Project description:The rhodopsin-guanylyl cyclase from the nematophagous fungus Catenaria anguillulae belongs to a recently discovered class of enzymerhodopsins and may find application as a tool in optogenetics. Here the rhodopsin domain CaRh of the rhodopsin-guanylyl cyclase from Catenaria anguillulae was studied by absorption and emission spectroscopic methods. The absorption cross-section spectrum and excitation wavelength dependent fluorescence quantum distributions of CaRh samples were determined (first absorption band in the green spectral region). The thermal stability of CaRh was studied by long-time attenuation measurements at room temperature (20.5 °C) and refrigerator temperature of 3.5 °C. The apparent melting temperature of CaRh was determined by stepwise sample heating up and cooling down (obtained apparent melting temperature: 62 ± 2 °C). The photocycle dynamics of CaRh was investigated by sample excitation to the first inhomogeneous absorption band of the CaRhda dark-adapted state around 590 nm (long-wavelength tail), 530 nm (central region) and 470 nm (short-wavelength tail) and following the absorption spectra development during exposure and after exposure (time resolution 0.0125 s). The original protonated retinal Schiff base PRSBall-trans in CaRhda photo-converted reversibly to protonated retinal Schiff base PRSBall-trans,la1 with restructured surroundings (CaRhla₁ light-adapted state, slightly blue-shifted and broadened first absorption band, recovery to CaRhda with time constant of 0.8 s) and deprotonated retinal Schiff base RSB13-cis (CaRhla₂ light-adapted state, first absorption band in violet to near ultraviolet spectral region, recovery to CaRhda with time constant of 0.35 s). Long-time light exposure of light-adapted CaRhla₁ around 590, 530 and 470 nm caused low-efficient irreversible degradation to photoproducts CaRhprod. Schemes of the primary photocycle dynamics of CaRhda and the secondary photocycle dynamics of CaRhla1 are developed.
Project description:The primary objective of this prospective observational study is to characterize the gut and oral microbiome as well as the whole blood transcriptome in gastrointestinal cancer patients and correlate these findings with cancer type, treatment efficacy and toxicity. Participants will be recruited from existing clinical sites only, no additional clinical sites are needed.
Project description:This study intends to explore the clinicopathological characteristics and survival prognosis of locally recurrent colorectal cancer patients with different treatment modes by retrospectively analyzing the medical records of locally recurrent colorectal cancer patients who received hospitalization in our center. Transcriptome sequencing and public databases were used to screen for molecular markers related to locally recurrent colorectal cancer and to explore molecular markers’ regulatory role in the progression of locally recurrent colorectal cancer.
Project description:In order to more accurately discover the cause of drug resistance in tumor treatment, and to provide a new basis for precise treatment.
Therefore, based on the umbrella theory of precision medicine, we carried out this single-center, prospective, and observational study to include patients with liver metastases from colorectal cancer. By combining genome, transcriptome, and proteomic sequencing data, we established a basis for colorectal cancer liver Transfer the multi-omics data of the sample, describe the reason for the resistance of the first-line treatment, and search for new therapeutic targets.
Project description:Liver circadian clock and daily rhythmic transcriptome are highly responsive to metabolic cues generated from daily feeding activity. The mechanisms that mediate metabolic inputs to the whole rhythmic transcriptome are still under investigation. Here, we explored the role of O-GlcNAcylation, a nutrient-sensitive post-translational modification (PTM) that integrates circadian and metabolic signals, in the diurnal regulation of nuclear proteins. We found daily oscillation of overall nuclear protein O-GlcNAcylation in the liver of mice subjected to natural night time-restricted feeding (NRF). O-GlcNAcomic analysis revealed that 11.54% of 719 O-GlcNAcylated proteins are rhythmically O-GlcNAcylated. Proteins involved in gene expression were enriched, suggesting rhythmic O-GlcNAcylation may directly shape diurnal transcriptome. Furthermore, we showed that rhythmic O-GlcNAcylation could indirectly modulate diurnal transcriptome by interacting with phosphorylation. Specifically, several proteins harboring O-GlcNAcylation-phosphorylation interplay motif exhibit rhythmic O-GlcNAcylation and phosphorylation. For example, O-GlcNAcylation may occur at a phosphor-degron of a key circadian transcriptional activator, circadian locomotor output cycles kaput (CLOCK), regulating the stability and transcriptional output of CLOCK. Lastly, unnatural day time-restricted feeding (DRF) dampens O-GlcNAcylation rhythm, suggesting the disruption of diurnal transcriptome could be mediated by protein O-GlcNAcylation. In summary, our results provide mechanistic insights into metabolic regulation of diurnal transcriptome at PTM level and shed light on the deleterious effects of improper mealtimes.