Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe

Evaluation and Applications of a Novel Glutathione Reductase Inhibitor as a Model of Thiol Oxidative Stress in H9C2 Rat Cardiomyocytes

Thiol redox state (TRS) refers to the balance between reduced thiols and their corresponding disulfides, and is mainly reflected by the ratio of GSH/GSSG. A decrease in GSH/GSSG, which reflects a state of thiol oxidative stress, and thiol modifications such as S-glutathionylation have been implicated in a variety of cardiovascular diseases. Research models that can selectively induce thiol oxidative stress are, therefore, valuable tools for studying the pathophysiology of these disease states and examining the impacts of pharmacological interventions on thiol pathways. In this project, the potential of 2-AAPA, a novel GR inhibitor, to be used as a pharmacological model of thiol oxidative stress was evaluated by determining the extent of thiol modifications induced in H9c2 rat cardiomyocytes and its impact on cellular functions. The extent of thiol oxidative stress produced by 2-AAPA was also compared to other models of oxidative stress including H2O2, diamide, BSO and BCNU. Results indicated that 2-AAPA effectively inhibited GR activity and decreased the GSH/GSSG ratio by causing a significant accumulation of GSSG. 2-AAPA also increased the formation of protein disulfides as well as protein S-glutathionylation. The alteration in TRS leads to loss of ΔΨm, release of cytochrome c and an increase in ROS production. Compared to other models, 2-AAPA is superior in selectively increasing GSSG and inducing thiol modification with lower cytotoxicity and more physiological relevance. 2-AAPA as a thiol oxidative stress model was then applied to study the cardioprotective effects of carvedilol and berberine in H9c2 cells. Both carvedilol and berberine were found to protect H9c2 cells against 2-AAPA induced cytotoxicity by increasing cell viability. However, the cells protection by carvedilol was associated with greater extent of thiol oxidative stress as carvedilol increased GSSG accumulation in 2- AAPA treated H9c2 cells. In contrast, berberine greatly decreased the GSSG accumulation as well as protein disulfides in 2-AAPA treated H9c2 cells. The decreased GSSG accumulation was found to associate with an increase in GR activity and GR mRNA expression. In conclusion, a model of thiol oxidative stress using a novel GR inhibitor, 2- AAPA, has been successfully developed and applied to study TRS related abnormal and normal biochemical processes in H9c2 rat cardiomyocytes

Patterns of Bullying Victimization among Adolescents in China: Based on a Latent Profile Analysis

This study was to explore potential patterns of bullying victimization among adolescents in China. By cluster sampling, Delaware Bullying Victimization Scale-Student (DBVS-S), Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Scale-7 (CAD-7) were administered to 3,761 school adolescents in Hunan Province. Latent profile analysis (LPA) was conducted on victimization by verbal, physical, social and cyberbullying. We found that (i) There is a high degree of co-occurrence among four subtypes of bullying victimization. Four latent classes were identified, including an all-type (traditional and cyber) bullying victimization class (1.5%), a traditional victimization class (3.9%), a mild traditional victimization class (14.9%), and a non-victimization class (79.6%). (ii) Males, middle school students, rural students and poor students were more likely to be all types of victims. (iii) There was a graded relationship between the four latent classes and the level of depression as well as anxiety

Evaluating a Psychoeducation Program to Foster Chinese Primary School Students’ Covitality

This investigation evaluated the Growth Psychoeducation Intervention (GPI) designed to increase primary school students’ covitality, a construct describing the beneficial combinatorial effects of positive psychological skills and mindsets. Students with higher covitality levels have stronger relationships with their teachers and classmates, and behave in more positive ways. This GPI intervention study employed a pretest-posttest-follow quasi-experimental design to evaluate a culturally adapted group counseling intervention designed to foster Chinese senior primary school students’ (n = 189, ages 9–12 years) covitality levels. The hypothesis was that covitality increases would positively correlate with school belonging and life satisfaction and less frequent bullying victimization. The Social Emotional Health Survey-Primary (SEHS-P) assessed the effectiveness of the GPI eight-week program to promote mental health and decrease bullying. GPI demonstrated effectiveness by improving students’ covitality and school belonging and reducing bullying victimization

WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer

Background/Aims: Dysregulated expression of WW domain-binding protein 2 (WBP2) is associated with poor prognosis in ER+ breast cancer patients. However, its role in triple negative breast cancer (TNBC) has not been previously assessed. Therefore, we aimed to elucidate the functional mechanism of WBP2 in TNBC cells. Methods: qRT-PCR, western blotting, and immunohistochemical staining were used to evaluate WBP2 expression in TNBC patient tumors and cell lines. HCC1937 and MDA-MB-231 cells transiently transfected with WBP2 small interfering RNA (siRNA), miR-613 mimics, or miR-613 inhibitors were subject to assays for cell viability, apoptosis and cell cycle distribution. Co-immunoprecipitation, western blotting or qRT-PCR were employed to monitor changes in signaling pathway-related genes and proteins. Luciferase assays were performed to assess whether WBP2 is a direct target of miR-613. The effect of miR-613 on tumor growth was assessed in vivo using mouse xenograft models. Results: The expression of WBP2 was upregulated in TNBC tissues and cells. Expression of WBP2 was significantly correlated with Ki67 in TNBC patients. Knockdown of WBP2 inhibited cellular proliferation, promoted apoptosis, and induced cell cycle arrest of TNBC cells. miR-613 directly bound to the 3’-untranslated region (3’-UTR) of WBP2 and regulated the expression of WBP2. Moreover, miR-613 reduced the expression of WBP2 and suppressed tumor growth of TNBC cells in vivo. Knockdown of WBP2 inhibited YAP transcription and the EGFR/PI3K/Akt signaling pathway in TNBC cells, and these effects were reversed by inhibition of miR-613. Conclusion: WBP2 overexpression is associated with the poor prognosis of TNBC patients and the miR-613-WBP2 axis represses TNBC cell growth by inactivating YAP-mediated gene expression and the EGFR/PI3K/Akt signaling pathway

Mir-30b-5p Promotes Proliferation, Migration, and Invasion of Breast Cancer Cells via Targeting ASPP2

Triple-negative breast cancer (TNBC) is the most aggressive subtypes of breast cancer, which has few effective targeted therapies. Various sources of evidence confirm that microRNAs (miRNAs) contribute to the progression and metastasis of human breast cancer. However, the molecular mechanisms underlying the changes in miRNAs expression and the regulation of miRNAs functions have not been well clarified. In this study, we found that the expression of miR-30b-5p was upregulated in breast cancer tissues and breast cancer cell lines, compared to paracancer tissues and normal breast cell lines. Moreover, induced overexpression of miR-30b-5p promoted the MDA-MB-231 and HCC 1937 cell growth, migration, and invasion and reduced the cellular apoptosis. Further studies confirmed that miR-30b-5p could directly target ASPP2 and then activate the AKT signaling pathway. Our results suggested that miR-30b-5p could act as a tumor promoter in TNBC. The newly identified miR-30b-5p/ASPP2/AKT axis represents a novel therapeutic strategy for treating TNBC