Risk factors associated with postoperative respiratory failure after esophagectomy for esophageal cancer

Aim: Respiratory failure is common after esophagectomy for esophageal cancer (EC). This study aimed to identify the risk factors associated with postoperative respiratory failure following esophagectomy for EC. Methods: A single-center observational study from China was conducted on 262 patients with EC who underwent thoracoscopic esophagectomy between April 2014 and June 2016. The patients were divided into two groups: group I (respiratory failure) and group II (without respiratory failure). Demographic and perioperative variables, tumor-related factors, surgical factors, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, and clinical course were compared between the groups. Univariable and multivariable logistic regression analyses were performed to assess the risk factors of postoperative respiratory failure after esophagectomy. Results: Among the 262 patients, 24 (9.2%) developed respiratory failure. Univariable analysis revealed several risk factors, including age, smoking, comorbidities, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), forced vital capacity (FVC), FVC percentage (FVC%), urine volume during surgery, and APACHE II score. Multivariable analysis showed that age, comorbidities of diabetes mellitus (DM), FVC%, urine volume during surgery, and APACHE II score were independent predictors of respiratory failure. Specifically, elderly patients (> 65 years) with comorbidities of DM, lower FVC%, higher urine volume during surgery, and elevated APACHE II score were found to be more susceptible to respiratory failure, resulting in prolonged hospitalization and increased healthcare burden. These findings emphasize the importance of considering these factors in the management and care of patients at risk of respiratory failure. Conclusions: As a common complication following esophagectomy for EC. Respiratory failure is significantly associated with age, comorbidities of DM, FVC%, urine volume during surgery, and APACHE II score in the dataset. The findings will contribute to the evaluation of the risk of respiratory failure and guide early intervention strategies in clinical decision-making

Molecular Dynamics Analysis Reveals Structural Insights into Mechanism of Nicotine N-Demethylation Catalyzed by Tobacco Cytochrome P450 Mono-Oxygenase

CYP82E4, a cytochrome P450 monooxygenase, has nicotine N-demethylase (NND) activity, which mediates the bioconversion of nicotine into nornicotine in senescing tobacco leaves. Nornicotine is a precursor of the carcinogen, tobacco-specific nitrosamine. CYP82E3 is an ortholog of CYP82E4 with 95% sequence identity, but it lacks NND activity. A recent site-directed mutagenesis study revealed that a single amino acid substitution, i.e., cysteine to tryptophan at the 330 position in the middle of protein, restores the NND activity of CYP82E3 entirely. However, the same amino acid change caused the loss of the NND activity of CYP82E4. To determine the mechanism of the functional turnover of the two molecules, four 3D structures, i.e., the two molecules and their corresponding cys–trp mutants were modeled. The resulting structures exhibited that the mutation site is far from the active site, which suggests that no direct interaction occurs between the two sites. Simulation studies in different biological scenarios revealed that the mutation introduces a conformation drift with the largest change at the F-G loop. The dynamics trajectories analysis using principal component analysis and covariance analysis suggests that the single amino acid change causes the opening and closing of the transfer channels of the substrates, products, and water by altering the motion of the F-G and B-C loops. The motion of helix I is also correlated with the motion of both the F-G loop and the B-C loop and; the single amino acid mutation resulted in the curvature of helix I. These results suggest that the single amino acid mutation outside the active site region may have indirectly mediated the flexibility of the F-G and B-C loops through helix I, causing a functional turnover of the P450 monooxygenase

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

QTL Mapping of Somatic Regeneration-Related Traits in Maize

The somatic regeneration of maize depends on its genotypes, so improving its variety with modern biotechnology is severely restricted. Locating the quantitative trait loci (QTLs) associated with somatic regeneration is important for breeding elite inbred lines that undergo genetic transformations. Here, by crossing the high-regeneration inbred line H99 and non-regeneration inbred line Fr993, an F2 population and its F2:3 and F2:4 population families were constructed. Immature embryos from the family populations were subjected to tissue culture in two independent seasons to determine their embryogenic callus induction rates (EIRs), green callus rates (GCRs) and plantlet regeneration rates (PRRs). Genetic linkage maps were constructed for the F2 population to locate somatic regeneration QTLs. The results showed that variation in the EIR, GCR and PRR ranged from 0.00–99.33%, and their broad-sense heritabilities were 0.50, 0.52 and 0.53, respectively. The total genetic distance of the linkage maps constructed by the GenoBaits 10 K chip was 2319.50 cM, and twelve QTLs were associated with somatic regeneration traits, accounting for 3.90–14.06% of the phenotypic variation. Expression analysis revealed six candidate genes screened from the QTLs with distinct responses to induction culture in the parental lines, suggesting that they may impact commitment to somatic cell fate. These results provide a basis for the molecular breeding of maize varieties with high-frequency somatic regeneration

Genome-scale identification of cell-wall related genes in <it>Arabidopsis</it> based on co-expression network analysis

<p>Abstract</p> <p>Background</p> <p>Identification of the novel genes relevant to plant cell-wall (PCW) synthesis represents a highly important and challenging problem. Although substantial efforts have been invested into studying this problem, the vast majority of the PCW related genes remain unknown.</p> <p>Results</p> <p>Here we present a computational study focused on identification of the novel PCW genes in <it>Arabidopsis</it> based on the co-expression analyses of transcriptomic data collected under 351 conditions, using a bi-clustering technique. Our analysis identified 217 highly co-expressed gene clusters (modules) under some experimental conditions, each containing at least one gene annotated as PCW related according to the Purdue Cell Wall Gene Families database. These co-expression modules cover 349 known/annotated PCW genes and 2,438 new candidates. For each candidate gene, we annotated the specific PCW synthesis stages in which it is involved and predicted the detailed function. In addition, for the co-expressed genes in each module, we predicted and analyzed their <it>cis</it> regulatory motifs in the promoters using our motif discovery pipeline, providing strong evidence that the genes in each co-expression module are transcriptionally co-regulated. From the all co-expression modules, we infer that 108 modules are related to four major PCW synthesis components, using three complementary methods.</p> <p>Conclusions</p> <p>We believe our approach and data presented here will be useful for further identification and characterization of PCW genes. All the predicted PCW genes, co-expression modules, motifs and their annotations are available at a web-based database: <url>http://csbl.bmb.uga.edu/publications/materials/shanwang/CWRPdb/index.html</url>.</p

Potential interaction between autophagy and auxin during maize leaf senescence

Leaf senescence is important for crop yield as delaying it can increase the average yield. In this study, population genetics and transcriptomic profiling were combined to dissect its genetic basis in maize. To do this, the progenies of an elite maize hybrid Jidan27 and its parental lines Si-287 (early senescence) and Si-144 (stay-green), as well as 173 maize inbred lines were used. We identified two novel loci and their candidate genes, Stg3 (ZmATG18b) and Stg7 (ZmGH3.8), which are predicted to be members of autophagy and auxin pathways, respectively. Genomic variations in the promoter regions of these two genes were detected, and four allelic combinations existed in the examined maize inbred lines. The Stg3(Si-144)/Stg7(Si-1)(44) allelic combination with lower ZmATG18b expression and higher ZmGH3.8 expression could distinctively delay leaf senescence, increase ear weight and the improved hybrid of NIL-Stg3(Si-144)/Stg7(Si-1)(44) significantly reduced ear weight loss under drought stress, while opposite effects were observed in the Stg3(Si-)(287)/Stg7(Si-)(287) combination with a higher ZmATG18b expression and lower ZmGH3.8 expression. Thus, we identify a potential interaction between autophagy and auxin which could modulate the timing of maize leaf senescence

天然气水合物物理化学性质和相平衡数据库系统的设计和开发

天然气水合物作为一种重要的潜在能源，一种导致全球气候变化的因素，一种地质灾害的诱发因素，已经引起了各领域科研工作者的广泛关注。因此，迫切需要建立一个天然气水合物信息系统，以便交流和共享各领域的研究成果。在本工作中，我们设计开发了关于天然气水合物基础性质的数据库系统。目前，本系统所收集的数据主要集中在与天然气水合物开采和应用技术相关的物理化学性质、晶体结构和相平衡数据。本系统不仅能够提供数据检索服务，还能够提供相平衡数据的网络计算功能。本文将对数据收集和数据库开发这两个方面进行讨论