SHMT2 promotes papillary thyroid cancer metastasis through epigenetic activation of AKT signaling.

Cancer cells alter their metabolism and epigenetics to support cancer progression. However, very few modulators connecting metabolism and epigenetics have been uncovered. Here, we reveal that serine hydroxymethyltransferase-2 (SHMT2) generates S-adenosylmethionine (SAM) to epigenetically repress phosphatase and tensin homolog (PTEN), leading to papillary thyroid cancer (PTC) metastasis depending on activation of AKT signaling. SHMT2 is elevated in PTC, and is associated with poor prognosis. Overexpressed SHMT2 promotes PTC metastasis both in vitro and in vivo. Proteomic enrichment analysis shows that AKT signaling is activated, and is positively associated with SHMT2 in PTC specimens. Blocking AKT activation eliminates the effects of SHMT2 on promoting PTC metastasis. Furthermore, SHMT2 expression is negatively associated with PTEN, a negative AKT regulator, in PTC specimens. Mechanistically, SHMT2 catalyzes serine metabolism and produces activated one-carbon units that can generate SAM for the methylation of CpG islands in PTEN promoter for PTEN suppression and following AKT activation. Importantly, interference with PTEN expression affects SHMT2 function by promoting AKT signaling activation and PTC metastasis. Collectively, our research demonstrates that SHMT2 connects metabolic reprogramming and epigenetics, contributing to the poor progression of PTC.

Identification and validation of key biomarkers associated with macrophages in nonalcoholic fatty liver disease based on hdWGCNA and machine learning.

BACKGROUND: NAFLD has attracted increasing attention because of its high prevalence and risk of progression to cirrhosis or even hepatocellular carcinoma. Therefore, research into the root causes and molecular indicators of NAFLD is crucial. METHODS: We analyzed scRNA-seq data and RNA-seq data from normal and NAFLD liver samples. We utilized hdWGCNA to find module-related genes associated with the phenotype. Multiple machine learning algorithms were used to validate the model diagnostics and further screen for genes that are characteristic of NAFLD. The NAFLD mouse model was constructed using the MCD diet to validate the diagnostic effect of the genes. RESULTS: We identified a specific macrophage population called NASH-macrophages by single-cell sequencing analysis. Cell communication analysis and Pseudo-time trajectory analysis revealed the specific role and temporal distribution of NASH-macrophages in NAFLD. The hdWGCNA screening yielded 30 genes associated with NASH-macrophages, and machine learning algorithms screened and obtained two genes characterizing NAFLD. The immune infiltration indicated that these genes were highly associated with macrophages. Notably, we verified by RT-qPCR, IHC, and WB that MAFB and CX3CR1 are highly expressed in the MCD mouse model and may play important roles. CONCLUSIONS: Our study revealed a macrophage population that is closely associated with NAFLD. Using hdWGCNA analysis and multiple machine learning algorithms, we identified two NAFLD signature genes that are highly correlated with macrophages. Our findings may provide potential feature markers and therapeutic targets for NAFLD.

Dynamic and static angry faces influence time perception differently-Evidence from ERPs.

The dynamic characteristics of facial expressions might affect time perception. Compared with static emotional faces, dynamic emotional faces are more intense, have higher ecological validity, and contain time series information, which may lead to time overestimation. In the present study, we aimed at investigating how dynamic characteristics of angry facial expressions affect time perception, as measured using event-related potentials (ERPs). Dynamic and static angry and neutral faces with different durations (400, 600, 800, 1000, 1200, 1400, and 1600 ms) were presented in the classical temporal bisection paradigm. Participants were asked to judge whether the duration of the presented face was closer to 400 or 1600 ms. The behavioral results showed a significant overestimation effect for dynamic angry faces compared with static faces, both in terms of proportion of long and Bisection Point. The ERP results indicated that the processing mechanisms are significantly different between judging the duration of dynamic and static angry faces. Dynamic angry faces evoked a larger N2 and Late Positive Potential than did static faces, while the static angry faces evoked a larger P2 and Early Posterior Negativity. The Contingent Negative Variation showed a complex change pattern over time. Our results indicate that dynamic angry facial expressions influence time perception differently than do static faces. Static angry faces were processed earlier and were considered to cause an overestimation of time through early emotional arousal and attentional bias, while dynamic angry faces may have caused the overestimation of time through response inhibition and late sustained attention.

Antitumor and toxicity study of mitochondria-targeted triptolide derivatives using triphenylphosphine (TPP+) as a carrier.

Based on the higher mitochondrial membrane potential (Δψm) of tumor cells than normal cells, a mitochondria-targeting strategy using delocalized lipophilic cations as carriers is a promising way to improve the antitumor effect of small molecules and to reduce toxicity. Triptolide (TP) has a strong antitumor effect but is limited in the clinic due to high systemic toxicity. Mitochondria-targeted TP derivatives were designed and synthesized using triphenylphosphine cations as carriers. The optimal derivative not only maintained the antitumor activity of TP but also showed a tumor cell selectivity trend. Moreover, the optimal derivative increased the release of lactate dehydrogenase and the production of ROS, decreased Δψm, and arrested HepG2 cells in G0/G1 phase. In a zebrafish HepG2 xenograft tumor model, the inhibitory effect of the optimal derivative was comparable to that of TP, while it had no obvious toxic effect on multiple indicators in zebrafish at the test concentrations. This work provided some evidence to support the mitochondria-targeting strategy.

Development of Young Children's Time Perception: Effect of Age and Emotional Localization.

Time perception is a fundamental aspect of young children's daily lives and is affected by a number of factors. The present study aimed to investigate the precise developmental course of young children's time perception from 3 to 5 years old and the effects of emotion localization on their time perception ability. A total of 120 children were tested using an adapted time perception task with black squares (Experiment 1) and emotional facial expressions (Experiment 2). Results suggested that children's time perception was influenced by stimulus duration and improved gradually with increasing age. Both accuracy and reaction time were affected by the presentation sequence of emotional faces, indicating an effect of emotion localization. To summarize, young children's time perception showed effects of age, stimulus duration, and emotion localization.

Anticancer Effects of Honokiol via Mitochondrial Dysfunction Are Strongly Enhanced by the Mitochondria-Targeting Carrier Berberine.

Mitochondrion is a favorable therapeutic target in cancer, given its regulation of bioenergetics and cell death. Honokiol exhibits antiproliferative effects through mitochondria-mediated death signaling. To enhance its anticancer potential and selectivity, we conjugated honokiol to berberine, a mitochondria-targeting carrier. All designed derivatives displayed 1 order of magnitude increased cytotoxicity compared with the parent compounds, especially with massive cytoplasmic vacuoles. Biological evaluation demonstrated the representative compound 6b localized within the mitochondria, and mitochondrial dilation resulted in vacuolization. 6b induced vacuolation-associated cell death and apoptosis with obvious mitochondrial dysfunction, as demonstrated by booming reactive oxygen species generation, opening mitochondrial permeability transition pore, and reducing mitochondrial membrane potential. The targeting property also conferred 6b with selectivity for tumor cells compared to normal cells. 6b inhibited cancer cell proliferation in the zebrafish xenograft model. These results demonstrate that berberine-linked honokiol derivatives open up a direction for novel mitochondrial-targeting antitumor agents.

A Rapid Coordinate Transformation Method Applied in Industrial Robot Calibration Based on Characteristic Line Coincidence.

Coordinate transformation plays an indispensable role in industrial measurements, including photogrammetry, geodesy, laser 3-D measurement and robotics. The widely applied methods of coordinate transformation are generally based on solving the equations of point clouds. Despite the high accuracy, this might result in no solution due to the use of ill conditioned matrices. In this paper, a novel coordinate transformation method is proposed, not based on the equation solution but based on the geometric transformation. We construct characteristic lines to represent the coordinate systems. According to the space geometry relation, the characteristic line scan is made to coincide by a series of rotations and translations. The transformation matrix can be obtained using matrix transformation theory. Experiments are designed to compare the proposed method with other methods. The results show that the proposed method has the same high accuracy, but the operation is more convenient and flexible. A multi-sensor combined measurement system is also presented to improve the position accuracy of a robot with the calibration of the robot kinematic parameters. Experimental verification shows that the position accuracy of robot manipulator is improved by 45.8% with the proposed method and robot calibration.

[Studies on the quality standard of "Lü Kang Yin Xing Ye Pian"].

OBJECTIVE: The quality control method of "Lü Kang Yin Xing Ye Pian" (LKYXYP) was studied and established. METHOD: The ginkgolides in LKYXYP were identified by TLC. The compounds of fatty acids in Perillae oil were determined by CC/MS. Flavones, ginkgolides and ginkgolic acids were determined by HPLC. RESULT: There were good linears relationship between the peak area and concentration, r = 0.999, RSD = 1.2% - 2.5% (n = 5), and recoveries of each composition was above 95%, the contation was stable in 24h. CONCLUSION: This method is proved to be accurate and able to be applied for the quality control of this preparation.