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Background: The Klf6 gene, belonging to Krüppel-like family of C2H2 zinc finger transcription factors, is strongly associated with tumor formation through high somatic mutations in carcinomas of the prostate, liver, colon, stomach, lung, neck, pituitary gland and nervous system. Recently, Klf6 super-enhancer which strongly regulates Klf6 gene expression has been identified, and the function of Klf6 super-enhancer which regulates cell growth was studied. Objective: The development of inhibitors targeting BRD4-binding super-enhancers is a potential target therapeutic strategy for tumor therapy. However, the suppression of Klf6 super-enhancer function by BRD4 inhibitors is not known. Methods: CRISPR-Cas9 editing technique was used for the Klf6 super-enhancer deletion experiment, and the expression levels of several genes for cell clones were detected by qRT-PCR analysis and Western blotting. Cell proliferation assay was applied to evaluate the functional role of Klf6 super-enhancer using several BRD4 inhibitors. The interaction of several BRD4 inhibitors against the target protein was analyzed by molecular docking simulation. Results: JQ-1, a human BRD4 inhibitor, inhibited Klf6 gene expression and its activity in HepG2 cells in a time and dose-dependent manner while simultaneously inhibiting cell growth. Besides, BETd-246, a human BRD4 inhibitor, strongly inhibited Klf6 gene expression, significantly inhibited cell growth, and exhibited higher efficacy than JQ-1. Molecular docking studies revealed that some key residues were critical for ligand-receptor interactions by forming hydrogen bonds with ligands (JQ-1: ASN140, BETd-246: ASN140, TYR106, LYS65, GLN58, MET105, and MET53). Conclusions: Our findings suggest that KLF6 is regulated by Klf6 super-enhancer and the targeting of Klf6 super-enhancer by BRD4 inhibitors may be an effective therapeutic strategy for liver cancer therapy.

The comet 27 P/Crommelin was discovered in 1457 and since then observed six times up to 1956, so its average period is 27.79 years. According to Korean ancient annals, however, comet 27 P/Crommelin was first observed in B.C. 44 and was observed 16 times up to 1457. We traced the records with a period of about 28 years, compiled a list of them and showed that all those records are concerned with the comet 27 P/Crommelin. According to extrapolation of the brightness, the comet 27 P/Crommelin might be one of the brightest comets observed in human history, so ancient people could easily observe this comet with the naked eye. We examined the parallel records in Chinese history and concluded that the Korean historians might have added more detail to their reports by referring to Chinese records.

The power-law distribution is ubiquitous and its mechanism seems to be various. We find a general mechanism for the distribution. The distribution of a geometrically growing system can be approximated by a log - completely squared chi distribution with 1 degree of freedom (log-CS$\chi_1$), which reaches asymptotically a power-law distribution, or by a log-normal distribution, which has an infinite asymptotic slope, at the upper limit. For the log-CS$\chi_1$, the asymptotic exponent of the power-law or the slope in a log-log diagram seems to be related only to the variances of the system parameters and their mutual correlation but independent of an initial distribution of the system or any mean value of parameters. We can take the log-CS$\chi_1$ as a unique approximation when the system should have a singular initial distribution. The mechanism shows a comprehensiveness to be applicable to wide practice. We derive a simple formula for the Zipf's exponent, which will probably demand that the exponent should be near -1 rather than exactly -1. We show that this approach can explain statistics of the COVID-19 pandemic.

We have investigated Korean records of naked-eye observations of sunspots and we have found evidence that implies a periodicity of about 200 yr. Adding Chinese records, we show that these historical naked-eye observations of sunspots have a similar periodicity. Recently, some authors have shown that there are no intrinsic periodicities except for the 11-yr cycle. We adopt a new approach called a samplogram to test the sampling stability of cycles in terms of power spectra and difference series. We show that the Suess/de Vries cycle of about 207 yr is a deterministic cycle of stochastic solar activity. Also, we show that occurrences of grand minima are not necessarily expected with the Suess/de Vries cycle and it is possible for double or multiple grand maxima to appear without a grand minimum within them.

We show that while the Fourier transform can figure only an “intensity” of a periodic signal, there is an additional information embedded, which is a “coherence” of the signal. Supposing that the periodicity is reflected only on the “coherence,” we introduce a time stability as a measure of “coherence” excluding the “intensity,” i.e. amplitude of signal. In stead of classical strength-based significance, where strength implies the power or amplitude, we adopt a stability-based significance as criterion to choose cycles in a random signal. We inspect the time-stable solar periodicities and show that most periodicities discovered in exterior solar activities such as the solar wind inhere in interior solar activity such as the sunspot and that the time stability can be an effective tool in spectral analysis of stochastic solar activity.