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Although the individual transcriptional regulators of the core circadian clock are distinct amongst different organisms, the autoregulatory feedback loops they form are conserved. This unified design principle explains how daily physiological activities oscillate across species. However, whether analogous design principles govern the gene expression output of circadian clocks is unknown. Herein, we performed a comparative analysis of rhythmic gene expression in eight diverse species and captured four common distribution patterns of cycling gene expression across these species. We hypothesized that maintenance of reduced energetic costs constrains the evolution of rhythmic gene expression. Our large-scale computational simulations support this hypothesis by showing that selection against high-energy expenditure completely regenerates all cycling gene patterns. Moreover, we find that the late- and early-phase peaks of rhythmic expression have been subjected to this type of selective pressure. Therefore, energetic costs have constricted the cycling transcriptome throughout evolutionary history.

Purpose An unmet clinical need in non-small cell lung cancer (NSCLC) management is the accurate prediction of radiation response in patients receiving radical radiation therapy. We explored the intrinsic radiosensitivity of NSCLC from the proteomic profiles of NSCLC cell lines and paraffin-embedded human samples. Methods and Materials To uncover radiosensitivity-specific proteomic and signaling pathways, we performed quantitative proteomics by data-independent acquisition mass spectrometry assay on 29 human NSCLC cell lines and 13 paraffin-embedded human NSCLC samples. We validated closely interacting radioresistant proteins by western blotting, immunofluorescence, real-time quantitative polymerase chain reaction in NSCLC cell lines, and immunohistochemistry in paraffin-embedded human samples. We validated the functions of 3 key hub proteins by lentivirus transfection, clonogenic survival assay, and flow cytometry. Results The proteomic profiling of NSCLC showed that the intrinsic radiosensitivity of NSCLC is mainly modulated by signaling pathways of proteoglycans in cancer, focal adhesion, and regulation of the actin cytoskeleton. We identified 71 differentially expressed proteins and validated 8 closely interacting proteins as radioresistant proteins of NSCLC. Moreover, we also validated the functionality of integrin-linked protein kinase, p21-activated kinase 1, and Ras GTPase-activating-like protein IQGAP1 in the radiation response of NSCLC cell lines. Finally, with the NSCLC radiosensitivity-specific proteins, we delineated the atlas network of NSCLC radiosensitivity-related signaling pathways. Conclusions Radiosensitivity-specific proteins could guide individualized radiation therapy in clinical practice by predicting the radiation response of patients with NSCLC. Moreover, the NSCLC radiosensitivity-related signaling pathway atlas could guide further exploration of the underlying mechanism.

Defective decidualization of human endometrial stromal cells (ESCs) has recently been highlighted as an underlying cause of implantation failure. FK-506-binding protein 51 (FKBP51) has been shown to participate in the steroid hormone response and the protein kinase B (AKT) regulation process, both of which are important pathways involved in decidualization. The objective of the present study was to investigate the potential effects and mechanisms of FKBP51 in the regulation of ESC decidualization. By performing immunohistochemical staining on an endometrial tissue microarray (TMA) derived from normal females, we found that FKBP51 expression was much higher in the luteal phase than in the follicular phase in ESCs. Primary ESCs were isolated from patients to build an in vitro decidualization model through co-culture with medroxyprogesterone acetate (MPA) and 8-bromoadenosine (cAMP). SC79, a specific AKT activator in various physiological and pathological conditions, and shRNA-FKBP51 were used to examine the roles of AKT and FKBP51 in decidualization. The Western blot and RT-PCR results showed that FKBP51, insulin-like growth factor-binding protein 1 (IGFBP1) and prolactin (PRL) expression increased in ESCs treated with MPA + cAMP; meanwhile, the level of p-Ser473 AKT (p-S473 AKT) decreased and forkhead box protein O1 (FOXO1A) expression increased. Decidualization was inhibited by the AKT activator SC79 and the transfection of FKBP51-shRNA by affecting protein synthesis, cell morphology, cell growth and cell cycle. Furthermore, this inhibition was rescued by FKBP51-cDNA transfection. The results supported that FKBP51 promotes decidualization by reducing the Ser473 phosphorylation levels in AKT.

In this study, we investigated the role of FK506 binding protein 51 (FKBP51) in human endometrial adenocarcinoma progression. Immunohistochemical analysis showed decreased FKBP51 expression in endometrial adenocarcinoma tissues. Moreover, higher FKBP51 expression was observed in the normal secretory phase than in proliferative-phase endometrial tissues. FKBP51-shRNA transfected KLE cells showed high Ser473-phospho Akt with decreased p21 and p27 levels, which promoted S-G2/M phase cell cycle progression and proliferation. Conversely, FKBP51 overexpressing Ishikawa cells showed low Ser473-phospho Akt, which led to increased p21 and p27 levels and, in turn, G0/G1 cell cycle arrest and decreased cell proliferation. FKBP51 overexpression in progesterone receptor-positive Ishikawa cells sensitized them to medroxyprogesterone acetate (MPA; progestin) treatment by repressing Akt signaling. Conversely, FKBP51-shRNA knockdown in RL95-2 cells attenuated progestin sensitivity. These findings indicate FKBP51 inhibits cell proliferation and promotes progestin sensitivity in endometrial adenocarcinoma by decreasing Akt signaling.

Endometrioid endometrial carcinoma (EEC) is the most common gynaecologic malignancy worldwide. Long non‐coding RNAs have previously been demonstrated to play important roles in regulating human diseases, particularly cancer. However, the biological functions and molecular mechanisms of long non‐coding RNAs in EEC have not been extensively studied. Here, we describe the discovery of Lnc‐NA from the promoter of the transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) gene. The role and function of Lnc‐NA in EEC remain unknown. In this study, we used quantitative real‐time polymerase chain reactions to confirm that Lnc‐NA expression was down‐regulated in 30 EEC cases (90%) and in EEC cell lines compared with that in the paired adjacent tissues and normal endometrial cells. In vitro experiments further demonstrated that overexpressing Lnc‐NA decreased EEC cell proliferation, migration and invasion and promoted apoptosis via inactivation of the apoptosis signalling pathway. Moreover, the results show that Lnc‐NA expression was positively correlated with NR4A1. Furthermore, Lnc‐NA regulated NR4A1 expression and activated the apoptosis signalling pathway to inhibit tumour progression. In summary, our results demonstrate that the Lnc‐NA‐NR4A1 axis could be a useful tumour suppressor and a promising therapeutic target for EEC.

FK506-binding protein 51 (FKBP51) is a member of the immunophilin family, with relevant roles in multiple signaling pathways, tumorigenesis and chemoresistance. However, the function of FKBP51 in papillary thyroid carcinoma (PTC) remains largely unknown. In the present study, increased FKBP51 expression was detected in PTC tissues as compared with adjacent normal tissues, and the expression level was associated with clinical tumor, node and metastasis stage. Using FKBP51-overexpressing K1 cells and FKBP51-knockdown TPC-1 cells, both human PTC cell lines, it was identified that FKBP51 promoted the migration and invasion of PTC, without affecting cell proliferation. Further investigation revealed that FKBP51 activated the NF-κB pathway and epithelial-to-mesenchymal transition (EMT) genes, and EMT was suppressed when NF-κB was inhibited. It was also assessed whether FKBP51 promoted the formation of cytoskeleton to promote migration and invasion of PTC using a tubulin tracker; however, no evidence of such an effect was observed. These results suggested that FKBP51 promotes migration and invasion through NF-κB-dependent EMT.

To explain the association of Bacillus thuringiensis (Bt) with animal feces, an ecological analysis in chickens was conducted by introducing a cry − strain marked by production of green fluorescent protein (GFP). After feeding with the tagged Bt strains, the feces of the tested chickens were collected at different times, isolated, and the morphology of Bt was observed. It was shown that Bt strain HD-73GFP in spore form could be isolated from feces of chickens for a period of 13 d, and then it disappeared thereafter. Bt could be detected only up to day 4 (but not thereafter), when chickens were fed with vegetative cells of HD-73GFP. To confirm the source of newly isolated strains, the gfp gene was examined by polymerase chain reaction (PCR), which showed that all the isolated strains harbored the marker gene. Recent data from isolation and PCR had suggested that fecal Bt strains had originated from food. Chicken tissues were thus dissected to isolate Bt strains and to investigate whether Bt could be located in vivo. Bt was located within the duodenum in spore form. Compared to the morphology of the isolated strains at different growth times, the growth rates of all the tested Bt had little changes when passing through the digestive system to the feces. Dissection of the chickens confirmed that Bt was safe for the tested animal.

Eight N-[3-(2,4-dichlorophenyl)-5-methylisoxazol-4-ylcarbonyl]-N′-(4,6-disubstituted pyrimidin-2-yl)thioureas and eight 5,7-disubstituted-2-[3-(2,4-dichlorophenyl)-5-methyl isoxazol-4-ylcarbonylimino]-2H-1,2,4-thiadiazolo[2,3-α]pyrimidines were synthesized by multi-step reactions in yields of 50–85%. The structures of the target compounds were confirmed by IR, 1H NMR spectra and elemental analyses. Phytotoxic activities against Echinochloa crus-galli L., Digitaria ciliaris L., Brassica napus L. and Chenopodium serotinum L. were evaluated by the culture dish method. Preliminary bioassay results indicated that some target compounds exhibited good phytotoxic activity at a dose of 100 mg/L, with an inhibitory rate of 76.0–85.6% on root growth, even higher than the control herbicide, fenoxaprop-P-ethyl.

1Key Laboratory of Biopesticide and Chemical Biology, Ministry of Education, Fujian Agriculture and Forestry University, 350002 Fuzhou, Fujian, People’s Republic of China 2Fujian International Travel Health Care Center, 350001 Fuzhou, Fujian, People’s Republic of China 3Biological Centre of the Academy of Sciences of the Czech Republic, Institute of Entomology, Branisovska 31, 37005 Ceske Budějovice, Czech Republic, gelbic@entu.cas.cz