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Interleukin-11 (IL-11) has recently been identified as a critical profibrotic cytokine, and IL-11 signaling pathway via IL-11Rα and GP130 receptors has been shown to be a promising therapeutic target for the treatment of fibrotic diseases. Herein, we devised two kinds of IL-11 dimer with receptor-biased binding ability through site-specific crosslinking at the interface involving GP130 binding and signaling, aiming to explore their therapeutic potentials for bleomycin-induced pulmonary fibrosis in mice. A single cysteine mutation at site W147 of human IL-11 (IL-11 W147C) was conducted for site-specific crosslinking. The ability of GP130 to bind to IL-11 W147C dimer was substantially weakened by cysteine-based dimerization, while the ability of IL-11 W147C dimer to bind to IL-11Rα was almost entirely preserved or even enhanced. The IL-11 W147C dimer potently inhibited TF-1 cell proliferation and TGF-β1-induced human lung fibroblast differentiation into myofibroblasts. We also showed that dimerization substantially extended the circulation time of IL-11 W147C dimer in healthy rats. Subcutaneous administration of IL-11 W147C dimer significantly reduced extracellular matrix deposition, preserved alveolar architecture and alleviated pulmonary fibrosis development in mice. The findings of this study may provide a general strategy for the design of cytokine-based receptor-biased antagonists and agonists targeting these multifaceted signaling pathways., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Postoperative recurrence and metastasis of gastric cancer (GC) are primary factors that contribute to poor prognosis. GC recurs at a rate of approximately 70%-80% within 2 years after local treatment and approximately 90% within 5 years. " Yang-deficient toxic node " is the core pathogenesis of GC recurrence and metastasis. The Yiqi Wenyang Jiedu prescription (YWJP), a form of complementary and alternative medicine in China, is an empirical remedy to prevent postoperative recurrence and metastasis of GC. Taking the main therapeutic principles of "nourishing Qi and warming Yang , strengthening Zhengqi , and detoxifying" can aid in preventing the recurrence and metastasis of GC in patients during the watchful waiting period after surgery and adjuvant chemotherapy. This approach aims to enhance the quality of life of patients. However, high-quality evidence to support this hypothesis is lacking. This study will aim to investigate the efficacy and safety of YWJP to prevent and treat postoperative metastasis and GC recurrence., Methods: The study will be a multicenter, randomized, double-blind, placebo-parallel-controlled clinical trial. A total of 212 patients who completed adjuvant chemotherapy within 8 months of radical gastrectomy will be enrolled. Patients in the intervention group will receive the YWJP, whereas those in the control group will receive a placebo. The main outcome was the disease-free survival (DFS) rate 2 years after surgery. The secondary outcomes included DFS time, overall survival, annual cumulative recurrence and rate of metastasis after 1-3 years, cumulative annual survival after 1-3 years, fat distribution-related indicators, tumor markers, peripheral blood inflammatory indicators, prognostic nutritional index, symptoms and quality of life evaluation, medication compliance, and adverse reaction rate., Discussion: There is a lack of effective therapy after the completion of adjuvant therapy during the postoperative period of watchful waiting. This study will be the first randomized clinical trial to evaluate whether complementary and alternative medical interventions can effectively prevent recurrence and metastasis during the watchful waiting period after GC surgery and to provide evidence for surveillance treatment management after GC surgery., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05229809., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao, Zhu, Wang, Kuang, Song, Ma, Zhu, Gao and Li.)

Labile carbon (C) continuously delivered from the rhizosphere profoundly affects terrestrial nitrogen (N) cycling. However, nitrous oxide (N 2 O) and dinitrogen (N 2 ) production in agricultural soils in the presence of continuous root C exudation with applied N remains poorly understood. We conducted an incubation experiment using artificial roots to continuously deliver small-dose labile C combined with 15 N tracers to investigate N 2 O and N 2 emissions in agricultural soils with pH and organic C (SOC) gradients. A significantly negative exponential relationship existed between N 2 O and N 2 emissions under continuous C exudation. Increasing soil pH significantly promoted N 2 emissions while reducing N 2 O emissions. Higher SOC further promoted N 2 emissions in alkaline soils. Native soil-N (versus fertilizer-N) was the main source of N 2 O (average 67%) and N 2 (average 80%) emissions across all tested soils. Our study revealed the overlooked high N 2 emissions, mainly derived from native soil-N and strengthened by increasing soil pH, under relatively real-world conditions with continuous root C exudation. This highlights the important role of N 2 O and N 2 production from native soil-N in terrestrial N cycling when there is a continuous C supply (e.g., plant-root exudate) and helps mitigate emissions and constrain global budgets of the two concerned nitrogenous gases.

Arable soil continues to be the dominant anthropogenic source of nitrous oxide (N 2 O) emissions owing to application of nitrogen (N) fertilizers and manures across the world. Using laboratory and in situ studies to elucidate the key factors controlling soil N 2 O emissions remains challenging due to the potential importance of multiple complex processes. We examined soil surface N 2 O fluxes in an arable soil, combined with in situ high-frequency measurements of soil matrix oxygen (O 2 ) and N 2 O concentrations, in situ 15 N labeling, and N 2 O 15 N site preference (SP). The in situ O 2 concentration and further microcosm visualized spatiotemporal distribution of O 2 both suggested that O 2 dynamics were the proximal determining factor to matrix N 2 O concentration and fluxes due to quick O 2 depletion after N fertilization. Further SP analysis and in situ 15 N labeling experiment revealed that the main source for N 2 O emissions was bacterial denitrification during the hot-wet summer with lower soil O 2 concentration, while nitrification or fungal denitrification contributed about 50.0% to total emissions during the cold-dry winter with higher soil O 2 concentration. The robust positive correlation between O 2 concentration and SP values underpinned that the O 2 dynamics were the key factor to differentiate the composite processes of N 2 O production in in situ structured soil. Our findings deciphered the complexity of N 2 O production processes in real field conditions, and suggest that O 2 dynamics rather than stimulation of functional gene abundances play a key role in controlling soil N 2 O production processes in undisturbed structure soils. Our results help to develop targeted N 2 O mitigation measures and to improve process models for constraining global N 2 O budget., (© 2023 John Wiley & Sons Ltd.)

Objective: To compare the ability of the step-by-step approach and the lab-score method in early identification of non-bacterial infection in febrile infants with less than 90 days old., Methods: A prospective study was conducted. The febrile infants with less than 90 days old hospitalized in the department of pediatrics of Xuzhou Central Hospital from August 2019 to November 2021 were enrolled. The basic data of the infants were recorded. The infants with high risk or low risk of bacterial infection was evaluated by the step-by-step approach and the lab-score method, respectively. The step-by-step approach was based on clinical manifestations, age, blood neutrophil absolute value or C-reactive protein (CRP), urine white blood cells, blood venous blood procalcitonin (PCT) or interleukin-6 (IL-6) to gradually assess the high risk or low risk of bacterial infection in infants with fever. The lab-score method was based on the levels of laboratory indicators such as blood PCT, CRP and urine white blood cells, which were assigned different scores to evaluate the high risk or low risk of bacterial infection in febrile infants according to the total score. Using clinical bacterial culture results as the "gold standard", the negative predictive value (NPV), positive predictive value (PPV), negative likelihood ratio, positive likelihood ratio, sensitivity, specificity, and accuracy of the two methods were calculated. The consistency of the two evaluation methods was tested by Kappa., Results: A total of 246 patients were enrolled in the analysis, and ultimately confirmed by bacterial culture as non-bacterial infections in 173 cases (70.3%), bacterial infection in 72 cases (29.3%), and unclear in 1 case (0.4%). There were 105 cases with low risk evaluated by the step-by-step approach, and 98 cases (93.3%) were ultimately confirmed as non-bacterial infection; 181 cases with low risk evaluated by the lab-score method, and 140 cases (77.4%) were ultimately confirmed as non-bacterial infection. The consistency of the two evaluation methods was poor (Kappa value = 0.253, P < 0.001). The ability of the step-by-step approach in early identification of non-bacterial infection in febrile infants with less than 90 days old was superior to the lab-score method (NPV: 0.933 vs. 0.773, negative likelihood ratio: 5.835 vs. 1.421), but the sensitivity of the former was lower than that of the latter (0.566 vs. 0.809). The ability of the step-by-step approach in early identification of bacterial infection in febrile infants with less than 90 days old was similar to the lab-score method (PPV: 0.464 vs. 0.484, positive likelihood ratio: 0.481 vs. 0.443), but the specificity of the former was higher than that of the latter (0.903 vs. 0.431). The overall accuracy of the step-by-step approach and the lab-score method was similar (66.5% vs. 69.8%)., Conclusions: The ability of the step-by-step approach in early identification of non-bacterial infections in febrile infants with less than 90 days old is superior to the lab-score method.

Biogenic nitrous oxide (N 2 O) from nitrification and denitrification in agricultural soils is a major source of N 2 O in the atmosphere, and its flux changes significantly with soil moisture condition. However, the quantitative relationship between N 2 O production from different pathways (i.e., nitrification vs. denitrification) and soil moisture content remains elusive, limiting our ability of predicting future agricultural N 2 O emissions under changing environment. This study quantified N 2 O production rates from nitrification and denitrification under various soil moisture conditions using laboratory incubation combined with literature synthesis. 15 N labeling approach was used to differentiate the N 2 O production from nitrification and denitrification under eight different soil moisture contents ranging from 40 to 120% water-filled pore space (WFPS) in the laboratory study, while 80 groups of data from 17 studies across global agricultural soils were collected in the literature synthesis. Results showed that as soil moisture increased, N 2 O production rates of nitrification and denitrification first increased and then decreased, with the peak rates occurring between 80 and 95% WFPS. By contrast, the dominant N 2 O production pathway switched from nitrification to denitrification between 60 and 70% WFPS. Furthermore, the synthetic data elucidated that moisture content was the major driver controlling the relative contributions of nitrification and denitrification to N 2 O production, while NH 4 + and NO 3 - concentrations mainly determined the N 2 O production rates from each pathway. The moisture treatments with broad contents and narrow gradient were required to capture the comprehensive response of soil N 2 O production rate to moisture change, and the response is essential for accurately predicting N 2 O emission from agricultural soils under climate change scenarios., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Yan, Ju, Song, Zhang, Li and Zhu-Barker.)

Background: Natural human ferritin generally contains 24 subunits with different ratios of heavy chain to light chain, and the ratio of both subunits varies depending on tissue distribution and pathological conditions. However, the production of recombinant hybrid ferritin with both subunits is more challenging., Objective: This study aimed to prepare the recombinant hybrid ferritin for prokaryotic expression and characterize its structure and physicochemical properties., Methods: A prokaryotic expression vector of pACYCDuet-1 harboring the two individual genes of human ferritin heavy chain and light chain (FTH/FTL-pACYCDuet-1) was constructed and transfected into Escherichia coli bacteria. Then the genes were co-induced by IPTG to express., Results: The ferritin was purified by hydrophobic interaction chromatography combining size exclusion chromatography and verified by mass spectrometry and characterized by spectral and morphological analysis., Conclusion: FTH and FTL subunits were successfully co-assembled into a hybrid ferritin nanoparticle (rhFTH/L). The structure of rhFTH/L was demonstrated highly ordered and fairly compact. Besides, the hybrid rhFTH/L nanoparticle was shown more sensitive to thermal stress and reduced stability when compared with that of both individual rhFTH and rhFTL., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Toll-like receptors (TLRs) recognize altered gut microbiota triggering an immune response. These responses play a critical role in the pathogenesis and treatment of inflammatory bowel disease (IBD). IBD is characterized by inflammation of the intestinal tracts as in Crohn's disease and ulcerative colitis. However, one challenge in determining the role of a specific TLR in IBD and its underlying mechanism is disparity. Variance in age, gender, race, and ethnicity shows a dramatic difference in the disease incidence, severity, and response to treatment. Delineating the role of TLRs in IBD relies on both a knockout mouse and a disease model. Here, we describe a detailed protocol on how to use nearly identical genetic backgrounds of TLR wild-type and knockout littermate mice in a dextran sodium sulfate (DSS)-induced colitis model., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Anodic titanium dioxide nanotubes (TNT) have a range of beneficial theranostic properties. However, a lack of effective osseointegration is a problem frequently associated with the titanium dental implant surface. Here, we investigated whether bone-shaped nanotube titanium implants could enhance osseointegration via promoting initial release of vascular endothelial growth factor 165 (VEGF165) and dual release of recombinant human bone morphogenetic protein-2 (rhBMP-2). Thus, we generated cylindrical-shaped nanotubes (TNT1) and bone-shaped nanotubes (TNT2) through voltage-varying and time-varying electrochemical anodization methods, respectively. Additionally, we prepared rhBMP-2-loaded cylindrical-shaped nanotubes/VEGF165-loaded hydrogel (TNT-F1) and rhBMP-2-loaded bone-shaped nanotubes/VEGF165-loaded hydrogel (TNT-F2) drug delivery systems. We evaluated the characteristics and release kinetics of the drug delivery systems, and then analyzed the cytocompatibility and osteogenic differentiation of these specimens with mesenchymal stem cells (MSCs) in vitro. Finally, we utilized a rat femur defect model to test the bone formation capacity of nanotube-hydrogel drug delivery system in vivo. Among these different nanotubes structures, the bone-shaped one was the optimum structure for growth factor release., (Copyright © 2022. Published by Elsevier B.V.)

Furfural wastewater (FWW) treatment is important in modern chemical production. However, traditional wastewater treatment methods are inappropriate for the treatment of FWW. In this work, Chlorella pyrenoidosa was employed to study the growth and pollutants removal with both heterotrophic and mixotrophic cultures. The results show that the biomass and removal efficiency for COD and TN were the highest under 10-fold dilution. However, TP removal were inconsistent when the algae were cultivated in both mixotrophic and heterotrophic modes. Compared to high nitrogen (0.75 g/L NaNO 3 ), the algal cells grew faster when adding 0.25 g/L NaNO 3 to the FWW, whether in mixotrophic or heterotrophic conditions. The total lipid content in heterotrophic conditions was 18.53%, which was higher than the values in mixotrophy when the concentration of NaNO 3 was 0.75 g/L. Different carbon assimilation mechanisms of the algal cells result in a discrepancy in cell growth and pollutant removal, under different culture modes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Hot moments of nitrous oxide (N 2 O) emissions induced by interactions between weather and management make a major contribution to annual N 2 O budgets in agricultural soils. The causes of N 2 O production during hot moments are not well understood under field conditions, but emerging evidence suggests that short-term fluctuations in soil oxygen (O 2 ) concentration can be critically important. We conducted high time-resolution field observations of O 2 and N 2 O concentrations during hot moments in a dryland agricultural soil in Northern China. Three typical management and weather events, including irrigation (Irr.), fertilization coupled with irrigation (Fer.+Irr.) or with extreme precipitation (Fer.+Pre.), were observed. Soil O 2 and N 2 O concentrations were measured hourly for 24 h immediately following events and measured daily for at least one week before and after the events. Soil moisture, temperature, and mineral N were simultaneously measured. Soil O 2 concentrations decreased rapidly within 4 h following irrigation in both the Irr. and Fer.+Irr. events. In the Fer.+Pre. event, soil O 2 depletion did not occur immediately following fertilization but began following subsequent continuous rainfall. The soil O 2 concentration dropped to as low as 0.2% (with the highest soil N 2 O concentration of up to 180 ppmv) following the Fer.+Pre. event, but only fell to 11.7% and 13.6% after the Fer.+Irr. and Irr. events, which were associated with soil N 2 O concentrations of 27 ppmv and 3 ppmv, respectively. During the hot moments of all three events, soil N 2 O concentrations were negatively correlated with soil O 2 concentrations (r = -0.5, P < 0.01), showing a quadratic increase as soil O 2 concentrations declined. Our results provide new understanding of the rapid short response of N 2 O production to O 2 dynamics driven by changes in soil environmental factors during hot moments. Such understanding helps improve soil management to avoid transitory O 2 depletion and reduce the risk of N 2 O production., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Enhanced efficiency nitrogen fertilizers (EENFs), including nitrification inhibitors (NIs) and slow-release fertilizer (SRF), are considered promising approaches for mitigating nitrous oxide (N 2 O) emissions while improving crop yield. This study investigated the combined application of EENFs with improved water and fertilizer management in an intensively irrigated spring maize rotation over five years in Northwestern China. High-frequency measurements of N 2 O fluxes were made throughout each year (both during crop growth and the fallow season) in five treatments: no N fertilizer as a control (CK), conventional N fertilization and irrigation (Con), optimum N fertilization and irrigation (Opt, 33% reduction in N fertilizer and 25% reduction of irrigation water), optimum N fertilization and irrigation with nitrification inhibitor (Opt + NI), and optimum N fertilization and irrigation with slow-release fertilizer (Opt-SRF). Annual mean cumulative N 2 O emissions reached 0.31 ± 0.07, 3.66 ± 0.19, 1.87 ± 0.16, 1.23 ± 0.13, and 1.61 ± 0.16 kg N 2 O-N ha -1 for CK, Con, Opt, Opt + NI, and Opt-SRF, respectively, with annual mean nitrogen use efficiency (NUE) of 36, 54, 61 and 59% for Con, Opt, Opt + NI, and Opt-SRF, respectively. The Opt, Opt + NI and Opt-SRF treatments significantly reduced cumulative N 2 O emissions by 49%, 66%, and 56% (P < 0.05), respectively, and increased NUE by 51%, 70%, and 66% (P < 0.05), respectively, relative to Con. However, mean above-ground N uptake (288-309 kg N ha -1 ) and mean grain yields (12.7-12.8 Mg ha -1 ) did not differ significantly between the Con, Opt, Opt + NI, and Opt-SRF treatments during the five-year study. High N 2 O emissions mainly occurred within a few days of fertilization with irrigation, which could have been produced by microbially-mediated nitrifier or nitrifier denitrification processes. The fallow seasons had significantly lower cumulative N 2 O emissions, which were mainly attributed to the low temperature, low N inputs of crop residues, and low soil moisture conditions. Our study clearly indicated that the combined application of EENFs with optimum N fertilization and irrigation management can reduce environmental impacts while maintaining high crop yields in dryland regions such as Northwest China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Celiac disease affects approximately 1% of the population and is a major public health problem worldwide. It is trigged by gluten-derived peptides, which have unusually high proline-glutamine motif content and are highly resistant to proteolysis by digestive enzymes of the gastrointestinal tract. The only treatment for celiac disease is strict, lifelong adherence to a gluten-free diet, which is effective but costly and difficult to maintain. Therefore, novel non-dietary therapies for celiac disease are urgently needed. Gluten-degrading enzymes are promising non-dietary treatments, and some enzymes have been investigated in preclinical or clinical studies. A combination of prolyl endopeptidase from Sphingomonas capsulata (SC PEP) and a glutamine-specific endoprotease (EP-B2 from barley) known as latiglutenase showed insufficient benefits in phase II clinical trials, likely because of its low enzyme activity in the gastric environment. Therefore, improving enzyme activity is essential for the clinical application of SC PEP. Enzyme activity can be enhanced using computer-aided rational protein design tools. In this study, we combined molecular docking and molecular dynamics simulation to rationally design SC PEP mutants and experimentally evaluated their activities. We identified mutants with up to 90-103% increases in specific activity and up to 80-202% increases in the catalytic rate. We have investigated the mechanism underlying the enhanced activity of these mutants, and found that a conformational transition of the β-propeller domain and catalytic domain of SC PEP was important for enzyme activity, and this transition was affected by residues in the catalytic domain and at the domain interface; a shorter distance between the substrate Pro and the oxyanion holes was also crucial for improving SC PEP catalytic activity. Our results provide useful information for the rational design of highly active SC PEPs to accelerate the development of enzyme therapeutics candidates for Celiac disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Baoyuan Jiedu (BYJD for short) decoction, a traditional Chinese medicine formula, is composed of Astragalus, Ginseng, Aconite root, Honeysuckle, Angelica, Licorice, which has the functions of nourishing qi and blood, enhancing immune function, improving quality of life and prolonging survival time of tumor patients. The present study aimed to investigate the effect and mechanism of BYJD decoction on reversing the pre-metastatic niche. We showed that BYJD decoction could prolong the survival time of 4T1 tumor-bearing mice. Moreover, we found that the BYJD decoction inhibited the formation of lung pre-metastatic niche and inhibited recruitment of myeloid derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and genes expression of TGF-β, Smad2, Smad3, p-Smad2/3, Smad4, CCL9 in the TGF-β/CCL9 signaling pathway were suppressed by BYJD decoction. In line with the above findings, our results confirm that BYJD decoction inhibits the accumulation of MDSC in pre-metastatic niche of lung via TGF-β/CCL9 pathway., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

T cells undergo metabolic rewiring to meet their bioenergetic, biosynthetic and redox demands following antigen stimulation. To fulfil these needs, effector T cells must adapt to fluctuations in environmental nutrient levels at sites of infection and inflammation. Here, we show that effector T cells can utilize inosine, as an alternative substrate, to support cell growth and function in the absence of glucose in vitro. T cells metabolize inosine into hypoxanthine and phosphorylated ribose by purine nucleoside phosphorylase. We demonstrate that the ribose subunit of inosine can enter into central metabolic pathways to provide ATP and biosynthetic precursors, and that cancer cells display diverse capacities to utilize inosine as a carbon source. Moreover, the supplementation with inosine enhances the anti-tumour efficacy of immune checkpoint blockade and adoptive T-cell transfer in solid tumours that are defective in metabolizing inosine, reflecting the capability of inosine to relieve tumour-imposed metabolic restrictions on T cells.

The properties of agricultural soils in various regions of the world are variable and can have a significant but poorly understood impact on soil nitrogen (N) transformations and nitrous oxide (N 2 O) emissions. For this reason, we undertook a study of gross N transformations and related N 2 O emissions in contrasting agricultural soils from China and the UK. Seven Chinese and three UK agricultural soils were collected for study using a 15 N tracing approach. The soil pH ranged from 5.4 to 8.7, with three acidic soils collected from Jinjing, Lishu and Boghall; one neutral soil collected from Changshu, and the other six alkaline soils collected from Quzhou, Zhangye, Changwu, Jinzhong, Boxworth and Stetchworth. Our results showed that the main N transformation processes were oxidation of ammonium (NH 4 + ) to nitrate (NO 3 - ) (O NH4 ), and mineralization of organic N to NH 4 + . The gross autotrophic nitrification rates calculated in the three acidic soils were between 0.25 and 4.15 mg N kg -1  d -1 , which were significantly lower (p < 0.05) than those in the remaining neutral and alkaline soils ranging from 6.94 to 14.43 mg N kg -1  d -1 . Generally, soil pH was positively correlated (p < 0.001) with gross autotrophic nitrification rate and cumulative N 2 O emissions, indicating that soil pH was an important factor regulating autotrophic nitrification and N 2 O emissions. There was also a significant positive correlation between the gross autotrophic nitrification rate and cumulative N 2 O emissions, highlighting the importance of this process for producing N 2 O emissions in these agricultural soils under aerobic conditions. Gross NH 4 + immobilization rates were very low in most soils except for the Jinjing soil with the lowest pH. In conclusion, the gross autotrophic nitrification rates and related N 2 O emissions were controlled by soil pH irrespectively of the soil's origin in these agricultural soils., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The aim of this study is to investigate the pharmacokinetics of 5'-valyl-cytarabine hydrochloride (OPC) when co-administered with cephalexin, which are both the substrates of PepT1. The drugs were administered orally by gavage. Blood samples were collected from the orbital plexus of the rats after oral administration of drug solutions. A new high-performance liquid chromatographic method was validated and used for determination of the two drugs. Pharmacokinetic parameters were calculated using DAS 2.1.1 software with noncompartmental analysis. After oral administration of OPC and co-administration of OPC and cephalexin, there were significant differences in the main pharmacokinetic parameters. The main pharmacokinetic parameters for the OPC group and the co-administrative group were as follows: AUC 0-10 (18,168.7 ± 2561.4) ng⋅h/ml and (13,448.5 ± 2544.73) ng⋅h/ml, AUC 0-∞ (18,683.1 ± 3066.5) ng⋅h/ml and (13,721.1 ± 2683.0) ng⋅h/ml, C max (6654.8 ± 481.3) ng/ml and (4765.1 ± 928.9) ng/ml, respectively. The results showed that the bioavailability of OPC could be reduced when co-administered with cephalexin, suggesting that the efficacy of a novel drug might be reduced when it came to combination use of β-lactam antibiotics., (© 2017 Shenyang Pharmaceutical University. Production and hosting by Elsevier B.V.)

α-Glucosidase inhibitors are known to prevent the digestion of carbohydrates and reduce the impact of carbohydrates on blood glucose. Three series of tetracyclic oxindole derivatives were designed, synthesized and evaluated for α-glucosidase inhibitory activity in vitro. Compound 6t exhibited the most potent inhibitory activity with IC50 0.7 μM and was about 170 times as active as acarbose (IC50 = 115.8 μM). The kinetic analysis of compound 6t revealed it inhibited α-glucosidase in an irreversible and mixed manner. Fluorescence spectra indicated that 6t directly bound to α-glucosidase. Docking simulation showed the existence of potential H-bonding, van der Waals, Pi and Sigma-Pi interactions between 6t and α-glucosidase., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

This paper aims to explore the antibacterial property of nano Ag/TiO2 coating bracket for the common bacteria in oral cavity, and discuss its biocompatibility. Micro morphology in the surface of nano Ag/TiO2 coating bracket was detected by scanning electron microscope (SEM), and surface roughness of ordinary mental bracket, nano TiO2 coating bracket and nano Ag/TiO2 coating bracket were measured. First, antibacterial property of nano Ag/TiO2 coating bracket on the common bacteria in oral cavity was studied by sticking membrane method. Secondly, bonding strength of nano TiO2 coating and nano Ag/TiO2 coating bracket in groups were detected by scratching test. The result showed that, the synthetic nano Ag/TiO2 coating was nanogranular films with rigorous organizational structure, presenting as smooth and clean surface, and antibacterial rate of nano Ag/TiO2 coating for the common bacteria in oral cavity for 20 min was more than 79% in the dark. All the findings suggested that, nano Ag/TiO2 coating bracket not only has antibacterial effect but also has good biocompatibility, therefore, it can satisfy the clinical request of orthodontic treatment.