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Background The aim of this study was to evaluate the association between CYP2A13 polymorphisms and lung cancer susceptibility using the HapMap database. Methods A case‐control analysis of 532 subjects with lung cancer and 614 controls with no personal history of the disease was performed. The tag SNPs rs1645690 and rs8192789 for CYP2A13 were selected, and the genetic polymorphisms were confirmed experimentally through real‐time PCR, cloning, and sequencing assay. Results SNP frequency in this study was consistent with the HapMap Project database of Han‐Chinese and lung cancer risk was associated with CYP2A13 polymorphisms in non‐smokers. CYP2A13 shares a 93.5% identity with CYP2A6 in the amino acid sequence and the homologous sequences may interfere with the study of SNPs of CYP2A13. Conclusions CYP2A13 may be a potential key metabolic enzyme gene in the carcinogenesis of lung cancer in non‐smokers. The common polymorphisms of CYP2A13 may be candidate biomarkers for lung cancer susceptibility in Han‐Chinese.

Abstract Porcine circovirus type 2 (PCV2) is an economically important swine pathogen but some extra trigger factors are required for the development of PCV2-associated diseases. By evaluating cap protein expression, viral DNA copies and the number of infected cells, the present study further confirmed that oxidative stress can promote PCV2 replication. The results showed that oxidative stress induced autophagy in PCV2-infected PK15 cells. Blocking autophagy with inhibitor 3-methyladenine or ATG5-specific siRNA significantly inhibited oxidative stress-promoted PCV2 replication. Importantly, autophagy inhibition significantly increased apoptosis in oxidative stress-treated PK15 cells. Suppression of apoptosis by benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone in conditions of autophagy inhibition restored PCV2 replication. Taken together, autophagy protected host cells against potential apoptosis and then contributed to PCV2 replication promotion caused by oxidative stress. Our findings can partly explain the pathogenic mechanism of PCV2 related to the oxidative stress-induced autophagy.

Somatic embryogenesis (SE), which leads to the formation of embryonic callus (EC) tissue, is the most promising method for large-scale production and selective breeding of woody plants. However, in many species, SE suffers from low proliferation rates, hindering the production of improved plant materials. One way of improving proliferation rates is achieved by improving the redox status of the culture medium. In this study, we investigated the effects of exogenous glutathione (GSH) and L-buthionine sulfoximine (BSO, the inhibitor of glutathione synthase) on the EC proliferation rate in Korean pine (Pinus koraiensis), using cell lines with both high (F: 001#-001) and low (S: 001#-010) proliferation potential. We found that exogenous GSH promoted cell proliferation in both cell lines, while exogenous BSO inhibited proliferation in both cell lines. At 35 d with exogenous GSH treatment, the fresh weight of F and S cell lines increased by 35.48% and 48.39%, respectively, compared with the control. The exogenous application of GSH increased the intracellular levels of GSH, total GSH (T-GSH), oxidized glutathione (GSSG), ascorbic acid (ASA), total ASA (T-ASA), and the ratios of GSH:T-GSH and ASA:T-ASA in both F and S cell lines. Furthermore, exogenous GSH increased the activity of both glutathione reductase (GR) and dehydroascorbate reductase (DHAR) while decreasing the activity of ascorbate peroxidase (APX) in both cell lines. It appears that the application of exogenous GSH promotes a reducing cultural environment, which is conducive to EC proliferation in Korean pine. By helping to reveal the mechanism whereby GSH regulates redox homeostasis in Korean pine EC cells, we have laid the foundation for a large-scale breeding of Korean pine somatic embryogenesis technology system.

Currently, the molecular mechanisms underlining male infertility are still poorly understood. Our previous study has demonstrated that PIWI-interacting RNAs (piRNAs) are downregulated in seminal plasma of infertile patients and can serve as molecular biomarkers for male infertility. However, the source and mechanism for the dysregulation of piRNAs remain obscure. In this study, we found that exosomes are present in high concentrations in human seminal plasma and confirmed that piRNAs are predominantly present in the exosomal fraction of seminal plasma. Moreover, we showed that piRNAs were significantly decreased in exosomes of asthenozoospermia patients compared with normozoospermic men. By systematically screening piRNA profiles in sperms of normozoospermic men and asthenozoospermia patients, we found that piRNAs were parallelly reduced during infertility. At last, we investigated the expression of some proteins that are essential for piRNAs biogenesis in sperms and therefore identified a tight correlation between the levels of spermatozoa piRNA and MitoPLD protein, suggesting that the loss-of-function of MitoPLD could cause a severe defect of piRNA accumulation in sperms. In summary, this study identified a parallel reduction of piRNAs and MitoPLD protein in sperms of asthenozoospermia patients, which may provide pathophysiological clues about sperm motility.

Background: Despite remarkable success of immunotherapies with checkpoint blockade antibodies targeting programmed cell death protein 1 (PD-1), the majority of patients with non-small-cell lung cancer (NSCLC) have yet to receive durable benefits. We used the metabolomic profiling of early on-treatment serum to explore predictors of clinical outcomes of anti-PD-1 treatment in patients with advanced NSCLC.Methods: We recruited 74 Chinese patients who had stage IIIB/IV NSCLC-proven tumor progression and were treated with PD-1 inhibitor. The study was comprised of a discovery cohort of patients treated with nivolumab and two validation cohorts of patients receiving tislelizumab or nivolumab. Serum samples were collected 2–3 weeks after the first infusion of PD-1 inhibitor. Metabolomic profiling of serum was performed using ultrahigh performance lipid chromatograph-mass spectrometry. The serum metabolite biomarkers were identified using an integral workflow of nontargeted metabolomic data analysis.Results: A serum metabolite panel consisting of hypoxanthine and histidine was identified and validated as a predictor of response to PD-1 blockade treatment in patients with advanced NSCLC. High levels of both hypoxanthine and histidine in early on-treatment serum were associated with improved progression-free survival [hazard ratio (HR) = 0.078, 95% confidence interval (CI), 0.027–0.221, p < 0.001] and overall survival (HR = 0.124, 95% CI, 0.039–0.397, p < 0.001) in the discovery cohort. The serum metabolite panel showed a high sensitivity and specificity in distinguishing responders and non-responders in the validation cohorts 1 and 2, with an area under the receiver-operating characteristic curve of 0.933 and 1.000, respectively. High levels of serum hypoxanthine and histidine were correlated with improved progression-free survival in the validation cohort 1 (HR = 0.137, 95% CI, 0.040–0.467, p = 0.001) and in the validation cohort 2 (HR = 0.084, 95% CI, 0.009–0.762, p = 0.028).Conclusion: Our results revealed that hypoxanthine and histidine in early on-treatment serum are predictive biomarkers of response to PD-1 blockade therapy in patients with advanced NSCLC. The serum biomarker panel would enable early identification of NSCLC patients who may benefit from PD-1 blockade therapy.

We synthesized a series of quinazolinone derivates as tyrosinase inhibitors and evaluated their inhibition constants. We synthesized 2-(2,6-dimethylhepta-1,5-dien-1-yl)quinazolin-4(3H)-one (Q1) from the natural citral. The concentration, which led to 50% activity loss of Q1, was 103 ± 2 μM (IC50 = 103 ± 2 μM). Furthermore, we considered Q1 to be a mixed-type and reversible tyrosinase inhibitor, and determined the KI and KIS inhibition constants to be 117.07 μM and 423.63 μM, respectively. Our fluorescence experiment revealed that Q1 could interact with the substrates of tyrosine and L-DOPA in addition to tyrosinase. Molecular docking studies showed that the binding of Q1 to tyrosinase was driven by hydrogen bonding and hydrophobicity. Briefly, the current study confirmed a new tyrosinase inhibitor, which is expected to be developed into a novel pigmentation drug.

Protein, which is the main component of meat, is degraded and oxidized during meat fermentation. During fermentation, macromolecular proteins are degraded into small peptides and free amino acids, and oxidation leads to amino acid side chain modification, molecular crosslinking polymerization, and peptide chain cleavage. At different metabolic levels, these reactions may affect the protein structure and the color, tenderness, flavor, and edible value of fermented meat products. Lactic acid bacteria are currently a research hotspot for application in the fermented meat industry. Its growth metabolism and derivative metabolites formed during the fermentation of meat products regulate protein degradation and oxidation to a certain extent and improve product quality. Therefore, this paper mainly reviews the changes occurring in proteins in fermented meat products and their effects on the quality of the products. Referring to studies on the effects of lactic acid bacteria on protein degradation and oxidation from all over the world, this review aims to provide a relevant reference for improving the quality of fermented meat products.

Background: This research explores the relationship between the unipolar electrogram (UP-EGM) and lesion size index (LSI) in different regions of continuous circular lesions (CCLs) and to assess the safety and efficacy of UP-EGM-guided versus LSI-guided radiofrequency catheter ablation (RFCA) in patients with paroxysmal atrial fibrillation (PAF). Methods: A total of 120 patients with drug-refractory PAF who underwent index RFCA were scheduled to be consecutively included from March 2020 to April 2021. All the patients were randomly divided 1:1 into two groups: the UP-EGM group and the LSI group. The first-pass PVI rate, acute PVI rate, and the sinus rhythm maintenance rate were compared. Results: A total of 120 patients with PAF were included in the study: the UP-EGM group (n = 60) and the LSI group (n = 60). All the LSI values in the UP-EGM group were less than those in the corresponding regions in the LSI group (all p < 0.001). There were no significant differences in the first-pass PVI rate and acute PVI rate between the two groups. After a mean follow-up period of 11.31 ± 1.70 months, the sinus rhythm maintenance rate in the UP-EGM group was comparable to that in the LSI group (90% vs. 91.7%, p = 0.752). Conclusion: UP-EGM-guided and LSI-guided RFCA are both effective and safe in patients with PAF. However, UP-EGM may be more suitable than LSI for guiding individual RFCA.

Many cell lines in the embryogenic callus cannot produce somatic embryos (SEs) even if they meet the optimal SE maturation culture conditions during conifer somatic embryogenesis. This phenomenon hinders the progress of the industrial-scale reproduction of conifers. Therefore, there is an urgent need to obtain morphological and physiological markers to screen embryogenic calli in response to SE maturation conditions. To detect cell lines with high somatic embryogenesis potential during the proliferation process, we counted the number of pro-embryos and early SEs (ESEs) in different cell lines and storage substances, endogenous hormones, and polyamine contents. The results showed that the yield of P. koraiensis SEs was heavily dependent on genotype (p = 0.001). There were high levels of PE III (pro-embryo III) number, ESE number, and soluble protein content, in the response cell lines (R cell lines), which were 1.6-, 3-, and 1.1-fold those of the obstructive cell lines (B cell lines), respectively. The B cell line had high levels of starch, auxin (IAA), Put, Spd, and putrescine: spermine (Put: Spm) compared to the R cell line. In addition, the numbers of PE III, ESEs, and soluble protein content were significantly positively correlated with SE yield. In contrast, the contents of starch, abscisic acid (ABA), Put, Spm, and Spd were significantly negatively correlated with SE yield. To ensure the accuracy of the results, we used nine cell lines to test the results. The PE III and ESE numbers and the Spm and Spd contents were positively correlated with SE yield, while the levels of starch, ABA, IAA, Put: Spd, and Put: Spm were negatively correlated with SE yield. Thus, we recommend using high PE III and ESEs as morphological indicators and low levels of starch, IAA, ABA, and Put: Spm as physiological markers to screen cell lines with a high somatic embryogenesis potential. In addition, we also found that the relationship between Spd, Spm, and SE yield was opposite in the two experimental results. Therefore, we speculate that the differences in Spd and Spm content are mainly affected by genotype. In conclusion, this study obtained the morphological and physiological markers of some high-somatic embryogenic cell lines by comparing the differences between nine somatic embryogenic cell lines. Our results can guide the improvement of conifer somatic embryogenesis technology and can provide a theoretical basis for accelerating the application of biotechnology in large-scale artificial breeding.

This paper reviews the effects of domestic and foreign influences on the substance metabolism pathways and the flavor and flora of LAB in fermented meat products to provide a new theoretical basis for developing new products for the industrial application of lactic acid bacteria (LAB) in fermented meat products. LAB are extensively used among commonly fermented ingredients, such as fermented meat products and yogurt. As fermenting agents, LAB metabolize proteins, lipids, and glycogen in meat products through their enzyme system, which affects the tricarboxylic acid cycle, fatty acid metabolism, amino acid decomposition, and other metabolic processes, and decompose biological macromolecules into small molecules, adding a special flavor with a certain functionality to the final product. Metabolites of LAB in the fermentation process also exert nitrite degradation, as well as antibacterial and antioxidant functions, which improve the physical and chemical qualities of fermented meat products. While fermenting meat products, LAB not only add unique flavor substances to the products, but also improve the safety profile of fermented foods.

Lateral flow assays (LFAs) have attracted much attention as rapid and affordable point-of-care devices for medical diagnostics. The global SARS-CoV-2 pandemic has further highlighted the importance of LFAs. Many efforts have been made to enhance the sensitivity of LFAs. In recent years, silica nanomaterials have been used to either amplify the signal of label materials or provide stability, resulting in better detection performance. In this review, the recent progress of silica-nanomaterial-assisted LFAs is summarized. The impact of the structure of silica nanomaterials on LFA performance, the challenges and prospects in this research area are also discussed.

Our objective was to optimize soil management practices to improve soil health to increase peanut (Arachis hypogaea L.) yield. We studied the effects of using rotary tillage with mulching film or without [rotary tillage with no mulching (RTNM)], plow tillage with mulching film or without, and green manure with mulching film (GMMF) or without [green manure with no mulching (GMNM)] over 3 years in Tai’an, China. Results showed that compared with RTNM treatment, GMNM and GMMF treatments significantly (P < 0.05) increased soil organic carbon, enzymatic activity, and the available nitrogen, phosphorus, and potassium content. The dominant bacterial phyla in the soil across all treatments were Proteobacteria, Acidobacteria, and Actinobacteria. Bacterial richness and diversity in the soil were significantly (P < 0.05) enhanced after GMMF and GMNM treatments compared with those after RTNM treatment. The linear discriminant analysis effect size analysis indicated that Chloroflexi abundance in the 0–10 and 10–20 cm soil layers changed significantly (P < 0.05) after rotary tillage with mulching film and RTNM treatments, respectively, whereas that of Bacteroidetes changed significantly (P < 0.05) in the 0–10 layer after GMNM treatment. The abundance of the Xanthobacteraceae family of Proteobacteria in both soil layers changed significantly (P < 0.05) after GMNM and GMMF treatments. Redundancy analysis revealed that soil physical (soil bulk density and water content), chemical (soil organic carbon, available nitrogen, phosphorus, and potassium), and biological (soil enzymatic activity and nutrient content) characteristics affect the soil bacterial community. Changed soil quality indices may be favorable for leaf photo-assimilate accumulation. Compared with RTNM treatment, GMNM and GMMF treatments significantly increased photosynthesis rate in the peanut leaf and decreased intercellular carbon dioxide concentration. Our results showed that compared with that after RTNM treatment, the average pod yield after GMMF and GMNM treatments increased by 27.85 and 21.26%, respectively, due to increases in the pods per plant and plant numbers. The highest yield of all treatments was obtained from the GMMF-treated plot, followed by that from the GMNM-treated plots. Thus, taking into consideration the residual pollution caused by plastic films, we propose GMNM as a suitable strategy to improve soil physicochemical and microbial properties and to increase the peanut pod yield.

Background: Although most health care is high quality, many patients and members of staff can recall episodes of a lack of empathy, respect or effective communication from health-care staff. In extreme form, this contributes to high-profile organisational failures. Reflective learning is a universally promoted technique for stimulating insight, constructive self-appraisal and empathy; however, its efficacy tends to be assumed rather than proven. The Patient Experience And Reflective Learning (PEARL) project has used patient and staff experience to co-design a novel reflective learning framework that is based on theories of behaviour and learning. Objective: To create a toolkit to help health-care staff obtain meaningful feedback to stimulate effective reflective learning that will promote optimal patient-, family- and colleague-focused behaviours. Design: A 3-year developmental mixed-methods study with four interlinked workstreams and 12 facilitated co-design meetings. The Capability, Opportunity, Motivation – Behaviour framework was used to describe factors influencing the behaviour of reflection. Setting: This took place at five acute medical units and three intensive care units in three urban acute hospital trusts in England. Participants: Patients and relatives, medical and nursing staff, managers and researchers took part. Data sources: Two anonymous surveys, one for patients and one for staff, were developed from existing UK-validated instruments, administered locally and analysed centrally. Ethnographers undertook interviews and observed clinical care and reflective learning activities in the workplace, as well as in the co-design meetings, and fed back their observations in plenary workshops. Main outcome measures: Preliminary instruments were rated by participants for effectiveness and feasibility to derive a final set of tools. These are presented in an attractively designed toolbox with multiple sections, including the theoretical background of reflection, mini guides for obtaining meaningful feedback and for reflecting effectively, guides for reflecting ‘in-action’ during daily activities, and a set of resources. Results: Local project teams (physicians, nurses, patients, relatives and managers) chaired by a non-executive director found the quarterly reports of feedback from the patient and staff surveys insightful and impactful. Patient satisfaction with care was higher for intensive care units than for acute medical units, which reflects contextual differences, but in both settings quality of communication was the main driver of satisfaction. Ethnographers identified many additional forms of experiential feedback. Those that generated an emotional response were particularly effective as a stimulus for reflection. These sources of data were used to supplement individual participant experiences in the nine local co-design meetings and four workshops to identify barriers to and facilitators of effective reflection, focusing on capability, opportunity and motivation. A logic model was developed combining the Capability, Opportunity, Motivation – Behaviour framework for reflection and theories of learning to link patient and staff experience to changes in downstream behaviours. Participants proposed practical tools and activities to enhance reflection ‘in-action’ and ‘on-action’. These tools were developed iteratively by the local and central project teams. Limitations: Paper-based surveys were burdensome to administer and analyse. Conclusions: Patients and health-care staff collaborated to produce a novel reflective learning toolkit. Future work: The toolkit requires evaluating in a cluster randomised controlled trial. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 32. See the NIHR Journals Library website for further project information.

Extant scales related to measuring the sensory aspect of a brand from the consumer’s perspective are typically either too abstract or too concrete. Thus, this study aimed to create a scale with a medium degree of abstraction by which to measure sensory brand experience. This entailed a process of scale development and validation. In study 1, we conducted a qualitative study to explore possible dimensions and items using semi-structured interviews. Several dimensions and items were proposed by combining findings from a literature review and the consumer interviews. In study 2, we examined the items and preliminarily tested the validity of the scale. The results show that, according to our scale, most of the brands considered could be differentiated in terms of the sensory experience they generate. The scale is thus deemed to have potential as a useful tool by which to evaluate the sensory quality of brands. In study 3, we further examined the items, verified the dimensions, tested the reliability and validity of the scale, and formally presented a final version of the scale. This final version comprises three dimensions and 10 items. The three dimensions represent, respectively, three important factors that may influence consumers’ perceptions and evaluations of the sensory quality of brands: the volume of sensory brand stimuli, the uniqueness of sensory brand stimuli, and the consistency between sensory brand stimuli and consumer. The scale’s reliability and validity are found to be satisfactory. Future research can thus employ the scale to assess the sensory experience of various brands, and even to rank brands accordingly. While the present study in the Chinese context is expected to provide valuable insights into the brand experience and sensory branding literature, further research could be conducted to validate the scale in other geographical and cultural contexts.

Agronomically optimizing the timing and rates of nitrogen (N) fertilizer application can increase crop yield and decrease N loss to the environment. Wheat (Triticum aestivum L.)–peanut (Arachis hypogaea L.) relay intercropping systems are a mainstay of economic and food security in China. We performed a field experiment to investigate the effects of N fertilizer on N recovery efficiency, crop yield, and N loss rate in wheat–peanut relay intercropping systems in the Huang-Huai-Hai Plain, China during 2015–2017. The N was applied on the day before sowing, the jointing stage (G30) or the booting stage (G40) of winter wheat, and the anthesis stage (R1) of peanut in the following percentage splits: 50-50-0-0 (N1), 35-35-0-30 (N2), and 35-0-35-30 (N3), using 300 kg N ha−1, with 0 kg N ha−1 (N0) as control. 15N-labeled (20.14 atom %) urea was used to trace the fate of N in microplots. The yields of wheat and peanut increased by 12.4% and 15.4% under the N2 and N3 treatments, relative to those under the N1 treatment. The 15N recovery efficiencies (15NRE) were 64.9% and 58.1% for treatments N2 and N3, significantly greater than that for the N1 treatment (45.3%). The potential N loss rates for the treatments N2 and N3 were 23.7% and 7.0%, significantly lower than that for treatment N1 (30.1%). Withholding N supply until the booting stage (N3) did not reduce the wheat grain yield; however, it increased the N content derived from 15N-labeled urea in peanuts, promoted the distribution of 15N to pods, and ultimately increased pod yields in comparison with those obtained by topdressing N at jointing stage (N2). In comparison with N2, the N uptake and N recovery efficiency (NRE) of N3 was increased by 12.0% and 24.1%, respectively, while the apparent N loss decreased by 16.7%. In conclusion, applying N fertilizer with three splits and delaying topdressing fertilization until G40 of winter wheat increased total grain yields and NRE and reduced N loss. This practice could be an environment-friendly N management strategy for wheat–peanut relay intercropping systems in China. Keywords: Nitrogen management, Wheat–peanut relay intercropping system, Crop yield, Nitrogen recovery efficiency, Apparent N loss

Purpose: Sarcopenia is a geriatric syndrome, and it is closely related to the prevalence of type 2 diabetes mellitus (T2DM). Until now, the diagnosis of sarcopenia requires Dual Energy X-ray Absorptiometry (DXA) scanning. This study aims to make risk assessment of sarcopenia with support vector machine (SVM) and random forest (RF) when DXA is not available.Methods: Firstly, we recruited 132 patients aged over 65 and diagnosed with T2DM in Changchun, China. Clinical data were collected for predicting sarcopenia. Secondly, we selected 3, 5, and 7 features out of over 40 features of patient's data with backward selection, respectively, to train SVM and RF classification models and regression models. Finally, to evaluate the performance of the models, we performed leave one out and 5-fold cross validation.Results: When training the model with 5 features, the sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were favorable, and it was better than the models trained with 3 features and 7 features. Area under the receiver operating characteristic (ROC) curve (AUC) were over 0.7, and the mean AUC of SVM models was higher than that of RF.Conclusions: Using SVM and RF to make risk assessment of sarcopenia in the elderly is an option in clinical setting. Only 5 features are needed to input into the software to run the algorithm for a primary assessment. It cannot replace DXA to diagnose sarcopenia, but is a good tool to evaluate sarcopenia.

Abstract In this paper, we investigate the existence of a set with 2kT $2kT$-periodic solutions for n-dimensional p-Laplacian neutral differential systems with a time-varying delay (φp(u(t)−Cu(t−τ))′)′+ddt∇F(u(t))+G(u(t−γ(t)))=ek(t) $(\varphi_{p}(u(t)-Cu(t-\tau ))')'+ \frac{d}{dt}\nabla F(u(t))+G(u(t-\gamma (t)))=e_{k}(t)$ based on the coincidence degree theory of Mawhin. Combining this with the conclusion about uniform convergence and limit, we obtain the corresponding results on the existence of homoclinic solutions.

Abstract Background Acute kidney injury (AKI) refers to a broad spectrum of kidney damage and is attributed a high morbidity and mortality rate at all degrees of severity. Obesity increases the risk for developing AKI. However, some studies have shown that obesity at onset of AKI is paradoxically associated with greater survival. The aim of this review is to explore the relationship between body mass index and survival in patients with AKI. Methods An electronic search will be conducted using MEDLINE, EMBASE, CINAHL and CENTRAL using predefined search strategies. The cited and citing references of selected key studies will also be searched for relevant articles. Risk of bias will be assessed using a modified Quality in Prognosis Studies (QUIPS) tool. The primary outcome will be an exploration of the association between BMI and mortality in patients presenting with AKI. Two authors will independently select, data extract, and risk of bias assess articles. Any discrepancies will be resolved by consensus or by consulting a third author. A narrative synthesis of the findings from the included studies will be presented. Meta-analyses will be conducted where the data is available from clinically and methodologically similar studies and in the same format. Heterogeneity in such analyses, beyond that expected by chance, will be quantified using the I 2 statistic. Sub-group analyses will be performed to determine the influence of gender, AKI duration, underlying aetiology, and intervening treatments, on pooled results. Discussion Body mass index may be an important modifiable risk factor for mortality in patients presenting with AKI. The proposed systematic review will help to elucidate the association between all categories of BMI and survival in this patient group. Systematic review registration PROSPERO CRD42017071124.

Background/Aims: Swine influenza virus (SIV) is a major pathogen of both animals and humans. Afatoxin B1 (AFB1) is one of the most common mycotoxins in feed and food. However, the central contribution of AFB1 to SIV infection remains unclear. Methods: Here, TCID50 assays, fluorescence-based quantitative real-time PCR, western blotting, immunofluorescence staining, histopathological examination, flow cytometry and scanning electron microscopy were performed to investigate the involvement and underlying mechanism of AFB1 in SIV infection in vivo and in vitro using mouse models and porcine alveolar macrophage (PAM) models, respectively. Results: The in vivo study showed that low levels of AFB1 promoted SIV infection and increased its severity, as demonstrated by the increased mRNA expression of viral matrix protein (M); by the increased protein expression of nucleoprotein (NP), matrix protein 1 and ion channel protein; and by animal weight loss, lung index and lung histologic damage. In addition, the increased occurrence of SIV infection accompanied by increases in the level of IL-10 in sera and lungs, in the spleen index and in the number of CD206-positive mouse alveolar macrophages but decreases in the level of TNF-α in sera and lungs, in the thymus index and in the number of CD80-positive mouse alveolar macrophages was observed in SIV-infected mice after low-level AFB1 exposure. The in vitro study showed that low concentrations of AFB1 promoted SIV infection, as demonstrated by the increases in viral titers and viral M mRNA and NP expression levels in SIV-infected PAMs as well as by the number of cells positive for NP protein expression. Furthermore, AFB1 promoted the polarization of SIV-infected PAMs to the M1 phenotype at 8 hpi and to the M2 phenotype at 24 hpi, as measured by the increases in IL-10 expression and in the number of CD206-positive PAMs as well as by the morphological changes observed by scanning electron microscopy. The administration of the immune stimulant lipopolysaccharide (LPS) reversed the switch in PAM polarization from M2 to M1 and thereby counteracted the promotion of influenza virus infection induced by AFB1. Conclusion: Our results are the first to confirm that low-level exposure to AFB1 promotes SIV infection and modulates a switch in macrophage polarization from M1 to M2. The work reported here provides important data that point to a role for AFB1 in SIV infection, and it opens a new field of study.

Abstract The study was carried out to investigate the effect of dietary selenium (Se) and vitamin E (VE) supplementation on mRNA level of heat shock proteins, selenoproteins, and antioxidant enzyme activities in the breast meat of broilers under summer heat stress conditions. A total of 200 male broilers (Ross 308) of 1 day age were randomly separated into 4 groups in a complete randomized design and were given a basal diet (Control, 0.08 mg Se/kg diet) or basal diet supplemented with VE (250 mg/kg VE), sodium selenite (0.2 mg/kg Se), or Se + VE (0.2 mg/kg Se + 250 mg/kg VE) to investigate the expression of key antioxidant and heat shock protein (HSP) genes under high temperature stress. Dietary Se, VE and Se + VE significantly enhanced the activities and mRNA levels of catalase as well as superoxide dismutase (SOD) but decreased the mRNA levels of HSP70 and HSP90. Se alone or combined with VE increased the concentration of selenoprotein P and selenoproteins mRNA level and decreased the expression of HSP60. In addition, Se and Se + VE significantly enhanced the glutathione peroxidase (GPx) activity and the expression of GPx1 and GPx4 in breast muscle tissues. It is noteworthy that all the treatments significantly decreased malondialdehyde (MDA) level in the breast meat. Overall results showed that Se in combination with VE has maximal effects to mitigate heat stress. Based on given results it can be recommended that Se + VE are a suitable dietary supplement for broilers to ameliorate the negative effects of summer heat stress conditions.

Respiratory distress: Clearing fluid on the lungs Treatment that involves boosting levels of a signaling molecule could help reduce fluid on the lungs in acute respiratory distress syndrome (ARDS). This condition usually affects critically ill patients with illnesses such as pneumonia or sepsis, and leads to severe inflammation and flooding of the lungs with fluid. This prevents microscopic air sacs called aveoli from processing oxygen and carbon dioxide effectively. At present there is no effective management for the condition. Now, Sheng-Wei Jin at Wenzhou Medical University, China, and co-workers have shown that boosting levels of a signaling molecule called protectin DX can help with aveolar fluid clearance in rats. They found that protectin DX activates sodium channels within the aveoli, helping clear fluid, and also acts as an anti-inflammatory and pro-resolving mediator to protect lung tissues from further injury.

Abstract Background Calcineurin (CaN) having a high expression in hippocampal neurons is closely related to apoptosis. Pretreatment with nimodipine can lower the apoptosis rate of hippocampal neuron to reduce the incidence of postoperative cognitive dysfunction (POCD). However, the relationship between cerebral protective effect of pretreatment with nimodipine and CaN is controversial in the literature. The aim of this study is to evaluate the relationship between neuroprotective effect of nimodipine and CaN on POCD in aged rats. Methods Ninety-six 18-month-old male Sprague-Dawley rats were randomly assigned into 4 groups (n = 24 each): control group (Group C), nimodipine group (Group N), surgery group (Group S) and nimodipine + surgery group (Group N + S). In Group N and Group N + S, nimodipine 1 mg/kg was intraperitoneally injected, while the equal volume of normal saline was given instead in Group S. 30 min later, Group N and Group C inhaled pure oxygen for 2 h, and Group S and N + S inhaled 3% sevoflurane for 2 h when exploratory laparotomy was performed. Morris water maze test was performed on 1 day before operation and 1, 3 and 7 days after operation. After the end of Morris water maze test at 1 day before operation and 1 and 7 days after operation, 8 rats were sacrificed, brains were removed and hippocampal tissues were obtained for detection of apoptosis in hippocampal neurons, cytoplasmic calcium ([Ca2+]i), and hippocampal CaN and caspase-3 expression. Results Compared with the 1st day before operation, the escape latency, apoptosis rate, [Ca2+]i, expression of CaN and caspase-3 increased significantly, but the frequency of crossing the original platform decreased dramatically in Group S and N + S(P

Abstract Background Sepsis is a common condition which kills between 36,000 and 64,000 people every year in the UK. Early recognition and management of sepsis has been shown to reduce mortality and improve the health and well-being of people with sepsis. Paramedics frequently come into contact with patients with sepsis and are well placed to provide early diagnosis and treatment. We aim to determine the feasibility of undertaking a fully powered randomised controlled trial (RCT) to test the clinical and cost-effectiveness of paramedics obtaining blood cultures from and administering IV antibiotics to patients with sepsis, so we can make a decision about whether to proceed to a fully powered randomised controlled trial, which will answer questions regarding safety and effectiveness for patients and benefit to the National Health Service (NHS). Methods/design This is an individually randomised, two-arm feasibility study for a randomised controlled trial with a 1:1 ratio. Sixty paramedics will receive training to assist them to recognise sepsis using a screening tool, obtain blood cultures, and provide IV antibiotics. If sepsis is suspected, paramedics will randomly allocate patients to intervention or usual care using their next sequential individually issued scratch card. Patients will be followed up at 90 days using linked anonymised data to capture length of hospital admission and mortality. We will also collect self-reported health-related quality of life (using SF-12) at this time. We will interview ten patients by telephone and hold a focus group with paramedics, to find out what they think about the intervention. Discussion At the end of this study, we will make a recommendation about whether a full randomised controlled trial of paramedics obtaining blood cultures and administering IV antibiotics for sepsis is warranted, and if so, we will develop a proposal for research funding in order to take the work forward. Trial registration ISRCTN, ISRCTN36856873

A continuous prediction model of carbon content of 120 t BOF is established in this paper. Based on the three-stage decarburization theory and combined with the production process of 120 t converter, the effects of oxygen lance height and top blowing oxygen flow rate are also considered in the model. The explicit finite difference method is used to realize continuous prediction of carbon content in the converter blowing process. The model parameters such as ultimate carbon content in molten pool are calculated according to the actual data of 120 t BOF, which improves the hit rate of the model. Process verification and end-point verification for the continuous prediction model have been carried out, and the results of process verification indicate that the continuous prediction model established in the paper basically accords with the actual behavior of decarburization. Moreover, the hit ratio of the continuous prediction model reached 85% for the prediction of end-point carbon content within a tolerance of ±0.02%.

Abstract Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. PCV2 replication could be promoted by low doses of ochratoxin A (OTA) as in our previous study and selenium has been shown to attenuate PCV2 replication. However, the underlying mechanism remains unclear. The aim of the study was to investigate the effects of selenomethionine (SeMet), the major component of organic selenium, on OTA-induced PCV2 replication promotion and its potential mechanism. The present study demonstrates that OTA could promote PCV2 replication as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells. In addition, OTA could activate autophagy as indicated by up-regulated light chain 3 (LC3)-II and autophagy-related protein 5 expressions and autophagosome formation. Further, OTA could down-regulate p-AKT and p-mTOR expressions and OTA-induced autophagy was inhibited when insulin was applied. SeMet at 2, 4 and 6 μM had significant inhibiting effects against OTA-induced PCV2 replication promotion. Furthermore, SeMet could attenuate OTA-induced autophagy and up-regulate OTA-induced p-AKT and p-mTOR expression inhibition. Rapamycin, an inhibitor of AKT/mTOR, could reverse the effects of SeMet on OTA-induced autophagy and the PCV2 replication promotion. In conclusion, SeMet could block OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR pathway. Therefore, SeMet supplementation could be an effective prophylactic strategy against PCV2 infections and autophagy may be a potential marker to develop novel anti-PCV2 drugs.

Summary: Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional Rbp-j knockout (Rbp-j cKO) and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the miR-342-5p host gene, the Ena-vasodilator stimulated phosphoprotein-like (Evl), was negatively regulated by Notch signaling, probably through HES5. Transfection of miR-342-5p promoted the differentiation of neural stem cells (NSCs) into intermediate neural progenitors (INPs) in vitro and reduced the stemness of NSCs in vivo. Furthermore, miR-342-5p inhibited the differentiation of neural stem/intermediate progenitor cells into astrocytes, likely mediated by targeting GFAP directly. Our results indicated that miR-342-5p could function as a downstream effector of Notch signaling to regulate the differentiation of NSCs into INPs and astrocytes commitment. : In this article, Han and colleagues show that miR-342-5p acts as a downstream effector of Notch signaling in the mouse CNS. Notch signal inhibits miR-342-5p expression by regulating its host gene Evl. And with attenuated Notch signal in NSCs, miR-342-5p is upregulated to promote NSCs transition into INPs, and to inhibit astrocyte commitment by targeting GFAP. Keywords: neural stem cells, intermediate neural progenitors, Notch, RBP-J, neuron, glia, miR-342-5p

Traditional Chinese medicines (TCMs) represent one form of complementary and alternative medicine. The popularity and complexity in production make them attractive and vulnerable to adulteration in stages ranging from planting to production. Adulteration refers to the addition of extraneous, improper, or inferior ingredients that should not be present in TCMs. To detect and combat adulterated TCMs, supplementary testing methods (STMs), which expand the capability of routine testing standards, have been applied in China since 2003. From 2003 to 2017, a total of 184 STMs for TCMs were approved by the Chinese national drug regulatory authority. By assessing these STMs, this research intends to identify those TCMs vulnerable to adulteration, to list common adulterants, and to characterize the techniques of analysis. The results show that adulteration of TCMs can be classified into three main categories: the addition of undeclared drugs/chemical substances, substitution with non-drug components, and the addition of foreign non-drug materials. The top five therapeutic areas of TCMs vulnerable to adulteration are diabetes, calm and sleep, sexual dysfunction, pain relief, and rheumatism. A total of 166 adulterants were detected in the adulterated TCM preparations and herbal products studied here, with 158 adulterants in TCM preparations and 43 in herbal products, with 35 adulterants in common. Each STM consists of different pharmaceutical analysis techniques, including tests for physical-chemical properties, chromatography, spectroscopic techniques, and mass spectrometry. The analytical methodology of STMs relies on the combination of these techniques, with HPLC ranking the highest percentage (76.1%) and physical-chemical techniques the lowest percentage (11.4%). This research shows that STMs have played a crucial role in combating adulterated TCMs. However, STMs represent merely a product testing-centered regulatory strategy. The inspection of cultivation and manufacturing processes should also be strengthened. More importantly, the awareness and self-discipline of TCM manufacturers in implementing good manufacturing practices and regulating the planting and cultivation of raw materials should be improved.

Background: Invasive mechanical ventilation (IMV) is a life-saving intervention. Following resolution of the condition that necessitated IMV, a spontaneous breathing trial (SBT) is used to determine patient readiness for IMV discontinuation. In patients who fail one or more SBTs, there is uncertainty as to the optimum management strategy. Objective: To evaluate the clinical effectiveness and cost-effectiveness of using non-invasive ventilation (NIV) as an intermediate step in the protocolised weaning of patients from IMV. Design: Pragmatic, open-label, parallel-group randomised controlled trial, with cost-effectiveness analysis. Setting: A total of 51 critical care units across the UK. Participants: Adult intensive care patients who had received IMV for at least 48 hours, who were categorised as ready to wean from ventilation, and who failed a SBT. Interventions: Control group (invasive weaning): patients continued to receive IMV with daily SBTs. A weaning protocol was used to wean pressure support based on the patient’s condition. Intervention group (non-invasive weaning): patients were extubated to NIV. A weaning protocol was used to wean inspiratory positive airway pressure, based on the patient’s condition. Main outcome measures: The primary outcome measure was time to liberation from ventilation. Secondary outcome measures included mortality, duration of IMV, proportion of patients receiving antibiotics for a presumed respiratory infection and health-related quality of life. Results: A total of 364 patients (invasive weaning, n = 182; non-invasive weaning, n = 182) were randomised. Groups were well matched at baseline. There was no difference between the invasive weaning and non-invasive weaning groups in median time to liberation from ventilation {invasive weaning 108 hours [interquartile range (IQR) 57–351 hours] vs. non-invasive weaning 104.3 hours [IQR 34.5–297 hours]; hazard ratio 1.1, 95% confidence interval [CI] 0.89 to 1.39; p = 0.352}. There was also no difference in mortality between groups at any time point. Patients in the non-invasive weaning group had fewer IMV days [invasive weaning 4 days (IQR 2–11 days) vs. non-invasive weaning 1 day (IQR 0–7 days); adjusted mean difference –3.1 days, 95% CI –5.75 to –0.51 days]. In addition, fewer non-invasive weaning patients required antibiotics for a respiratory infection [odds ratio (OR) 0.60, 95% CI 0.41 to 1.00; p = 0.048]. A higher proportion of non-invasive weaning patients required reintubation than those in the invasive weaning group (OR 2.00, 95% CI 1.27 to 3.24). The within-trial economic evaluation showed that NIV was associated with a lower net cost and a higher net effect, and was dominant in health economic terms. The probability that NIV was cost-effective was estimated at 0.58 at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year. Conclusions: A protocolised non-invasive weaning strategy did not reduce time to liberation from ventilation. However, patients who underwent non-invasive weaning had fewer days requiring IMV and required fewer antibiotics for respiratory infections. Future work: In patients who fail a SBT, which factors predict an adverse outcome (reintubation, tracheostomy, death) if extubated and weaned using NIV? Trial registration: Current Controlled Trials ISRCTN15635197. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 48. See the NIHR Journals Library website for further project information.

Objectives Thoracotomy is considered one of the most painful surgical procedures. The incidence of chronic post-thoracotomy pain (CPTP) is up to 50%. Paravertebral blockade (PVB) may be superior to thoracic epidural blockade (TEB) in preventing CPTP. The specific objective of this pilot study was to assess the feasibility of conducting a larger trial to determine whether PVB at thoracotomy is more effective in reducing CPTP compared with TEB.Design A randomised, parallel, external pilot study was conducted to assess whether a large randomised trial of TEB and PVB with CPTP as the primary outcome is feasible.Setting Two adult thoracic centres in the UK.Participants All adult patients admitted for elective open thoracotomy. Participants were excluded if they were American Society of Anesthesiologists physical status IV or V; or if there is contraindication to local anaesthetics; infection near the proposed puncture site; coagulation/thoracic spine disorders; required chest wall resection or emergency thoracic surgery or had a previous thoracotomy.Results All patients presenting for thoracotomy were screened over a 12-month period with 194 found to be eligible. Of these, 69 (36%) were randomised (95% CI 29% to 42%). Discounting five participants who died, 54 of 64 participants (84%) returned questionnaire booklets at 6 months. The number of participants indicating at least a moderate level of chest pain at 6 months was lower with PVB but with high levels of uncertainty (RR: 0.7; 95% CI 0.3 to 1.7 for worst pain; RR: 0.3; 95% CI 0.0 to 2.8 for average pain). There were no safety concerns.Conclusions A large, multicentre randomised controlled trial of PVB versus TEB is feasible as it is possible to randomise and follow up participants with high fidelity. Pain scores were lower on average with PVB compared with TEB but a much larger trial is required to confirm this reliably.Trial registration number ISRCTN45041624

Introduction Patient and staff experiences are strongly influenced by attitudes and behaviours, and provide important insights into care quality. Patient and staff feedback could be used more effectively to enhance behaviours and improve care through systematic integration with techniques for reflective learning. We aim to develop a reflective learning framework and toolkit for healthcare staff to improve patient, family and staff experience.Methods & analysis Local project teams including staff and patients from the acute medical units (AMUs) and intensive care units (ICUs) of three National Health Service trusts will implement two experience surveys derived from existing instruments: a continuous patient and relative survey and an annual staff survey. Survey data will be supplemented by ethnographic interviews and observations in the workplace to evaluate barriers to and facilitators of reflective learning. Using facilitated iterative co-design, local project teams will supplement survey data with their experiences of healthcare to identify events, actions, activities and interventions which promote personal insight and empathy through reflective learning. Outputs will be collated by the central project team to develop a reflective learning framework and toolkit which will be fed back to the local groups for review, refinement and piloting. The development process will be mapped to a conceptual theory of reflective learning which combines psychological and pedagogical theories of learning, alongside theories of behaviour change based on capability, opportunity and motivation influencing behaviour. The output will be a locally-adaptable workplace-based toolkit providing guidance on using reflective learning to incorporate patient and staff experience in routine clinical activities.Ethics & dissemination The PEARL project has received ethics approval from the London Brent Research Ethics Committee (REC Ref 16/LO/224). We propose a national cluster randomised step-wedge trial of the toolkit developed for large-scale evaluation of impact on patient outcomes.

We first compared long-term clinical outcomes in treating critical limb ischemia (CLI) and foot ulcer in patients with diabetes between autologous bone marrow mesenchymal stem cell (BMMSC) and bone-marrow-derived mononuclear cell (BMMNC) transplants. Forty-one patients were enrolled and followed up for 3 years. They received an 18-day standard treatment before stem cell transplantation. Patients with bilateral CLI and foot ulcer were injected intramuscularly or basally with BMMSC, BMMNC, or normal saline (NS). Cox model analysis showed significant differences in the hazard ratio (HR) for amputation with treatment by BMMSC (HR 0.21 [95% CI (0.05, 0.95)], P = 0.043), infection of foot (HR 5.30 [95% CI (1.89, 14.92)], P = 0.002), and age ≥64 (HR 3.01 [95% CI (1.11, 8.15)], P = 0.030), but no significant differences by BMMNC at 9 months after transplantation. Regarding ulcer healing and recurrence rate, the BMMSC group demonstrated a significant difference from the NS group during the 3–6 months after transplantation or healing, but the BMMNC group did not. This trial suggests that, compared with BMMNC treatment, BMMSC treatment leads to a longer time of limb salvage and blood flow improvement, and, when compared with conventional therapy, it can promote limb blood flow and ulcerative healing, and reduce ulcer recurrence and amputation within 9 months.

Acute respiratory distress syndrome (ARDS) has a significant impact on post-operative morbidity and mortality following oesophagectomy. Smoking is a risk factor for the development of ARDS, although the mechanism is unclear. We examined the effect of smoking on alveolar and systemic inflammation, in addition to alveolar–capillary permeability, leading to ARDS in patients undergoing oesophagectomy. We compared clinical, biomarker and PiCCO system data between current smokers (n=14) and ex-smokers (n=36) enrolled into a translational substudy of the BALTI-P (Beta Agonist Lung Injury Trial Prevention) trial. Current smokers compared with ex-smokers had significantly higher numbers of circulating neutrophils, elevated bronchoalveolar lavage (BAL) interleukin (IL)-1 receptor antagonist (IL-1ra), soluble tumour necrosis factor receptor-1 and pre-operative plasma soluble intercellular adhesion molecule-1, and lower BAL vascular endothelial growth factor and post-operative plasma IL-17 (p

Typhoid conjugate vaccines (TCV) are effective in preventing enteric fever caused by Salmonella enterica serovar Typhi in Southeast Asia and Africa. To facilitate vaccination with the Vi capsular polysaccharide–tetanus toxoid conjugate vaccine, Typbar TCV, and allow it to be transported and stored outside a cold chain just prior to administration, an extended controlled-temperature conditions (ECTC) study was performed to confirm the quality of the vaccine at 40 °C for 3 days at the end of its shelf-life (36 months at 2–8 °C). Studies performed in parallel by the vaccine manufacturer, Bharat Biotech International Limited, and an independent national control laboratory (NIBSC) monitored its stability-indicating parameters: O-acetylation of the Vi polysaccharide, integrity of the polysaccharide–protein conjugate, and its molecular size and pH. ECTC samples stored at 40 °C and 45 °C in comparison with control samples stored at 4 °C and 55 or 56 °C, were shown to have stable O-acetylation and pH; only very slight increases in the percentage of free saccharide and corresponding decreases in molecular size were observed. The deoxycholate method for precipitating conjugated polysaccharide was very sensitive to small incremental increases in percentage of free saccharide, in line with storage temperature and duration. This extended ECTC study demonstrated minimal structural changes to the Vi polysaccharide and conjugate vaccine and a stable formulation following extended exposure to elevated temperatures for the desired durations. This outcome supports the manufacturer’s ECTC claim for the vaccine to be allowed to be taken outside the cold chain before its administration.

Point cloud classification is a key technology for point cloud applications and point cloud feature extraction is a key step towards achieving point cloud classification. Although there are many point cloud feature extraction and classification methods, and the acquisition of colored point cloud data has become easier in recent years, most point cloud processing algorithms do not consider the color information associated with the point cloud or do not make full use of the color information. Therefore, we propose a voxel-based local feature descriptor according to the voxel-based local binary pattern (VLBP) and fuses point cloud RGB information and geometric structure features using a random forest classifier to build a color point cloud classification algorithm. The proposed algorithm voxelizes the point cloud; divides the neighborhood of the center point into cubes (i.e., multiple adjacent sub-voxels); compares the gray information of the voxel center and adjacent sub-voxels; performs voxel global thresholding to convert it into a binary code; and uses a local difference sign–magnitude transform (LDSMT) to decompose the local difference of an entire voxel into two complementary components of sign and magnitude. Then, the VLBP feature of each point is extracted. To obtain more structural information about the point cloud, the proposed method extracts the normal vector of each point and the corresponding fast point feature histogram (FPFH) based on the normal vector. Finally, the geometric mechanism features (normal vector and FPFH) and color features (RGB and VLBP features) of the point cloud are fused, and a random forest classifier is used to classify the color laser point cloud. The experimental results show that the proposed algorithm can achieve effective point cloud classification for point cloud data from different indoor and outdoor scenes, and the proposed VLBP features can improve the accuracy of point cloud classification.

Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against Neisseria meningitidis serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM197), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide O-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India.

With the rapid development of information technology,cloud computing has become a hot topic.More and more companies and individuals will be their computing needs and storage needs to be delivered to the cloud,so the security problem of cloud computing can not be ignored.First,the security requirements of the four key technologies,such as multi tenant,node communication,remote storage and virtualization in the cloud computing environment were analyzed,the necessity of the construction of cloud computing security was expounded.Then,according to the security requirements of cloud computing,fuzzy comprehensive evaluation model based on ana-lytic hierarchy process was established,and taking a cloud service platform as an example to evaluate its security,get the security level of the service platform is ＆quot;good＆quot;.Finally,according to the security requirements of cloud computing environment and the results of model evaluation,some suggestions in in virtualization security,applica-tion security and data security was put forward,in order to strengthen the cloud computing security,some direction was provided.

"Signals and Systems" is the core professional course of electronic information majors. Aiming at its characteristics of strong theory, abstract content, and high memory requirements, a virtual teaching platform based on LabVIEW is designed to strengthen students' understanding of this course It is of great significance to reduce the difficulty of students' learning, improve students' learning efficiency, and stimulate students' interest in learning. At the same time, with the synchronous teaching of relevant course experiments, it can greatly reduce the difficulty of teachers' teaching and improve the quality of teaching.

At the stage where China’s economic growth has shifted from high speed to high quality, how to build a sustainable development system with complementary high-quality resources through the integration of culture and tourism industries is the core issue. Since the 26 proposals for the integration of Beijing’s culture and tourism industries were put forward, Beijing is gradually building a sample of integrated culture and tourism development. In this paper, the theory of physics coupling is applied to the research on industrial integration, and a comprehensive evaluation index system is formulated. At the same time, the relative development model, coupling degree model, and coupling coordination degree model were used to empirically analyze the integrated development of the culture and tourism industries in Beijing from 2005 to 2017. The research results show that the degree of coupling and coordination of Beijing’s culture and tourism industry experienced three phases of mild imbalance, primary coordination, moderate coordination during the statistical period, and the integration effect gradually improved. Based on this, this article puts forward policy suggestions that are conducive to the further coordinated development of Beijing’s culture industry and tourism industry.

Based on the background that China enterprises are becoming more and more active in capital operation in the international scope, this paper selects 14 cultural and creative enterprises in Beijing as the research objects, and analyzes the relationship between cultural distance, geographical distance, capital elements of the board of directors and enterprises' FDI performance. This paper crawled data from the stock exchange and other websites, and further used SPSS data processing software to model and analyze the data obtained, and obtained the empirical research results as follows. The empirical results showed that cultural distance and geographical distance were significantly negatively correlated with FDI performance, which was consistent with the original research hypothesis of the paper. And among the capital factors of the board of directors, the gender diversity, education level, scale and internationalization degree of the board are significantly positively correlated with FDI performance. Finally, the corresponding conclusions and Suggestions are put forward according to the empirical analysis results.

In power inspection tasks, the insulator and spacer are important inspection objects. UAV (unmanned aerial vehicle) power inspection is becoming more and more popular. However, due to the limited computing resources carried by a UAV, a lighter model with small model size, high detection accuracy, and fast detection speed is needed to achieve online detection. In order to realize the online detection of power inspection objects, we propose an improved SSD (single shot multibox detector) insulator and spacer detection algorithm using the power inspection images collected by a UAV. In the proposed algorithm, the lightweight network MnasNet is used as the feature extraction network to generate feature maps. Then, two multiscale feature fusion methods are used to fuse multiple feature maps. Lastly, a power inspection object dataset containing insulators and spacers based on aerial images is built, and the performance of the proposed algorithm is tested on real aerial images and videos. Experimental results show that the proposed algorithm can efficiently detect insulators and spacers. Compared with existing algorithms, the proposed algorithm has the advantages of small model size and fast detection speed. The detection accuracy can achieve 93.8%. The detection time of a single image on TX2 (NVIDIA Jetson TX2) is 154 ms and the capture rate on TX2 is 8.27 fps, which allows realizing online detection.

Better management of N fertilizer is essential for improving crop productivity. Wheat (Triticum aestivum L.)–peanut (Arachis hypogaea L.) relay intercropping rotation systems are a mainstay of the measures to improve the economic and food security situation in China. Therefore, a 2-year field study (2015–2017) was conducted to evaluate the effect of different N fertilizer management regimes on the photosynthetic characteristics and uptake and translocation of N in peanut in the wheat–peanut rotation system. We used common compound fertilizer (CCF) and controlled-release compound fertilizer (CRF) at the same N–P2O5–K2O proportion (The contents of N, P2O5, and K2O in the two kinds of fertilizer were 20, 15, and 10%, respectively.). The fertilizer was applied on the day before sowing, at the jointing stage or the flag leaf stage of winter wheat, and at the initial flowering stage of peanut in various proportions, with 0 kg N ha-1 as the control. Results showed that split applications of N significantly increased leaf area index (LAI) and chlorophyll content and improved photosynthetic rate, thus increasing the pod yield of peanut. Topdressing N at the jointing stage (S1) or at the flag leaf stage of wheat (S2) and supplying part of the N at the initial flowering stage of peanut increased pod yield. Withholding N until the flag leaf stage (S2) did not negatively affect wheat grain yield; however, it increased N accumulation in each organ and N allocation proportions in the peanut pod, ultimately improving pod yield. With the same N–P2O5–K2O proportion and equivalent amounts of nutrient, CRF can decreased malondialdehyde (MDA) and maintain a relatively high LAI and chlorophyll content at the late growth stage of peanut, prolong the functional period of peanut leaves and delay leaf senescence, resulting in an increase of pod yield over that with CCF. At S1, CRF resulted in a better pod yield than CCF by 9.4%, and at S2 it was 12.6% higher. In summary, applying N fertilizer in three splits and delaying the topdressing fertilization until the flag leaf stage of winter wheat increases total grain yields of wheat and peanut. This method could therefore be an appropriate N management strategy for wheat–peanut relay intercropping rotation systems in China.

To understand how a Li pellet affects the background plasma, the edge plasma code SOLPS combined with a neutral-gas-shield ablation model has been employed to simulate the transport of Li species in the edge plasma during Li pellet injections in a typical EAST H-mode plasma. The simulation results show that a Li pellet 0.5 mm with velocity ∼100 m/s can penetrate the separatrix, and that the electron temperature drops quickly where the pellet passes by while the electron density needs a longer time to respond. The plasma pressure in the pedestal region grows significantly with the pellet size; the pressure gradient changes even more drastically. This work indicates that without accumulative contributions, a pellet 0.7 mm or above in diameter at an injection velocity of 100 m/s is likely to provide a pressure perturbation enough to trigger ELMs in the typical EAST H-mode plasmas used in this work.

Multiple system atrophy (MSA) is regarded as a progressive neurodegenerative disease mainly divided into MSA-p type with Parkinsonism and MSA-c type with cerebellar ataxia as the main symptom. However, its neural mechanism is still unclear. In this study, we only focus on the MSA-c type. The purpose of this study is to explore the functional connectivity changes of the cerebello-cortical circuit in MSA-c type by using resting state functional magnetic resonance imaging (rs-fMRI). Thirty-six subjects (18 MSA and 18 normal controls) participated in this study and the rs-fMRI data were collected by applying resting state amplitude of low-frequency fluctuations (ALFF), we found the significant decreased ALFF in the MSA patients relative to controls, which included left cerebellum 8 area, 9 area, 7b area and Cru1 as well as vermis 7. Then we select the brain region of cerebellum 8 area as seed to investigate whole brain functional connectivity alteration in the MSA patients. When comparing to controls, several regions showed decreased connectivity in the MSA patients including bilateral cerebellum anterior lobe, left cerebellum posterior lobe, left dentate, bilateral pons, inferior parietal lobule (IPL), lingual gyrus (LG), parahippocampus (PHG), and middle temporal gyrus (MTG). In addition, there were closely correlation between functional connectivities and clinical performances in the MSA patients. The current study confirmed that the disrupted functional connectivity of specific cerebello-cortical circuit in the MSA patients, which is responsible for the clinical performances.

Maresin1 (MaR1), a new anti-inflammatory and proresolving lipid mediator, has been proven to exert organ-protective effects in septic animal models. However, the potential mechanisms are still not fully elucidated. In this study, we sought to explore the impact of MaR1 on metabolic dysfunction in cecal ligation and puncture- (CLP-) induced septic mice. We found that MaR1 significantly increased the overall survival rate and attenuated lung and liver injuries in septic mice. In addition, MaR1 markedly reduced the levels of proinflammatory cytokines (TNF-α and IL-6) and alleviated mitochondrial damage. Based on a 1H NMR-based metabolomics analysis, CLP-induced septic mice had increased levels of acetate, pyruvate, and lactate in serum and decreased levels of alanine, aspartate, glutamate, and fumarate in lungs. However, these metabolic disorders, mainly involving energy and amino acid metabolism, can be recovered by MaR1 treatment. Therefore, our results suggest that the protective effects of MaR1 on sepsis could be related to the recovery of metabolic dysfunction and the alleviation of inflammation and mitochondrial damage.

Aflatoxin B1 (AFB1), which alters immune responses to mammals, is one of the most common mycotoxins in feeds and food. Swine influenza virus (SIV) is a major pathogen of both animals and humans. However, there have been few studies about the relationship between AFB1 exposure and SIV replication. Here, for the first time, we investigated the involvement of AFB1 in SIV replication in vitro and in vivo and explored the underlying mechanism using multiple cell lines and mouse models. In vitro studies demonstrated that low concentrations of AFB1 (0.01–0.25 μg/ml) markedly promoted SIV replication as revealed by increased viral titers and matrix protein (M) mRNA and nucleoprotein (NP) levels in MDCK cells, A549 cells and PAMs. In vivo studies showed that 10–40 μg/kg of AFB1 exacerbated SIV infection in mice as illustrated by significantly higher lung virus titers, viral M mRNA levels, NP levels, lung indexes and more severe lung damage. Further study showed that AFB1 upregulated TLR4, but not other TLRs, in SIV-infected PAMs. Moreover, AFB1 activated TLR4 signaling as demonstrated by the increases of phosphorylated NFκB p65 and TNF-α release in PAMs and mice. In contrast, TLR4 knockdown or the use of BAY 11-7082, a specific inhibitor of NFκB, blocked the AFB1-promoted SIV replication and inflammatory responses in PAMs. Furthermore, a TLR4-specific antagonist, TAK242, and TLR4 knockout both attenuated the AFB1-promoted SIV replication, inflammation and lung damage in mice. We therefore conclude that AFB1 exposure aggravates SIV replication, inflammation and lung damage by activating TLR4-NFκB signaling.

Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA) is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC) function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA. We found that the optimized parameters of EA inhibiting chronic pain were the low frequency and high intensity (2 Hz + 1 mA). EA reversed the reduced expression of CB1 receptors and the 2-arachidonoylglycerol (2-AG) level in the midbrain in chronic pain. Microinjection of the CB1 receptor antagonist AM251 into the ventrolateral periaqueductal gray (vlPAG) can reversed the EA effect on pain hypersensitivity and DNIC function. In addition, CB1 receptors on GABAergic but not glutamatergic neurons are involved in the EA effect on DNIC function and descending inhibitory control of 5-HT in the medulla, thus inhibiting chronic pain. Our data suggest that endocannabinoid (2-AG)-CB1R-GABA-5-HT may be a novel signaling pathway involved in the effect of EA improving DNIC function and inhibiting chronic pain.

The ablation of liver tumors located close to the gallbladder is likely to lead to complications. The aim of this article is to compare the safety and efficacy of irreversible electroporation (IRE) and cryoablation in rabbit livers at a location close to the gallbladder.

Background: Caesarean section is associated with blood loss and maternal morbidity. Excessive blood loss requires transfusion of donor (allogeneic) blood, which is a finite resource. Cell salvage returns blood lost during surgery to the mother. It may avoid the need for donor blood transfusion, but reliable evidence of its effects is lacking. Objectives: To determine if routine use of cell salvage during caesarean section in mothers at risk of haemorrhage reduces the rates of blood transfusion and postpartum maternal morbidity, and is cost-effective, in comparison with standard practice without routine salvage use. Design: Individually randomised controlled, multicentre trial with cost-effectiveness analysis. Treatment was not blinded. Setting: A total of 26 UK obstetric units. Participants: Out of 3054 women recruited between June 2013 and April 2016, we randomly assigned 3028 women at risk of haemorrhage to cell salvage or routine care. Randomisation was stratified using random permuted blocks of variable sizes. Of these, 1672 had emergency and 1356 had elective caesareans. We excluded women for whom cell salvage or donor blood transfusion was contraindicated. Interventions: Cell salvage (intervention) versus routine care without salvage (control). In the intervention group, salvage was set up in 95.6% of the women and, of these, 50.8% had salvaged blood returned. In the control group, 3.9% had salvage deployed. Main outcome measures: Primary – donor blood transfusion. Secondary – units of donor blood transfused, time to mobilisation, length of hospitalisation, mean fall in haemoglobin, fetomaternal haemorrhage (FMH) measured by Kleihauer–Betke test, and maternal fatigue. Analyses were adjusted for stratification factors and other factors that were believed to be prognostic a priori. Cost-effectiveness outcomes – costs of resources and service provision taking the UK NHS perspective. Results: We analysed 1498 and 1492 participants in the intervention and control groups, respectively. Overall, the transfusion rate was 2.5% in the intervention group and 3.5% in the control group [adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42 to 1.01; p = 0.056]. In a planned subgroup analysis, the transfusion rate was 3.0% in the intervention group and 4.6% in the control group among emergency caesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 1.8% in the intervention group and 2.2% in the control group among elective caesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46, suggesting that the difference in effect between subgroups was not statistically significant). Secondary outcomes did not differ between groups, except for FMH, which was higher under salvage in rhesus D (RhD)-negative women with RhD-positive babies (25.6% vs. 10.5%, adjusted OR 5.63, 95% CI 1.43 to 22.14; p = 0.013). No case of amniotic fluid embolism was observed. The additional cost of routine cell salvage during caesarean was estimated, on average, at £8110 per donor blood transfusion avoided. Conclusions: The modest evidence for an effect of routine use of cell salvage during caesarean section on rates of donor blood transfusion was associated with increased FMH, which emphasises the need for adherence to guidance on anti-D prophylaxis. We are unable to comment on long-term antibody sensitisation effects. Based on the findings of this trial, cell salvage is unlikely to be considered cost-effective. Future work: Research into risk of alloimmunisation among women exposed to cell salvage is needed. Trial registration: Current Controlled Trials ISRCTN66118656. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 2. See the NIHR Journals Library website for further project information.

Background. Neutrophil dysfunction in sepsis has been implicated in the pathogenesis of multiorgan failure; however, the role of neutrophil extracellular traps (NETs) remains uncertain. We aimed to determine the sequential changes in ex vivo NETosis and its relationship with mortality in patients with sepsis and severe sepsis. Methods. This was a prospective observational cohort study enrolling 21 healthy age-matched controls and 39 sepsis and 60 severe sepsis patients from acute admissions to two UK hospitals. Patients had sequential bloods for the ex vivo assessment of NETosis in response to phorbol-myristate acetate (PMA) using a fluorometric technique and chemotaxis using time-lapse video microscopy. Continuous data was tested for normality, with appropriate parametric and nonparametric tests, whilst categorical data was analysed using a chi-squared test. Correlations were performed using Spearman’s rho. Results. Ex vivo NETosis was reduced in patients with severe sepsis, compared to patients with sepsis and controls (p=0.002). PMA NETosis from patients with septic shock was reduced further (p