A preliminary study on the pathology and molecular mechanism of fumonisin B1 nephrotoxicity in young quails.

Fumonisin B1 (FB1) is a widely present mycotoxin that accumulates in biological systems and poses a health risk to animals. However, few studies have reported the molecular mechanism by which FB1 induces nephrotoxicity. The aim of this study was to assess the extent of nephrotoxicity during FB1 exposure and the possible molecular mechanisms behind it. Therefore, 180 young quails were equally divided into two groups. The control group was fed typical quail food, while the experimental group was fed quail food containing 30 mg·kg-1 FB1. Various parameters were assessed, which included histopathological, ultrastructural changes, levels of biochemical parameters, oxidative indicators, inflammatory factors, possible target organelles mitochondrial and endoplasmic reticulum (ER)-related factors, nuclear xenobiotic receptors (NXR) response, and cytochrome P450 system (CYP450s)-related factors in the kidneys on days 14, 28, and 42. The results showed that FB1 can induce oxidative stress through NXR response and disorder of the CYP450s system, leading to mitochondrial dysfunction and ER stress, promoting the expression of inflammatory factors (including IL-1ß, IL-6, and IL-8) and causing kidney damage. This study elucidated the possible molecular mechanism by which FB1 induces nephrotoxicity in young quails.

The effects of cultivation patterns and nitrogen levels on fertility and bacterial community characteristics of surface and subsurface soil.

The cropping system affects the physicochemical property and microbial community of paddy soil. Previous research mostly focused on the study of soil 0-20 cm underground. However, there may be difference in the laws of nutrient and microorganism distribution at different depths of arable soil. In surface (0-10 cm) and subsurface (10-20 cm) soil, a comparative analysis including soil nutrients, enzymes, and bacterial diversity was carried out between the organic and conventional cultivation patterns, low and high nitrogen levels. Analysis results suggested that under the organic farming pattern, the contents of total nitrogen (TN), alkali-hydrolyzable nitrogen (AN), available phosphorus (AP), and soil organic matter (SOM) as well as alkaline phosphatase and sucrose activity increased in surface soil, but the SOM concentration and urease activity decreased in subsurface soil. A moderate reduction of nitrogen applied to soil could enhance soil enzyme activity. It was demonstrated by α diversity indices that high nitrogen levels remarkably undermined soil bacterial richness and diversity. Venn diagrams and NMDS analysis manifested great difference in bacterial communities and an apparent clustering tendency under different treatment conditions. Species composition analysis indicated that the total relative abundance of Proteobacteria, Acidobacteria, and Chloroflexi retained stable in paddy soil. LEfSe results revealed that a low nitrogen organic treatment could elevate the relative abundance of Acidobacteria in surface soil and Nitrosomonadaceae in subsurface soil, thereby tremendously optimizing the community structure. Moreover, Spearman's correlation analysis was also performed, which proved the significant correlation of diversity with enzyme activity and AN concentration. Additionally, redundancy analysis disclosed that the Acidobacteria abundance in surface soil and Proteobacteria abundance in subsurface soil exerted conspicuous influence on environmental factors and the microbial community structure. According to the findings of this study, it was believed that reasonable nitrogen application together with an organic agriculture cultivation system could effectively improve soil fertility in Gaoyou City, Jiangsu Province, China.

MBD5 regulates NMDA receptor expression and seizures by inhibiting Stat1 transcription.

Epilepsy is considered to result from an imbalance between excitation and inhibition of the central nervous system. Pathogenic mutations in the methyl-CpG binding domain protein 5 gene (MBD5) are known to cause epilepsy. However, the function and mechanism of MBD5 in epilepsy remain elusive. Here, we found that MBD5 was mainly localized in the pyramidal cells and granular cells of mouse hippocampus, and its expression was increased in the brain tissues of mouse models of epilepsy. Exogenous overexpression of MBD5 inhibited the transcription of the signal transducer and activator of transcription 1 gene (Stat1), resulting in increased expression of N-methyl-d-aspartate receptor (NMDAR) subunit 1 (GluN1), 2A (GluN2A) and 2B (GluN2B), leading to aggravation of the epileptic behaviour phenotype in mice. The epileptic behavioural phenotype was alleviated by overexpression of STAT1 which reduced the expression of NMDARs, and by the NMDAR antagonist memantine. These results indicate that MBD5 accumulation affects seizures through STAT1-mediated inhibition of NMDAR expression in mice. Collectively, our findings suggest that the MBD5-STAT1-NMDAR pathway may be a new pathway that regulates the epileptic behavioural phenotype and may represent a new treatment target.

Phase Stability Control of Optical Fiber Partial Discharge Ultrasonic Sensing System.

Optic fiber interferometers are highly sensitive ultrasonic sensors for partial discharge detection. However, low-frequency vibration and environmental noise will disturb the sensors in the field, and cause a phase fading suppression effect that reduces sensitivity. This paper analyzed the problems existing in the phase feedback control system based on PZT, and an improved scheme incorporating a high-frequency carrier phase demodulation is proposed. Based on an acousto-optic modulator, the proposed phase feedback control system overcomes the phase fading suppression effect. A test is carried out on an ultrasonic calibration platform and a transformer oil discharge platform. The test results show that the stability of the improved phase demodulation system has been significantly improved, and meets the requirements of field applications. Compared with the signal-to-noise ratio at the time of phase fading of the system before the improvement, the signal-to-noise ratio of the improved system is improved by 69 dB.

Serum CHI3L1 as a Biomarker for Non-invasive Diagnosis of Liver Fibrosis.

BACKGROUND: Liver fibrosis is the early pathological manifestation of various chronic liver diseases (including schistosomiasis, alcoholic, viral, nonalcoholic, fatty liver, etc.), which can progress to cirrhosis and even liver cancer. Out of the 7.7 billion world population, approximately 2 billion individuals have evidence of hepatitis B virus (HBV) infection; of these, 350 to 400 million suffer from chronic HBV infection, accounting for about 5% of the global population. The global prevalence of hepatitis C is 3%. These figures indicate that liver fibrosis is quite common. METHODS: 98 patients with liver fibrosis were included in this study. The serum chitinase-3 Like Protein-1 (CHI3L1) level was measured by the double antibody Sandwich ELISA method. RESULTS: Serum levels of CHI3L1 were significantly different between no-fibrosis and fibrosis groups (P < 0.01). There was a strong correlation between the levels of CHI3L1, elastometry, hyaluronan, CIV (P < 0.01) and age and sex, TBIL, DBIL, ALB, AST, ALT, GGT, ALP, PLT, LN, PIINP, FIB-4, and APRI (P < 0.05). The expression of CHI3L1 was different from fibrosis grades S1, S3, and S4 (P < 0.05, P < 0.001). The expression of CHI3L1 was significantly different between F1 and F4 (P < 0.05). Serum CHI3L1 expression level can be a valuable metric for diagnosing liver fibrosis, with an AUC value of 0.812. Out of the 98 patients who had undergone liver puncture, 79 patients (30.38%) had ALT ≤ 2ULN. CONCLUSIONS: The expression level of serum CHI3L1 was significantly higher in patients with liver fibrosis than that in patients without liver fibrosis. The expression levels of serum CHI3L1 were different in different grades of liver fibrosis and increased with the severity of liver fibrosis. Serum CHI3L1 can distinguish early stage (S1) of liver fibrosis from late stage (S3-4) of liver fibrosis. Serum CHI3L1 combined with HA is even more effective in the diagnosis of S2-4 hepatic fibrosis. The diagnostic efficacy of serum CHI3L1 in patients with ALT ≤ 2ULN was better than that of the other non-invasive diagnostic models.

Formation of V6O11@Ni(OH)2/NiOOH hollow double-shell nanoflowers for the excellent cycle stability of supercapacitors.

The rational design of multi-shelled hollow structured electrode materials is of great importance and has met with fundamental challenges in recent years. Herein, we demonstrate a combination approach of self-templating and sacrificial templating method for synthesizing double-shelled hollow nanoflower-structured V6O11@Ni(OH)2/NiOOH. Firstly, highly uniform vanadium-glycerate (VG) solid nanospheres are controllably synthesized and employed as the template, then Ni(OH)2/NiOOH nanosheets grow vertically on it, following with VG solid nanospheres changing to the V6O11 hollow structure. By controlling the amount of Ni(OH)2/NiOOH nanosheets, the optimized V6O11@Ni(OH)2/NiOOH-6 (VN-6) delivers high performance for supercapacitors. Specifically, the specific capacitance of VN-6 is 1018.2 F g-1 at the current density of 1 A g-1 and the energy density is 24.3 W h kg-1 at the power density of 850 W kg-1. Impressively, an outstanding cycling stability of over 120% specific capacitance retention can be obtained after 5000 cycles in the three-electrode and two-electrode systems. The excellent performance can be ascribed to the compositional and structural advantages.

Long noncoding RNA ARRDC1-AS1 is activated by STAT1 and exerts oncogenic properties by sponging miR-432-5p/PRMT5 axis in glioma.

Dysfunction of long noncoding RNA (lncRNA) is associated with tumorigenesis of various malignancies, including glioma. Previously, lncRNA ARRDC1 antisense RNA 1(ARRDC1-AS1) has been reported to be dysregulated in several tumors. However, the roles of ARRDC1-AS1 in glioma have not been investigated. In this study, we firstly reported that ARRDC1-AS1 expression was distinctly increased in both glioma specimens and cell lines, and high ARRDC1-AS1 expression was associated with advanced clinical progression and poor prognosis of glioma patients. Additionally, STAT1 could activate the transcription of ARRDC1-AS1. Functional studies revealed that knockdown of ARRDC1-AS1 suppressed the proliferation, migration and invasion of glioma cells. Mechanisms exploration indicated ARRDC1-AS1 served as a sponge of miR-432-5p to upregulate PRMT5 expressions. Rescue experiments indicated that knockdown of miR-432-5p reversed the inhibiting effects of ARRDC1-AS1 knockdown on glioma cells. Overall, our findings highlighted the importance of STAT1/ARRDC1-AS1/miR-432-5p/PRMT5 axis in glioma progression and offered novel strategies for glioma treatments.

2D nanosheet/3D cubic framework Ni-Co sulfides for improved supercapacitor performance via structural engineering.

The construction of multi-dimensional structured battery-type electrode materials is a promising strategy to develop high performance electrodes for supercapacitors. Herein, a series of battery-type Ni3S2@Co3S4 electrodes with different morphologies are synthesized by controlling the hydrothermal reaction time. Owing to the unique structure with independent but interconnected 2D nanosheets and 3D cubic frameworks, NCS-60 displays high conductivity, numerous active sites and good wettability behavior. It can deliver a high specific capacity of 388.9 mA h g-1 (3500 F g-1) at 1 A g-1, an outstanding rate capacity of maintaining 88.6% at 10 A g-1 and long cycle stability. The battery-type supercapacitor hybrid (BSH) device with active carbon (AC) as the negative electrode delivers an energy density of 41.8 W h kg-1 at the power density of 800 W kg-1. This study provides a feasible route for regulating the morphologies of in situ growth materials that improve the electrochemical performance of supercapacitors.

Increasing the Thermostable Sugar-1-Phosphate Nucleotidylyltransferase Activities of the Archaeal ST0452 Protein through Site Saturation Mutagenesis of the 97th Amino Acid Position.

The ST0452 protein is a bifunctional protein exhibiting sugar-1-phosphate nucleotidylyltransferase (sugar-1-P NTase) and amino-sugar-1-phosphate acetyltransferase activities and was isolated from the thermophilic archaeon Sulfolobus tokodaii Based on the previous observation that five single mutations increased ST0452 sugar-1-P NTase activity, nine double-mutant ST0452 proteins were generated with the intent of obtaining enzymes exhibiting a further increase in catalysis, but all showed less than 15% of the wild-type N-acetyl-d-glucosamine-1-phosphate uridyltransferase (GlcNAc-1-P UTase) activity. The Y97A mutant exhibited the highest activity of the single-mutant proteins, and thus site saturation mutagenesis of the 97th position (Tyr) was conducted. Six mutants showed both increased GlcNAc-1-P UTase and glucose-1-phosphate uridyltransferase activities, eight mutants showed only enhanced GlcNAc-1-P UTase activity, and six exhibited higher GlcNAc-1-P UTase activity than that of the Y97A mutant. Kinetic analyses of three typical mutants indicated that the increase in sugar-1-P NTase activity was mainly due to an increase in the apparent kcat value. We hypothesized that changing the 97th position (Tyr) to a smaller amino acid with similar electronic properties would increase activity, and thus the Tyr at the corresponding 103rd position of the Escherichia coli GlmU (EcGlmU) enzyme was replaced with the same residues. The Y103N mutant EcGlmU showed increased GlcNAc-1-P UTase activity, revealing that the Tyr at the 97th position of the ST0452 protein (103rd position in EcGlmU) plays an important role in catalysis. The present results provide useful information regarding how to improve the activity of natural enzymes and how to generate powerful enzymes for the industrial production of sugar nucleotides. IMPORTANCE: It is typically difficult to increase enzymatic activity by introducing substitutions into a natural enzyme. However, it was previously found that the ST0452 protein, a thermostable enzyme from the thermophilic archaeon Sulfolobus tokodaii, exhibited increased activity following single amino acid substitutions of Ala. In this study, ST0452 proteins exhibiting a further increase in activity were created using a site saturation mutagenesis strategy at the 97th position. Kinetic analyses showed that the increased activities of the mutant proteins were principally due to increased apparent kcat values. These mutant proteins might suggest clues regarding the mechanism underlying the reaction process and provide very important information for the design of synthetic improved enzymes, and they can be used as powerful biocatalysts for the production of sugar nucleotide molecules. Moreover, this work generated useful proteins for three-dimensional structural analysis clarifying the processes underlying the regulation and mechanism of enzymatic activity.

[Effect of xinkeshu tablet on heart rate variability in patients with coronary heart disease].

OBJECTIVE: To evaluate the effect of Xinkeshu Tablet (XKS) on heart rate variability (HRV) in patients with coronary heart disease (CHD). METHODS: Sixty patients with their diagnosis of CHD confirmed by coronary angiography were randomized into two groups equally. Besides the conventional treatment for CHD, XKS and Metoprolol were given respectively to patients in the treated group and the control group for 8 weeks. Symptoms and 24 h dynamic ECG were observed before and after treatment. RESULTS: Episode of angina pectoris decreased obviously in both groups after treatment, from 8.8 +/- 3.2 times per week (the same hereafter) to 4.4 +/- 2.1 in the treated group (P<0.05), and from 8.4 +/- 3.1 to 3.9 +/- 2.0 in the control group (P <0.05). HRV analysis showed that after treatment the average heart rate lowered from 85.44 +/- 2.89 beat/min to 77.32 +/- 2.17 beat/min in the treated group and from 83.80 +/- 4.30 beat/min to 76.70 +/- 2.93 beat/min in the control group (both P < 0.05), showing no significant difference in extent of lowering between groups (P > 0.05). The time-domain indexes elevated in both groups, showing no statistical difference between groups (P >0.05). As for the frequency-domain indexes, low frequency (LF), high frequency (HF) and total power raised, while LF/HF and very low frequency lowered in both groups, but the changes were more significant in the treated group (P <0.05). CONCLUSION: XKS could improve HRV in patients of CHD and reduce the episode of angina pectoris in them.

[Effects of blood-cooling and promoting drugs on rats with radiation-induced lung injury].

OBJECTIVE: To investigate the effect of blood-cooling and promoting drugs (BCPD) on the dy-namic changes of collagens and the expressions of interleukin-6 (IL-6) and transforming growth factor beta (TGF-beta) in lung tissue of rats with radiation-induced lung injury (RILI) to explore the effects and action mech-anism of BCPD in preventing and treating RILI. METHODS: One hundred and sixty Wistar female rats were ran-domly divided into the radiation group, the treatment group, the blank control group and the drug control group. The rats in the first two groups received right hemithoracic fractionated radiation, and those in the treatment group were given BCPD. Rats in the other two groups were not irradiated and BCPD was given to rats in the drug control group. The rats were sacrificed in batches (8 of each group in every batch) at the 3rd, 5th, 8th, 12th and 26th week of the experimental period, and their lung was taken for observing the dynamic changes and distribution of collagen and the expressions of IL-6 and TGF-beta with HE staining, picrosirius red staining and immunohistochemical staining respectively. RESULTS: The fibroblast proliferated obviously from the 3rd week after the first radiation in the radiation group, and the type I collagen and the proportion of type I and III collagen were significantly elevated along the time going and the radiation dose increasing, became significantly higher than those in the treatment group at all the time points (P <0.01). In the radiation group the expression of IL-6 and TGF-beta reached their peaks at the 8th and 12th week, respectively, and the levels was significantly lower in the treatment than that in the radiation group at any detecting time points (P <0.01). CONCLUSION: BCPD applied in the early stage of radiation can suppress the inflammatory and fibrogenic cytokine expressions, inhibit the synthesis of collagens and adjust the proportion of type I and III collagen, so as to re-lieve the early-stage inflammatory reaction and the anaphase lung fibrosis in RILI rats.