Nuclear Factor Erythroid 2-Related Factor 2-Histone Deacetylase 2 Pathway in the Pathogenesis of Refractory Sudden Sensorineural Hearing Loss and Glucocorticoid Resistance.

INTRODUCTION: A significant number of sensorineural hearing loss (SSNHL) patients had no noticeable hearing improvement after glucocorticoid (GC) treatment. In the present study, we examined expression of the nuclear factor erythroid 2-related factor 2 (NRF2) and histone deacetylase 2 (HDAC2) in peripheral blood mononuclear cells (PBMCs) of refractory SSNHL patients to study the role of NRF2-HDAC2 pathway in GC insensitivity hearing improvement after GC treatment, which is usually referred to as refractory SSNHL or GC insensitivity. MATERIALS AND METHODS: Forty-four refractory SSNHL patients were treated by intratympanic GC infusion. Hearing was tested in all patients before and after treatment by pure tone hearing test. NRF2/HDAC2 mRNA and protein levels were examined in PBMCs of refractory SSNHL patients before and after treatment. PBMCs from healthy volunteers were used as normal controls. RESULTS: According to the hearing improvement after treatment, patients were assigned into 2 groups: the intratympanic GC sensitive (IGCS) group (hearing recovery ≥15 dB HL) and the intratympanic GC insensitive (IGCI) group (hearing recovery <15 dB HL). Before treatment, the NRF2 mRNA level was lower in all patients than the normal control group. After treatment, NRF2 and HDAC2 mRNA and protein levels were increased in the IGCS group, while no significant change was observed in the IGCI group. CONCLUSION: Low response of NRF2/HDAC2 proteins is associated with GC insensitivity in SSNHL. We speculate that the NRF2-HDAC2 pathway affects GC sensitivity in SSNHL patients.

Fungal community structure shifts in litter degradation along forest succession induced by pine wilt disease.

Fungi play a crucial role in decomposing litter and facilitating the energy flow between aboveground plants and underground soil in forest ecosystems. However, our understanding how the fungal community involved in litter decomposition responds during forest succession, particularly in disease-driven succession, is still limited. This study investigated the activity of degrading enzyme, fungal community, and predicted function in litter after one year of decomposition in different types of forests during a forest succession gradient from coniferous to deciduous forest, induced by pine wilt disease. The results showed that the weight loss of needles/leaves and twigs did not change along the succession process, but twigs degraded faster than needles/leaves in both pure pine forest and mixed forest. In pure pine forest, peak activities of enzymes involved in carbon degradation (ß-cellobiosidase, ß-glucosidase, ß-D-glucuronidase, ß-xylosidase), nitrogen degradation (N-acetyl-glucosamidase), and organic phosphorus degradation (phosphatase) were observed in needles, which subsequently declined. The fungal diversity and evenness (Shannon's diversity and Shannon's evenness) dropped in twig from coniferous forest to mixed forest during the succession. The dominant phyla in needle/leaf and twig litters were Ascomycota (46.9%) and Basidiomycota (38.9%), with Lambertella pruni and Chalara hughesii identified as the most abundant indicator species. Gymnopus and Desmazierella showed positively correlations with most measured enzyme activities. Functionally, saprotrophs constituted the main trophic mode (47.65%), followed by Pathotroph-Saprotroph-Symbiotroph (30.95%) and Saprotroph-Symbiotroph (10.57%). The fungal community and predicted functional structures in both litter types shifted among different forest types along the succession. These findings indicate that the fungal community in litter decomposition responds differently to disease-induced succession, leading to significant shifts in both the fungal community structure and function.

[Simulating the Fate of Typical Organochlorine Pesticides in the Multimedia Environment of the Pearl River Delta].

A level Ⅳ multimedia fugacity model was established to simulate the fate of p,p'-DDT and γ-HCH in special climatic conditions, such as in the high temperature and humidity environment of the Pearl River Delta, China. The law of migration and transformation of p,p'-DDT and γ-HCH were approached by the Ⅳ multimedia fugacity model, corrected for time and temperature change during 1952-2030. The simulation results showed a better response of the variation of pollutant concentrations to the changes in the pesticide application policy; the concentrations of these two targets in air, water, soil, and sediment were found continuing to increase with the growth of application rates, and decreased with the prohibition in the use of pesticide. We predicted that concentrations will decrease to 6.1×10-12, 3.2×10-9, 6.07×10-7, and 8.72×10-7 mol·m-3 for p,p'-DDT, and to 3.37×10-11, 1.14×10-8, 1.21×10-6, and 4.18×10-7 mol·m-3 for γ-HCH, in air, water, soil, and sediment, respectively, by 2030. The output values of the Ⅳ multimedia fugacity model corrected by designating temperature as a variable parameter, was closer to the survey results than the simulation results obtained by using the model with a constant temperature parameter. The results also showed the pattern of organochlorine pesticides transformation in the whole environmental media in the study area as follow:the pollutants transferred from air to soil, air to water, soil to water, and from water to sediment, and were lastly stored in the soil and sediment. The results of sensitivity analysis indicated that the emission rate, degradation rate, temperature, and lgKow had significant influences on the concentrations of p,p'-DDT and γ-HCH in all the above-mentioned environmental medias. Uncertainty analysis showed that changes in the whole parameter sets had great impact on air concentrations. There were seasonal variations in the distribution of organochlorine pesticide concentrations, and temperature change had influence on its partition in the environment.