Filamentous GLS1 promotes ROS-induced apoptosis upon glutamine deprivation via insufficient asparagine synthesis.

GLS1 orchestrates glutaminolysis and promotes cell proliferation when glutamine is abundant by regenerating TCA cycle intermediates and supporting redox homeostasis. CB-839, an inhibitor of GLS1, is currently under clinical investigation for a variety of cancer types. Here, we show that GLS1 facilitates apoptosis when glutamine is deprived. Mechanistically, the absence of exogenous glutamine sufficiently reduces glutamate levels to convert dimeric GLS1 to a self-assembled, extremely low-Km filamentous polymer. GLS1 filaments possess an enhanced catalytic activity, which further depletes intracellular glutamine. Functionally, filamentous GLS1-dependent glutamine scarcity leads to inadequate synthesis of asparagine and mitogenome-encoded proteins, resulting in ROS-induced apoptosis that can be rescued by asparagine supplementation. Physiologically, we observed GLS1 filaments in solid tumors and validated the tumor-suppressive role of constitutively active, filamentous GLS1 mutants K320A and S482C in xenograft models. Our results change our understanding of GLS1 in cancer metabolism and suggest the therapeutic potential of promoting GLS1 filament formation.

Using resting thalamic connectivity to identify the relationship between Eysenck personality traits and intelligence in healthy adults.

Personality refers to a set of relatively stable psychological characteristics of individuals and has been associated with intelligence. It is well known that the thalamus plays an important role in cognitive processes and personality traits, but the relationship between personality traits, thalamic function, and intelligence has rarely been directly explored. Hence, we investigated the relationship between Eysenck personality traits, resting-state functional connectivity (rsFC) of the thalamus, and intelligence in a large sample of healthy adults (N = 176). We found that the trait of psychoticism was negatively associated with intelligence. The high intelligence group showed significantly lower psychoticism and demonstrated enhanced thalamic connectivity to the amygdala, inferior parietal lobules, pallidum, medial superior/middle frontal gyrus, and precuneus. Furthermore, a mediation analysis indicated that the FC between the left thalamus and left amygdala significantly mediated the correlation between psychoticism and full IQ (FIQ). These findings suggest that intelligent people may be less prone to psychoticism. Meanwhile, thalamic rsFC may reflect individual differences in intelligence and play a key role in the relationship between personality traits and intellectual abilities.

Mechanism differences between typical yin and typical yang personality individuals assessed by Five-Pattern Personality Inventory (FPPI): Evidence from resting-state brain functional networks.

BACKGROUND: Most studies assessing brain-personality mechanisms have used Western personality questionnaires. However, Western personality questionnaires may not objectively reflect the personality characteristics of individuals in Eastern cultures such as China. Hence, we adopted the functional magnetic resonance imaging (fMRI) and the Chinese localized scale, FPPI, to explore the brain mechanisms differences of typical yin and typical yang personalities of individuals in China. METHODS: 30 typical yin personality participants (TYI) and 34 typical yang personality participants (TYA) were enrolled according to the FPPI. The group differences of the functional brain networks among 90 specific brain regions were mapped using fMRI data and then analyzed by the conventional network metrics (CNM) and frequency subgraph mining (FSM). RESULTS: The CNM and FSM differences between two typical personality groups were traced to the frontal, temporal, and parietal cortices. The yin group, reflecting the rich emotions and feelings of individuals, showed higher betweenness centrality (BCi) and nodal efficiency (Ei) values in putamen and middle frontal gyrus. The yang group, reflecting active behaviors and tendency to adapting to the changing surroundings, showed higher BCi and Ei values in precuneus, posterior cingulate gyrus, and inferior parietal lobule, brain areas in the default mode network (DMN). CONCLUSION: These results supplied evidence for the neurobiological differences between typical yin and typical yang personality participants based on Chinese culture. These results also provide a new perspective to help researchers understand brain mechanism differences between yin and yang personality groups in the Chinese culture.

Anticancer effect of the traditional Chinese medicine herb Maytenus compound via the EGFR/PI3K/AKT/GSK3ß pathway.

BACKGROUND: Cancer is a leading cause of death worldwide; folk anticancer medicinal plants have applied for cancer treatment. The Maytenus compound tablet as traditional Chinese compound medicine has been approved for alleviating hyperplasia of mammary glands, whether it can inhibit cancer still unknown. The study was to evaluate the anticancer activity of the Maytenus compound tablet. METHODS: MTS assay evaluated the anti-proliferation effect of the Maytenus compound on H226, A2058, 786O and HeLa cancer cells and two normal epithelial cell lines, namely, 16HBE and Hecate. Nude mouse xenograft tumor model using H226 and HeLa cells examined the drug's anticancer effect in vivo. Western blot assay studied the possible mechanism. RESULTS: The Maytenus compound indicated obvious ability to against proliferation in four strains of cancer cells, particularly against H226 cells by an IC50 of 85.47±10.06 µg/mL and against HeLa cells by an IC50 of 128.74±17.46 µg/mL. However, it had a low cytotoxicity in human normal epithelial cell lines 16HBE with an IC50 of 4,555.86±25.21 µg/mL and Hecate with an IC50 of 833.56±181.88 µg/mL. The Maytenus compound at the 2.45 g/kg oral dosages inhibited the proliferation of H226 cells and HeLa cells in nude mouse with inhibitory rates of 36.06% and 26.45%, respectively, and no organ toxicity. The Maytenus compound could significantly downregulate the expression of pEGFR, pPI3K, pAKT, pGSK3ß, ß-catenin, and c-MYC and upregulate the protein expression of GSK3ß. CONCLUSIONS: The Maytenus compound has significant anticancer activities against human cancer H226 and HeLa cells both in vitro and in vivo, highlighting it may be an anticancer medicine.