Attractylone attenuates sepsis-associated encephalopathy and cognitive dysfunction by inhibiting microglial activation and neuroinflammation.

Multiple studies demonstrated that sepsis is a life-threatening state of organ dysfunction caused by infection and can induce neuroinflammation and cognitive impairment. The aim of this study was to evaluate the protective effects of attractylone (Atr) on sepsis-associated encephalopathy (SAE) and cognitive dysfunction. Moreover, we studied the underlying molecular mechanisms. We used an LPS-induced sepsis mouse model and evaluated the cognitive function with the Morris water maze and open field test. Neuronal damage in the hippocampus was assessed by immunohistochemical analysis. BV2 cells were used to identify the protective mechanism of Atr. The result showed that Atr attenuated LPS-induced cognitive impairment, neural apoptosis, inflammatory factors, and microglial activation. The in vitro experiment showed that Atr promoted silent information regulator 1 (SIRT1) expression and suppressed NFκB expression. Downregulation of SIRT1 reversed the protective effect of Atr in the LPS condition. Moreover, Atr-induced SIRT1 expression promoted BV2 from LPS-induced M1 to M2 phenotype. Taken together, these results indicated that Atr was a potential therapeutic agent for SAE and cognitive dysfunction.

Distinct Hippocampal Expression Profiles of lncRNAs in Rats Exhibiting a PTSD-like Syndrome.

Posttraumatic stress disorder (PTSD) refers to a series of clinical syndromes, including symptoms such as nightmares, hallucinations, severe anxiety, fear, and trauma related to the environment. These symptoms tend to occur after intense psychological trauma or physiological stress. Long non-coding RNAs (lncRNAs) have been shown to play key roles in various biological processes, although it is unknown whether they have important functions in PTSD. Here, we present the first study exploring the connection between lncRNAs and a PTSD-like syndrome in rats. We find distinct expression profiles of lncRNAs between PTSD-like syndrome rats and a control group, which provides information for further research on the differentiation of PTSD and transdifferentiation between the PTSD-like syndrome and the control group. This information will be helpful for finding new therapeutic targets for the treatment of PTSD.

Transformation of (14)C-pyrimidynyloxybenzoic herbicide ZJ0273 in aerobic soils.

A soil metabolism study of propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)benzoate (ZJ0273), a novel broad-spectrum herbicide, was carried out using (14)C labeled on two different rings, i.e., [pyrimidine-4,6-(14)C] ZJ0273 and [benzyl-U-(14)C] ZJ0273. Ultralow liquid scintillation counting and LC-MS/MS were used to identify the degradation intermediates and quantify their dynamics in aerobic soils. Four aromatic intermediates, 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)benzoic acid (M1), 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzamido)benzoic acid (M2), 2-(4,6-dimethoxypyrimidin-2-yloxy)benzoic acid (M3), and 4,6-dimethoxypyrimidin-2-ol (M4), were identified and their identity was further confirmed against authentic standards. Analysis of metabolites suggested two degradation pathways: (1) Upon loss of the propyl group, M1 was produced via hydrolysis of propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)benzoate after which the C-N bond between rings A and B was cleaved by oxidation and biochemical degradation to yield M3, which was further converted into M4 and finally mineralized to CO(2); and (2) the first step was the same as in pathway 1, but M1 first underwent a carbonylation to form M2. The C-N bond between rings A and B of M2 was cleaved by hydrolysis to yield M3. Dynamic changes in the four metabolites in aerobic soils were also investigated by HPLC coupled analysis of radioactivity of isolated peaks. After a 100-day incubation, 1.7-9.7% of applied (14)C was found as M1, 0.3-1.1% as M2, 14.5-20.9% as M3, and 3.7-6.7% as M4 in the soils, and pH appeared to be the most influential soil property affecting the formation and dissipation of these metabolites.