Dexmedetomidine attenuates acute stress-impaired learning and memory in mice by maintaining the homeostasis of intestinal flora.

Dexmedetomidine (Dex) has been used in surgery to improve patients' postoperative cognitive function. However, the role of Dex in stress-induced anxiety-like behaviors and cognitive impairment is still unclear. In this study, we tested the role of Dex in anxiety-like behavior and cognitive impairment induced by acute restrictive stress and analyzed the alterations of the intestinal flora to explore the possible mechanism. Behavioral and cognitive tests, including open field test, elevated plus-maze test, novel object recognition test, and Barnes maze test, were performed. Intestinal gut Microbe 16S rRNA sequencing was analyzed. We found that intraperitoneal injection of Dex significantly improved acute restrictive stress-induced anxiety-like behavior, recognition, and memory impairment. After habituation in the environment, mice (male, 8 weeks, 18-23 g) were randomly divided into a control group (control, N = 10), dexmedetomidine group (Dex, N = 10), AS with normal saline group (AS + NS, N = 10) and AS with dexmedetomidine group (AS + Dex, N = 10). By the analysis of intestinal flora, we found that acute stress caused intestinal flora disorder in mice. Dex intervention changed the composition of the intestinal flora of acute stress mice, stabilized the ecology of the intestinal flora, and significantly increased the levels of Blautia (A genus of anaerobic bacteria) and Coprobacillus. These findings suggest that Dex attenuates acute stress-impaired learning and memory in mice by maintaining the homeostasis of intestinal flora.

Suitability of reduced dose glucocorticoids therapy regimen for antibody-associated vasculitis patients with TB: a retrospective study.

INTENTION: Immunosuppressive therapy is the major treatment approach for patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Due to impaired cellular immunological function and the use of glucocorticoids and immunosuppressants, AAV patients are predisposed to opportunistic infections, including tuberculosis (TB). This retrospective study aims to analyze the clinical characteristics of patients with AAV and TB and explore suitable glucocorticoid regimens for them. So as to provide a basis for future clinical guidelines and have important value for guiding clinical treatment. METHODS: This study retrospectively reviewed 58 AAV patients (18-80 years old) with TB admitted to Changsha Central Hospital Affiliated with the University of South China from 2016.1 to 2023.4 Patients were divided into standard-dose and reduced-dose glucocorticoid groups before retrospectively analyzing their medical records. RESULTS: A total of 58 AAV patients with TB were enrolled, with 15 dying throughout the monitoring period. Through analysis data, compared with the standard-dose group, the reduced group had less proteinuria and hematuria. In survival analysis, the reduced-dose glucocorticoid group had lower mortality than the standard-dose group (P = 0.03); however, no significant difference was noted in the use of immunoglobulin (P = 0.39), tuberculosis activity (P = 0.64), and age stratification (P = 0.40). The BVAS score before treatment and 6 months post-treatment suggest that the two regimens cause the same risk of ESKD (P > 0.05). CONCLUSION: In conclusion, the reduced glucocorticoid dose group can achieve the same curative effect as the standard dose group and has less damage to the kidney in hematuria and proteinuria. Therefore, the reduced glucocorticoid dose treatment regimen may be more suitable for AAV patients with TB.

Fluorofenidone alleviates liver fibrosis by inhibiting hepatic stellate cell autophagy via the TGF-ß1/Smad pathway: implications for liver cancer.

Objectives: Liver fibrosis is a key stage in the progression of various chronic liver diseases to cirrhosis and liver cancer, but at present, there is no effective treatment. This study investigated the therapeutic effect of the new antifibrotic drug fluorofenidone (AKF-PD) on liver fibrosis and its related mechanism, providing implications for liver cancer. Materials and Methods: The effects of AKF-PD on hepatic stellate cell (HSC) autophagy and extracellular matrix (ECM) expression were assessed in a carbon tetrachloride (CCl4)-induced rat liver fibrosis model. In vitro, HSC-T6 cells were transfected with Smad2 and Smad3 overexpression plasmids and treated with AKF-PD. The viability and number of autophagosomes in HSC-T6 cells were examined. The protein expression levels of Beclin-1, LC3 and P62 were examined by Western blotting. The Cancer Genome Atlas (TCGA) database was used for comprehensively analyzing the prognostic values of SMAD2 and SMAD3 in liver cancer. The correlation between SMAD2, SMAD3, and autophagy-related scores in liver cancer was explored. The drug prediction of autophagy-related scores in liver cancer was explored. Results: AKF-PD attenuated liver injury and ECM deposition in the CCl4-induced liver fibrosis model. In vitro, the viability and number of autophagosomes in HSCs were reduced significantly by AKF-PD treatment. Meanwhile, the protein expression of FN, α-SMA, collagen III, Beclin-1 and LC3 was increased, and P62 was reduced by the overexpression of Smad2 and Smad3; however, AKF-PD reversed these effects. SMAD2 and SMAD3 were hazardous factors in liver cancer. SMAD2 and SMAD3 correlated with autophagy-related scores in liver cancer. Autophagy-related scores could predict drug response in liver cancer. Conclusions: AKF-PD alleviates liver fibrosis by inhibiting HSC autophagy via the transforming growth factor (TGF)-ß1/Smadpathway. Our study provided some implications about how liver fibrosis was connected with liver cancer by SMAD2/SMAD3 and autophagy.

[Effect of aeration intensity on the nitrogen and phosphorus removal performance of AOA membrane bioreactors].

The ability of simultaneous phosphorus and nitrogen removal of sequencing batch membrane bioreactor run in anaerobic/oxic/ anoxic mode (AOA MBR) was examined under three aeration intensities [2.5, 3.75 and 5.0 m3 x (m2 x h)(-10]. The results showed that the averaged removals of COD were over 90% at different aeration intensities. And the higher aeration intensity was, the more ammonia nitrogen removal rate achieved. The removal rates of NH4(+) under the three aeration intensities were 84.7%, 90.6% and 93.8%, respectively. Total nitrogen removal rate increased with the increasing aeration intensity. But excessive aeration intensity reduced TN removal. The removal rates of TN under the three aeration intensities were 83.4%, 87.4% and 80.6%, respectively. Aeration intensity affected the denitrifying phosphorus ability of the AOA MBR. The ratio of denitrification phosphorus removal under the three aeration intensities were 20%, 30.2% and 26.7%, respectively.

[Denitrifying phosphorus removal in MUCT-MBR].

The self-designed MUCT-MBR simplifies the MUCT process with reducing reactors from 5 to 2, which greatly reduces land occupied by equipment. Instead of secondary sedimentation tank, the membrane effluent quality is quite safe, and the operation is simple. In the investigation about simultaneous phosphorus and nitrogen removal of MUCT-MBR, the results showed that: when the proportions of C, N and P in the influent were 33.3/5/1-25/5.5/1, the average removal rate of COD, TN and TP in the whole experimental process were 89.3%, 75.4% and 79.2%, respectively. And the sludge settling capacity had no influence on the membrane effluent quality. The key factor of N and P removal rates is denitrifying phosphorus removal in anoxic condition. The proportion of denitrifying phosphate accumulating organisms (DPAOs) and the rate of denitrifying phosphorous removal were 84.2% and 67.07% on the 58th day, respectively.

Enhanced biological nutrient removal using MUCT-MBR system.

Biological nutrient removal was investigated in a combined modified University of Cape Town and membrane bioreactor system. When the influent nutrient mass ratio (COD/TN/TP) was 28.5/5.1/1 to 28.5/7.2/1, average removal efficiencies of COD, TN and TP were 90%, 81.6%, 75.2%. Obvious denitrifying phosphorus removal occurred with C/N ratio 3.98. When nitrite was the main electron acceptor, the ratio of denitrifying phosphate uptake to the total phosphate uptake were 99.8% and the sludge yield was 0.28kg VSS/kg COD; when nitrate was the main electron acceptor, the ratio was 92% and the yield was 0.32kg VSS/kg COD. In case of nitrite, the system not only kept TP and TN removal at 89.1% and 82.2%, but also ensured less sludge production. Batch tests showed that the proportion of denitrifying phosphorus-accumulating organisms in the total phosphorus-accumulating organisms in the system was higher than 80%.

[Enrichment of denitrifying phosphate accumulating organisms in sequencing batch membrane bioreactors].

The enrichment and characteristics of denitrifying phosphate accumulating organisms (DPAO), which are capable of utilizing nitrate as electron acceptor, was investigated in a laboratory-scale sequencing batch membrane bioreactors (SBMBR). The results demonstrated that the proportion of DPAO increased from 19.4% to 69.6% of total phosphate accumulating organisms after anaerobic-aerobic and anaerobic-anoxic-aerobic phases. SBMBR system could operate steadily when 120 mg nitrate was added continuously during the anoxic phase every period. Simultaneous phosphate uptake and biological denitrification with good performance could be obtained in SBMBR operated in steady-state. Nitrate and phosphorus removal efficiency were above 100% and 84% respectively during anoxic phase, however, the effluent TP concentration was low than 0.5 mg/L, the total phosphorus removal efficiency was 96.1%. Furthermore, the ammonium nitrogen removal efficiency of SBMBR could be maintained at 92.2%, and the cumulation of nitrite and nitrate was not observed clearly.

[Comparisons of simultaneous phosphorus and nitrogen removal in sequencing batch membrane bioreactors].

Two SBMBRs run in AO and A2O mode were operated in parallel to compare their ability of simultaneous phosphorus and nitrogen removal. The results showed that the removals of COD and ammonium nitrogen were averaged over 90% and 95%, respectively. A2O MBR has the stronger anaerobic phosphorus release ability; its SPRR30 outdoes 47.5% compared to AO MBR. SPUR30 of A2O MBR was lower which may attribute to the higher effluent TP content. The ratio of DPAO was enhanced 57% compared to AO MBR. And when nitrate as the only electron accepter, the phosphorus uptake mass with unit electron transfer was 30% higher in A2O MBR. This two factors lead to the stronger denitrifying phosphorus removal ability of A2O MBR. Furthermore, the membrane fouling was mitigated in A2O MBR though the aerobic time was half to that of AO MBR. The membrane filter function made SBMBR's effluent free of the sludge settlement ability.