Role of KCC2 in the Regulation of Brain-Derived Neurotrophic Factor on Ethanol Consumption in Rats.

Alcohol use disorder (AUD) is a common and complex disorder resulting from repetitive alcohol drinking. The mesocorticolimbic dopamine (DA) system, originating from the ventral tegmental area (VTA) in the midbrain, is involved in the rewarding effect of ethanol. The γ-aminobutyric acid (GABA) neurons in VTA appear to be key substrates of acute and chronic ethanol, which regulates DA neurotransmission indirectly in the mesocorticolimbic system. Despite significant research on the relationship between brain-derived neurotrophic factor (BDNF) and reduced alcohol consumption in male rats involving tropomyosin-related kinase B (TrkB), the mechanisms of BDNF-TrkB regulating alcohol behavior remain scarce. K+-Cl- cotransporter 2 (KCC2) plays a crucial role in synaptic function in GABAergic neurons by modulating intracellular chlorine homeostasis. Here, we found that 4-week intermittent alcohol exposure impaired the function of KCC2 in VTA, evidenced by a lower expression level of phosphorylated KCC2 and decreased ratio of phosphorylated KCC2 to total KCC2, especially 72 h after withdrawal from 4-week ethanol exposure in male rats. CLP290 (a KCC2 activator) reduced excessive alcohol consumption after alcohol withdrawal, whereas VU0240551 (a specific KCC2 inhibitor) further enhanced alcohol intake. Importantly, VU0240551 reversed the attenuating effects of BDNF and 7,8-dihydroxyflavone (7,8-DHF) on alcohol consumption after withdrawal. Moreover, intraperitoneal injection of 7,8-DHF upregulated KCC2 expression and phosphorylated KCC2 in VTA 72 h after withdrawal from ethanol exposure in male rats. Collectively, our data indicate that KCC2 may be critical in the regulating action of BDNF-TrkB on ethanol consumption in AUD.

Effect of Phase Composition on Leaching Behavior and Mechanical Properties of Ceramics from Ferrochrome Slag and Tundish Slag.

Ferrochrome slag (FS) and tundish slag (TS) are two typical slags containing high contents of Cr2O3 (3.88 wt.%) and MnO (18.69 wt.%), respectively. In this study, batches of ceramics were prepared from FS and TS, and their Cr/Mn leaching behaviors, mechanical properties and microstructures were investigated. Results showed that ceramics with 80 wt.% FS or 85 wt.% TS had acceptable properties. By controlling its composition and sintering temperature, pyroxene or spinel phases could become the main crystalline phases of the fired ceramics containing either of the two slags. For both slag series, pyroxene phases contributed to higher bending strengths, whereas spinel phases led to lower Cr/Mn leaching rates. Both ceramic containing 20 wt.% FS and ceramic containing 85 wt.% TS had the main crystals of pyroxene phases and possessed the highest bending strengths (FS20: 114.52 MPa and TS85: 124.61 MPa). However, both ceramic containing 80 wt.% FS and ceramic containing 25 wt.% TS with main crystals from the spinel phases had the lowest Cr/Mn leaching rates (FS80: Cr 0.05% and TS25: Mn 0.43%). Therefore, optimum designs for the compositions of ceramics from different slags were achieved by changing the proportions of pyroxene and spinel phases to obtain a balance between the high strengths of materials and the stable retention of heavy metal ions. This study provides an important basis for long-term research on the large-scale reuse of heavy metal-containing slags in the ceramic industry.

An Analysis of the Potential Relationship of Triglyceride Glucose and Body Mass Index With Stroke Prognosis.

Background: The inverse association between obesity and outcome in stroke patients (known as the obesity paradox) has been widely reported, yet mechanistic details explaining the paradox are limited. The triglyceride glucose (TYG) index has been proposed as a marker of insulin resistance. We sought to explore possible associations of the TYG index, body mass index (BMI), and stroke outcome. Methods: We identified 12,964 ischemic stroke patients without a history of diabetes mellitus from the China National Stroke Registry and classified patients as either low/normal weight, defined as a BMI <25 kg/m2, or overweight/obese, defined as a BMI ≥ 25 kg/m2. We calculated TYG index and based on which the patients were divided into four groups. A Cox or logistic regression model was used to evaluate the association between BMI and TYG index and its influence on stroke outcomes, including stroke recurrence all-cause mortality and poor outcome (modified Rankin Scale score of 3-6) at 12 months. Results: Among the patients, 63.3% were male, and 36.7% were female, and the mean age of the patient cohort was 64.8 years old. The median TYG index was 8.62 (interquartile range, 8.25-9.05). After adjusting for multiple potential covariates, the all-cause mortality of overweight/obese patients was significantly lower than that of the low/normal weight patients (6.17 vs. 9.32%; adjusted hazard ratio, 0.847; 95% CI 0.732-0.981). The difference in mortality in overweight/obese and low/normal weight patients with ischemic stroke was not associated with TYG index, and no association between BMI and TYG index was found. Conclusion: Overweight/obese patients with ischemic stroke have better survival than patients with low/normal weight. The association of BMI and stroke outcome is not changed by TYG index.

Effects of Na2O additions to copper slag on iron recovery and the generation of ceramics from the non-magnetic residue.

A novel process is proposed in this paper for a green and efficient utilization of copper slag. The basic premise involved the addition of different amounts of Na2O into molten copper slag and evaluation of the effects on the magnetic fraction and the properties of ceramics generated from the non-magnetic residue, and mechanisms of the effects were further studied by XRD, SEM, EDS, viscosity test, hysteresis loop and FTIR. The results showed that Na2O additions dropped the viscosity of the slag markedly, which promoted the growth of magnetite, but decrease quantity of magnetite due to oxidization of Fe2+ and precipitation of crystals containing Fe3+. With the addition of 4 % Na2O, solidification temperature of slag decreased from 1790 K to 1530 K, optimum iron recovery rate of 81.08 % was achieved. Na2O as flux in ceramics obviously reduced its sintering temperature and meantime decreased its bending strength because of insufficient crystallization of its main minerals. The non-magnetic residue from magnetic separation of slag with addition of 4% Na2O was converted into ceramics with a much low sintering temperature of 1268 K (995 °C) and qualified bending strength of 64.5 MPa.

Methylation of the suppressor of cytokine signaling 3 gene (SOCS3) in bladder cancer.

BACKGROUND: It has been identified consequences of dysregulation of JAK-STAT signalling, particularly in regard to JAK-STAT signalling that has been shown to have roles in the oncogenesis of several cell types. SOCS3 protein, the negative regulatory protein of JAK-STAT signaling pathway, may also plays critical regulatory roles in cancer initiation and progression. SOCS3 promoter hypermethylation has often been identified in human cancers; however, the precise role of SOCS3 in bladder cancer is unclear. METHODS: The methylation status of the SOCS3 was analyzed in an age (±5 years) and sex-matched case-control study, including 112 bladder cancer cases and 118 normal controls, using the MassARRAY EpiTYPER system. RESULTS: Methylation rate of JAK2, SOCS3 and STAT3 gene were shown to vary among different CpG island. The methylation rate of SOCS3 gene was also much higher in BCa than in normal control participants, but the methylation rate of JAK2, STAT3 gene weren't different in Bca and normal control participants. CONCLUSIONS: Our study demonstrates that promoter hypermethylation of SOCS3 gene is associated with BCa and thus, may serve as an independent prognostic biomarker.

Exploring the Goat Rumen Microbiome from Seven Days to Two Years.

Rumen microbial communities play important roles in feed conversion and the physiological development of the ruminants. Despite its significance, little is known about the rumen microbial communities at different life stages after birth. In this study, we characterized the rumen bacterial and the archaeal communities in 11 different age groups (7, 15, 30, 60, 90, 120, 150, 180, 360, 540 and 720 days old) of a crossbred F1 goats (n = 5 for each group) by using an Illumina MiSeq platform targeting the V3-V4 region of the 16S rRNA gene. We found that the bacterial communities were mainly composed of Bacteroidetes, Firmicutes, and Proteobacteria across all age groups. The relative abundance of Firmicutes was stable across all age groups. While changes in relative abundance were observed in Bacteroidetes and Proteobacteria, these two phyla reached a stable stage after weaning (day 90). Euryarchaeota (82%) and Thaumarchaeota (15%) were the dominant phyla of Archaea. Crenarchaeota was also observed, although at a very low relative abundance (0.68% at most). A clear age-related pattern was observed in the diversity of bacterial community with 59 OTUs associated with age. In contrast, no age-related OTU was observed in archaea. In conclusion, our results suggested that from 7 days to 2 years, the ruminal microbial community of our experimental goats underwent significant changes in response to the shift in age and diet.

Association of selenoprotein S gene polymorphism with ischemic stroke in a Chinese case-control study.

Previous studies showed that selenoprotein S (SELS) was associated with a range of inflammatory markers, and its gene expression was influenced by a polymorphism in the promoter region. The genetic basis of the ischemic stroke has now been largely determined, so the aim of the study was to examine the role of SELS genetic variants in the ischemic stroke risk in a Chinese population. We conducted a case-control study with 239 ischemic stroke patients and 240 controls. Two single-nucleotide polymorphisms (SNPs) in SELS genes were analyzed for association with the risk of ischemic stroke in the Chinese Han population. No evidence of ischemic stroke association was observed with the SNP rs34713741. Interestingly, the strongest evidence showed that SELS SNP rs4965814 was associated with ischemic stroke (P < 0.05). We found a significant association with increased ischemic stroke risk in women carrying the CC genotype of rs4965814 [hazard ratio: 2.43(1.03-5.75)]; a similar trend was also found in men carrying the TC genotype of rs4965814 [hazard ratio: 1.81(1.06-3.08)]. SNP rs4965814 of SELS may affect the susceptibility to ischemic stroke. Understanding the inflammatory mechanisms of ischemic stroke may give new therapeutic targets to pharmacologists.

[Association study of apolipoprotein e gene polymorphism and cerebral infarction in type 2 diabetic patients].

In order to explore the association of apolipoprotein E (ApoE) gene polymorphism with cerebral infarction in type 2 diabetic patients of Han nationality in Northeast China , the genotypes of ApoE gene were analyzed by polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) in the 208 cases, including 69 cases in control (CON) group and 67 in type 2 diabetes mellitus (T2DM) group as well as 72 in type 2 diabetes mellitus with cerebral infarction (T2DMCI) group. Plasma lipid content in T2DMCI was also detected for 70 cases. The distribution of genotypes in ApoE gene,epsilon(2)epsilon(3),epsilon(3)epsilon(3) as well as epsilon(3)epsilon(4) was no significant difference in three groups (epsilon(2)epsilon(3) : 13.2%,epsilon(3)epsilon(3) : 67.6%,epsilon(3)epsilon(4) : 16.2%in CON group;epsilon(2)epsilon(3) : 19.4%,epsilon(3)epsilon(3): : 70.1%epsilon(3)epsilon(4) : 9%in T2DM group;epsilon(2)epsilon(3) : 15.2%,epsilon(3)epsilon(3) : 75%,epsilon(3)epsilon(4) : 4.2%in T2DMCI group). The allele frequencies of epsilon(2),epsilon(3) and epsilon(4) were not significantly different in the three groups, either(epsilon(2) : 9.6%,epsilon(3) : 82.4%,epsilon(4) : 8.1%in CON group; epsilon(2) :10.5%,epsilon(3) :84.3%,epsilon(4) : 5.2%in T2DM group; epsilon(2) :11.8%,epsilon(3) :84.7%,epsilon(4) : 3.5%in T2DMCI group). The levels of total cholesterol (TC), tryglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were not significantly different among the different genotypes in T2DMCI group. The study confirmed that the polymorphisms of ApoE gene are neither associated with the T2DMCI, nor with the levels of plasma lipid in T2DMCI.