Although prime editors (PEs) have the potential to facilitate precise genome editing in therapeutic, agricultural and research applications, their specificity has not been comprehensively evaluated. ...To provide a systematic assessment in plants, we first examined the mismatch tolerance of PEs in plant cells and found that the editing frequency was influenced by the number and location of mismatches in the primer binding site and spacer of the prime editing guide RNA (pegRNA). Assessing the activity of 12 pegRNAs at 179 predicted off-target sites, we detected only low frequencies of off-target edits (0.00~0.23%). Whole-genome sequencing of 29 PE-treated rice plants confirmed that PEs do not induce genome-wide pegRNA-independent off-target single-nucleotide variants or small insertions/deletions. We also show that ectopic expression of the Moloney murine leukemia virus reverse transcriptase as part of the PE does not change retrotransposon copy number or telomere structure or cause insertion of pegRNA or messenger RNA sequences into the genome.
Obesity exhibits a correlation with metabolic inflammation and endoplasmic reticulum stress, promoting the progression of metabolic disease such as diabetes, hyperlipidemia, hyperuricemia and so on. ...Adipose tissue macrophages (ATMs) are central players in obesity-associated inflammation and metabolic diseases. Macrophages are involved in lipid and energy metabolism and mitochondrial function in adipocytes. Macrophage polarization is accompanied by metabolic shifting between glycolysis and mitochondrial oxidative phosphorylation. Here, this review focuses on macrophage metabolism linked to functional phenotypes with an emphasis on macrophage polarization in adipose tissue physiological and pathophysiological processes. In particular, the interplay between ATMs and adipocytes in energy metabolism, glycolysis, OXPHOS, iron handing and even interactions with the nervous system have been reviewed. Overall, the understanding of protective and pathogenic roles of ATMs in adipose tissue can potentially provide strategies to prevent and treat obesity-related metabolic disorders.
SIRT6 is a member of the Sir2-like family in mammals. Recent structural and biochemical studies have characterized SIRT6 as having deacetylation, defatty-acylation, and mono-ADP-ribosylation ...activities, which determine its important regulatory roles during physiological and pathological processes. This review focuses mainly on the regulatory functions of SIRT6 in aging, cancer, and, especially, immunity. Particular attention is paid to studies illustrating the critical role of SIRT6 in the regulation of immune cells from the viewpoints of immunesenescence, immunometabolism, and tumor immunology. Owing to its role in regulating the function of the immune system, SIRT6 can be considered to be a potential therapeutic target for the treatment of diseases.
•Actinidia chinensis Planch(ACP) suppresses proliferation and migration of gastric cancer cells.•ACP treatment elevated the apoptosis and ferroptosis but suppressed mesenchymal phenotype in HGC-27 ...cells.•ACP suppressed tumor growth in the zebrafish xenograft model.
Actinidia chinensis Planch (ACP) was the kiwifruit plant Chinese kiwifruit Actinidia chinensis Planch Root, which had been approved to be an anti-tumor drug widespread in clinical. However, the specific mechanism of ACP in resistance to gastric cancer remained unclear. Therefore, our study was dedicated to investigate the anti-proliferation and anti-migration effects of ACP on gastric cancer cells and its molecular mechanisms. Firstly, we utilized HPLC-MS to analyze the composition of ACP decoction, the results showed that ACP contained two main anti-tumor components, Ursolic acid and Oleanolic acid. The proliferation and migration ability of HGC-27 were examined by CCK-8 and cell scratch tests respectively. In addition, we also investigated HGC-27 cells apoptosis, mesenchymal phenotype and ferroptosis after ACP rat drug-containing serum (ACPs) treatment. EGFP-expressing lentiviral vectors were utilized to construct HGC-27 cells which containing green fluorescence. Then we take advantages of containing green fluorescence cells to establish a zebrafish xenograft model in vivo. The CCK-8 and cell scratch experiments verified that ACPs significantly inhibited proliferation and migration of HGC-27 in vitro. ACPs increased cells apoptosis rate, while were rescued by apoptosis inhibitor Z-VAD-FMK. Furthermore, ACPs downregulated the expression levels of Vimentin protein and Snail protein markedly. Intriguingly, ACPs increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. Furthermore, the zebrafish xenograft study further confirmed that administration of ACP suppressed the xenograft growth and metastasis of transplanted HGC-27 cells in vivo. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype.
Mental health literacy is considered an important factor in promoting professional psychological help-seeking attitudes. However, it is important to clarify the emotional and behavioral factors that ...underlie this association. Drawing from the ABC model of attitudes and the Health Disclosure Decision-Making Model, this study aimed to examine the mediating role of psychological help-seeking stigma and distress disclosure in the relationship between mental health literacy and professional psychological help-seeking attitudes.
We collected data from 827 participants in seven regions of China (597 female; M
= 26.019, SD = 5.592 years old) using self-report measures, including the Mental Health Literacy Scale, Questionnaire of Stigma for Seeking Professional Psychological Help, Distress Disclosure Index, and Attitudes Toward Seeking Professional Psychological Help-Short Form. A chain mediation model was built to examine the relationships among mental health literacy, psychological help-seeking stigma, distress disclosure, and professional psychological help-seeking attitudes.
The results of the analyses showed a positive association between mental health literacy and professional psychological help-seeking attitudes, with psychological help-seeking stigma and distress disclosure playing mediating roles in this relationship. Furthermore, even after controlling for participants' age, gender, and education, the chain mediation effect of psychological help-seeking stigma and distress disclosure on the relationship between mental health literacy and professional psychological help-seeking attitudes was observed among the Chinese population.
These findings underscore the significance of mental health literacy in shaping professional psychological help-seeking attitudes, while emphasizing the need to account for psychological help-seeking stigma and distress disclosure when examining this association. Additionally, the model proposed in this study provides a valuable framework for promoting the utilization of professional mental health services.
COVID-19 has intensified the influence on medical students by changing the lifestyle, online study and clinical practice which bring out series of stress, sleep disturbance and mental health ...problems. This cross-sectional study aim to explore the association between perceived stress and sleep quality among medical students and investigated whether anxiety and depression mediated this association during pandemic. A total of 1,021 medical students in two universities who were from Guangdong Province, China participated this study and from January to September 2020 through the online question are, with 28.80% reporting sleep disturbances. The medical students were finished various self-reported questionnaires, including the Perceived Stress Scale-10, Pittsburgh Sleep Quality Index, Generalized Anxiety Disorder-7 Scale, and Patient Health Questionnaire-9, the study found positive correlations among sleep quality, perceived stress, anxiety, and depression. The data was analyzed with The Amos 26.0 system. Result demonstrated that perceived stress was associated with poor sleep quality. Anxiety and depression partially mediated the association between perceived stress and poor sleep quality, explaining 73.08% of the association. This study's structural equation model offers a useful framework for assessing mechanisms mediating associations between perceived stress and sleep quality. The findings emphases the importance of addressing psychological factors in high-pressure situations, which can exacerbate sleep disturbances among medical students. It is important to screen the level of stress, mental health problems and investigate the risk factors of sleep quality among medical students during emergency public health events.
The red mud (RM) coated catalytic filter was developed as efficient multifunctional material to simultaneously remove NO
x
and dust in the high temperature range of 300–450 °C, which exhibits ...excellent deNO
x
activity/durability as well as low pressure drop with more than 80% NO conversion in the presence of H
2
O/SO
2
. The performance of the RM coated catalytic filter is obviously superior to that of the reference samples of V–W–Ti and Fe–Ti based filter. The multiple characterization data (including XRD, XRF, BET, SEM, TPX and LPSA) reveals the amorphous state of the RM catalyst with high dispersity of Fe active sites accounts for the high adsorption capacity of NH
3
and thus excellent deNO
x
performance. Moreover, the prepared colloidal RM slurry is very uniform and stable with the smallest average particle size, which reduces the blocking up of the channel of filter and facilitates the decrease of pressure drop as well as the improvement of deNO
x
activity. The excellent deNO
x
performance, low pressure drop together with the low cost make the RM coated catalytic filter to be promising application prospect for purification of the high-temperature flue gas with high content of dust such as in cement and glass furnaces.
Graphic Abstract
The preparation of RM catalytic filter and the comparison of SCR performance between three kinds of catalytic filters.
Lysine lactylation (Kla) is a recently discovered histone mark derived from metabolic lactate. The NAD+‐dependent deacetylase SIRT3, which can also catalyze removal of the lactyl moiety from lysine, ...is expressed at low levels in hepatocellular carcinoma (HCC) and has been suggested to be an HCC tumor suppressor. Here we report that SIRT3 can delactylate non‐histone proteins and suppress HCC development. Using SILAC‐based quantitative proteomics, we identify cyclin E2 (CCNE2) as one of the lactylated substrates of SIRT3 in HCC cells. Furthermore, our crystallographic study elucidates the mechanism of CCNE2 K348la delactylation by SIRT3. Our results further suggest that lactylated CCNE2 promotes HCC cell growth, while SIRT3 activation by Honokiol induces HCC cell apoptosis and prevents HCC outgrowth in vivo by regulating Kla levels of CCNE2. Together, our results establish a physiological function of SIRT3 as a delactylase that is important for suppressing HCC, and our structural data could be useful for the future design of activators.
Synopsis
Delactylation of cyclin E2 (CCNE2) by SIRT3 suppresses hepatocellular carcinoma (HCC) development.
SIRT3 is negatively correlated with lysine lactylation levels in HCC tissues.
SIRT3‐mediated delactylation of CCNE2 suppresses HCC cell growth.
Honokiol induces SIRT3 delactylation activity to prevent HCC growth in vivo.
Delactylation of cyclin E2 (CCNE2) by SIRT3 suppresses hepatocellular carcinoma (HCC) development.
The torsional viscoelastic creeping and recovery of an SU-8 spring is reported by studying the deflection angle variation of a vertical comb-drive actuator suspended by an SU-8 spring at three ...different stress levels. A maximum creep of 0.43° (corresponding to a relative change of strain of 5.7%) is observed under a constant stress of 8.3 MPa in 1 h (V = 22.7 V). A capacitive readout circuit is designed to sense the torsional deflection of the comb-drive actuator. The circuit is capable of actuating and sensing the capacitance change by the same combdrives with a resolution of 0.03° (corresponding to a capacitance resolution of 0.05 pF). The readout capacitance is then used as the input variable for a proportional-integral (PI) controller in order to eliminate the time and load dependent drift by creeping of the SU-8 spring. The PI controller is tuned by the Ziegler-Nichols method and has a settling time of ~2.3 s for the output. Compared with the open loop deflection of 0.43°, the closed-loop deflection is reduced by a factor of 7 down to 0.06°. This controller error is prominent at high actuation voltages, and is attributed to the actuator's lateral and vertical cross-sensitivity.
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