Promoted production of Fe(IV)/Fe(V) intermediates in the calcium peroxide/ferrate(VI) process for low-damage removal of algal contaminants and membrane fouling control.

Ultrafiltration (UF) is widely employed for harmful algae rejection, whereas severe membrane fouling hampers its long-term operation. Herein, calcium peroxide (CaO2) and ferrate (Fe(VI)) were innovatively coupled for low-damage removal of algal contaminants and fouling control in the UF process. As a result, the terminal J/J0 increased from 0.13 to 0.66, with Rr and Rir respectively decreased by 96.74 % and 48.47 %. The cake layer filtration was significantly postponed, and pore blocking was reduced. The ζ-potential of algal foulants was weakened from -34.4 mV to -18.7 mV, and algal cells of 86.15 % were removed with flocs of 300 µm generated. The cell integrity was better remained in comparison to the Fe(VI) treatment, and Fe(IV)/Fe(V) was verified to be the dominant reactive species. The membrane fouling alleviation mechanisms could be attributed to the reduction of the fouling loads and the changes in the interfacial free energies. A membrane fouling prediction model was built based on a long short-term memory deep learning network, which predicted that the filtration volume at J/J0= 0.2 increased from 288 to 1400 mL. The results provide a new routine for controlling algal membrane fouling from the perspective of promoting the generation of Fe(IV)/Fe(V) intermediates.

Quercetin restores respiratory mucosal barrier dysfunction in Mycoplasma gallisepticum-infected chicks by enhancing Th2 immune response.

BACKGROUND: Mycoplasma gallisepticum (MG) has long been a pathogenic microorganism threatening the global poultry industry. Previous studies have demonstrated that the mechanism by which quercetin (QUE) inhibits the colonization of MG in chicks differs from that of antibiotics. However, the molecular mechanism by which QUE facilitates the clearance of MG remains unclear. PURPOSE: The aim of this study was to investigate the molecular mechanism of MG clearance by QUE, with the expectation of providing new options for the treatment of MG. METHODS: A model of MG infection in chicks and MG-induced M1 polarization in HD-11 cells were established. The mechanism of QUE clearance of MG was investigated by evaluating the relationship between tracheal mucosal barrier integrity, antibody levels, Th1/Th2 immune balance and macrophage metabolism and M1/M2 polarization balance. Furthermore, network pharmacology and molecular docking techniques were employed to explore the potential molecular pathways connecting QUE, M2 polarization, and fatty acid oxidation (FAO). RESULTS: The findings indicate that QUE remodels tracheal mucosal barrier function by regulating tight junctions and secretory immunoglobulin A (sIgA) expression levels. This process entails the regulatory function of QUE on the Th1/Th2 immune imbalance that is induced by MG infection in the tracheal mucosa. Moreover, QUE intervention impeded the M1 polarization of HD-11 cells induced by MG infection, while simultaneously promoting M2 polarization through the induction of FAO. Conversely, inhibitors of the FAO pathway impede this effect. The results of computer network analysis suggest that QUE may induce FAO via the PI3K/AKT pathway to promote M2 polarization. Notably, inhibition of the PI3K/AKT pathway was found to effectively inhibit M2 polarization in HD-11 cells, while having a limited effect on FAO. CONCLUSIONS: QUE promotes M2 polarization of HD-11 cells to enhance Th2 immune response through FAO and PI3K/AKT pathways, thereby restoring tracheal mucosal barrier function and ultimately inhibiting MG colonization.

Lactobacillus salivarius ameliorates Mycoplasma gallisepticum-induced inflammation via the JAK/STAT signaling pathway involving respiratory microbiota and metabolites.

Mycoplasma gallisepticum (MG) can cause chronic respiratory disease (CRD) in chickens, which has a significant negative economic impact on the global poultry sector. Respiratory flora is the guardian of respiratory health, and its disorder is closely related to respiratory immunity and respiratory diseases. As a common probiotic in the chicken respiratory tract, Lactobacillus salivarius (L. salivarius) has potential antioxidant, growth performance enhancing, and anti-immunosuppressive properties. However, the specific mechanism through which L. salivarius protects against MG infection has not yet been thoroughly examined. This study intends to investigate whether L. salivarius could reduce MG-induced tracheal inflammation by modulating the respiratory microbiota and metabolites. The results indicated that L. salivarius reduced MG colonization significantly and alleviated the anomalous morphological changes by using the MG-infection model. L. salivarius also reduced the level of Th1 cell cytokines, increased the level of Th2 cell cytokines, and ameliorated immune imbalance during MG infection. In addition, L. salivarius improved the mucosal barrier, heightened immune function, and suppressed the Janus kinase/Signal transducer, and activator of transcription (JAK/STAT) signaling pathway. Notably, MG infection changed the composition of the respiratory microbiota and metabolites, and L. salivarius therapy partially reversed the aberrant respiratory microbiota and metabolite composition. Our results highlighted that these findings demonstrated that L. salivarius played a role in MG-mediated inflammatory damage and demonstrated that L. salivarius, by altering the respiratory microbiota and metabolites, could successfully prevent MG-induced inflammatory injury in chicken trachea.

Counteracting TGM2 by a Fibroin peptide ameliorated Adriamycin-induced nephropathy via regulation of lipid metabolism through PANX1-PPAR α/PANK1 pathway.

Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence 'YEVEDYR') from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing. Further analysis showed that YR-7 alleviated the accumulation of lipid droplets via regulation of the lipid metabolism-related proteins PPAR α and PANK1. Using chemical proteomics, fluorescence polarization, microscale thermophoresis, surface plasmon resonance, and molecular docking, YR-7 was proven to directly bind to ß-barrel domains of TGM2 protein to inhibit lipid accumulation. TGM2 knockdown in vivo increased the protein levels of PPAR α and PANK1 while decreased the levels of fibrotic-related proteins to alleviate nephropathy. In vitro, overexpression TGM2 reversed the protective effects of YR-7. Co-immunoprecipitation indicated that TGM2 interacted with PANX1 to promote lipid deposition, and pharmacological inhibition or knockdown of PANX1 decreased the levels of PPAR α and PANK1 induced by ADR. Taken together, our findings revealed that TGM2-PANX1 interaction in promoting lipid deposition may be a new signaling in promoting ADR-induced nephropathy. And a novel natural peptide could ameliorate renal fibrosis through TGM2-PANX1-PPAR α/PANK1 pathway, which highlight the potential of it in the treatment of CKD.

Insight into N2O emission and denitrifier communities under different aeration intensities in composting of cattle manure from perspective of multi-factor interaction analysis.

Nitrous oxide (N2O) emission from composting is a significant contributor to greenhouse effect and ozone depletion, which poses a threat to environment. To address the challenge of mitigating N2O emission during composting, this study investigated the response of N2O emission and denitrifier communities (detected by metagenome sequencing) to aeration intensities of 6 L/min (C6), 12 L/min (C12), and 18 L/min (C18) in cattle manure composting using multi-factor interaction analysis. Results showed that N2O emission occurred mainly at mesophilic phase. Cumulative N2O emission (QN2O, 9.79 mg·kg-1 DW) and total nitrogen loss (TN loss, 16.40 %) in C12 composting treatment were significantly lower than those in the other two treatments. The lower activity of denitrifying enzymes and the more complex and balanced network of denitrifiers and environmental factors might be responsible for the lower N2O emission. Denitrification was confirmed to be the major pathway for N2O production. Moisture content (MC) and Luteimonas were the key factors affecting N2O emission, and nosZ-carrying denitrifier played a significant role in reducing N2O emission. Although relative abundance of nirS was lower than that of nirK significantly (P < 0.05), nirS was the key gene influencing N2O emission. Community composition of denitrifier varied significantly with different aeration treatments (R2 = 0.931, P = 0.001), and Achromobacter was unique to C12 at mesophilic phase. Physicochemical factors had higher effect on QN2O, whereas denitrifying genes, enzymes and NOX- had lower effect on QN2O in C12. The complex relationship between N2O emission and the related factors could be explained by multi-factor interaction analysis more comprehensively. This study provided a novel understanding of mechanism of N2O emission regulated by aeration intensity in composting.

Association between oxidative balance score and metabolic syndrome and its components in US adults: a cross-sectional study from NHANES 2011-2018.

Background: Metabolic syndrome (MetS) is a global health concern that threatens human well-being. The oxidative balance score (OBS) is a tool to identify the level of oxidative stress that is correlated with MetS risk. However, association between OBS and MetS and its components has not been reported. Methods: This cross-sectional study included adult individuals with complete OBS and MetS data from National Health and Nutrition Examination Survey (NHANES) 2011-2018. A weighted logistic regression analysis was conducted to identify the association of the total, dietary, and lifestyle OBS scores with MetS. Subgroup analyses and restricted cubic splines were used to further explore associations. Results: In total, 10,025 eligible adult individuals (51.48% were males at a median age of 46 years) were included, with a MetS prevalence of 29.98%. In fully adjusted model, higher total OBS was associated with reduced risk of MetS (Q3 vs. Q1: odds ratio [OR] = 0.57, 95% confidence interval [CI], 0.46-0.71, p < 0.001; Q4 vs. Q1: OR = 0.42, 95% CI, 0.33-0.53, p < 0.001; P for trend <0.001). Significant differences were observed in the relationship between dietary OBS and lifestyle OBS and MetS risk (continuous dietary OBS: OR = 0.97, 95% CI, 0.96-0.98, p < 0.001; continuous lifestyle OBS: OR = 0.61, 95% CI, 0.58-0.64, p < 0.001), as well as negative relationship between total OBS and risk of five MetS components (all p < 0.05). Subgroup analysis showed marital status modified the negative association between OBS and MetS in subgroup analysis (P for interaction = 0.014). Moreover, a nonlinear correlation between OBS and MetS (including its components) was found, further elucidating associations (all p < 0.05). Restricted cubic splines demonstrated not obviously U-shape correlation between OBS and MetS components (elevated triglyceride and blood pressure). Conclusion: This study suggests a strong association between the OBS and MetS and its components. Our data indicated that a higher OBS score was correlated with a decreased risk of MetS and its components in a nonlinear manner. Hence, the OBS may serve as an effective marker for identifying individuals with MetS, with a higher score indicating a predominance of more antioxidants.

Improving prediction of N2O emissions during composting using model-agnostic meta-learning.

Nitrous oxide (N2O) represents a significant environmental challenge as a harmful, long-lived greenhouse gas that contributes to the depletion of stratospheric ozone and exacerbates global anthropogenic greenhouse warming. Composting is considered a promising and economically feasible strategy for the treatment of organic waste. However, recent research indicates that composting is a source of N2O, contributing to atmospheric pollution and greenhouse effect. Consequently, there is a need for the development of effective, cost-efficient methodologies to quantify N2O emissions accurately. In this study, we employed the model-agnostic meta-learning (MAML) method to improve the performance of N2O emissions prediction during manure composting. The highest R2 and lowest root mean squared error (RMSE) values achieved were 0.939 and 18.42 mg d-1, respectively. Five machine learning methods including the backpropagation neural network, extreme learning machine, integrated machine learning method based on ELM and random forest, gradient boosting decision tree, and extreme gradient boosting were adopted for comparison to further demonstrate the effectiveness of the MAML prediction model. Feature analysis showed that moisture content of structure material and ammonium concentration during composting process were the two most significant features affecting N2O emissions. This study serves as proof of the application of MAML during N2O emissions prediction, further giving new insights into the effects of manure material properties and composting process data on N2O emissions. This approach helps determining the strategies for mitigating N2O emissions.

Geniposide ameliorates acute kidney injury via enhancing the phagocytic ability of macrophages towards neutrophil extracellular traps.

Acute kidney injury (AKI) is a clinically serious disorder associated with high mortality rates and an increased risk of progression to end-stage renal disease. As an essential supportive treatment for patients with respiratory failure, mechanical ventilation not only save many critically ill patients, but also affect glomerular filtration function by changing renal hemodynamics, neurohumoral and positive end-expiratory pressure, eventually leading to AKI. AMP-activated protein kinase (AMPK), a crucial energy homeostasis regulator, could enhance macrophage phagocytic ability and inhibit inflammation, but whether it can engulf neutrophil extracellular traps (NETs) and alleviate mechanical ventilation-associated AKI is still unclear. In this study, we found that geniposide significantly ameliorated histopathological damage, reduced serum Cre and BUN levels. Besides, geniposide can also induce AMPK activation and enhance macrophage phagocytic ability toward NETs. Moreover, geniposide can markedly reduce the levels of high mobility group box 1 (HMGB1), and these effects were dependent on AMPK-PI3K/Akt signaling. Altogether, these results indicated that geniposide promoted macrophage efferocytosis by inducing AMPK-PI3K/Akt signaling activation, clearing NETs and ameliorating AKI.

Quercetin alleviates Mycoplasma gallisepticum-induced inflammatory damage and oxidative stress through inhibition of TLR2/MyD88/NF-κB pathway in vivo and in vitro.

Chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum (MG) in chickens leads to enormous economic damage to the poultry industry yearly. The active components and mechanism of action of the traditional herbal remedy Ephedra houttuynia powder (EHP), which had been approved for clinical treatment against MG infection in China, remain unknown. In this study, the active components of EHP against MG were screened using a network pharmacological method, additionally, we studied the mechanism of action of the screened results (quercetin (QUE)). The findings demonstrated that QUE was an essential element of EHP against MG infection, effectively attenuating MG-induced oxidative stress and activation of the TLR2/MyD88/NF-κB pathway. Following QUE therapy, IL-1, IL-6, and TNF-α content and expression were downregulated, whereas IL-4 and IL-10 expression were upregulated, eventually suppressing the inflammatory response both in vitro and in vivo. Together, this study presents a strong rationale for using QUE as a therapeutic strategy to inhibit MG infection-induced inflammatory damage and oxidative stress.

Dietary full-fat rice bran prevents the risk of heart ferroptosis and imbalance of energy metabolism induced by prolonged cold stimulation.

The threat to human health from cold stimulation is increasing due to the frequent occurrence of temperature extremes. It is a challenge for people to resist the negative effects of prolonged cold stimulation on the heart. In this study, we created prolonged cold stimulation pig models to investigate the cardiac energy metabolism and injury during prolonged cold stimulation, and the molecular mechanisms by which dietary supplementation with full-fat rice bran reduces cardiac injury. The results showed that lesions in the morphological structure of the heart were detected under prolonged cold stimulation. At the same time, dystrophin was downregulated under the effect of prolonged cold stimulation. Cardiac fatty acid transport and utilization were promoted, and oxidative stress was increased under prolonged cold stimulation. It also increased MDA content and decreased T-AOC level in the heart, while promoting the mRNA expression of Nrf2 and NQO1, as well as the protein content of Nrf2 and HO-1. Prolonged cold stimulation induced mitochondrial lesions, mitochondrial fusion, and mitophagy in the heart. Prolonged cold stimulation promoted the mRNA expression of PTGS2, TLR4, MyD88, NLRP3, and IL-1ß; and protein expression of PTGS2, NLRP3, and mature-IL-1ß. GCH1 and FtH inhibited by prolonged cold stimulation caused the activation of heart ferroptosis. In addition, dietary supplementation with full-fat rice bran improved oxidative stress in the heart and inhibited mitophagy, ferroptosis, and pyroptosis. In conclusion, prolonged cold stimulation heightens the risk of cardiac ferroptosis and imbalance of energy metabolism, whereas dietary supplementation with full-fat rice bran mitigates the adverse effects of prolonged cold stimulation on the heart.

Virus-like Particles for TEM Regulation and Antitumor Therapy.

Tumor development and metastasis are intimately associated with the tumor microenvironment (TME), and it is difficult for vector-restricted drugs to act on the TME for long-term cancer immunotherapy. Virus-like particles (VLPs) are nanocage structures self-assembled from nucleic acid free viral proteins. Most VLPs range from 20-200 nm in diameter and can naturally drain into lymph nodes to induce robust humoral immunity. As natural nucleic acid nanocarriers, their surfaces can also be genetically or chemically modified to achieve functions such as TME targeting. This review focuses on the design ideas of VLP as nanocarriers and the progress of their research in regulating TME.

Nonvolatile chirality switching in terahertz chalcogenide metasurfaces.

Actively controlling the polarization states of terahertz (THz) waves is essential for polarization-sensitive spectroscopy, which has various applications in anisotropy imaging, noncontact Hall measurement, and vibrational circular dichroism. In the THz regime, the lack of a polarization modulator hinders the development of this spectroscopy. We theoretically and experimentally demonstrate that conjugated bilayer chiral metamaterials (CMMs) integrated with Ge2Sb2Te5 (GST225) active components can achieve nonvolatile and continuously tunable optical activity in the THz region. A THz time-domain spectroscopic system was used to characterize the device, showing a tunable ellipticity (from ‒36° to 0°) and rotation of the plane polarization (from 32° to 0°) at approximately 0.73 THz by varying the GST225 state from amorphous (AM) to crystalline (CR). Moreover, a continuously tunable chiroptical response was experimentally observed by partially crystallizing the GST225, which can create intermediate states, having regions of both AM and CR states. Note that the GST225 has an advantage of nonvolatility over the other active elements and does not require any energy to retain its structural state. Our work allows the development of THz metadevices capable of actively manipulating the polarization of THz waves and may find applications for dynamically tunable THz circular polarizers and polarization modulators for THz emissions.

Polypharmacology-based approach for screening TCM against coinfection of Mycoplasma gallisepticum and Escherichia coli.

Natural products and their unique polypharmacology offer significant advantages for finding novel therapeutics particularly for the treatment of complex diseases. Meanwhile, Traditional Chinese Medicine exerts overall clinical benefits through a multi-component and multi-target approach. In this study, we used the previously established co-infection model of Mycoplasma gallisepticum and Escherichia coli as a representative of complex diseases. A new combination consisting of 6 herbs were obtained by using network pharmacology combined with transcriptomic analysis to reverse screen TCMs from the Chinese medicine database, containing Isatdis Radix, Forsythia Fructus, Ginkgo Folium, Mori Cortex, Licorice, and Radix Salviae. The results of therapeutic trials showed that the Chinese herbal compounds screened by the target network played a good therapeutic effect in the case of co-infection. In summary, these data suggested a new method to validate target combinations of natural products that can be used to optimize their multiple structure-activity relationships to obtain drug-like natural product derivatives.

Study on the angiogenesis ability of Polymethyl methacrylate-mineralized collagen/Mg-Ca composite material in vitro and the bone formation effect in vivo.

Magnesium (Mg) and its alloys show high degrees of biocompatibility and biodegradability, used as biodegrad able materials in biomedical applications. In this study, Polymethyl methacrylate (PMMA) - mineralized collagen (nano-Hydroxyapatite/collagen; nHAC)/Mg-Ca composite materials were prepared, to study the angiogenesis ability of its composite materials on Human umbilical vein endothelial cells (HUVECs) and its osteogenesis effect in vivo. The results showed that the PMMA-nHAC reinforcement materials can promote the proliferation and adhesion in HUVECs of Mg matrix significantly, it can enhance the migration motility and VEGF expression of HUVECs. In vivo, Micro-CT examination showed that with coated samples presenting the highest bone formation. Histologically, the materials and their corrosion products caused no systematic or local cytotoxicological effects. Therefore, the Mg matrix composites prepared in the present study has good biocompatibility and PMMA-nHAC/Mg-Ca composite may be an ideal orthopedic material to improve the bone formation, and biodegradable magnesium based implants with bioactivity have potential applications in bone tissue.

Automatic Surgery and Anesthesia Emergence Duration Prediction Using Artificial Neural Networks.

Cost control is becoming increasingly important in hospital management. Hospital operating rooms have high resource consumption because they are a major part of a hospital. Thus, the optimal use of operating rooms can lead to high resource savings. However, because of the uncertainty of the operation procedures, it is difficult to arrange for the use of operating rooms in advance. In general, the durations of both surgery and anesthesia emergence determine the time requirements of operating rooms, and these durations are difficult to predict. In this study, we used an artificial neural network to construct a surgery and anesthesia emergence duration-prediction system. We propose an intelligent data preprocessing algorithm to balance and enhance the training dataset automatically. The experimental results indicate that the prediction accuracies of the proposed serial prediction systems are acceptable in comparison to separate systems.

Methylsulfonylmethane ameliorates inflammation via NF-κB and ERK/JNK-MAPK signaling pathway in chicken trachea and HD11 cells during Mycoplasma gallisepticum infection.

Mycoplasma gallisepticum (MG) is an avian pathogen that commonly causes respiratory diseases in poultry. Methylsulfonylmethane (MSM) is a sulfur-containing natural compound that could alleviate inflammatory injury through its excellent anti-inflammatory and antioxidant properties. However, it is still unclear whether MSM prevents MG infection. The purpose of this study is to determine whether MSM has mitigative effects on MG-induced inflammatory injury in chicken and chicken like macrophages (HD11 cells). In this research, White Leghorn chickens and HD11 cells were used to build the MG-infection model. Besides, the protective effects of MSM against MG infection were evaluated by detecting MG colonization, histopathological changes, oxidative stress and inflammatory injury of trachea, and HD11 cells. The results revealed that MG infection induced inflammatory injury and oxidative stress in trachea and HD11 cells. However, MSM treatment significantly ameliorated oxidative stress, partially alleviated the abnormal morphological changes and reduced MG colonization under MG infection. Moreover, MSM reduced the mRNA expression of proinflammatory cytokines-related genes and decreased the number of death cells under MG infection. Importantly, the protective effects of MSM were associated with suppression of nuclear factor-kappa B (NF-κB) and extracellular signal-related kinases (ERK)/Jun amino terminal kinases (JNK)-mitogen-activated protein kinases (MAPK) pathway in trachea and HD11 cells. These results proved that MSM has protective effects on MG-induced inflammation in chicken, and supplied a better strategy for the protective intervention of this disease.

Mycoplasma gallisepticum induced inflammation-mediated Th1/Th2 immune imbalance via JAK/STAT signaling pathway in chicken trachea: Involvement of respiratory microbiota.

The respiratory microbiota plays a significant role in the host defense against Mycoplasma gallisepticum (MG) infection. The results showed that MG infection changed respiratory microbiota composition, which lead to the tracheal inflammation injury and oxidative stress. MG infection significantly induced immunosuppression in chickens at day 3 and 5 post-infection. In addition, MG infection increased the expressions of pro-inflammatory cytokines in tracheal tissues and activated TLR4 mediated JAK/STAT signaling pathway at day 3 post-infection compared to the control group. Meanwhile, the expressions of pro-inflammatory cytokines were decreased and the expressions of JAK/STAT signaling pathway were decreased at day 5 and day 7 post-infection. On the contrary, the expressions of anti-inflammatory cytokines were significantly decreased at day 3 post-infection and were increased at day 5 and day 7 post-infection in the MG infection group. The antibiotic cocktail group received the respiratory microbiota from the MG infection group, which induced inflammatory injury and oxidative stress, induced mucosal barrier damage by down regulating tight junction-related genes and altered the expressions of mucin, which could be the possible causes of dysregulated immune responses. Importantly, the expressions of pro-inflammatory cytokines were significantly decreased and TLR4 mediated JAK/STAT signaling pathway was downregulated at day 1 and 3 post-transplantation. While, respiratory microbiota transplanted from MG infection significantly increased the expressions of pro-inflammatory cytokines and activated JAK/STAT signaling at day 7 post-transplantation. These results highlighted the role of respiratory microbiota in MG-induced tracheal inflammation injury, and offered a new strategy for the preventive intervention of this disease.

Pharmacokinetic/pharmacodynamic profiles of baicalin against Mycoplasma gallisepticum in an in vivo infection model.

Mycoplasma gallisepticum (M. gallisepticum), a devastating avian pathogen that commonly causes chronic respiratory disease in chicken, is responsible for tremendous economic losses to the poultry industry. Baicalin is the main constituent of Scutellaria baicalensis that shows potential therapeutic effects against M. gallisepticum. However, the pharmacokinetic/pharmacodynamics (PK/PD) profiles of baicalin against M. gallisepticum are not well understood. The main objective of the present study was to determine the relationship between the PK/PD index and efficacy of baicalin in the M. gallisepticum infection model in chickens. The experiments were carried out on 10-day-old chickens that were challenged with M. gallisepticum in the bilateral air sacs. While, baicalin was orally administrated once in a day for 3 consecutive days, started from d 3 postinfection. Ultra-performance liquid chromatography (UPLC) was used to evaluate the PK parameters of baicalin at doses of 200, 400, and 600 mg/kg in M. gallisepticum-infected chickens. Real-time PCR (RT-PCR) was used for the quantitative detection of M. gallisepticum in lungs. The PK and PD data were fitted to WinNonlin software to evaluate the PK/PD profiles of baicalin against M. gallisepticum. The minimum inhibitory concentration (MIC) of baicalin against M. gallisepticum strain Rlow was 31.25 µg/mL. The in vivo data suggested that baicalin concentration in the lung tissues was higher than plasma (1.21-1.73 times higher). The ratios of AUC24h/MIC of baicalin against bacteriostatic, bactericidal, and eradication were 0.62, 1.33, and 1.49 h, respectively. In conclusion, these results provided potential reference for future clinical dose selection of baicalin and evaluation of susceptibility breakpoints.

Activating AhR alleviates cognitive deficits of Alzheimer's disease model mice by upregulating endogenous Aß catabolic enzyme Neprilysin.

Rationale: Neprilysin (NEP) is a major endogenous catabolic enzyme of amyloid ß (Aß). Previous studies have suggested that increasing NEP expression in animal models of Alzheimer's disease had an ameliorative effect. However, the underlying signaling pathway that regulates NEP expression remains unclear. The aryl hydrocarbon receptor (AhR) is a ligand-activated cytoplasmic receptor and transcription factor. Recent studies have shown that AhR plays essential roles in the central nervous system (CNS), but its physiological and pathological roles in regulating NEP are not entirely known. Methods: Western blotting, immunofluorescence, quantitative RT-PCR and enzyme activity assay were used to verify the effects of AhR agonists on NEP in a cell model (N2a) and a mouse model (APP/PS1). Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were conducted to investigate the roles of AhR in regulating NEP transcription. Object recognition test and the Morris water maze task were performed to assess the cognitive capacity of the mice. Results: Activating AhR by the endogenous ligand L-Kynurenine (L-KN) or FICZ, or by the exogenous ligand diosmin or indole-3-carbinol (I3C) significantly increases NEP expression and enzyme activity in N2a cells and APP/PS1 mice. We also found that AhR is a direct transcription factor of NEP. Diosmin treatment effectively ameliorated the cognitive disorder and memory deficit of APP/PS1 transgenic mice. By knocking down AhR or using a small molecular inhibitor targeting AhR or NEP, we found that diosmin enhanced Aß degradation through activated AhR and increased NEP expression. Conclusions: These results indicate a novel pathway for regulating NEP expression in neurons and that AhR may be a potential therapeutic target for the treatment of Alzheimer's disease.

Preventing nickel-titanium rotary instrument from breakage by continuous irrigation with different fluids during root canal preparation.

ABSTRACT: To study the effect of continuous irrigation of rotating nickel-titanium instrument with several common clinical fluids on the diameter, breaking length and breaking position of nickel-titanium instrument, so as to provide some reference and theoretical basis for clinical operation and instrument improvement.A standardized curved root canal model was established, and ProTaper Universal (PTU) F1 instrument was selected for root canal preparation. The nickel-titanium F1 instrument was flushed with distilled water, 0.9% NaCl, 0.2% chlorhexidine, 1% sodium hypochlorite and 5% sodium hypochlorite, and the diameter, length and position of the instrument before and after breakage were recorded.Only 5% sodium hypochlorite influenced the diameter of 6 mm marker points under different irrigation conditions (P < .05). There was no statistical difference in the length of broken instruments among all the groups, and torsional deformation mainly occurred at the end of broken instruments. The broken positions of instruments in all the groups were located at the bending segment of the root canal. The breaking frequency of the 5% sodium hypochlorite group was the highest in the area 3-5.5 mm away from apical foramen, while the other 4 groups had the highest breaking frequency in the area 0 to 1.5 mm away from apical foramen.External irrigation with different fluids did not influence the breaking length of instruments. The closer to the apical foramen was, the higher the breaking frequency of instruments was. However, only 5% sodium hypochlorite can affect the diameter of rotary nickel-titanium instruments, and may lead to early breakage of the instrument, indicating that the use of disinfectants, except 5% sodium hypochlorite, cannot reduce breakage resistance of nickel-titanium instrument compared with distilled water flushing. Furthermore, 5% hypochlorite could not be recommended for irrigation in clinical practice.