neuroblastoma.

[Effects of Panax notoginseng saponins on liver graft rejection in rats and the mechanisms].

OBJECTIVE: To investigate the effects of Panax notoginseng saponins (PNS) on the functional status of Kupffer cells (KCs) and immune environment after liver transplantation and explore the possible mechanisms. METHODS: KCs were isolated from rats and assessed for phagocytic activity and viability using ink and Trypan blue staining. The cells were exposed to lipopolysaccharide (LPS) alone or in combination with PNS treatment at 0, 10 or 20 µmol/L. The expressions of the inflammatory factors and the oxidative stress products in the cells and the supernatant were assayed with Western blotting and ELISA; the expression of CD206 was detected using immunofluorescence assay, and the expressions of NF-κB and Keap1-Nrf2-ARE pathway proteins were detected using Western blotting. We established an orthotopic liver transplantation (LT) model in rats and assessed the effect of 200 mg/kg PNS on the graft function, inflammatory factors, pathology of the liver tissue, hepatocyte apoptosis and survival time of the rats in comparison with those in rats receiving a sham operation or PBS treatment following LT. RESULTS: Treatment with PNS significantly lowered the levels of inflammatory factors and oxidative stress products and increased the levels of interleukin-10 (IL-10) and SOD in a concentration-dependent manner in the KCs (P < 0.05). Immunofluorescence assay showed that PNS treatment obviously increased the expression of CD206 in the KCs. PNS treatment also significantly reduced the expressions of IRAK4, p-IKKα, p-IκBα, p-p65 and Keap1 proteins and increased the expression levels of Nrf2 and ARE proteins in the KCs (P < 0.05). In the rat models of LT, PNS treatment significantly improved the liver graft function, lowered the expression of the pro-inflammatory factors, and reduced hepatocyte apoptosis as compared with PBS treatment. PNS treatment obviously alleviated pathological changes in the liver graft and significantly prolonged the survival time of the rats following LT (P < 0.05). In addition, injection of GdCl3 to block KC function resulted in severe acute graft rejection in the rats regardless of PNS treatment (P > 0.05). CONCLUSIONS: PNS can reduce inflammatory response and oxidative stress in activated KCs by inhibiting NF-κB and Keap1-Nrf2-ARE pathways and promote the polarization of KCs into M2 phenotype to prolong the survival time of rats after LT.

Light induced expression of ß-glucosidase in Escherichia coli with autolysis of cell.

BACKGROUND: ß-Glucosidase has attracted substantial attention in the scientific community because of its pivotal role in cellulose degradation, glycoside transformation and many other industrial processes. However, the tedious and costly expression and purification procedures have severely thwarted the industrial applications of ß-glucosidase. Thus development of new strategies to express ß-glucosidases with cost-effective and simple procedure to meet the increasing demands on enzymes for biocatalysis is of paramount importance. RESULTS: Light activated cassette YF1/FixJ and the SRRz lysis system were successfully constructed to produce Bgl1A(A24S/F297Y), a mutant ß-glucosidase tolerant to both glucose and ethanol. By optimizing the parameters for light induction, Bgl1A(A24S/F297Y) activity reached 33.22 ± 2.0 U/mL and 249.92 ± 12.25 U/mL in 250-mL flask and 3-L fermentation tank, respectively, comparable to the controls of 34.02 ± 1.96 U/mL and 322.21 ± 10.16 U/mL under similar culture conditions with IPTG induction. To further simplify the production of our target protein, the SRRz lysis gene cassette from bacteriophage Lambda was introduced to trigger cell autolysis. As high as 84.53 ± 6.79% and 77.21 ± 4.79% of the total ß-glucosidase were released into the lysate after cell autolysis in 250 mL flasks and 3-L scale fermentation with lactose as inducer of SRRz. In order to reduce the cost of protein purification, a cellulose-binding module (CBM) from Clostridium thermocellum was fused into the C-terminal of Bgl1A(A24S/F297Y) and cellulose was used as an economic material to adsorb the fusion enzyme from the lysate. The yield of the fusion protein could reach 92.20 ± 2.27% after one-hour adsorption at 25 °C. CONCLUSIONS: We have developed an efficient and inexpensive way to produce ß-glucosidase for potential industrial applications by using the combination of light induction, cell autolysis, and CBM purification strategy.

Interaction of elemental mercury with defective carbonaceous cluster.

The interaction of elemental mercury with defective carbonaceous clusters is investigated by the density-functional theory calculation. The defective carbonaceous cluster is represented by seven-fused benzene ring and single atomic vacancy at the surface. Also, the non-defective carbonaceous surface is employed for comparison. The defective carbonaceous cluster with chlorine is carried out to evaluate the effect of the statured carbon at the neighboring sites of vacancy on mercury adsorption. The results indicate that vacancy can promote the activity of its neighboring sites, and the defective carbonaceous cluster has much larger mercury adsorption energy than the non-defective carbonaceous cluster with and without chlorine. Cl atom can improve the activity of its neighboring sites on the non-defective carbonaceous surface, but the effect of Cl atom on mercury adsorption of vacancy is very complex, which depends on the Cl concentration. High concentration of Cl decreases the mercury adsorption because Cl competes for the active sites with mercury. Hence, we find that vacancy can be regarded as a potential functional group to improve the mercury adsorption on carbonaceous surface, but the saturated carbon at the neighboring sites of vacancy can rapidly decrease the mercury capture capacity.

Characterization of a novel ß-glucosidase from Gongronella sp. W5 and its application in the hydrolysis of soybean isoflavone glycosides.

A novel ß-glucosidase named BglW5 from Gongronella sp. was isolated, purified, and characterized for the first time. Under solid state fermentation, the yield of BglW5 was 49.9 U/g fermented medium. BglW5 was stable over a wide pH range of 3.0-8.5 and retained more than 50% of its maximal activity after incubation at 25 °C for 96 h. The half-lives of BglW5 were 20 h at 60 °C, and 1 h at 70 °C. The activity of BglW5 was stimulated by xylose and fructose at concentrations up to 500 mM, with maximal stimulatory effect of 1.6-fold and 2.2-fold, respectively. BglW5 converted isoflavone glycosides to aglycones, with a hydrolysis rate of 96.2% for daidzin and 96.7% for genistin. The productivities were 1.5 mmol L(-1) h(-1) for daidzein and 1.23 mmol L(-1) h(-1) for genistein, respectively. These features suggest that BglW5 has great application potential in the hydrolysis of soybean isoflavone glycosides.

Degradation efficiency and mechanism of azo dye RR2 by a novel ozone aerated internal micro-electrolysis filter.

A newly designed ozone aerated internal micro-electrolysis filter (OIEF) was developed to investigate its degradation efficiencies and correlated reaction mechanisms of RR2 dye. Complete decolorization and 82% TOC removal efficiency were stably achieved in OIEF process. Based on the comprehensive experimental results, an empirical equation was proposed to illustrate the effects of initial dye concentration and ozone dosage rate on color removal. The results indicated that OIEF process could be operated at wide pH range without significant treatment efficiencies change, while the optimum pH for RR2 dye degradation was 9.0. There were 15, 8 and 6 kinds of identified intermediates during ozonation, IE and OIEF treatment processes, respectively. Less identified intermediates and their lower concentrations in OIEF may attribute to its rather excellent mineralization performance. It was found that ozonation, Fe(2+)/Fe(3+) catalyzed ozonation, the redox reactions of electro-reduction and electro-oxidation are the most important mechanisms in OIEF process. The catalytic effect of Fe(2+)/Fe(3+) would induce mutual conversion between dissolved Fe(2+) and Fe(3+), and then decrease the dissolution rate of ZVI. The excellent treatment performance proved that the OIEF process is one promising technology applied for reactive azo dyes and other refractory wastewater treatment.

Enhanced denitrification with external carbon sources in a biological anoxic filter.

Three parallel biological anoxic filters (BaFs) were operated to investigate the denitrification kinetics of methanol, brewery wastewater and bakery wastewater. The experiment was conducted within the temperature range of 15-20 °C, with an influent nitrate and carbon dosage of 30 mg/L and 150 mg COD/L (COD: chemical oxygen demand). The denitrification efficiencies of brewery wastewater, bakery wastewater and methanol were 84, 66 and 74%, specific denitrification rates were 1.44, 1.11 and 1.24 kg NO(3)-N/m(3) d, and total nitrogen (TN) removal rates were 74, 62 and 66%, respectively. The volatile attached solid (VAS) tests reveal that methanol has the minimum net biomass yield, so it needs the least carbon to nitrogen (expressed in COD to nitrate, C/N) ratio for complete denitrification. While the brewery wastewater and bakery wastewater need higher C/N ratio to remove all nitrate nitrogen, and they both may need pretreatment to remove phosphate when used as external carbon sources.