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The aim of the present study was to synthesize and characterize florfenicol sustained-release granules (FSRGs) in vitro and in vivo. FSRGs were synthesized using monostearate, polyethylene glycol 4000 and amylum starch. In vitro dissolution profiles were studied using the rotating basket method in pH1.2 HCl solution and pH 4.3 acetate buffer. Twenty-four male healthy Landrace×Yorkshire pigs were equally divided into three groups and administered a 20 mg/kg i.v bolus of florfenicol solution and dosed orally with FSRGs in fasted and fed condition. The Higuchi model was the best fit for the drug release profile in pH1.2 and pH 4.3 media and the mechanism of drug dissolution was governed by both diffusion and dissolution. We established a level A in vitro - in vivo correlation for FSRGs and the in vivo profile of the FSRGs can be estimated by the in vitro drug release

SummaryReducing antibiotic treatment duration is a key stewardship intervention to mitigate antimicrobial resistance (AMR). We performed a systematic review of antibiotic duration randomised controlled trials for treatment or prevention of bacterial infections in humans, appraised their methodologies and identified gaps in evidence. All randomised trials indexed in MEDLINE and EMBASE up to October 2022 which compared different treatment durations were included. We found 296 trials, of which 85% showed equivalence or non-inferiority. The majority (73%) considered treatment for respiratory tract infections, genitourinary infections, and post-surgical prophylaxis. Few trials studied severe infections, such as bloodstream infections and ventilator-associated pneumonia. Trial designs shifted from superiority (74%, 178/242 before 2016) to non-inferiority (74%, 40/54 after 2016). 94% of the trials that defined a per- protocol population reported non-adherence, which may increase the probability of concluding non-inferiority. Only 9 trials collected data to demonstrate the effect of antibiotic duration on AMR colonisation.RegistrationPROSPERO 2021 CRD42021276209FundingNational Research Foundation Singapore Central Gap Fund; National Medical Research Council, Singapore; Medical Research Council, UK

Aeromonas veronii (A. veronii) is an important zoonotic pathogen that causes substantial economic losses in aquaculture. In this study, we aimed to develop a safe and effective immune enhancer to protect Carassius auratus (C. auratus) from A. veronii infections. With recognized safety, lactic acid bacteria are used as antigen delivery vehicles to present antigens. Lipopolysaccharide (LPS), a protective antigen, induces immune responses in animals. Therefore, we created recombinant Lactobacillus plantarum (L. plantarum) with surface-displayed LPS of A. veronii TH0426 and tested its effects on immune responses in C. auratus. The results showed that recombinant L. plantarum Lp-pPG-611.1-LPS, as an immune enhancer, could improve the innate and adaptive immune responses of C. auratus when it was added to the diet of C. auratus. The challenge test showed that the survival rate of C. auratus fed with L. plantarum Lp-pPG-611.1-LPS was higher than that of the control groups, indicating that the recombinant L. plantarum Lp-pPG-611.1-LPS increased the resistance of C. auratus to A. veronii infection. The present results provide a theoretical basis for the development of recombinant L. plantarum Lp-pPG-611.1-LPS as an immune enhancer in aquaculture.

Since the Global Financial Crisis hit in 2008, economic inequality has been a topic that has attracted considerable interest. To date, however, there has been very little work that can speak to the impact of inequality on the social and political life in a society. This research aims to investigate whether perceptions of greater inequality affect people's desire for wealth, perceived fairness, which in turn, lead to corrupt behavior.

Fatty acid profile was one of the important characteristic parameters of edible oil. With the intensification of interest in microalgae as a potential source of edible oil, rapid methods are needed to determine the fatty acid composition of microalgae. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) was applied to determine the lipid and fatty acid contents of Nannochloropsis oceanica, a species rich in eicosapentaenoic acid. Samples with different intracellular components were obtained by setting different culture conditions (light intensity and nitrogen concentration). In the spectra of FTIR, some characteristic bands for lipids (3025–2800 cm−1, 1770–1710 cm−1, 1480–1350 cm−1) were identified. Partial least square regression (PLSR) models were developed to predict total biomass, lipid contents, and main fatty acid contents (palmitic acid C16:0, palmitoleic acid C16:1, eicosatetraenoic acid C20:4, eicosapentaenoic acid C20:5). Generally, the prediction ability of the model established with full spectra was slightly better than that of the model established with specific bands. In the optimized model, excellent coefficients of determination (R2 ≥ 0.90), both for calibration and prediction, were found for all variables, except for fatty acid C20:4, which was slightly worse (R2 = 0.8797). The pretreatment methods of samples were further studied. It was found that the acid-heating method (0.1 M HCl, 100 °C, 0.5 h) effectively reduced the interference of the carbohydrate in samples, thus improving the measurement of the characteristic fatty acids C20:4 and C20:5 of N. oceanica. This study showed the feasibility of FTIR as a rapid screening method for evaluating biomass and lipid content, especially some special fatty acid profile of microalgae.

Background Diet analysis is essential to understanding the functional role of large bird species in food webs. Morphological analysis of regurgitated bird pellet contents is time intensive and may underestimate biodiversity. DNA metabarcoding has the ability to circumvent these issues, but has yet to be done. Methods We present a pilot study using DNA metabarcoding of MT-RNR1 and MT-CO1 markers to determine the species of origin and prey of 45 pellets collected in Qinghai and Gansu Provinces, China. Results We detected four raptor species [Eurasian Eagle Owl (Bubo bubo), Saker Falcon (Falco cherrug), Steppe Eagle (Aquila nipalensis), and Upland Buzzard (Buteo hemilasius)] and 11 unique prey species across 10 families and 4 classes. Mammals were the greatest detected prey class with Plateau Pika (Ochotona curzoniae) being the most frequent. Observed Shannon’s and Simpson’s diversity for Upland Buzzard were 1.089 and 0.479, respectively, while expected values were 1.312 ± 0.266 and 0.485 ± 0.086. For Eurasian Eagle Owl, observed values were 1.202 and 0.565, while expected values were 1.502 ± 0.340 and 0.580 ± 0.114. Interspecific dietary niche partitioning between the two species was not detected. Conclusions Our results demonstrate successful use of DNA metabarcoding for understanding diet via a novel noninvasive sample type to identify common and uncommon species. More work is needed to understand how raptor diets vary locally, and the mechanisms that enable exploitation of similar dietary resources. This approach has wide ranging applicability to other birds of prey, and demonstrates the power of using DNA metabarcoding to study species noninvasively.

A breeding approach combining genome shuffling with streptomycin resistance was developed in this research to improve the poly-γ-L-diaminobutanoic acid (γ-PAB) production in Bacillus pumilus LS-1. By this unique strategy, recombinants from the third round of genome shuffling could tolerate 18 µg/L of streptomycin and exhibited higher γ-PAB yield as 152.2 mg/L in shake-flask fermentation, 3-fold over the parent. In batch fermentation, B. pumilus GS3-9 could produce γ-PAB as high as 1284.7 mg/L in two days, 2.4-fold higher than the control, which was the highest productivity ever reported. In addition, the optimal pH in B. pumilus for γ-PAB synthesis was changed after atmospheric and room temperature plasma (ARTP) mutagenesis and protoplast fusion, because lower pH environment is favorable for accumulation of intracellular ATP. Some key enzymes in GS3-9 showed higher activities than those in parent, suggesting a greater flux to TCA circle and DAP pathway, which was a reason for enhanced γ-PAB production.

The development of a Multiple Airport Region (MAR) could lead to fierce competition. To evaluate the level of homogenization between airports in a MAR, a homogenization evaluation method based on multi-dimensional indicators was developed. A multi-dimensional indicator system is proposed that takes into account infrastructure, integrated support, operational efficiency and airline networks. Then the Critic method and the Delphi method are used to assign hierarchical weights for each dimension of the indicators. The multi-layer homogenization matrix of the airport pairs within the MAR is derived. For airport pairs with high comprehensive homogenization, suggestions are provided according to analysis of the indicators. This study paper selected three typical MARs internationally to demonstrate the advantage of the proposed approach. The airport pairs with high a homogenous coefficient (greater than 0.5) were selected to analyze the reasons causing high homogeneity. Results show that the multi-dimensional indicators and hierarchical fusion captured the characteristics of the homogenization of MAR. Most airport pairs in New York MAR and in London MAR had strong differentiation of route network layout, airport pairs in Greater Bay MAR had ambiguous division of labor and low homogenization of route network, except CAN and SZX airports. Suggestions are discussed separately to mitigate the homogeneity of the airports in the MAS, thus, to improve the operation performance of the MARs.

Prim-O-glucosylcimifugin, cimifugin and 5-O-methylvisamminoside are three major chromone derivatives of Saposhnikovia divaricata that have many pharmacological activities, such as anti-inflammatory and antitumor activities. In the present work, an effective method for the simultaneous separation of prim-O-glucosylcimifugin, cimifugin and 5-O-methylvisamminoside with high purities was established using HPD-300 resin coupled with preparative high-performance liquid chromatography. The adsorption kinetics curves of the three compounds on the HPD-300 resin were studied and found to fit well according to the pseudo-second-order equation. The adsorption isotherm results indicated that the adsorption process of the three compounds was exothermic. After a one-run treatment with the resin, the contents of prim-O-glucosylcimifugin, cimifugin and 5-O-methylvisamminoside increased from 0.29%, 0.06% and 0.37% to 13.07%, 2.83% and 16.91% with recovery yields of 76.38%, 78.25% and 76.73%, respectively. Finally, the purities of the three compounds were found to reach more than 95% after further separation using preparative high-performance liquid chromatography. The method developed in this study was effective and could simultaneously separate three chromones from Saposhnikovia divaricate. The experimental results also showed that the HPD-300 resin is suitable for the separation of chromone derivatives. This article is protected by copyright. All rights reserved.

Ceiling gas temperature rise is an important evaluation indicator determining the level of risk in a subway tunnel fire. However, very little literature has been found that has addressed the emergency when a fired subway train with lateral multiple openings stops in the interval tunnel. Hence, a battery of full-scale numerical simulations were employed to address the impact of train fire location on the gas temperature beneath the train ceiling. Numerical results showed that the ceiling gas temperature rise is affected by the pressure difference on both sides of fire source and the backflow from the end wall, which depends on the heat release rate and the fire location. The ceiling gas temperature rise decays exponentially in the process of longitudinal spread, and it can be predicted by a dimensionless model with a sum of two exponential equations. Finally, based on a critical fire location (L cr ⋆ = 0.667), two exponential equations were developed to quantitatively express the influences of the fire size and the fire location on the maximum ceiling gas temperature. The research results can be utilized for providing an initial understanding of the smoke propagation in a subway train fire.

Papillary thyroid carcinoma (PTC) is one of the fastest growing endocrine system malignant carcinomas detected over the past decade. Unfortunately, more than 25% of PTC patients are characterized by their aggressiveness and subsequent metastasis; these characteristics usually indicate poor prognosis. Recently, increasing evidence has suggested that solute carrier (SLC) transporters may play a pivotal role in the initiation, invasion and metastasis of human carcinoma. However, the expression and clinicopathological significance of SLC transporters in patients with PTC remains undetermined. In this study, we aimed to elucidate how the differential expression of SLC transporters affects clinicopathological features, as well as determine the possible regulatory signaling pathways involved. Three differentially expressed SLC transporters were screened from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database using a bioinformatics approach. The results indicated that high SLC34A2 and low SLC4A4 protein expression exhibited a higher percentage of capsular invasion and extra-thyroid metastasis in patients. Logistic regression analysis showed that high SLC34A2 expression in tumors was identified as an independent risk factor for capsular invasion [odds ratio (OR)=11.400, 95% confidence interval (CI)=1.733-74.995, P=0.011] and extra-thyroid metastasis (OR=4.920, 95%CI=1.234-19.623, P=0.024), while low SLC4A4 expression in tumors was only identified as independent risk factors for extra-thyroid metastasis (OR=8.568, 95%CI =1.186-61.906, P=0.033). Specifically, for tumors with capsular invasion and extra-thyroid metastasis, the protein expression staining of SLC34A2 was markedly enhanced in the cytoplasm of follicular epithelial cells, contrastingly, SLC4A4 expression was notably weakened in the cytomembrane and nucleus. Intriguingly, both high SLC34A2 and low SLC4A4 protein expression were significantly linked to a high urinary iodine concentration in patients with PTC. Mechanistically, compared with adjacent normal thyroids, p-ERK was significantly up-regulated by 17.8% in the invading tumor; p-ERK, p-JNK, and p-P38 were markedly up-regulated by 29.2%, 67.1%, and 38.9% for metastatic tumors, respectively. Importantly, SLC4A4 negatively correlated with p-JNK (r=-0.696, P= 0.004) and p-P38 (r=-0.534, P=0.049). In conclusion, we suggest that up-regulated SLC34A2 (mainly in the cytoplasm) and down-regulated SLC4A4 (mainly in the cytomembrane and nucleus), which might be attributed to excess iodine intake, were closely linked to extra-thyroid metastasis in PTCs. Furthermore, this effect of SLC4A4 may be through the activation of JNK/P38 MAPK signaling pathway. Future in vivo and in vitro gain- or loss-of-function experiments are needed to verify these findings and further elucidate the deeper molecular mechanisms.

This annual review is the sixth of its kind since 2016 (see references). Our objective is to explore and share articles which we deem influential and significant in the field of biotransformation and bioactivation. These fields are constantly evolving with new molecular structures and discoveries of corresponding pathways for metabolism that impact relevant drug development with respect to efficacy and safety. Based on the selected articles, we created three sections: (1) drug design, (2) metabolites and drug metabolizing enzymes, and (3) bioactivation and safety (Table 1). Unlike in years past, more biotransformation experts have joined and contributed to this effort while striving to maintain a balance of authors from academic and industry settings.[Table: see text]. ispartof: DRUG METABOLISM REVIEWS vol:53 issue:3 pages:384-433 ispartof: location:England status: published