Myricetin alleviates H2O2-induced senescence and apoptosis in rat nucleus pulposus-derived mesenchymal stem cells.

INTRODUCTION: Transplantation of mesenchymal stem cells (MSCs) has been reported to be a novel promising target for the regeneration of degenerated intervertebral discs (IVDs). However, the culture and survival limitations of MSCs remain challenging for MSC-based biological therapy. Myricetin, a common natural flavonoid, has been suggested to possess antiaging and antioxidant abilities. Therefore, we investigated the biological function of myricetin, and its related mechanisms involving cell senescence in intervertebral disc degeneration (IDD). MATERIAL AND METHODS: The nucleus pulposus-derived mesenchymal stem cells (NPMSCs) were isolated from 4-month-old Sprague-Dawley (SD) rats and identified by examining surface markers and multipotent differentiation. Rat NPMSCs were cultured in an MSC culture medium or culture medium with different concentrations of H2O2. Myricetin or the combination of myricetin and EX527 were added to the culture medium to investigate the effects of myricetin. Cell viability was evaluated by cell counting kit-8 assays (CCK-8). The apoptosis rate was determined using Annexin V/PI dual staining. The mitochondrial membrane potential (MMP) was analyzed by a fluorescence microscope after JC-1 staining. The cell senescence was determined by SA-ß-Gal staining. MitoSOX green was used to selectively estimate mitochondrial reactive oxygen species (ROS) Apoptosis-associated proteins (Bax, Bcl2, and cleaved caspase-3), senescence markers (p16, p21, and p53), and SIRT1/PGC-1α signaling pathway-related proteins (SIRT1 and PGC-1α) were evaluated by western blotting. RESULTS: The cells isolated from nucleus pulposus (NP) tissues met the criteria for MSCs. Myricetin showed no cytotoxicity up to a concentration of 100 µM in rat NPMSCs cultured for 24 h. Myricetin pretreatment exhibited protective effects against H2O2-induced apoptosis. Myricetin could also alleviate H2O2-induced mitochondrial dysfunctions of increased mitochondrial ROS production and reduced MMP. Moreover, myricetin pretreatment delayed rat NPMSC senescence, as evidenced by decreased exppression of senescence indicators. Pretreatment of NPMSCs with 10 µM EX527, a selective inhibitor of SIRT1, prior to exposure to 100 µM H2O2, reversed the inhibitory effects of myricetin on cell apoptosis. CONCLUSIONS: Myricetin could affect the SIRT1/PGC-1α pathway to protect mitochondrial functions and alleviate cell senescence in H2O2-treated NPMSCs.

Tumor DNA Methylation Profiles Enable Diagnosis, Prognosis Prediction, and Screening for Cervical Cancer.

Background: DNA-methylation-based machine learning algorithms have demonstrated powerful diagnostic capabilities, and these tools are currently emerging in many fields of tumor diagnosis and patient prognosis prediction. This work aimed to identify novel DNA methylation diagnostic biomarkers for differentiating cervical cancer (CC) from normal tissues, as well as a prognostic prediction model to predict survival of CC patients. Methods: The methylation profiles with the available clinical characteristics were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) program. We first screened out the differential methylation sites in CC and normal tissues and performed multiple statistical analyses to discover DNA methylation diagnostic markers that are used to distinguish CC and normal control. Then, we developed a methylation-based survival model to improve risk stratification. Results: A diagnostic prediction panel consists of five CpG markers that could predict cervical cancer versus normal tissue with highly correct rate of 100%, and cg16428251, cg22341310, and cg23316360 which in diagnostic prediction panel all could yield high sensitivity and specificity for detection of CC and normal in six cohorts (area under curve [AUC] > 0.8), in addition to excellent performance in discriminating between CC and normal sample. The diagnostic marker panel also effectively predicted the CIN3 versus normal tissue with high accuracy in two datasets (AUC = 0.80, 0.789, respectively). Furthermore, a prognostic prediction model aggregated two CpG markers that effectively stratified the prognosis of high-risk and low-risk groups (training cohort: hazard ratio [HR] 4, 95% CI: 1.7-9.6, P = 0.0021; testing cohort: hazard ratio [HR] 1.9, 95% CI: 1.2-3.1, P = 0.0072). Conclusion: The findings of our study showed that DNA methylation markers are of great value in the diagnosis and prognosis of CC.

Increases in Anxiety and Depression During COVID-19: A Large Longitudinal Study From China.

Although accumulating evidence suggests the COVID-19 pandemic is associated with costs in mental health, the development of students' mental health, including the change from their previous levels of depression and anxiety and the factors associated with this change, has not been well-studied. The present study investigates changes in students' anxiety and depression from before the pandemic to during the lockdown and identifies factors that are associated with these changes. 14,769 university students participated in a longitudinal study with two time points with a 6-month interval. Students completed the Anxiety and Depression subscales of the Symptom Checklist 90 (SCL-90) before the COVID-19 outbreak (October 2020, Time 1), and the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) during the pandemic (April 2020, Time 2). The prevalence of anxiety and depression symptoms were 1.44 and 1.46% at Time 1, and 4.06 and 22.09% at Time 2, respectively, showing a 181.94% increase in anxiety and a 1413.01% increase in depression. Furthermore, the increases in anxiety and depression from pre-pandemic levels were associated with students' gender and the severity of the pandemic in the province where they resided. This study contributes to the gap in knowledge regarding changes in students' mental health in response to the pandemic and the role of local factors in these changes. Implications for gender and the Typhoon Eye effect are discussed.

Prognostic and predictive value of a mRNA signature in peripheral T-cell lymphomas: A mRNA expression analysis.

Current international prognostic index is widely questioned on the risk stratification of peripheral T-cell lymphoma and does not accurately predict the outcome for patients. We postulated that multiple mRNAs could combine into a model to improve risk stratification and helping clinicians make treatment decisions. In this study, the gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to screening genes in selected module which most closely related to PTCLs, and then built a mRNA signature using a LASSO Cox regression model and validated the prognostic accuracy of it. Finally, a nomogram was constructed and the performance was assessed. A total of 799 WGCNA-selected mRNAs in black module were identified, and a mRNA signature which based on DOCK2, GSTM1, H2AFY, KCNAB2, LAPTM5 and SYK for PTCLs was developed. Significantly statistical difference can be seen in overall survival of PTCLs between low-risk group and high-risk group (training set:hazard ratio [HR] 4.3, 95% CI 2.4-7.4, P < .0001; internal testing set:hazard ratio [HR] 2.4, 95% CI 1.2-4.8, P < .01; external testing set:hazard ratio [HR] 2.3, 95% CI 1.10-4.7, P = .02). Furthermore, multivariate regression demonstrated that the signature was an independently prognostic factor. Moreover, the nomogram which combined the mRNA signature and multiple clinical factors suggesting that predicted survival probability agreed well with the actual survival probability. The signature is a reliable prognostic tool for patients with PTCLs, and it has the potential for clinicians to implement personalized therapeutic regimen for patients with PTCLs.

Adaptability Promotes Student Engagement Under COVID-19: The Multiple Mediating Effects of Academic Emotion.

In response to the COVID-19 pandemic, millions of students in China followed an emergency policy called "Suspending Classes without Stopping Learning" to continue their study online as schools across the country were closed. The present study examines how students adapted to learning online in these unprecedented circumstances. We aimed to explore the relationship between adaptability, academic emotion, and student engagement during COVID-19. 1,119 university students from 20 provinces participated in this longitudinal study (2 time points with a 2-week interval). The results showed that adaptability (the ability to respond to changes) and student engagement are significantly positively correlated with positive academic emotion and negatively correlated with negative academic emotion. Furthermore, adaptability not only directly predicts student engagement, but also affects student engagement through the chain mediation of positive academic emotion and negative academic emotion. The results contribute to the gap in knowledge regarding changes in students' learning in response to the outbreak. This study further explains the internal mechanisms mediating the relationship between adaptability and student engagement. It may provide references for educational researchers and universities in dampening the negative effects of COVID-19 on students' learning by improving their adaptability and developing positive academic emotions.

Comfortable lifestyle-induced imbalance of neuro-endocrine-immunity network: a possible mechanism of vascular endothelial dysfunction.

OBJECTIVE: To observe the changes of vascular endothelial functions and general neuro-endocrine-immunity (NEI) network under the state of qi-deficiency syndrome induced by excessive idleness and to approach their internal relevance and illuminate initially the pathophysiological mechanism of vascular lesion induced by excessive idleness. METHODS: A total of 100 male Wistar rats were randomly divided into the control group and the qi-deficiency syndrome model group, 50 rats in each group. The qi-deficiency syndrome model was established by feeding the animals with hyper-alimentation diet in combination with restricting movement for 10 weeks. Changes of common chemical signal molecules related to NEI and vascular endothelial functions were measured by the end of the experiment. Furthermore, their internal relevance was analyzed by the method of canonical correlation analysis. RESULTS: The vascular endothelial structure and function were obviously injured in the model group. Compared with the control group, the chemical signal molecules, such as 5-hydroxytryptamine (5-HT), corticosterone (CORT), triiodothyronine (T3), tetraiodothyronine (T4), angiotensin II (Ang II), interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha) in peripheral blood of the model group (n=43) were changed significantly (P<0.05 or P<0.01). Canonical correlation analysis showed that vascular endothelial dysfunction was correlated to the changes of these signal molecules in the NEI network. CONCLUSIONS: Comfort-based lifestyle induced not only vascular endothelial dysfunction but also an imbalance of the NEI network. Vascular endothelial dysfunction and the imbalanced NEI network interacted with each other, and an imbalance of the NEI network may be the pathophysiologic basis for the genesis and development of vascular endothelial dysfunction, even diseases of the blood vessel.

Doping-induced structure variation of 1,3-cyclohexane- bis(methylamine)-templated zinc-phosphorus open structures.

By using 1,3-cyclohexane-bis(methylamine) (CHBMA) as the template, a novel zinc phosphatophosphite (TJPU-3) with extra-large 20-ring channels was synthesized. Cobalt doping produced a bimetallic phosphite (TJPU-6) with 12-ring apertures. While the templates sit in the cis configuration in TJPU-3, they are in the trans configuration in TJPU-6. This result has the potential for separation and recognition of CHBMA isomers.

[Species diversity and seasonal change of entomogenous fungi in Langya Mountains Nature Reserve].

672 specimens of entomogenous fungi belonging to 20 species, 8 genera and 4 families were collected from 20 sampling quadrates in the Langya Mountains Nature Reserve of East Anhui. The dominant species were Beauveria bassiana, Paecilomyces farinosus, P. cateinannulatus, B. brongniartii and P. fumosoroseus, and B. bassiana was most dominant, with the relative abundance of 73.8%. The entomogenous fungi in the Reserve were high in amount but low in diversity. The amount of isolates and the abundance of each species were the highest in summer and decreased with decreasing air temperature and rainfall, while the Pielou evenness changed from relatively low to relatively high. Paecilomyces spp. had a less seasonal fluctuation of quantity than Beauveria spp.