Cholecystokinin neurons in mouse suprachiasmatic nucleus regulate the robustness of circadian clock.

The suprachiasmatic nucleus (SCN) can generate robust circadian behaviors in mammals under different environments, but the underlying neural mechanisms remained unclear. Here, we showed that the activities of cholecystokinin (CCK) neurons in the mouse SCN preceded the onset of behavioral activities under different photoperiods. CCK-neuron-deficient mice displayed shortened free-running periods, failed to compress their activities under a long photoperiod, and developed rapid splitting or became arrhythmic under constant light. Furthermore, unlike vasoactive intestinal polypeptide (VIP) neurons, CCK neurons are not directly light sensitive, but their activation can elicit phase advance and counter light-induced phase delay mediated by VIP neurons. Under long photoperiods, the impact of CCK neurons on SCN dominates over that of VIP neurons. Finally, we found that the slow-responding CCK neurons control the rate of recovery during jet lag. Together, our results demonstrated that SCN CCK neurons are crucial for the robustness and plasticity of the mammalian circadian clock.

Gossypol ameliorates the IL-1ß-induced apoptosis and inflammation in chondrocytes by suppressing the activation of TLR4/MyD88/NF-κB pathway via downregulating CX43.

The effects of anti-inflammatory drug gossypol on osteoarthritis (OA) treatment were discussed in this paper. After identified using toluidine blue and immunofluorescence staining of type II collagen, chondrocytes from OA patients were treated with interleukin-1ß (IL-1ß), gossypol, and overexpressed connexin43 (CX43). In treated chondrocytes, according to MTT assay and flow cytometry, gossypol increased viability and reduced apoptosis of IL-1ß induced chondrocytes. Enzyme linked immunosorbent assay (ELISA) suggested that gossypol downregulated inflammatory tumor necrosis factor (TNF)-α level. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot confirmed that gossypol downregulated CX43, nuclear factor-kappa B (NF-κB) p65, TNF-α, toll like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88) and interleukin-6 (IL-6) expressions. Besides, overexpressed CX43 reversed the effects of gossypol on viability, apoptosis, and expressions of factors related to TLR4/MyD88/NF-κB pathway of IL-1ß-induced chondrocytes. In conclusion, gossypol ameliorates IL-1ß-induced apoptosis and inflammation in chondrocytes by suppressing TLR4/MyD88/NF-κB pathway via downregulating CX43.

Genome-wide analysis of lncRNA stability in human.

Transcript stability is associated with many biological processes, and the factors affecting mRNA stability have been extensively studied. However, little is known about the features related to human long noncoding RNA (lncRNA) stability. By inhibiting transcription and collecting samples in 10 time points, genome-wide RNA-seq studies was performed in human lung adenocarcinoma cells (A549) and RNA half-life datasets were constructed. The following observations were obtained. First, the half-life distributions of both lncRNAs and messanger RNAs (mRNAs) with one exon (lnc-human1 and m-human1) were significantly different from those of both lncRNAs and mRNAs with more than one exon (lnc-human2 and m-human2). Furthermore, some factors such as full-length transcript secondary structures played a contrary role in lnc-human1 and m-human2. Second, through the half-life comparisons of nucleus- and cytoplasm-specific and common lncRNAs and mRNAs, lncRNAs (mRNAs) in the nucleus were found to be less stable than those in the cytoplasm, which was derived from transcripts themselves rather than cellular location. Third, kmers-based protein-RNA or RNA-RNA interactions promoted lncRNA stability from lnc-human1 and decreased mRNA stability from m-human2 with high probability. Finally, through applying deep learning-based regression, a non-linear relationship was found to exist between the half-lives of lncRNAs (mRNAs) and related factors. The present study established lncRNA and mRNA half-life regulation networks in the A549 cell line and shed new light on the degradation behaviors of both lncRNAs and mRNAs.