Gastric cancer is one of the most common malignant cancers, with poor prognosis and high mortality rates worldwide. Therefore, development of an effective therapeutic method without side effects is ...an urgent need. It has been reported that cationic antimicrobial peptides can selectively bind to negatively charged prokaryotic and cancer cell membranes and exert cytotoxicity without causing severe drug resistance. In the current study, we prepared a series of peptide fragments derived from bovine lactoferrin and evaluated their anticancer potency toward the gastric cancer cell line AGS. Cell viability assay revealed that a 25-AA peptide fragment, lactoferricin B25 (LFcinB25), exhibited the most potent anticancer capability against AGS cells. Lactoferricin B25 selectively inhibited AGS cell growth in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) value of 64μM. Flow cytometry showed a notable increment of the sub-G1 populations of the cell cycle, indicating the induction of apoptosis by LFcinB25. Western blot analysis further revealed that upon LFcinB25 treatment for 2 to 6h, apoptosis-related caspases-3, 7, 8, 9, and poly(ADP-ribose) polymerase (PARP) were cleaved and activated, whereas autophagy-related LC3-II and beclin-1 were concomitantly increased. Thus, both apoptosis and autophagy are involved in the early stage of LFcinB25-induced cell death of AGS cells. However, upon treatment with LFcinB25 for 12 to 24h, LC3-II began to decrease, whereas cleaved beclin-1 increased in a time-dependent manner, suggesting that consecutive activation of caspases cleaved beclin-1 to inhibit autophagy, thus enhancing apoptosis at the final stage. These findings provide support for future application of LFcinB25 as a potential therapeutic agent for gastric cancer.
We report the discovery of 1.97 ms period gamma-ray pulsations from the 75 minute orbital-period binary pulsar now named PSR J1653−0158. The associated Fermi Large Area Telescope gamma-ray source ...4FGL J1653.6−0158 has long been expected to harbor a binary millisecond pulsar. Despite the pulsar-like gamma-ray spectrum and candidate optical/X-ray associations-whose periodic brightness modulations suggested an orbit-no radio pulsations had been found in many searches. The pulsar was discovered by directly searching the gamma-ray data using the GPU-accelerated Einstein@Home distributed volunteer computing system. The multidimensional parameter space was bounded by positional and orbital constraints obtained from the optical counterpart. More sensitive analyses of archival and new radio data using knowledge of the pulsar timing solution yield very stringent upper limits on radio emission. Any radio emission is thus either exceptionally weak, or eclipsed for a large fraction of the time. The pulsar has one of the three lowest inferred surface magnetic-field strengths of any known pulsar with Bsurf 4 × 107 G. The resulting mass function, combined with models of the companion star's optical light curve and spectra, suggests a pulsar mass 2 M . The companion is lightweight with mass ∼0.01 M , and the orbital period is the shortest known for any rotation-powered binary pulsar. This discovery demonstrates the Fermi Large Area Telescope's potential to discover extreme pulsars that would otherwise remain undetected.
The mTOR (mammalian target of rapamycin) inhibitor rapamycin caused growth arrest in both androgen-dependent and androgen-independent prostate cancer cells; however, long-term treatment induced ...resistance to the drug. The aim of this study was to investigate methods that can overcome this resistance. Here, we show that rapamycin treatment stimulated androgen receptor (AR) transcriptional activity, whereas suppression of AR activity with the antiandrogen bicalutamide sensitized androgen-dependent, as well as AR-sensitive androgen-independent prostate cancer cells, to growth inhibition by rapamycin. Further, the combination of rapamycin and bicalutamide, but not the individual drugs, induced significant levels of apoptosis in prostate cancer cells. The net effect of rapamycin is determined by its individual effects on the mTOR complexes mTORC1 (mTOR/raptor/GbetaL) and mTORC2 (mTOR/rictor/sin1/GbetaL). Inhibition of both mTORC1 and mTORC2 by rapamycin-induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity resulted from the inhibition of mTORC1, but not mTORC2. The effect of rapamycin on AR transcriptional activity was mediated by the phosphorylation of the serine/threonine kinase Akt, which also partially mediated apoptosis induced by rapamycin and bicalutamide. These results indicate the presence of two parallel cell-survival pathways in prostate cancer cells: a strong Akt-independent, but rapamycin-sensitive pathway downstream of mTORC1, and an AR-dependent pathway downstream of mTORC2 and Akt, that is stimulated by mTORC1 inhibition. Thus, the combination of rapamycin and bicalutamide induce apoptosis in prostate cancer cells by simultaneously inhibiting both pathways and hence would be of therapeutic value in prostate cancer treatment.
Sea Surface Temperature (SST) is of great importance to study several major phenomena due to ocean interactions with other earth systems. Previous studies on SST based on statistical inference ...methods were less accurate for longer prediction lengths. A considerable number of studies in recent years involve machine learning for SST modeling. These models were able to mitigate this problem to some length by modeling SST patterns and trends. Sequence analysis by decomposition is used for SST forecasting in several studies. Ensemble Empirical Mode Decomposition (EEMD) has been proven in previous studies as a useful method for this. The application of EEMD in spatiotemporal modeling has been introduced as Multidimensional EEMD (MEEMD). The aim of this study is to employ fast MEEMD methods to decompose the SST spatiotemporal dataset and apply a Convolutional Long Short-Term Memory (ConvLSTM)-based model to model and forecast SST. The results show that the fast MEEMD method is capable of enhancing spatiotemporal SST modeling compared to the Linear Inverse Model (LIM) and ConvLSTM model without decomposition. The model was further validated by making predictions from April to May 2023 and comparing them to original SST values. There was a high consistency between predicted and real SST values.
Abstract
KAGRA is a newly built gravitational-wave telescope, a laser interferometer comprising arms with a length of 3 km, located in Kamioka, Gifu, Japan. KAGRA was constructed under the ground and ...it is operated using cryogenic mirrors that help in reducing the seismic and thermal noise. Both technologies are expected to provide directions for the future of gravitational-wave telescopes. In 2019, KAGRA finished all installations with the designed configuration, which we call the baseline KAGRA. For this occasion, we present an overview of the baseline KAGRA from various viewpoints in a series of articles. In this article, we introduce the design configurations of KAGRA with its historical background.
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