Comparative Study of Antibacterial Properties of Emodin and Enrofloxacin Against Aeromonas hydrophila

Antibacterial properties of emodin, extracted from rhubarb, and enrofloxacin, against Aeromonas hydrophila, were assessed in this study. The minimum inhibitory concentration (MIC) values of emodin and enrofloxacin to fight A. hydrophila WJ2011BJ44 were found to be 100ug/ml and 9.375ug/ml, respectively. To understand the mechanisms of action of emodin and enrofloxcain against A. hydrophila we studied antibacterial activity, bacterial membrane permeability, and ultrastructure of A. hydrophila cells treated with emodin, enrofloxacin individually, and the combination of both. The results shown in the growth curve of A. hydrophila treated with different concentrations (from 0 MIC to 4 MIC) of emodin and enrofloxacin were similar and stable, and there was no significant difference in the growth curve of different treatment groups. There were significant differences in the K+ concentration among all treatment groups from 1 h to 8 h after incubation compared with the control. The highest K+ concentration was observed in the emodin+enrofloxacin group from 1 h to 8 h after incubation. PI fluorescence signal of untreated A. hydrophila cells and A. hydrophila cells treated with emodin, or enrofloxacin individually, or the combination of both were 0.89, 11.4, 13.98 and 18.3, respectively. The mortality of A. hydrophila cells treated with the combination of emodin and enrofloxacin was greatest compared with other groups. These results indicated that 2 MIC emodin, 2 MIC enroflxacin, and combination of 1 MIC emodin and 1 MIC enrofloxacin can inhibit the growth of A. hydrophila, increase bacterial membrane permeability, and damage cell membrane integrity. The combination of 1 MIC concentration emodin and 1 MIC concentration enrofloxacin produced the best antibacterial activity against A. hydrophila

Effects of Dietary Protein Level on Growth Performance, Muscle Composition, Blood Composition, and Digestive Enzyme Activity of Wuchang Bream (Megalobrama amblycephala) Fry

The purpose of this study was to determine the dietary protein requirement and effects of dietary protein level on growth performance, muscle composition, blood composition, and digestive enzyme activity in Wuchang bream fry. Five isoenergetic and isolipidic semi-purified diets were formulated to contain 28%, 30%, 32%, 34%, or 36% (dry matter) dietary protein. Diets were fed to triplicate groups of 25 fishes (16.08±0.03 g) to near satiation three times a day in a closed recirculation system for 10 weeks. Weight gain, specific growth rate, and feed conversion ratio significantly improved as the dietary protein content increased up to 34%. The protein efficiency ratio, hepatosomatic index, and viscerosomatic index significantly dropped as the dietary protein rose while the Fulton condition factor was positively correlated to the dietary protein level. Increased dietary protein resulted in increased muscle protein content and decreased lipid content. Red blood cell, hemoglobin, and hematocrit counts increased significantly with the increase in dietary protein. Serum triiodothyronine and thyroxine significantly rose as the dietary protein rose but serum aspartate aminotransferase significantly dropped. Intestinal protease and amylase activity rose significantly with the increase in dietary protein while lipase tended to drop. On the basis of broken-line regression analysis of weight gain and FCR, the dietary protein requirement of Wuchang bream fry is 32-33%

Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives and Analogs Targeting the NLRP3 Inflammasome

A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their antiinflammatory activities toward NLRP3 (nucleotide‐binding domain leucine‐rich repeat containing protein family，pyrin domain‐containing 3，also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ‐09 and TBZ‐21, were identified by antiproduction of IL‐1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti‐inflammatory activities were investigated. Several compounds were identified as anti‐inflammatory agents that can reduce IL‐1β expression in a dosedependent manner. A preliminary structure–activity relationship is also summarized here

Energy Dissipation and Performance Assessment of the Connected Structure with a One-Side Damping Layer

Due to aesthetic demands and the necessity for multi-functionality, a unique structure with one or multiple links connecting adjacent buildings has attracted the attention of researchers. In order to improve vibration control, this study investigates the seismic mitigation performance of a connected structure with a one-side damping layer. The simplified shear model is employed to derive the structure’s motion equation. Based on the Kanai-Tajimi filtered spectrum model, the seismic response variances are calculated using the Lyapunov equation. To investigate the seismic energy distribution and mitigation performance, three models of the connected structure with a damping layer are analyzed using the index of the mean kinetic energy. The results shows that the stiffness and damping coefficient affects the vibration energy, while the excessive stiffness of the damping layer is shown to be detrimental to the damping effects. In sum, the novel connected structure shows excellent damping ability and effectively reduces the vibration energy. Damping layers placed at a lower position with a stiffer structure are shown to enhance the damping effect and lead to more energy dissipation through the damping layer. Thus, this study concludes that the introduction of a One-Side damping layer into the connected structure is an excellent alternative strategy for adjusting the energy distribution of the connected structure and meeting the design requirements

Exploration and machine learning model development for T2 NSCLC with bronchus infiltration and obstructive pneumonia/atelectasis

Abstract In the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for Non-Small Cell Lung Cancer (NSCLC), tumors exhibiting main bronchial infiltration (MBI) near the carina and those presenting with complete lung obstructive pneumonia/atelectasis (P/ATL) have been reclassified from T3 to T2. Our investigation into the Surveillance, Epidemiology, and End Results (SEER) database, spanning from 2007 to 2015 and adjusted via Propensity Score Matching (PSM) for additional variables, disclosed a notably inferior overall survival (OS) for patients afflicted with these conditions. Specifically, individuals with P/ATL experienced a median OS of 12 months compared to 15 months (p < 0.001). In contrast, MBI patients demonstrated a slightly worse prognosis with a median OS of 22 months versus 23 months (p = 0.037), with both conditions significantly correlated with lymph node metastasis (All p < 0.001). Upon evaluating different treatment approaches for these particular T2 NSCLC variants, while adjusting for other factors, surgery emerged as the optimal therapeutic strategy. We counted those who underwent surgery and found that compared to surgery alone, the MBI/(P/ATL) group experienced a much higher proportion of preoperative induction therapy or postoperative adjuvant therapy than the non-MBI/(P/ATL) group (41.3%/54.7% vs. 36.6%). However, for MBI patients, initial surgery followed by adjuvant treatment or induction therapy succeeded in significantly enhancing prognosis, a benefit that was not replicated for P/ATL patients. Leveraging the XGBoost model for a 5-year survival forecast and treatment determination for P/ATL and MBI patients yielded Area Under the Curve (AUC) scores of 0.853 for P/ATL and 0.814 for MBI, affirming the model's efficacy in prognostication and treatment allocation for these distinct T2 NSCLC categories

Antimicrobial and Antivirulence Activities of Carvacrol against Pathogenic Aeromonas hydrophila

Aeromonas hydrophila is a ubiquitous Gram-negative opportunistic pathogen in the freshwater environment and the most common cause of bacterial septicemia in aquaculture. In this study, we investigated the impact of carvacrol, a natural monoterpenoid found in herbs, on the virulence of A. hydrophila in vitro and the antibacterial effect in combination with antibiotics. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of carvacrol against A. hydrophila NJ-35 were 125 &micro;g/mL and 250 &micro;g/mL, respectively. Carvacrol could inhibit the virulence factors (biofilm, protease, exopolysaccharide, and hemolysin) of A. hydrophila, and the antibiofilm potential of carvacrol was further verified by microscopic detection. Transcriptional analyses showed that the gene expression of flaB, ompA, aha, ahp, ela, act, aerA, AhyR, and hly were marked as downregulated. The checkerboard assay results showed that carvacrol did not have an antagonistic effect in combination with antibiotics (florfenicol, enrofloxacin, thiamphenicol, or doxycycline hydrochloride) commonly used in aquaculture but possessed an additive-synergistic effect with neomycin sulfate. In vivo studies demonstrated that carvacrol protected grass carp (Ctenopharyngodon idella) from A. hydrophila infection. Our results indicated that carvacrol possessed significant anti-bacterial and anti-virulence effects on A. hydrophila

In Vitro Antibiofilm Activity of Resveratrol against <i>Aeromonas hydrophila</i>

Aeromonas hydrophila is a Gram-negative bacterium that widely exists in various aquatic environments and causes septicemia in fish and humans. Resveratrol, a natural polyterpenoid product, has potential chemo-preventive and antibacterial properties. In this study, we investigated the effect of resveratrol on A. hydrophila biofilm formation and motility. The results demonstrated that resveratrol, at sub-MIC levels, can significantly inhibit the biofilm formation of A. hydrophila, and the biofilm was decreased with increasing concentrations. The motility assay showed that resveratrol could diminish the swimming and swarming motility of A. hydrophila. Transcriptome analyses (RNA-seq) showed that A. hydrophila treated with 50 and 100 μg/mL resveratrol, respectively, presented 230 and 308 differentially expressed genes (DEGs), including 90 or 130 upregulated genes and 130 or 178 downregulated genes. Among them, genes related to flagellar, type IV pilus and chemotaxis were significantly repressed. In addition, mRNA of virulence factors OmpA, extracellular proteases, lipases and T6SS were dramatically suppressed. Further analysis revealed that the major DEGs involved in flagellar assembly and bacterial chemotaxis pathways could be regulated by cyclic-di-guanosine monophosphate (c-di-GMP)- and LysR-Type transcriptional regulator (LTTR)-dependent quorum sensing (QS) systems. Overall, our results indicate that resveratrol can inhibit A. hydrophila biofilm formation by disturbing motility and QS systems, and can be used as a promising candidate drug against motile Aeromonad septicemia

The stress hormone norepinephrine increases the growth and virulence of Aeromonas hydrophila

Abstract Stress is an important contributing factor in the outbreak of infectious fish diseases. To comprehensively understand the impact of catecholamine stress hormone norepinephrine (NE) on the pathogenicity of Aeromonas hydrophila, we assessed variations in bacterial growth, virulence‐related genes expression and virulence factors activity after NE addition in serum‐SAPI medium. Further, we assessed the effects of NE on A. hydrophila virulence in vivo by challenging fish with pathogenic strain AH196 and following with or without NE injection. The NE‐associated stimulation of A. hydrophila strain growth was not linear‐dose‐dependent, and only 100 μM, or higher concentrations, could stimulate growth. Real‐time PCR analyses revealed that NE notably changed 13 out of the 16 virulence‐associated genes (e.g. ompW, ahp, aha, ela, ahyR, ompA, and fur) expression, which were all significantly upregulated in A. hydrophila AH196 (p < 0.01). NE could enhance the protease activity, but not affect the lipase activity, hemolysis, and motility. Further, the mortality of crucian carp challenged with A. hydrophila AH196 was significantly higher in the group treated with NE (p < 0.01). Collectively, our results showed that NE enhanced the growth and virulence of pathogenic bacterium A. hydrophila

Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives and Analogs Targeting the NLRP3 Inflammasome

A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their antiinflammatory activities toward NLRP3 (nucleotide‐binding domain leucine‐rich repeat containing protein family，pyrin domain‐containing 3，also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ‐09 and TBZ‐21, were identified by antiproduction of IL‐1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti‐inflammatory activities were investigated. Several compounds were identified as anti‐inflammatory agents that can reduce IL‐1β expression in a dosedependent manner. A preliminary structure–activity relationship is also summarized here

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