Programmed cell death-1 (PD-1) has demonstrated impressive clinical outcomes in several malignancies, but its therapeutic efficacy in the majority of colorectal cancers is still low. Therefore, methods to improve its therapeutic efficacy in colorectal cancer (CRC) patients need further investigation. Here, we demonstrate that immunogenic chemotherapeutic agents trigger the induction of tumor PD-L1 expression in vitro and in vivo, a fact which was validated in metastatic CRC patients who received preoperatively neoadjuvant chemotherapy (neoCT) treatment, suggesting that tumor PD-L1 upregulation by chemotherapeutic regimen is more feasible via PD-1/PD-L1 immunotherapy. However, we found that the epigenetic control of tumor PD-L1 via DNA methyltransferase 1 (DNMT1) significantly influenced the response to chemotherapy. HTS assay We demonstrate that decitabine (DAC) induces DNA hypomethylation, which not only directly enhances tumor PD-L1 expression but also increases the expression of immune-related genes and intratumoral T cell infiltration in vitro and in vivo. DAC was found to profoundly enhance the therapeutic efficacy of PD-L1 immunotherapy to inhibit tumor growth and prolong survival in vivo. Therefore, it can be seen that DAC remodels the tumor microenvironment to improve the effect of PD-L1 immunotherapy by directly triggering tumor PD-L1 expression and eliciting stronger anti-cancer immune responses, providing potential clinical benefits to CRC patients in the future.First-week mortality is an important performance index as well as an important welfare indicator. The aim of the present study was to identify internal (individual-dependent) and external (management or environmental) factors that could influence the cumulative first-week mortality of broilers. To carry out this study, field data obtained from a hatchery company were used, in which 2267 flocks of broiler chicks (from 2015 to 2018), were analyzed. A generalized linear mixed model was used to analyze the data. Farm ID and house by farm were incorporated as random effects. The Odds Ratio was estimated for each factor, determining the effect of each explanatory variable. First-week mortality was significantly related to breeder age (p less then 0.0001), chick gender (p less then 0.0001) and breed (p less then 0.0001) as internal factors, and type of broiler house (p = 0.0129), presence or absence of drip cup (p less then 0.0001), egg storage (p less then 0.0001), study year (p less then 0.0001) and season (p less then 0.0001) as external factors. Therefore, these factors should be considered in the decision making of poultry breeding companies, in order to reduce possible welfare problems and increase productive performance.Diatoms are major primary producers in polar environments where they can actively grow under extremely variable conditions. Integrative modeling using a genome-scale model (GSM) is a powerful approach to decipher the complex interactions between components of diatom metabolism and can provide insights into metabolic mechanisms underlying their evolutionary success in polar ecosystems. We developed the first GSM for a polar diatom, Fragilariopsis cylindrus, which enabled us to study its metabolic robustness using sensitivity analysis. We find that the predicted growth rate was robust to changes in all model parameters (i.e., cell biochemical composition) except the carbon uptake rate. Constraints on total cellular carbon buffer the effect of changes in the input parameters on reaction fluxes and growth rate. We also show that single reaction deletion of 20% to 32% of active (nonzero flux) reactions and single gene deletion of 44% to 55% of genes associated with active reactions affected the growth rate, as well as the production fluxes of total protein, lipid, carbohydrate, DNA, RNA, and pigments by less than 1%, which was due to the activation of compensatory reactions (e.g., analogous enzymes and alternative pathways) with more highly connected metabolites involved in the reactions that were robust to deletion. Interestingly, including highly divergent alleles unique for F. cylindrus increased its metabolic robustness to cellular perturbations even more. Overall, our results underscore the high robustness of metabolism in F. cylindrus, a feature that likely helps to maintain cell homeostasis under polar conditions.Retinoic acid (RA) was one of the first molecules in the modern era of experimental embryology to be shown capable of generating profound effects on limb development. In this review, we focus on the earliest events of limb development and specifically on the role of RA in establishing the domain of cells that will go on to form the limb itself. Although there is some consensus on the role of RA during the earliest stages of limb formation, some controversy remains on the mechanism of RA action and the requirement for RA signaling in forming the hindlimb buds.Soft tissue sarcoma (STS) patients undergoing surgery may experience reduced functional outcome (FO) and quality of life (QoL) compared to the general population. The aim of this study was to evaluate the development of FO and QoL in patients with STS in the extremities within the first year after first-time limb-sparing surgery. Twenty-nine out of 40 eligible patients were included in the present study. QoL and FO were evaluated by questionnaires while FO was also evaluated by objective tests. Patients were assessed before surgery and at fixed time points within the first year after surgery. Patients with STS in the extremities had an average strength of 82.34% (95% CI 68.57-96.11) of the expected strength at one year post surgery. Multivariate, repeated ANOVA showed statistically significant reductions in strength in the disease-affected extremity when compared with the healthy side after surgery. Multivariate, repeated ANOVA showed a statistically significant improvement in FO and QoL within the first year post surgery. Limb-sparing surgery for STS significantly reduced strength in the disease-affected extremity and generally reduced FO and QoL in the first months after surgery. Improvements were observed for FO and QoL at one year after surgery.