关键词： Surgical Oncology   Oncology   Surgery  

摘要： Background Lymph node ratio (LNR) and the log odds of positive lymph nodes (LODDS) have been proposed as alternative lymph node (LN) classification schemes. Various cut-off values have been defined for each system, with the question of the most appropriate for patients with medullary thyroid cancer (MTC) still remaining open. We aimed to retrospectively compare the predictive impact of different LN classification systems and to define the most appropriate set of cut-off values regarding accurate evaluation of overall survival (OS) in patients with MTC. Methods 182 patients with MTC who were operated on between 1985 and 2018 were extracted from our medical database. Cox proportional hazards regression models and C-statistics were performed to assess the discriminative power of 28 LNR and 28 LODDS classifications and compare them with the N category according to the 8th edition of the AJCC/UICC TNM classification in terms of discriminative power. Regression models were adjusted for age, sex, T category, focality, and genetic predisposition. Results High LNR and LODDS are associated with advanced T categories, distant metastasis, sporadic disease, and male gender. In addition, among 56 alternative LN classifications, only one LNR and one LODDS classification were independently associated with OS, regardless of the presence of metastatic disease. The C-statistic demonstrated comparable results for all classification systems showing no clear superiority over the N category. Conclusion Two distinct alternative LN classification systems demonstrated a better prognostic performance in MTC patients than the N category. However, larger scale studies are needed to further verify our findings.

关键词： 制造业   ERP环境   财务系统   业务系统集成  

摘要： 随着社会经济的高速发展,我国企业的规模也不断扩大,党的十九届五中全会指出,坚持把发展经济着力点放在实体经济上,坚定不移建设制造强国、质量强国、网络强国、数字中国.打造具有国际竞争力的制造业,是我国提升综合国力、保障国家安全、建设世界强国的必由之路,这为制造业的发展起到良好的促进作用.为了更好的促进制造业稳定发展,对企业财务信息化建设也提出更高的要求.因此,本文首先对制造业与ERP系统的基本概述以及存在的问题加以明确;其次,对ERP环境下系统集成的必要性以及可行性展开深入分析;在此基础上,提出制造业ERP环境下财务系统与其他业务系统集成的具体措施.

关键词： Cottonseed protein concentrate   Largemouth bass   Paraprobiotic   Gut health   Gut microbiome  

摘要： Cottonseed protein concentrate (CPC) is a potential fishmeal alternative but may negatively influence the gut health of fish. A specific paraprobiotic consisting of multi-strain yeast fractions (MsYF) was recently shown to improve gut health via immune modulation. This study aimed to evaluate the effects of MsYF on the growth performance, gut health and microbiome of largemouth bass fed a diet using CPC as 40% fishmeal alternative. Juvenile largemouth bass (body-weight = 31 g) were fed for 65 days with three iso-nitrogen and isoenergetic experimental diets: 1/ one Control diet (50% fishmeal), 2/ one low fishmeal diet (LFM;30% fishmeal, 23.5% CPC) and 3/ one LFM diet + MsYF at 800 mg/kg (LFMY). The highest growth performance, estimated as specific growth rate and protein efficiency ratio, was observed in the LFMY followed by the LFM. Histopathology identified some specimens with distal intestinal lesions in the Control and LFM groups but not of the LFMY group. The gene expression level of il-10 (anti-inflammatory) was up-regulated in the LFM and LFMY groups but only LFMY down-regulated il-1 beta (pro-inflammatory) and hypoxia-inducible factor 1-alpha (hif1 alpha) protein expression level compared to the Control group. Further, LFM and LFMY up-regulated occ-1b (tight-junction) and slc15a2 (peptide transporter) suggesting enhanced intestinal permeability and peptide transport compared to the Control group. Moreover, dietary CPC increased the abundance of genus Clostridium_sensu_stricto_12 and decreased the abundance of genus Escherichia-Shigella compared to the Control group, while the inclusion of MsYF increased the abundance of the potentially beneficial genus Cetobacterium compared to the LFM group. Our results showed 40% substitution of fishmeal protein by CPC could enhance growth performance and regulate the intestinal barrier and peptide transport relevant functions in largemouth bass. Moreover, in a low fishmeal basal diet, MsYF supplementation could increase gr

关键词： calcium   alternative splicing   embryo   protein isoforms   amino acids   exons   skeletal muscles   cell lines   tissue membrane   calcium channels   alanine   sensor   voltage gated calcium channel  

摘要： The skeletal muscle voltage-gated calcium channel (Ca(v)1.1) primarily functions as a voltage sensor for excitation-contraction coupling. Conversely, its ion-conducting function is modulated by multiple mechanisms within the pore-forming a is subunit and the auxiliary alpha(2)delta-1 and gamma(1) subunits. In particular, developmentally regulated alternative splicing of exon 29, which inserts 19 amino acids in the extracellular IVS3-S4 loop of Ca(v)1.1a, greatly reduces the current density and shifts the voltage dependence of activation to positive potentials outside the physiological range. We generated new HEK293 cell lines stably expressing alpha(2)delta-1, beta(3), and STAC3. When the adult (Ca(v)1.1a) and embryonic (Ca(v)1.1e) splice variants were expressed in these cells, the difference in the voltage dependence of activation observed in muscle cells was reproduced, but not the reduced current density of Ca(v)1.1a. Only when we further coexpressed the gamma(1) subunit was the current density of Ca(v)1.1a, but not that of Ca(v)1.1e, reduced by >50%. In addition, gamma(1) caused a shift of the voltage dependence of inactivation to negative voltages in both variants. Thus, the current-reducing effect of gamma(1), unlike its effect on inactivation, is specifically dependent on the inclusion of exon 29 in Ca(v)1.1a. Molecular structure modeling revealed several direct ionic interactions between residues in the IVS3-S4 loop and the y i subunit. However, substitution of these residues by alanine, individually or in combination, did not abolish the gamma(1)-dependent reduction of current density, suggesting that structural rearrangements in Ca(v)1.1a induced by inclusion of exon 29 may allosterically empower the gamma(1) subunit to exert its inhibitory action on Ca-v1.1 calcium currents.

摘要： Alternative polyadenylation (APA) plays an important role in gene regulation. With the recent application of novel sequencing technology in APA profiling, an ever-increasing number of APA genes/sites have been identified. However, the phenotypic relevance of most of these APA isoforms remains elusive, which is largely due to the lack of a convenient genetics tool for APA interference. To address this issue, herein, an efficient method is developed based on the CRISPR-dCas13 system, termed as CRISPR-iPAS. Out of eight different dCas13 proteins, Porphyromonas gulae (Pgu) dCas13b, is identified as the most effective one in blocking the usage of the polyadenylation site (PAS). With guide RNAs targeting at core regulatory elements, dPguCas13b enabled APA regulation of endogenous genes with different APA types, including tandem 3 ' UTR, alternative terminal exon, as well as intronic PAS. Finally, we demonstrated that the proposed APA perturbation tool could be used to investigate the functional relevance of APA isoforms.

摘要： Most human protein-coding genes produce alternative polyadenylation (APA) isoforms that differ in 3 ' UTR size or, when coupled with splicing, have variable coding sequences. APA is an important layer of gene expression program critical for defining cell identity. Here, by using a catalytically dead Cas9 and coupling its target site with polyadenylation site (PAS), we develop a method, named CRISPRpas, to alter APA isoform abundance. CRISPRpas functions by enhancing proximal PAS usage, whose efficiency is influenced by several factors, including targeting strand of DNA, distance between PAS and target sequence and strength of the PAS. For intronic polyadenylation (IPA), splicing features, such as strengths of 5 ' splice site and 3 ' splice site, also affect CRISPRpas efficiency. We show modulation of APA of multiple endogenous genes, including IPA of PCF11, a master regulator of APA and gene expression. In sum, CRISPRpas offers a programmable tool for APA regulation that impacts gene expression.

摘要： Ssd1, a conserved fungal RNA-binding protein, is important in stress responses, cell division and virulence. Ssd1 is closely related to Dis3L2 of the RNase II family of nucleases, but lacks catalytic activity and likely suppresses translation of bound mRNAs. Previous studies identified RNA motifs enriched in Ssd1-associated transcripts, yet the sequence requirements for Ssd1 binding are not defined. Here, we identify precise binding sites of Ssd1 on RNA using in vivo cross-linking and cDNA analysis. These sites are enriched in 5 ' untranslated regions of a subset of mRNAs encoding cell wall proteins. We identified a conserved bipartite motif that binds Ssd1 with high affinity in vitro. Active RNase II enzymes have a characteristic, internal RNA binding path;the Ssd1 crystal structure at 1.9 angstrom resolution shows that remnants of regulatory sequences block this path. Instead, RNA binding activity has relocated to a conserved patch on the surface of the protein. Structure-guided mutations of this surface prevent Ssd1 from binding RNA in vitro and phenocopy Ssd1 deletion in vivo. These studies provide a new framework for understanding the function of a pleiotropic post-transcriptional regulator of gene expression and give insights into the evolution of regulatory and binding elements in the RNase II family.

关键词： Medical assistance   crisis communication   risk management   travel   epidemic intelligence   medical intelligence  

摘要： Introduction A crisis of ‘alternative truths’ represents a threat to global health security. Access to accurate, vetted information is now increasingly key to analysing and addressing travel risk. Yet keeping up to date with travel health can be challenging. Travellers are more at risk of health problems than non-travellers, from gastroenteritis to burnout. Workers on remote sites are particularly exposed to long-term isolation, frequently lacking relevant, accurate clinical advice at the time of medical decision-making. 1 Travel-related diseases such as Zika, Ebola or yellow fever have all been associated with misinformation campaigns. During travel, stressors are amplified, compounding information overload, which typifies the immediate aftermath of any major crisis, worsened in a pandemic when access to health advice ordinarily obtained from trusted local health services is hampered. During the Fukushima crisis for example, we received calls enquiring about the validity of taking iodised salt to prevent the aftermath of nuclear fallout....

关键词： Spray penetration   spray cone angle   injection pressure   alternative fuels   evaporation model  

摘要： Spray characteristics and transient behaviour of alternative fuel droplets at different spray cone angles, injection pressures and droplet diameters are presented, using a simple spray evaporation model. The model only considers drag force acting on the droplet. Radiation heat transfer during the evaporation process is neglected. The model incorporates temperature-dependent fuel properties, drag coefficient and Reynolds number for robustness. It is tested for alternative fuels, namely Jatropha Bio-synthetic Paraffinic Kerosen (JSPK), Camelina Bio-synthetic Paraffinic Kerosene (CSPK) and biodiesel, while Jet-A is used for comparison. The transient behaviour of fuel droplets is visualised through a time-history of the normalised squared diameter. Changes in the particles' temperature, mass, density, velocity and heat transfer coefficient over time are observed. Moreover, penetration of the fuels at different spray cone angles, injection pressures and droplet diameters is compared. Among the tested fuels, biodiesel is found to have the farthest penetration due to its high vapour pressure. Notably, increasing spray cone angle reduces penetration length. A similar trend is observed when injection pressure is increased. However, at constant injection pressure, increasing droplet diameter increases spray cone angle and spray penetration. To obtain optimum penetration, therefore, a larger cone angle should be used for fuel with high density and vapour pressure, and vice versa.