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BackgroundRecent research in machine-learning techniques has led to significant progress in various research fields. In particular, knowledge discovery using this method has become a hot topic in traditional Chinese medicine. As the key clinical manifestations of patients, symptoms play a significant role in clinical diagnosis and treatment, which evidently have their underlying traditional Chinese medicine mechanisms. ObjectiveWe aimed to explore the core symptoms and potential regularity of symptoms for diagnosing insomnia to reveal the key symptoms, hidden relationships underlying the symptoms, and their corresponding syndromes. MethodsAn insomnia dataset with 807 samples was extracted from real-world electronic medical records. After cleaning and selecting the theme data referring to the syndromes and symptoms, the symptom network analysis model was constructed using complex network theory. We used four evaluation metrics of node centrality to discover the core symptom nodes from multiple aspects. To explore the hidden relationships among symptoms, we trained each symptom node in the network to obtain the symptom embedding representation using the Skip-Gram model and node embedding theory. After acquiring the symptom vocabulary in a digital vector format, we calculated the similarities between any two symptom embeddings, and clustered these symptom embeddings into five communities using the spectral clustering algorithm. ResultsThe top five core symptoms of insomnia diagnosis, including difficulty falling asleep, easy to wake up at night, dysphoria and irascibility, forgetful, and spiritlessness and weakness, were identified using evaluation metrics of node centrality. The symptom embeddings with hidden relationships were constructed, which can be considered as the basic dataset for future insomnia research. The symptom network was divided into five communities, and these symptoms were accurately categorized into their corresponding syndromes. ConclusionsThese results highlight that network and clustering analyses can objectively and effectively find the key symptoms and relationships among symptoms. Identification of the symptom distribution and symptom clusters of insomnia further provide valuable guidance for clinical diagnosis and treatment.

Harmonious doctor-patient and nurse-patient communication are prerequisite for establishing a strong relationship with patients and ensuring the quality of nursing. This paper introduced the basic concept of doctor-patient communication, analyzed the role of doctor-patient and nurse-patient communication in clinical nursing work, investigated effective strategies of doctor-patient and nurse-patient communication, and provided reference for clinical nursing practice. (合理的医患沟通是建立良好护患关系、保证护理服务质量的前提和基础。本研究介绍医患沟通基本概念, 分析医患沟通在临床护理工作中的重要性, 研究临床护理中医患沟通的有效策略, 以期为临床开展医疗服务提供参考。)

Abstract Bladder carcinoma (BC) recurrence is a major clinical challenge, and targeting the tumor microenvironment (TME) is a promising therapy. However, the relationship between individual TME components, particularly cancer‐associated fibroblasts (CAFs), and tumor recurrence is unclear. Here, TME heterogeneity in primary and recurrent BC is investigated using single‐cell RNA sequence profiling of 62 460 cells. Two cancer stem cell (CSC) subtypes are identified in recurrent BC. An inflammatory CAF subtype, ICAM1+ iCAFs, specifically associated with BC recurrence is also identified. iCAFs are found to secrete FGF2, which acts on the CD44 receptor of rCSC‐M, thereby maintaining tumor stemness and epithelial‐mesenchymal transition. Additionally, THBS1+ monocytes, a group of myeloid‐derived suppressor cells (MDSCs), are enriched in recurrent BC and interacted with CAFs. ICAM1+ iCAFs are found to secrete CCL2, which binds to CCR2 in MDSCs. Moreover, elevated STAT3, NFKB2, VEGFA, and CTGF levels in iCAFs reshape the TME in recurrent tumors. CCL2 inhibition in an in situ BC mouse model suppressed tumor growth, decreased MDSCs and Tregs, and fostered tumor immune suppression. The study results highlight the role of iCAFs in TME cell–cell crosstalk during recurrent BC. The identification of pivotal signaling factors driving BC relapse is promising for the development of novel therapies.

The Belt and Road Initiative aims to achieve common development and prosperity for all countries. Building a scientific and reasonable geopolitical risk assessment system is an important prerequisite for participating countries to prevent and resolve geopolitical risk. Taking 64 countries in the six economic corridors of the Belt and Road Initiative as the assessment object, this study builds a geopolitical risk assessment system based on post-transaction costs. It analyzes the geopolitical risk level, spatial and temporal distribution characteristics, and influencing factors using the full array polygon graphical indicator method, Global Moran's I, and the spatial Durbin model. The research results show that: 1) From the time dimension, the geopolitical risks of participating countries show a trend of first rising and then falling, reaching a peak in 2015. 2) From the perspective of spatial distribution, high-risk areas are mainly concentrated in the Middle East and South Asia, while medium to high risk areas are concentrated in Indochina and the Arabian Peninsula. Most of the low to medium risk countries are Western Pacific island countries, while low-risk countries are mainly in Central Europe. The clustering characteristics of geopolitical risks are obvious. The results of Global Moran's I show that from 2011-2020, the geopolitical risk concentration area was initially located in the Middle East and South Asia, and then in 2015, Europe and East Asia also experienced high geopolitical risks. By 2020, it was still mainly concentrated in the Middle East and Eastern Europe, however, generally, the regions with high geopolitical risk will still be mainly concentrated in the Middle East and Eastern Europe. 3) The research results on the factors influencing geopolitical risks indicate that political stability, economic freedom, economic growth, increased education expenditure, and better natural resources have a significant inhibitory effect on geopolitical risk, while increases in the unemployment rate, population size, and oil resources, will to some extent, promote the generation of geopolitical risks. The indirect effect results show that political stability, economic freedom, and the unemployment rate of the host country have a significant impact on surrounding countries. Based on this, we believe that countries participating in the Belt and Road Initiative need to improve their government governance capabilities, accelerate their modernization transformation, effectively utilize the resources, funds, and technologies brought about by the Belt and Road Initiative. Furthermore, actively integrate into the regional economic cooperation framework of the Belt and Road Initiative and improve their ability to manage geopolitical risks. This study enriched the evaluation system of geopolitical risks. During the construction of the evaluation indicators, the results emphasized the sudden and violent characteristics of geopolitical risks, further explained the violent confrontation and economic game existing in geopolitical risks, and effectively enriched the literature on the spatial characteristics and influencing factors of geopolitical risks of countries participating in the Belt and Road Initiative. It should be pointed out that there are still some limitations in this study. This study is based on countries participating in the Belt and Road Initiative and there are deficiencies in the discussion of geopolitical risk for countries not in the region. Future research can be based on a global perspective, further enriching the evaluation index system of geopolitical risk, and conducting more in-depth research on the spatial transmission path and geopolitical risk avoidance measures.

Abstract Background As the common delayed complication of supracondylar fractures in children, cubitus valgus/varus deformity might lead to pain and loss of motion of the elbow. The current corrective treatment might not be accurate enough and even contribute to postoperative deformity. This study retrospectively analyzed the clinical value of preoperative simulated surgery on 3D model-assisted osteotomy feasibility verification and surgical guidance for cubitus valgus/varus deformity. Methods Seventeen patients were selected from January 2017 and November 2019. Deformities were analyzed from imaging data and 3D models and corrected after the simulated operations. The radiographic evaluation comprised osseous union, carrying angle, and anteversion angle of the distal humerus. The clinical evaluation was performed according to the Hospital for Special Surgery (HSS) scoring system. Results All patients underwent the operation successfully and had no postoperative deformity. The carrying angle was significantly improved postoperatively (P 0.05). The HSS score rose after surgery (P

Objective To investigate the application of nurse-led chain management in extended care of children undergoing surgical treatment for Hirschsprung’s disease. Methods Totally 60 children with Hirschsprung’s disease were divided into control group and observation group according to the sequence of hospital admission, with 30 cases in each group. The control group received routine perioperative nursing management, and a nurse-led chain management model was adopted in perioperative nursing management and extended care of children in the observation group. Intervention efficacy was evaluated via incidence of postoperative complications and satisfaction of children’s parents. Results The incidence of postoperative complications in the observation group was lower than that in the control group(P＜0. 05). Parents of children in the observation group were more satisfied with nursing service compared with those in the control group(P＜0. 01). Conclusion The nurse-led chain management in extended care is potentially effective to reduce the risk of postoperative complications and improve the quality of life of children with Hirschsprung’s disease. (目的 探讨以护士为主导的链式管理模式在先天性巨结肠患儿术后延续性护理中的应用效果。方法 将60例先天性巨结肠患儿按照入院时间分为对照组与观察组, 各30例。对照组接受常规先天性巨结肠围手术期管理模式, 观察组采用链式管理协同延续护理模式。干预6个月后评价效果。结果 观察组术后并发症发生率低于对照组, 差异有统计学意义(P＜0. 05)。观察组患儿家属对护理工作的满意度高于对照组, 差异有统计学意义(P＜0. 01)。结论 以护士为主导的链式管理模式有利于减少术后并发症的发生, 对提升先天性巨结肠患儿术后生活质量具有积极意义。)

For a uranium purification enterprise in the south of China, the waste residue (uranium grade 12000%), which is a mixture of rubble from the extraction in the purification system and other wastewater passing through the plate and frame after resting, has a complex composition, with the presence of diatomaceous earth as a filter aid in addition to the impurities such as acidic solids and organic matter produced in the uranium leaching process. The conventional natural treatment method has a poor leaching effect and a low uranium recovery rate with nitric acid heating. To this end, low-temperature chlorination roasting nitric acid leaching study was conducted, in which sodium chloride was added to the specimen for roasting pretreatment. Then the roasted model was leached using nitric acid. The effects of roasting temperature, sodium chloride addition, roasting time, sample size and other influencing factors on the leaching behavior of uranium were investigated. The experimental results show that the uranium leaching rate reaches 95.97% under the conditions of 20% NaCl addition, 200 ℃ roasting temperature, 2 hour roasting time, 7.4 mol/L nitric acid concentration, 80 ℃ leaching temperature and 2 hour leaching time, which is 19.52% higher than that of the conventional acid leaching process. The results show that the waste slag’s specific surface area and porosity increase significantly after pretreatment with sodium chloride roasting, which promots the dissociation of uranium and increased the contact area between uranium and acid, thus leading to a significant increase in the uranium leaching rate. And the chlorination roasting can have an activating effect on the metal components in the specimen. It can play a role in screening some oxides, such as silica, iron oxide, etc. Combined with the specimen’s physical and chemical composition analysis, it is due to the formation process of the illustration mixed with iron-containing flocculants, binders, and other substances to form uranium wrapping. At the same time, the chlorine and hydrogen chloride gas generated by sodium chloride roasting can be part of the iron components chlorinated into ferric chloride, and with the iron oxide in the process of confinement due to chemical gas phase migration reaction to generate chloride, which not only to uranium wrapping structure. This not only causes damage to the uranium wrapper structure, which allows more exposure of the uranium component but also has a catalytic effect on the uranium leaching process, which leads to a significant increase in the leaching rate of uranium. At the same time, because solid sodium chloride is used, the roasting conditions are relatively mild, and therefore the generation of contaminating gases is within the control range.

Background: Tumour mutational burden (TMB) has emerged as a predictive marker for responsiveness to immune checkpoint inhibitors (ICI) in multiple tumour types. It can be calculated from somatic mutations detected from whole exome or targeted panel sequencing data. As mutations are unevenly distributed across the cancer genome, the clinical implications from TMB calculated using different genomic regions are not clear. Methods: Pan-cancer data of 10,179 samples were collected from The Cancer Genome Atlas cohort and 6,831 cancer patients with either ICI or non-ICI treatment outcomes were derived from published papers. TMB was calculated as the count of non-synonymous mutations and normalised by the size of genomic regions. Dirichlet method, linear regression and Poisson calibration models are used to unify TMB from different gene panels. Results: We found that panels based on cancer genes usually overestimate TMB compared to whole exome, potentially leading to misclassification of patients to receive ICI. The overestimation is caused by positive selection for mutations in cancer genes and cannot be completely addressed by the removal of mutational hotspots. We compared different approaches to address this discrepancy and developed a generalised statistical model capable of interconverting TMB derived from whole exome and different panel sequencing data, enabling TMB correction for patient stratification for ICI treatment. We show that in a cohort of lung cancer patients treated with ICI, when using a TMB cutoff of 10 mut/Mb, our corrected TMB outperforms the original panel-based TMB. Conclusion: Cancer gene-based panels usually overestimate TMB, and these findings will be valuable for unifying TMB calculations across cancer gene panels in clinical practice.

Intending to decarbonize the chemical admixtures and promote the sustainable development of the construction industry, this paper investigated the feasibility of coffee extract as a renewable natural admixture to adjust the performance of cementitious materials. The influences of coffee extract with various concentrations on the compressive strength, setting time, hydration properties and microstructure development of cementitious materials were studied. Results showed that both hydration promoting and hydration retarding effects were brought about when using the coffee extract as the mixing water in preparing cementitious materials. The hydration promotion was attributed to the polyphenols in the coffee extract, which functioned as a Ca2+ captor in the pore solution of pastes through a complexation mechanism. The complex of polyphenols-Ca may form the initial seeds for the promoted hydration of cementitious materials. A low concentration of the coffee extract (≤0.05%) exerted a prominent hydration promoting effect on the hydration of cement, while the hydration retarding effect gradually became apparent for a coffee extract with high concentrations. Overall, the compressive strength of cementitious mortars with 0.05% coffee extract was increased by 18.6% at 28d owing to the formation of more hydration products, a 25.1% reduction in porosity, and the thick Ca(OH)2 crystals. As a result, a 5% optimum concentration of coffee extract achieved the best economic and environmental benefits for cementitious mortars. This study contributes a new solution for sustainable development in the construction industry, as the coffee extract is low carbon, natural, non-toxic, renewable and can be a superior alternative to chemical admixtures.

Objective To understand the current awareness of hemodialysis access-related knowledge in maintenance hemodialysis patients, summarize the existing problems and health needs, and provide opinions and suggestions for the development of health education plan. Methods The phenomenological research method of qualitative research was used to interview 15 maintenance hemodialysis patients, and the data were analyzed to refine the theme. Results After in-depth analysis, four themes were obtained: Insufficient knowledge of hemodialysis access; One-sided understanding of hemodialysis access protection; Dialysis patients have many doubts about diet knowledge, blood pressure control and thrombosis; Various sources of health education information. Conclusion Maintenance hemodialysis patients have a poor knowledge of hemodialysis access, and their awareness of protecting access is not strong. Medical staff should optimize the form of health education to meet the health needs of patients and improve the attention of patients to hemodialysis access. (目的 了解目前维持性血液透析患者血液透析血管通路(血透通路)相关知识的知晓情况, 总结其存在的问题以及健康需求, 为制定健康教育计划提供意见和建议。方法 采用质性研究中的现象学研究法, 深入访谈15名维持性血液透析患者, 并对资料进行分析, 提炼主题。结果 经过深入分析, 提炼出4个主题: 血透通路相关知识掌握不足; 对血透通路的保护认识片面; 透析患者对饮食知识、血压控制以及血栓形成方面存在许多疑惑; 健康教育信息来源多样。结论 维持性血液透析患者对血透通路相关知识的掌握程度较差, 保护通路的意识不强。医护人员应创新健康教育形式, 满足患者的健康需求, 提高患者对血透通路的重视程度。)

Objective To understand the feelings and to explore the motivations of domestic obese people undergoing bariatric surgery. Methods Phenomenological research design and semi-structural interviews were conducted on 15 obesity patients who undergoing bariatric surgery, and the collected data were analyzed with the method of Colaizzi Phenomenological analysis. Results By analyzing and sorting out the data, 5 themes related to the motivation of pursuing bariatric surgery were put forward: improving health and longevity; treating obesity-related complications; improving quality of life; improving appearance, self-image and social interaction, and controlling poor eating behavior. Conclusion Improving health and prolonging life, treating obesity-related diseases and optimizing quality of life are the biggest reasons for obesity patients to seek bariatric surgery. When giving patients the choice of obesity treatment and outcome education, these factors should be taken into account, which will help to individualization encourage obese patients to better accept bariatric surgery. (目的 了解国内肥胖人群进行减重手术的心理感受, 探索国内肥胖症患者寻求减重手术的动机。方法 对15名进行减重手术的肥胖症患者进行半结构访谈, 并用质性研究中的Colaizzi现象学研究方法整理、分析资料。结果 通过分析和整理资料提炼出减重手术动机相关的5个主题: 改善健康和寿命; 治疗肥胖相关合并症; 提高生活质量; 改善外表、自我形象和社会互动以及控制不良饮食行为。结论 改善健康延长寿命、治疗肥胖相关疾病和优化生活质量是促使肥胖症患者寻求减重手术的最主要的原因。当对患者进行肥胖症治疗方案选择和结果教育时, 医护人员应考虑上述因素, 个性化激励国内肥胖人群更好地接受减重手术。)

The adequate intake of energy and lysine for primiparous sows are necessary for maternal growth of sows and growth of their progeny. This study was conducted to evaluate the effects of dietary energy and lysine levels on primiparous sows and their progeny. A total of 48 gilts (Yorkshire × Landrace), with an initial body weight (BW) of 168.1 ± 9.71 kg and at day 35 of gestation, were allotted to eight treatment groups with a 2 × 4 factorial arrangement. The first factor was metabolizable energy levels in diet (3,265 or 3,365 kcal of ME/kg), and the second factor was lysine levels in diet (gestation 0.55%, 0.65%, 0.75%, 0.85%, lactation 0.70%, 0.85%, 1.00%, 1.15%). The BW gain (p = 0.07) and backfat thickness (p = 0.09) in the gestation period showed a tendency to be increased in sows fed the high-energy diets. In the lactation period, sows fed the high-energy diets tended to be greater BW (p = 0.09) and less BW loss (p = 0.05) than those of sows fed the low-energy diets. Sows fed high-energy diets had a tendency of greater piglet weight at day 21 of lactation and greater piglet weight gain (p = 0.08 and p = 0.08, respectively). Although the blood urea nitrogen (BUN) was increased linearly as dietary lysine level increased at day 110 of gestation (Linear, p = 0.03), the BUN was decreased linearly as dietary lysine level increase at day 21 of lactation (Linear, p < 0.01). In the composition of colostrum, sows fed high-energy diets had greater casein, protein, total solid, solid not fat, and free fatty acid concentrations than those of sows fed low-energy diets (p < 0.05). Supplementation of total lysine 0.75% for gestation and 1.00% for lactation with 3,365 kcal of ME/kg energy level could be applied to the primiparous sows’ diet to improve performance of sows and growth of their progeny.

This study was performed to evaluate the effects of dietary vitamin levels on physiological responses, blood profiles, and reproductive performance in gestating sows. A total of 52 F1 multiparous sows (Yorkshire × Landrace) with an average body weight of 223.5 ± 31.7 kg, an average parity of 6.4 ± 2.7, and an average backfat thickness of 18.5 ± 4.9 mm were divided into four treatment groups considering body weight, backfat thickness, and parity in a completely randomized design with 13 replicates. The treatments were 100% (V1), 300% (V3), 600% (V6) and 900% (V9) of the National Research Council (NRC) Nutrient Requirements of Swine. The gestation diet was formulated based on corn-soybean meal (SBM) and contained 3,265 kcal of metabolizable energy (ME)/kg and 12.00% crude protein. During the lactation period, all sows were fed the same commercial lactation diet. There was no significant difference in body weight of gestating sows. However backfat thickness tended to increase when higher levels of vitamins were provided to gestating sows (p < 0.10). When high levels of dietary vitamins were provided, the body weight change of lactating sows increased (p < 0.01). When sows were fed higher levels of vitamins, the feed intake of lactating sows tended to decrease (p = 0.06). There were no treatment differences in the number of total born, born alive, stillbirth piglets, or the body weight of piglets according to different dietary vitamin level. As dietary vitamin level increased, the serum concentration of 25(OH)D3 in sows at 90 days of gestation linearly increased (p < 0.01). Furthermore, the serum vitamin E level of gestating sows was linearly increased with increasing dietary vitamin level (p < 0.05). The current NRC vitamin requirements are sufficient for gestating sows and higher levels of vitamins in the gestation diet did not show any beneficial effects for gestating and lactating sows.

Amoxicillin and sulbactam are widely used compound drugs in animal food. The amoxicillin–sulbactam hybrid molecule can achieve better curative effects through the combination of the two drugs. However, its pharmacokinetic behavior needs to be explored. In this study, a randomized crossover experiment was performed to investigate the metabolism of the novel amoxicillin–sulbactam hybrid molecule in rats after gastric administration. Ultrahigh performance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) was used to isolate and to identify the metabolites in rats. Amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and sulbactam were eventually detected in the plasma, liver, urine, and kidneys; no hybrid molecules and their metabolites were detected in feces. The in vivo metabolism results showed that the hybrid molecule was absorbed into the body in the intestine, producing amoxicillin and sulbactam, then amoxicillin was partially metabolized to amoxicilloic acid and amoxicillin diketopiperazine, which are eventually excreted in the urine by the kidneys. In this study, four major metabolites of the amoxicillin–sulbactam hybrid molecule were identified and their metabolic pathways were speculated, which provided scientific data for understanding the metabolism of the hybrid molecule and for its clinical rational use.

Abstract Background The WRKY gene family is one of the most important families in higher plants. As transcription factors, they actively respond to biotic and abiotic stress and are also involved in plant development. Chinese jujube (Ziziphus jujuba Mill.) is the largest type of dried fruit tree in China in terms of production, but its production is largely limited by phytoplasma infection, and the information about the role of WRKY genes under phytoplasma stress was still limited. Results We identified 54 ZjWRKYs in the jujube genome and classified them into three subgroups according to conserved WRKY domains and zinc-finger structure. 41 ZjWRKYs were distributed on 11 of 12 pseudo chromosomes in Chinese jujube. The majority of ZjWRKYs were highly expressed in the seven examined tissues, indicating that they play multiple roles in these vegetative and reproductive organs. Transcriptome data showed that most of the characterised ZjWRKYs were highly expressed at later stages of fruit development. RT-qPCR demonstrated that the expression of 23 ZjWRKYs changed following phytoplasma infection, suggesting that they are involved in signalling pathways that respond to phytoplasma stress. Then, STRING analysis and yeast two-hybrid screening proved that some ZjWRKY proteins were interacting with ZjMAPKK proteins, which were also involved in phytoplasma invasion. Moreover, their differential expressions were further confirmed in resistant and susceptible jujube varieties under phytoplasma stress. These results suggest that ZjWRKYs play significant roles in phytoplasma tolerance and should be crucial candidate genes for jujube-phytoplasma interaction. Conclusions 54 ZjWRKYs in Chinese jujube were identified and classified into three subgroups. 41 ZjWRKYs were unevenly distributed along the chromosomes. The majority of ZjWRKYs were highly expressed in various tissues. Most of the ZjWRKYs were positive responses to phytoplasma invasion, and that provided candidate genes for the future studies of jujube-phytoplasma interaction.

Objective This experiment was conducted to investigate the effect of reducing dietary metabolic energy (ME) and crude protein (CP) levels on growth performance, blood profiles, and nutrient digestibility in weaning pigs. Methods A total of 240 crossbred pigs (Duroc×[Landrace×Yorkshire]) with an average body weight of 8.67±1.13 kg were used for a 6-week feeding trial. Experimental pigs were allotted to a 2×3 factorial arrangement using a randomized complete block design. The first factor was two levels of dietary ME density (low ME level, 13.40 MJ/kg or high ME level, 13.82 MJ/kg) and the second factor was three dietary CP levels based on subdivision of early and late weaning phases (low CP level, 19.7%/16.9%; middle CP level, 21.7%/18.9%; or high CP level, 23.7%/20.9%). Results Over the entire experimental period, there were no significant difference in body weight among groups, but a decrease in diet energy level was associated with an increase in average daily feed intake (p = 0.02) and decrease in gain-feed ratio (G:F) ratio (p

Objective This study was conducted to evaluate the effects of dietary cashew nut testa (CNT) as an alternative feed ingredient to wheat bran on reproductive performance, litter performance, milk composition, and blood profiles of gestating sows. Methods Forth multiparous sows (Yorkshire×Landrace) were fed experimental diets starting at 35 days of pregnancy and an initial average body weight (BW) of 211.53±8.86 kg. Each sow was assigned to a treatment based on BW, backfat thickness (BF) and parity with 10 sows per treatment. Treatments were as follows: i) corn-soybean meal based diet with 6% of wheat bran (C0); ii) basal diet with 2% of CNT and 4% of wheat bran (C2); iii) basal diet with 4% of CNT and 2% of wheat bran (C4); and iv) basal diet with 6% of CNT (C6). Results There were no statistically significant differences in BW and BF of gestating sows throughout the experimental period. However, changes in BF (p = 0.09) and the daily feed intake of sows (p = 0.09) tended to linearly increase during the lactation period. The weaning to estrus interval (WEI) showed a quadratic response to CNT treatment (p = 0.02), and the C2 diet showed the shortest WEI. Litter birth weight (p = 0.04) and piglet birth weight (p = 0.06) were linearly decreased with increase in CNT. Furthermore, there had no significant differences in piglet weight and litter weight in 21 day. Insulin concentration at day 70 of gestation was linearly reduced with increasing CNT level in diets (p = 0.03). Conclusion When 6% CNT replaced wheat bran in gestating sow diets, there were no negative effects on sow performance, but litter birth weight and piglet birth weight were decreased when CNT level increased in gestating sow diets.

Abstract Background Chinese jujube (Ziziphus jujuba Mill.) is one of the most important members in the Rhamnaceae family. The whole genome sequence and more than 30,000 proteins of Chinese jujube have been obtained in 2014. Mitogen-activated protein kinase cascades are universal signal transduction modules in plants, which is rapidly activated under various biotic and abiotic stresses. To date, there has been no comprehensive analysis of the MAPK and MAPKK gene family in Chinese jujube at the whole genome level. Results By performing a series of bioinformatics analysis, ten MAPK and five MAPKK genes were identified from the genome database of Chinese jujube, and then compared with the homologous genes from Arabidopsis. Phylogenetic analysis showed that ZjMAPKs was classified into four known groups, including A, B, C and D. ZjMAPKs contains five members of the TEY phosphorylation site and five members with the TDY motif. The ZjMAPKK family was subsequently divided into three groups, A, B and D. The gene structure, conserved motifs, functional annotation and chromosome distribution of ZjMAPKs and ZjMAPKKs were also predicted. ZjMAPKs and ZjMAPKKs were distributed on nine pseudo-chromosomes of Chinese jujube. Subsequently, expression analysis of ZjMAPK and ZjMAPKK genes using reverse transcription PCR and quantitative real-time PCR was carried out. The majority of ZjMAPK and ZjMAPKK genes were expressed in all tested organs/tissues with considerable differences in transcript levels indicating that they might be constitutively expressed. Moreover, ZjMKK5 was specific expressed in early development stage of jujube flower bud, indicating it plays some roles in reproductive organs development. The transcript expression of most ZjMAPK and ZjMAPKK genes was down-regulated in response to plant growth regulators, darkness treatment and phytoplasma infection. Conclusions We identified ten ZjMAPK and five ZjMAPKK genes from the genome database of Chinese jujube, the research results shown that ZjMPKs and ZjMKKs have the different expression patterns, indicating that they might play different roles in response to various treatments. The results provide valuable information for the further elucidation of physiological functions and biological roles of jujube MAPKs and MAPKKs.

Objective This study was conducted to evaluate various wheat supplementation levels on growth performance, blood profiles, nutrient digestibility, and pork quality in growing-finishing pigs. Methods A total of 120 growing pigs ([Yorkshire×Landrace]×Duroc), with an average 27.75± 1.319 kg body weight, were used in growth trial. Pigs were allotted into each treatment by body weight and sex in 4 replicates with 6 pigs per pen in a randomized complete block design. Four-phase feeding programs were used in this experiment. The treatments included the following: i) corn-soybean meal (SBM) – based diet (CON), ii) corn-SBM – based diet+15% of wheat (W15), iii) corn-SBM – based diet+30% of wheat (W30), iv) corn-SBM – based diet+45% of wheat (W45), and 5) corn-SBM–based diet+60% of wheat (W60). Results There was no significant difference in growth performance among the dietary treatments. However, the gain-to-feed (G:F) ratio tended to increase (quadratic, p

24 cycles Ti-TiN-Zr-ZrN soft-hard alternating multilayer film was deposited on TC11 titanium alloy by vacuum cathodic arc deposition method. The structure and performance of the multilayer film, especially wear and sand erosion resistance were investigated by various analytical methods including pin on disc wear tester, sand erosion tester, 3D surface topography instrument, scanning electron microscopy (SEM), X-ray diffraction(XRD), micro-hardness tester and scratch adhesion tester. The results indicate that the Vickers-hardness of the multilayer film with thickness of 5.8μm can reach up to 28.10GPa. The adhesive strength of these coatings can be as high as 56N. Wear rate of the multilayer coated alloy is one order of magnitude smaller than bare one, which decreased from 7.06×10-13 m3·N-1·m-1 to 3.03×10-14m3·N-1·m-1. Multilayer films can play the role in hindering the extension of cracks, and thus sand erosion properties of the TC11 titanium alloy substrates are improved.

The problem of inaccurate results was presented based on irregular shell finite element analysis using traditional modeling methods,a finite element modeling method was presented based on simplified of transmission components. The paper introduced the bearings,gears and fasteners of simplified model method. For example,finite element analysis of automobile main reducer shell based on finite element software environment. Two finite element analysis models were established based on traditional method and simplify component method; Comparing simulation results of the two models found: stress distribution on the overall trend of automobile main reducer Shell was the same,but the value of the local area to install the bearing stress positions were quite different. Stress tests show in 100 N. m,200 N. m and 400 N. m of input torque main reducer: Simplified model approach closer to actual value of test results,verify the correctness and accuracy of the method.

This study was conducted to evaluate the effects of L-arginine supplementation levels during late gestation on reproductive performance and piglet uniformity in high prolific sows. A total of 60 F1 multiparous sows (Yorkshire × Landrace), with an average body weight of 238.2 kg, were allotted to one of three treatment groups in a completely randomized design. The dietary treatments were divided by the supplementation level of arginine during the late-gestation period, from day 70 to farrowing, as follows—(1) CON: corn-soybean meal-based basal diet (Arg 0.72%), (2) Arg10: basal diet + L-Arg 0.28% (Arg 1.0%), and (3) Arg15: basal diet + L-Arg 0.79% (Arg 1.5%). The same lactation diet was provided ad libitum to sows during the lactation period. There were no significant differences in body weight and backfat thickness in sows during late-gestation and lactation. Dietary arginine levels had no significant influences on the number of total born, stillbirth, and born alive. However, increasing inclusion level of L-arginine supplementation tended to increase (p < 0.10) alive litter weight linearly, and also linearly increased (p < 0.05) the piglet weight gain and litter weight gain during the lactation period. In piglet uniformity, the standard deviation of piglet birth weight (p < 0.05) and the coefficient of variation for piglet birth weight (p < 0.10) increased linearly, as dietary arginine levels increased in the late gestation period. Increasing L-arginine supplementation to late gestating sows linearly increased (p < 0.05) the blood concentrations of arginine and ornithine at day 90 and day 110 of gestation. On the other hand, dietary arginine levels in late gestation did not affect the blood parameters related to the nitrogen utilization. Increasing dietary arginine levels for the late gestating sows did not affect the milk composition for colostrum and milk at day 21 of lactation. In conclusion, the inclusion level of arginine in the diet for late gestating sows, by up to 1.5%, could improve the alive litter weight at birth and litter weight gain during lactation, whereas the piglet uniformity at birth was decreased due to the increase of survival for fetuses with light birth weight.

Enrofloxacin is a poorly soluble antibacterial drug of the fluoroquinolones class used in veterinary medicine. The main purpose of this work was to investigate the structural and pharmaceutical properties of new enrofloxacin salts. Enrofloxacin anhydrate and its organic salts with tartaric acid, nicotinic acid and suberic acid formed as pure crystalline anhydrous solids. All the crystals were grown from a mixed solution by slow evaporation at room temperature. These products were then characterized by field-emission scanning electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry. Further, X-ray single crystal diffraction analysis was used to study the crystal structure. The intermolecular interactions and packing arrangements in the crystal structures were studied, and the solubility of these salts in water was determined using high-performance liquid chromatography. The results show that the new salts of enrofloxacin developed in this study exhibited excellent water solubility.

Post-ischemic changes in cellular metabolism alter myocardial and neurological function. Pyruvate dehydrogenase (PDH), the limiting step in mitochondrial glucose oxidation, is inhibited by increased expression of PDH kinase (PDK) during ischemia/reperfusion injury. This results in decreased utilization of glucose to generate cellular ATP. Post-cardiac arrest (CA) hypothermia improves outcomes and alters metabolism, but its influence on PDH and PDK activity following CA are unknown. We hypothesized that therapeutic hypothermia (TH) following CA is associated with the inhibition of PDK activity and increased PDH activity. We further hypothesized that an inhibitor of PDK activity, dichloroacetate (DCA), would improve PDH activity and post-CA outcomes.Anesthetized and ventilated adult female C57BL/6 wild-type mice underwent a 12-minute KCl-induced CA followed by cardiopulmonary resuscitation. Compared to normothermic (37°C) CA controls, administering TH (30°C) improved overall survival (72-hour survival rate: 62.5% vs. 28.6%, P

Granulocyte-colony stimulating factor (G-CSF) has molecular structures and intracellular signaling pathways that are similar to those of leptin and ciliary neurotropic factor (CNTF). It also has immune-modulatory properties. Given that leptin and CNTF play important roles in energy homeostasis and that obesity is an inflammatory condition in adipose tissue, we hypothesized that G-CSF could also play a role in energy homeostasis. We treated 12 38-week-old male Otsuka-Long-Evans-Tokushima fatty rats (OLETF, diabetic) and 12 age-matched male Long-Evans-Tokushima rats (LETO, healthy) with 200 µg/day G-CSF or saline for 5 consecutive days. Body weight reduction was greater in G-CSF-treated OLETF (G-CSF/OLETF) than saline-treated OLETF (saline/OLETF) following 8 weeks of treatment (-6.9±1.6% vs. -3.1±2.2%, p

BACKGROUND: The protective effects of granulocyte colony-stimulating factor (G-CSF) have been demonstrated in a variety of renal disease models. However, the influence of G-CSF on diabetic nephropathy (DN) remains to be examined. In this study, we investigated the effect of G-CSF on DN and its possible mechanisms in a rat model. METHODS: Otsuka Long-Evans Tokushima Fatty (OLETF) rats with early DN were administered G-CSF or saline intraperitoneally. Urine albumin creatinine ratio (UACR), creatinine clearance, mesangial matrix expansion, glomerular basement membrane (GBM) thickness, and podocyte foot process width (FPW) were measured. The levels of interleukin (IL)-1β, transforming growth factor (TGF)-β1, and type IV collagen genes expression in kidney tissue were also evaluated. To elucidate the mechanisms underlying G-CSF effects, we also assessed the expression of G-CSF receptor (G-CSFR) in glomeruli as well as mobilization of bone marrow (BM) cells to glomeruli using sex-mismatched BM transplantation. RESULTS: After four weeks of treatment, UACR was lower in the G-CSF treatment group than in the saline group (p

Nonalcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome. In this study, we investigated histological and biochemical changes in NAFLD and the gene expression involving de novo lipogenesis in Otsuka Long-Evans Tokushima fatty (OLETF) rats. We used OLETF rats and Long-Evans Tokushima Otsuka (LETO) rats as animal models of NAFLD and as controls, respectively. Consistent observations were made at 4-week intervals up to 50 weeks of age, and all rats were fed ad libitum with standard food. Biochemical and histological changes were observed, and gene expression involved in de novo lipogenesis was measured using real-time polymerase chain reactions. As a results hepatic micro- and macrovesicular steatosis and hepatocyte ballooning were evident in the OLETF rats at 22–38 weeks of age but disappeared after 42 weeks; no fibrosis or collagen deposition was observed. Gene expression involved in de novo lipogenesis followed a pattern similar to that of the histological changes. In conclusion, in the absence of dietary manipulation, hepatic steatosis in OLETF rats is evident at 22–38 weeks and declines after 42 weeks. Therefore, OLETF rats at 22–38 weeks are recommended as animal models of hepatic steatosis.

Human amniotic epithelial cells (h-AECs), which have various merits as a cell source for cell therapy, are known to differentiate into cardiomyocytes in vitro. However, the ability of h-AECs to differentiate into cardiomyocytes in vivo and their cell transplantation effects on myocardial infarction are still unknown. In this study, we assessed whether h-AECs could differentiate into cardiomyocytes in vivo and whether h-AECs transplantation can decrease infarct size and improve cardiac function, in comparison to transplantation of cord blood-derived mesenchymal stem cells (MSCs) or adipose tissue-derived MSCs. For our study, we injected h-AECs, cord blood-derived MSCs, adipose tissue-derived MSCs, and saline into areas of myocardial infarction in athymic nude rats. After 4 weeks, 3% of the surviving h-AECs expressed myosin heavy chain, a marker specific to the myocardium. Compared with the saline group, all cell-implanted groups showed a higher ejection fraction, lower infarct area by positron emission tomography and histology, and more abundant myocardial gene and protein expression in the infarct area. We showed that h-AECs can differentiate into cardiomyocyte-like cells, decrease infarct size, and improve cardiac function in vivo. The beneficial effects of h-AECs were comparable to those of cord blood and adipose tissue-derived MSCs. These results support the need for further studies of h-AECs as a cell source for myocardial regeneration due to their plentiful availability, low immunity, and lack of ethical issues related to their use.

Abstract Background There is ample evidence that psychological stress adversely affects many diseases. Recent evidence has shown that intense stressors can increase inflammation within the brain, a known mediator of many diseases. However, long-term outcomes of chronic psychological stressors that elicit a neuroinflammatory response remain unknown. Methods To address this, we have modified previously described models of rat/mouse predatory stress (PS) to increase the intensity of the interaction. We postulated that these modifications would enhance the predator-prey experience and increase neuroinflammation and behavioral dysfunction in prey animals. In addition, another group of mice were subjected to a modified version of chronic unpredictable stress (CUS), an often-used model of chronic stress that utilizes a combination of stressors that include physical, psychological, chemical, and other. The CUS model has been shown to exacerbate a number of inflammatory-related diseases via an unknown mechanism. Using these two models we sought to determine: 1) whether chronic PS or CUS modulated the inflammatory response as a proposed mechanism by which behavioral deficits might be mediated, and 2) whether chronic exposure to a pure psychological stressor (PS) leads to deficits similar to those produced by a CUS model containing psychological and physical stressors. Finally, to determine whether acute PS has neuroinflammatory consequences, adult mice were examined at various time-points after PS for changes in inflammation. Results Adolescent mice subjected to chronic PS had increased basal expression of inflammation within the midbrain. CUS and chronic PS mice also had an impaired inflammatory response to a subsequent lipopolysaccharide challenge and PS mice displayed increased anxiety- and depressive-like behaviors following chronic stress. Finally, adult mice subjected to acute predatory stress had increased gene expression of inflammatory factors. Conclusion Our results demonstrate that predatory stress, an ethologically relevant stressor, can elicit changes in neuroinflammation and behavior. The predatory stress model may be useful in elucidating mechanisms by which psychological stress modulates diseases with an inflammatory component.

Abstract Background Haematological traits, which consist of mainly three components: leukocyte traits, erythrocyte traits and platelet traits, play extremely important role in animal immune function and disease resistance. But knowledge of the genetic background controlling variability of these traits is very limited, especially in swine. Results In the present study, 18 haematological traits (7 leukocyte traits, 7 erythrocyte traits and 4 platelet traits) were measured in a pig resource population consisting of 368 purebred piglets of three breeds (Landrace, Large White and Songliao Black Pig), after inoculation with the swine fever vaccine when the pigs were 21 days old. A whole-genome scan of QTL for these traits was performed using 206 microsatellite markers covering all 18 autosomes and the X chromosome. Using variance component analysis based on a linear mixed model and the false discovery rate (FDR) test, 35 QTL with FDR < 0.10 were identified: 3 for the leukocyte traits, 28 for the erythrocyte traits, and 4 for the platelet traits. Of the 35 QTL, 25 were significant at FDR < 0.05 level, including 9 significant at FDR < 0.01 level. Conclusions Very few QTL were previously identified for hematological traits of pigs and never in purebred populations. Most of the QTL detected here, in particular the QTL for the platelet traits, have not been reported before. Our results lay important foundation for identifying the causal genes underlying the hematological trait variations in pigs.

Abstract Background Ganciclovir (GCV) is widely used in solid organ and haematopoietic stem cell transplant patients for prophylaxis and treatment of cytomegalovirus. It has long been considered a mutagen and carcinogen. However, the contribution of GCV to cancer incidence and other factors that influence its mutagenicity remains unknown. Methods This retrospective cohort study analysed genomics data for 121,771 patients who had undergone targeted sequencing compiled by the Genomics Evidence Neoplasia Information Exchange (GENIE) or Foundation Medicine (FM). A statistical approach was developed to identify patients with GCV-associated mutational signature (GCVsig) from targeted sequenced data of tumour samples. Cell line exposure models were further used to quantify mutation burden and DNA damage caused by GCV and other antiviral and immunosuppressive drugs. Results Mutational profiles from 22 of 121,771 patient samples in the GENIE and FM cohorts showed evidence of GCVsig. A diverse range of cancers was represented. All patients with detailed clinical history available had previously undergone solid organ transplantation and received GCV and mycophenolate treatment. RAS hotspot mutations associated with GCVsig were present in 9 of the 22 samples, with all samples harbouring multiple GCV-associated protein-altering mutations in cancer driver genes. In vitro testing in cell lines showed that elevated DNA damage response and GCVsig are uniquely associated with GCV but not acyclovir, a structurally similar antiviral. Combination treatment of GCV with the immunosuppressant, mycophenolate mofetil (MMF), increased the misincorporation of GCV in genomic DNA and mutations attributed to GCVsig in cell lines and organoids. Conclusions In summary, GCV can cause a diverse range of cancers. Its mutagenicity may be potentiated by other therapies, such as mycophenolate, commonly co-prescribed with GCV for post-transplant patients. Further investigation of the optimal use of these drugs could help reduce GCV-associated mutagenesis in post-transplant patients.

Objective To evaluate the effect of the proximal and central bundles of the interosseous membrane on the stability of proximal radioulnar joint. Methods Twenty fresh samples of human forearm provided by the anatomy room of the Department of Human Anatomy of Nanjing Medical University were included in this study. They were used to explore the effect of proximal interosseous membrane bundle on the stability of proximal radioulnar joint. The proximal bundle was reconstructed along the original attachment point. The reconstructions of central bundle were divided into the reconstruction of original attachment point on radius‐midpoint of the ulnar original attachment point (reconstruction A) and original attachment point reconstruction (reconstruction B). The loads of the proximal radioulnar joint in different positions were measured. The load of the proximal radioulnar joint was analyzed in neutral, pronation, and supination positions. Results After resection of proximal and central fascicles, the loads of proximal radioulnar joint in neutral, pronation, and supination positions were significantly lower than those before resection (P 0.05). In supination position, the load of reconstruction B was higher than that of reconstruction A (P

Tulathromycin is a semi-synthetic macrolide antimicrobial that has an important role in veterinary medicine for respiratory disease. The objective of the study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model to examine the efficacy and determine an optimal dosage of tulathromycin intramuscular (IM) treatment against Haemophilus parasuis infection induced after intraperitoneal inoculation in neutropenic guinea pigs. The PKs of tulathromycin in serum and lung tissue after intramuscular administration at doses of 1, 10, and 20 mg/kg in H. parasuis-infected neutropenic guinea pigs were evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The tulathromycin minimum inhibitory concentration (MIC) against H. parasuis was ~16 times lower in guinea pig serum (0.03 μg/mL) than in cation-adjusted Mueller-Hinton broth (CAMHB) (0.5 μg/mL). The ratio of the 168-h area under the concentration-time curve (AUC) to MIC (AUC168h/MIC) positively correlated with the in vivo antibacterial effectiveness of tulathromycin (R2 = 0.9878 in serum and R2 = 0.9911 in lung tissue). The computed doses to achieve a reduction of 2-log10 CFU/lung from the ratios of AUC72h/MIC were 5.7 mg/kg for serum and 2.5 mg/kg for lung tissue, which lower than the values of 13.2 mg/kg for serum and 8.9 mg/kg for lung tissue with AUC168h/MIC. In addition, using as objective a 2-log10 reduction and an AUC0−72h as the value of the PK/PD index could be more realistic. The results of this study could provide a solid foundation for the application of PK/PD models in research on macrolide antibiotics used to treat respiratory diseases.

Environments where antibiotics are used indiscriminately exhibit microbial communities that can represent hot-spots of resistance gene enrichment, which in turn could spread to humans. Here, the authors characterize how exposure to swine farms environment lead to temporal changes in the gut microbiome and resistome of healthy veterinary students.

This experiment was conducted to evaluate the effect of dietary energy and crude protein (CP) levels on growth performance, blood profiles, and carcass traits in growing-finishing pigs. A total of 180 crossbred pigs ([Yorkshire × Landrace] × Duroc) with an average body weight of 30.96 ± 3.068 kg were used for a 12-week feeding trial. Experimental pigs were allotted to a 2 × 3 factorial arrangement using a randomized complete block (RCB) design. The first factor was two levels of dietary metabolizable energy (ME) density (13.40 MJ/kg or 13.82 MJ/kg), and the second factor was three dietary CP levels based on subdivision of growing-finishing phases (high: 18%/16.3%/16.3%/13.2% middle: 17%/15.3%/15.3%/12.2% and low: 16%/14.3%/14.3%/11.2%). Average daily gain (ADG) and gain-feed ratio (G:F ratio) decreased as dietary CP level was decreased linearly (linear, p < 0.05; p < 0.05, respectively) in the early growing period, and G:F ration also decreased as dietary CP level was decreased linearly (linearly, p < 0.05) over the whole growing phase. Over the entire experimental period, G:F ratio decreased as dietary ME level decreased (p = 0.01). Blood urea nitrogen (BUN) concentration was increased as dietary energy level decreased in growing period (p < 0.01). During finishing period, total protein concentration was decreased by lower dietary energy level (p < 0.05). In this study, there were no significant differences in proximate factors, physiochemical properties, muscle TBARS assay results, pH changes, or color of pork by dietary treatments. However, saturated fatty acid (SFA) increased (p < 0.01) and polyunsaturated fatty acid (PUFA) decreased (p < 0.05) when ME was decreased by 0.42 MJ/kg in growing-finishing pig diets. In addition, monounsaturated fatty acid (MUFA) tended to increase when CP level was decreased in growing-finishing pig diets (p = 0.06). A growing-finishing diet of 13.82 MJ/kg diet of ME with the high CP level can improve growth performance and show better fatty acids composition of pork.

This experiment was conducted to evaluate the effect of dietary energy and crude protein (CP) levels on reproductive performance, litter performance, milk quality, and blood profiles in gestating sows. A total of 59 multiparous sows (Yorkshire × Landrace) with similar body weights (BW), backfat thickness (BF), and parity were assigned to one of six treatments with 9 or 10 sows per treatment using a 2 × 3 factorial arrangement and completely randomized design. The first factor was two levels of dietary metabolizable energy (ME) density (13.40 or 13.82 MJ/kg) and the second factor was three dietary protein levels based from 35 day in gestating phases (10.5%, 12%, and 13.5%). Backfat thickness change in lactating sows decreased linearly as CP level increased (p = 0.03). Increased energy level in the gestating sow diet tended to increase the total number of piglets born (p = 0.07), but piglet weight decreased (p = 0.02). Dietary CP level had a negative effect on colostrum quality. Casein, protein, total solid, and solids-not-fat concentrations decreased linearly and lactose level increased linearly as CP level in the gestating sow diet increased (casein%: p = 0.03; protein%: p = 0.04; lactose%: p = 0.06; total solids: p = 0.03; solid-not-fat: p = 0.03, respectively). However, improving ME by 0.42 MJ/kg had no significant effect on the chemical composition of sow colostrum. There were no significant differences in blood glucose concentration in gestating sows when sows were fed different levels of energy during gestation, but blood glucose increased at 21 day of lactation when energy increased by 0.42 MJ/kg (p = 0.04). Blood urea nitrogen concentration increased linearly when dietary CP levels increased at 110 day in gestation, 24-hours postpartum, and 21 days of lactation (linear, p < 0.05, p < 0.05, and p < 0.05, respectively), and it also increased when dietary energy increased at 110 days of gestation and 24-hours postpartum (p < 0.01, and p < 0.01, respectively). A gestating sow diet containing 13.82 MJ/kg ME and 10.5% CP can improve reproductive performance, litter performance, and colostrum quality.

Cancer genomes with mutations in the exonuclease domain of Polymerase Epsilon (POLE) present with an extraordinarily high somatic mutation burden. In vitro studies have shown that distinct POLE mutants exhibit different polymerase activity. Yet, genome-wide mutation patterns and driver mutation formation arising from different POLE mutants remains unclear. Here, we curated somatic mutation calls from 7,345 colorectal cancer samples from published studies and publicly available databases. These include 44 POLE mutant samples including 9 with whole genome sequencing data available. The POLE mutant samples were categorized based on the specific POLE mutation present. Mutation spectrum, associations of somatic mutations with epigenomics features and co-occurrence with specific driver mutations were examined across different POLE mutants. We found that different POLE mutants exhibit distinct mutation spectrum with significantly higher relative frequency of C>T mutations in POLE V411L mutants. Our analysis showed that this increase frequency in C>T mutations is not dependent on DNA methylation and not associated with other genomic features and is thus specifically due to DNA sequence context alone. Notably, we found strong association of the TP53 R213* mutation specifically with POLE P286R mutants. This truncation mutation occurs within the TT[C>T]GA context. For C>T mutations, this sequence context is significantly more likely to be mutated in POLE P286R mutants compared with other POLE exonuclease domain mutants. This study refines our understanding of DNA polymerase fidelity and underscores genome-wide mutation spectrum and specific cancer driver mutation formation observed in POLE mutant cancers.

Objective This experiment was conducted to investigate the influence of rapeseed meal (RSM) supplementation in weaning pig diet on growth performance, blood profile, carcass characteristics and economic analysis on weaning to finishing pigs. Methods A total of 120 cross bred ([Yorkshire×Landrace]×Duroc) weaning pigs were allotted to 5 treatments in a randomized complete block design. Each treatment had 4 replications with 6 pigs per pen. Five different levels of RSM (0%, 2%, 4%, 6%, and 8%) were used as dietary treatments. Results Overall, no treatment showed significant differences in growth performance with increased dietary RSM levels. The concentration of blood urea nitrogen (BUN) decreased as dietary RSM levels increased in 6 weeks (linear response, p

Pharmacokinetics of cyadox (CYX) and its major metabolites in healthy swine was investigated in this paper. 1,4-Bisdesoxycyadox (BDCYX), cyadox-1-monoxide (CYX-1-O) and quinoxaline-2-carboxylic acid (QCA), three main metabolites of cyadox, were synthesized by College of Science, China Agricultural University. Cyadox (CYX) was administered to 8 healthy cross-bread swine intravenously (i.v.) and orally (p. o.) at a dosage of 1 mg kg−1 body weight and 40 mg kg−1 body weight respectively in a randomized crossover design test with 2-wk washout period. A sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the determination of cyadox and its major metabolites in plasma. CYX and its major metabolites BDCYX, and CYX-1-O can be detected after intravenous administration of cyadox while CYX and its metabolites BDCYX, CYX-1-O and QCA can be detected after oral administration of CYX. Plasma concentration vs. time profiles of CYX and its major metabolites were analyzed by non-compartmental pharmacokinetic method. Following i.v. administration, the areas under the plasma concentration-time curve (AUC0-∞) were (0.38±0.03) μg mL−1 h (CYX), (0.018±0.002) μg mL−1 h (BDCYX) and (0.17±0.02) μg mL−1 h (CYX-1-O), respectively. The terminal elimination half-lives (t1/2lz) were determined to be (0.93±0.07) h (CYX), (1.45±0.04) h (BDCYX), and (0.92±0.04) h (CYX-1-O), respectively. Steady-state distribution volume (Vss) of (2.14±0.11) L kg−1 and total body clearance (CL) of (2.84±0.19) L h−1 kg−1 were determined for CYX after i.v. dosing. The bioavailability (F) of CYX was 2.85% for oral administration. After single i.v. administration, peak plasma concentrations (Cmax) of (1.08±0.06) μg mL−1 (CYX), (0.0068± 0.0004) μg mL−1 (BDCYX) and (0.25±0.03) μg mL−1 (CYX-1-O) were observed at Tmax of 0.033 h (CYX), 1 h (BDCYX) and 0.033 h (CYX-1-O), respectively. The main pharmacokinetic parameters after p.o. administration were as follows: AUC0-∞ were (0.42±0.04) μg mL−1 h (CYX), (1.38±0.14) μg mL−1 h (BDCYX), (0.59±0.02) μg mL−1 h (CYX-1-O) and (1.48±0.09) μg mL−1 h (QCA), respectively. t1/2lz were (4.77±0.33) h (CYX), (5.77±0.56) h (BDCYX), (4.12±0.28) h (CYX-1-O), and (8.51±0.39) h (QCA), respectively. After p.o. administration, Cmaxs of (0.033±0.002) μg mL−1 (CYX), (0.22±0.03) μg mL−1 (BDCYX), (0.089±0.005) μg mL−1 (CYX-1-O), and (0.17± 0.01) μg mL−1 (QCA) were observed at Tmax of (7.38±0.33) h (CYX), (7.25±0.31) h (BDCYX), (7.38±0.33) h (CYX-1-O), and (7.25±0.31) h (QCA), respectively. The results showed that CYX was slowly absorbed after oral administration and most of CYX was transformed to its metabolites in swine. The area under plasma concentration-time curve (AUC0-∞) of metabolites were higher than that of CYX after p.o. administration, and the elimination half-lives (t1/2lz) of QCA were longer than those of CYX, CYX-1-O, and BDCYX after oral administration.

Background and rationale. Non-alcoholic hepatic steatosis refers to the accumulation of triglycerides in the liver in the absence of alcohol consumption. Granulocyte colony-stimulating factor (G-CSF) has been reported to be an effective treatment for a variety of liver diseases. We examined the possible therapeutic effects of G-CSF on non-alcoholic hepatic steatosis in rats.Material and methods. Thirty-week-old Otsuka Long Evans Tokushima Fatty (OLETF) rats received water containing 30% sucrose for 8 weeks to promote the development of non-alcoholic hepatic steatosis. After development of the model, the rats were injected with G-CSF (100 Mg/kg/day) or saline for 5 days. Four weeks after this treatment, serum levels of glucose, total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and free fatty acids (FFA) were measured. Histology was examined by hematoxylin and eosin (H-E) and periodic acid Schiff (PAS) staining, and levels of expression of hepatic lipogenic enzymes were determined by RT-PCR.Results. The G-CSF-treated rats displayed significantly fewer lipid droplets than the saline-treated rats (P < 0.01), and their levels of sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) mRNAs were also lower (P < 0.01), as were their liver weight and serum levels of TG and FFA (P < 0.05).Conclusion. Our results indicate that G-CSF ameliorated non-alcoholic hepatic steatosis in the OLETF rat, and this therapeutic effect involved a reduction of SREBP-1c expression. Therefore, G-CSF deserves further study as a potential treatment for non-alcoholic hepatic steatosis.

An accurate and precise method for the determination of tulathromycin in swine plasma was developed and validated. Plasma samples were analyzed by high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS) using electrospray ionization (ESI). Tulathromycin was extracted from plasma by precipitation with acetonitrile and separated using a Phenomenex Luna 5 μm C18 column (150 mm×2.0 mm) at a flow rate of 0.25 mL min−1. Solvent A consisted of 0.002 mol L−1 ammonium acetate and formic acid (999:1, v/v), and solvent B was acetonitrile. The mass spectrometer was operated in the selected-ion mode with atmospheric pressure chemical ionization to monitor the respective MH+ ions, namely, m/z 577.3 for tulathromycin and m/z 679.3 for the internal standard roxithromycin. The calibration curves were linear in a dynamic range of 2.0-500 ng mL−1 on the column. The accuracy was ranged from 95.25 to 109.75%, and the precision was ranged from 2.81 to 7.72%. The recoveries measured at 3 concentration levels (20, 250, and 500 ng mL−1) were higher than 98%. The method described above is efficient, and has the required accuracy and precision for rapid determination of tulathromycin in plasma. The method was applied to study the pharmacokinetics of tulathromycin in swine, and tulathromycin demonstrated a rapid absorption, wide distribution, and slow elimination after intramuscular administration.