A study on EEG differences between active counting and focused breathing tasks for more sensitive detection of consciousness.

Introduction: In studies on consciousness detection for patients with disorders of consciousness, difference comparison of EEG responses based on active and passive task modes is difficult to sensitively detect patients' consciousness, while a single potential analysis of EEG responses cannot comprehensively and accurately determine patients' consciousness status. Therefore, in this paper, we designed a new consciousness detection paradigm based on a multi-stage cognitive task that could induce a series of event-related potentials and ERD/ERS phenomena reflecting different consciousness contents. A simple and direct task of paying attention to breathing was designed, and a comprehensive evaluation of consciousness level was conducted using multi-feature joint analysis. Methods: We recorded the EEG responses of 20 healthy subjects in three modes and reported the consciousness-related mean event-related potential amplitude, ERD/ERS phenomena, and the classification accuracy, sensitivity, and specificity of the EEG responses under different conditions. Results: The results showed that the EEG responses of the subjects under different conditions were significantly different in the time domain and time-frequency domain. Compared with the passive mode, the amplitudes of the event-related potentials in the breathing mode were further reduced, and the theta-ERS and alpha-ERD phenomena in the frontal region were further weakened. The breathing mode showed greater distinguishability from the active mode in machine learning-based classification. Discussion: By analyzing multiple features of EEG responses in different modes and stimuli, it is expected to achieve more sensitive and accurate consciousness detection. This study can provide a new idea for the design of consciousness detection methods.

Simplified hybrids of two anticancer bistetrahydroisoquinoline alkaloids ecteinascidin 743 and cribrostatin 4 and inhibitory activity against proliferation of cancer cells.

Ecteinascidin 743 is a famous marine drug used in anticancer treatments. In this work, a series of simplified hybrids/analogues have been synthesized by employing a newly developed chemistry that integrates the partial structural features of two anticancer bis-tetrahydroisoquinoline alkaloids ecteinascidin 743 and cribrostatin 4. The described Suzuki-coupling protocol enabled us to easily introduce variable functionalities at the C3 position of the basic skeleton of bis-tetrahydroisoquinoline alkaloids for the first time. Cytotoxic examination showed that analogue 21f exhibited inhibitory activities with IC50 values in the low 10-6 M range against the proliferation of the cancer cell lines A549, HepG2, and MDA-MB-231. This work reveals that diversifying the C3/C4 olefin in the skeleton of tetrahydroisoquinoline alkaloids is a useful means to generate potential pharmaceuticals.

Annonaceous Acetogenin Mimic AA005 Inhibits the Growth of TNBC MDA-MB-468 Cells by Altering Cell Energy Metabolism.

Triple-negative breast cancer (TNBC) is a serious health issue for women worldwide and there is still no suitable treatment option. AA005, a structurally simplified mimic of natural Annonaceous acetogenins, presents outstanding properties with impressive cytotoxicity and cell-type selective actions. The present study was aimed at evaluating the potential of AA005 as a therapeutic agent for TNBC. AA005 potently inhibited the growth of TNBC cells at 50 nM level. Inspired by the finding of the phosphatase and tensin homologue (PTEN) tumor suppressor, the effect of AA005 on aerobic glycolysis was investigated in TNBC MDA-MB-468 cells. A short-term AA005 exposure markedly suppressed mitochondrial function in MDA-MB-468 cells, thus activating the aerobic glycolysis to lessen the risk of decreased ATP generation in mitochondria. Prolonging the incubation time of AA005 clearly weakened the aerobic glycolysis in the cells. This was in part attributed to the PI3K-AKT pathway inactivation and subsequent declined glucose uptake. As a consequence, the energy supply was completely cut from the two major energy-producing pathways. Further experiments showed that AA005 resulted in irreversible damage on cell activity including cell cycle and growth, inducing mitochondrial oxidative stress and ultimately leading to cell death. In addition, the in vivo therapeutic efficacy of AA005 was proved on 4T1 xenograft tumor mice model. Our data demonstrate that AA005 exhibited a great potential for future clinical applications in TNBC therapy.

Cytotoxic analogues of marine diterpenoid plumisclerin A by shifting the lipophilic branch on the characteristic tricyclic core.

Plumisclerin A is one of the most complex cytotoxic xenicane diterpenes from marine sources, featuring a unique congested and rigid tricyclo[4.3.1.01,5]decane core and a lipophilic acyl chain. This work explored a number of new analogues of plumisclerin A through modifying the characteristic tricyclo[4.3.1.01,5]decane core with lipophilic chains starting from a common lactone intermediate. Bioactivity examination of all the synthetic analogues shows that new analogues 2a, 18 and 21 exhibited comparable inhibitory potencies to that of the natural product against the proliferation of cancer cells. Structural comparison of these bioactive natural and unnatural compounds reveals that the location of lipophilic substituent(s) on the tricyclo[4.3.1.01,5]decane core is spatially flexible, and this work thus offers a new channel to diverse bioactive analogues of plumisclerin A.