y proposes the important IBS associated pathways and the network regulation mechanisms of the crucial ingredients. It reveals the multi-target synergistic effect of the crucial ingredient combinations for the novel therapy on IBS.Total dissolved gas (TDG) supersaturation caused by dam operations can cause fish gas bubble disease (GBD) and even fish kill. Few studies have examined the effects on pelagic species. Here, we examined the tolerance and avoidance characteristics of silver carp (Hypophthalmichthys molitrix), a pelagic fish widely distributed in the Yangtze River basin in China, under stress caused by TDG supersaturation. Silver carp had an average mortality rate of 7.5% ± 1.8%, 92.5% ± 1.8%, and 97.5% ± 1.8% under 130%, 140% and 150% TDG supersaturation for 72 h of exposure, respectively. The average median lethal time (LT50) of silver carp was 18.1 h and 8.0 h under 140% and 150% TDG supersaturation, respectively. Bubbles and congestion appeared in the fins, gills and skin of silver carp. Silver carp can detect and avoid high TDG supersaturation. Significant avoidance behaviors were displayed by silver carp and the final avoidance rate was over 80% under 130% or above TDG conditions. The results of this study indicate that 130% TDG supersaturation triggered silver carp avoidance behaviors, and can be considered as the tolerance threshold.The mitoepigenetic modifications may be closely related to cellular fate. Both the replicative and hydrogen peroxide (H2O2)-induced premature senescence models were used to detect the mitochondrial biological characteristics and the epigenetic factors during senescence of human embryonic lung fibroblasts. The mitochondrial quantity was decreased in two senescence stages, while the mitochondrial DNA (mtDNA) copy number was increased significantly and the methyltransferases activity likewise. And the acute mtROS accumulation could launch premature senescence. Later, the persistent premature senescence owned the higher level of adenosine triphosphate (ATP) and mitochondrial 5-methylcytosine (mt-5-mC), and the less level of 8-hydroxydeoxyguanosine (8-OHdG) than those of replicative senescence. The mtDNA methylation-related enzymes, binding protein and the mitochondrial transcription regulators presented the differentially expressed profiles in both senescent states. Interestingly, the hypermethylation in the CpG region of mitochondrial transcription factor B2 (TFB2M) contributed to its downregulation of mRNA level in replicative senescence. The alterations of the mitochondrial biological functions and mtDNA features would be novel candidate biomarkers involved in cellular senescence. The specific methylation status of mtDNA may also have a crosstalk with oxidative stress to the mitochondrial function, contributing to cellular senescence.The extensive recorded environmental and occupational dispersal of hexavalent chromium (CrVI) dust contributes to an increased interest in its toxicological consequences. check details A previous study of our team described a brain injury induced by acute intranasal instillation of Cr(VI) in rats, which was characterized by oxidative stress and inflammation. This proposed a high risk of brain damage among Cr(VI) exposed individuals either environmentally or occupationally especially through the nasal cavity. Accordingly, the main aim of this study was to evaluate the effects of subacute/subsubacute/subchronic exposure to intranasal potassium dichromate (inPDC) solution in three dose levels (0.125, 0.25, or 0.5 mg/kg/day for five successive days/week) for 3 different intervals/dose two weeks, one month, and two months, on the brain of rats. The rats were sacrificed 24 h following the last inPDC dose. The locomotor activity, motor coordination, and object recognition behavior of the rats have been measured. Evaluation of oxidative stress; evidenced by lipid peroxidation and reduced glutathione, and inflammatory markers; evidenced by interleukin 1-beta in the brain tissues, as well as the brain PI3K and PKB contents were performed. Furthermore, the brain anti-glial fibrillary acidic protein (GFAP); marker of neurotoxicity was assessed immunohistochemically. Brain histopathological alterations were also studied. The findings of the current study revealed a dose- and time-dependent inPDC-induced brain toxicity in rats, as displayed by the biochemical, immunohistochemical and histopathological evaluation. Behaviorally, the major toxic effects of inPDC were observed on the locomotor and cognition functions, however, minor effects were observed on the motor coordination. The results suggest that short-term exposure to intranasal Cr(VI), in theses doses, does not trigger a major brain injury in rats; however, observation of more toxic alterations in a time-dependent manner is a threat of more sever toxicity upon longer exposure.

A human chorionic gonadotropin (hCG) cut-off of ≤300 IU/l for starting actinomycin D (ActD) in post-molar gestational trophoblastic neoplasia (GTN) patients developing methotrexate resistance (MTX-R) reduced the number of women needing toxic multi-agent chemotherapy (etoposide, MTX and ActD alternating weekly with cyclophosphamide and vincristine; EMA/CO) without affecting survival. Here we assess whether an increased hCG cut-off of ≤1000 IU/l spares more women EMA/CO.

All post-molar GTN patients treated with first-line methotrexate and folinic acid (MTX/FA) were identified in a national cohort between 2009 and 2016. Data collected included age, FIGO score, the hCG levels at MTX-R, and treatment outcomes.

In total, 609 GTN patients commenced treatment with MTX/FA achieving a complete response in 57% (348/609). Resistance developed in 25.1% (153/609) at an hCG ≤ 1000 IU/l and switching to ActD achieved remission in 92.8% without any major toxicity with the remaining 7.2% remitting on EMA/CO. Comparative analysis of patients switching at an hCG <100 versus 100-300 versus 300-1000 IU/l revealed a significant fall in the cure rate with second-line ActD from 97% (93/96) to 87% (34/39) to 78% (14/18), respectively, P= 0.009. However, by increasing the hCG cut-off from ≤300 to ≤1000 IU/l, 14 patients were spared EMA/CO chemotherapy. Moreover, in the present series, all post-molar GTN remain in remission.

This study demonstrates that increasing the hCG cut-off from ≤300 to ≤1000 IU/l for choosing patients for ActD following MTX-R spares more women with GTN from the greater toxicity of EMA/CO without compromising 100% survival outcomes.

This study demonstrates that increasing the hCG cut-off from ≤300 to ≤1000 IU/l for choosing patients for ActD following MTX-R spares more women with GTN from the greater toxicity of EMA/CO without compromising 100% survival outcomes.