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g., palbociclib). Nuclear immunostaining of CDK4 significantly correlated with mRNA expression (R = 0.52, P less then 0.005). We exposed both NCI-H295R and MUC1 cell lines to palbociclib and found a concentration- and time-dependent reduction of cell viability, which was more pronounced in the NCI-H295R cells in line with higher CDK4 expression. Furthermore, we tested palbociclib in combination with insulin-like growth factor 1/insulin receptor inhibitor linsitinib showing an additive effect. In conclusion, we demonstrate that RNA profiling is useful to discover potential drug targets and that CDK4/6 inhibitors are promising candidates for treatment of selected patients with ACC. Copyright © 2020 Liang, Weigand, Lippert, Kircher, Altieri, Steinhauer, Hantel, Rost, Rosenwald, Kroiss, Fassnacht, Sbiera and Ronchi.Giant pandas represent one of the most endangered species worldwide, and their reproductive capacity is extremely low. They have a relatively long gestational period, mainly because embryo implantation is delayed. Giant panda cubs comprise only a small proportion of the mother's body weight, making it difficult to determine whether a giant panda is pregnant. Timely determination of pregnancy contributes to the efficient breeding and management of giant pandas. Meanwhile, metabolomics studies the metabolic composition of biological samples, which can reflect metabolic functions in cells, tissues, and organisms. This work explored the urinary metabolites of giant pandas during pregnancy. A sample of 8 female pandas was selected. Differences in metabolite levels in giant panda urine samples were analyzed via ultra-high-performance liquid chromatography/mass spectrometry comparing pregnancy to anoestrus. Pattern recognition techniques, including partial least squares-discriminant analysis and orthogonal partial lr fetuses. Copyright © 2020 Cao, Li, Liu, Cai, Chen, Yuan, Zhao, Zhang, Hou and Zhou.Metabolic profile of follicular fluid (FF) has been investigated to look for biomarkers for oocyte quality. Resolvin E1 (RvE1), a potent pro-resolving mediator, was reported to have protective action in cell function. The study aimed to examine the predictive value of RvE1 for oocyte quality and to explore the cellular mechanism of RvE1 in improving oocyte competence. Metabolic profiles of 80 FF samples showed a higher level of RvE1 in group A (blastocysts scored ≥ B3BC and B3CB according to Gardner's blastocyst scoring system, N = 36) than that of group B (blastocysts scored less then B3BC and B3CB, N = 44, P = 0.0018). The receiver operating characteristic (ROC) curve analysis showed that RvE1 level in FF below 8.96 pg/ml (AUC0.75; 95%CI 0.64-0.86; P = 0.00012) could predict poor oocyte quality with specificity of 97.22%, suggesting RvE1 as a potential biomarker to exclude inferior oocytes. Besides, the level of RvE1 was found to be significantly lower in FF than in serum (57.49 to 17.62 pg/ml; P=.0037) and was gradually accumulated in the culture medium of cumulus cells (CCs) during cell culture, which indicated that RvE1 came from both blood exudates and local secretion. The in vitro experiment revealed thecellular mechanism of RvE1 in improvingoocyte qualityby decreasing the cumulus cellapoptotic rate and increasing cell viability and proliferation. It is the first time thatthe role of RvE1 in reproduction is explored. In conclusion, RvE1 is valuable as a potential exclusive biomarker for oocyte selection andplays a role in improving oocyte quality. Copyright © 2020 Zhang, Zhu, Li, Zhu, Peng, Xin, Qu, He, Fu and Sun.Research Question Does reproductive outcome differ among the various subgroups of poor ovarian responders according to the Bologna criteria? Design This was a retrospective, cohort study including poor ovarian responders according to Bologna criteria, undergoing an ICSI cycle from January 2011 until December 2017. Patients were divided into four groups (1) age ≥ 40 years and abnormal ovarian response test, (2) age ≥ 40 years, abnormal ovarian reserve test and one previous poor response to stimulation, (3) age ≥ 40 years and one previous poor response, (4) abnormal ovarian reserve test and one previous poor response. Result(s) Overall, 846 cycles in 706 Bologna poor ovarian responders were included 310 cycles in group 1, 169 in group 2, 52 in group 3, and 315 in group 4. There were significant differences in age, antral follicle count, antimüllerian hormone, cycle cancellation rates, and number of retrieved oocytes between the four groups. Live birth and cumulative live birth rate differed significantly between groups and were highest in Group 4 [Live birth rate 7.4% (1) vs. 4.1% (2) vs. 5.8% (3) vs. 13.4% (4), p = 0.001 and Cumulative live birth rate 8.3% (1) vs. 4.1 % (2) vs. 9.6% (3) vs. 16.8% (4) p less then 0.001]. The multivariate GEE analysis revealed that the number of MIIs and the Bologna criteria pattern were the variables which were significantly associated with cumulative live birth rate. Conclusion(s) Poor ovarian responders represent a heterogeneous population. The young subpopulation has a better clinical prognosis in terms of fresh and cumulative live birth rate. Copyright © 2020 Romito, Bardhi, Errazuriz, Blockeel, Santos-Ribeiro, Vos, Racca, Mackens, Kelen, Panici, Vaiarelli, Tournaye and Drakopoulos.Neuropeptides are among the structurally most diverse signaling molecules and participate in intercellular information transfer from neurotransmission to intrinsic or extrinsic neuromodulation. Many of the peptidergic systems have a very ancient origin that can be traced back to the early evolution of the Metazoa. click here In recent years, new insights into the evolution of these peptidergic systems resulted from the increasing availability of genome and transcriptome data which facilitated the investigation of the complete neuropeptide precursor sequences. Here we used a comprehensive transcriptome dataset of about 200 species from the 1KITE initiative to study the evolution of single-copy neuropeptide precursors in Polyneoptera. This group comprises well-known orders such as cockroaches, termites, locusts, and stick insects. Due to their phylogenetic position within the insects and the large number of old lineages, these insects are ideal candidates for studying the evolution of insect neuropeptides and their precursors.
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