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Abstract Lacking effective therapeutic targets heavily restricts the improvement of clinical prognosis for patients diagnosed with esophageal squamous cell carcinoma (ESCC). Ubiquitin Specific Peptidase 21 (USP21) is dysregulated in plenty of human cancers, however, its potential function and relevant molecular mechanisms in ESCC malignant progression as well as its value in clinical translation remain largely unknown. Here, in vitro and in vivo experiments revealed that aberrant upregulation of USP21 accelerated the proliferation and metastasis of ESCC in a deubiquitinase-dependent manner. Mechanistically, we found that USP21 binds to, deubiquitinates, and stabilizes the G3BP Stress Granule Assembly Factor 1 (G3BP1) protein, which is required for USP21-mediated ESCC progression. Further molecular studies demonstrated that the USP21/G3BP1 axis played a tumor-promoting role in ESCC progression by activating the Wnt/β-Catenin signaling pathway. Additionally, disulfiram (DSF), an inhibitor against USP21 deubiquitylation activity, markedly abolished the USP21-mediated stability of G3BP1 protein and significantly displayed an anti-tumor effect on USP21-driving ESCC progression. Finally, the regulatory axis of USP21/G3BP1 was demonstrated to be aberrantly activated in ESCC tumor tissues and closely associated with advanced clinical stages and unfavorable prognoses, which provides a promising therapeutic strategy targeting USP21/G3BP1 axis for ESCC patients.

BackgroundPrevious studies have shown a connection between physical activity and migraines, but they don’t prove a cause-and-effect relationship due to potential biases in observational methods.MethodsUtilizing accelerometer-measured physical activity data from a cohort of 377,234 participants in the UK Biobank and information from 599,356 European migraine patients (including 48,975 cases and 550,381 controls) obtained from 24 cohorts, we performed a bidirectional Mendelian randomization analysis to investigate the genetic bidirectional causal relationship between accelerometer-measured physical activity and migraines.ResultsResearch findings indicated a slight negative genetic correlation between “average acceleration” physical activity (rg = −0.091, p = 0.011), overall physical activity (rg = −0.081, p = 0.017), and migraine. Nevertheless, no shared genetic components were observed between migraine and “fraction of accelerations > 425 mg” of physical activity (rg = −0.124, p = 0.076). The study results also demonstrated a lack of genetic bidirectional causality between accelerometer-measured physical activity and migraine (“average acceleration”, OR = 1.002, 95% CI 0.975–1.031, p = 0.855, “fraction of accelerations > 425 mg”, OR = 1.127, 95% CI 0.802–1.583, p = 0.488, overall physical activity, OR = 0.961, 95% CI 0.713–1.296, p = 0.799), and vice versa. Additionally, this lack of causal association persists even after adjusting for obesity (OR = 1.005, p = 0.578), education (OR = 1.019, p = 0.143), and depression (OR = 1.005, p = 0.847), either separately or simultaneously.ConclusionThe Mendelian randomization results based on genetic data do not provide support for a causal association between physical activity and migraine.

BackgroundInternet addiction poses a significant threat to the health of college students worldwide, but physical activity, as a highly safe and effective rehabilitative measure, has shown promise for alleviating this issue nowadays. However, during the COVID-19 pandemic, the mediating processes in this association remained unclear. This study aims to explore the impact of physical activity on internet addiction among college students and the mediating role of subjective well-being.MethodsA survey was conducted on 216 eligible college students using the physical activity level scale, the internet addiction test, and the subjective well-being scale. For data analysis, independent sample t-tests, correlation analysis, hierarchical regression analysis, and mediating effect tests were in turn carried out in this work.ResultsThe study revealed noteworthy gender disparities in physical activity and internet addiction among college students (β = −0.356, p

BackgroundNowadays, it is widely acknowledged that mobile phone addiction is a risky factor for insomnia symptoms, but to date, people know little about the underlying relationship between them among undergraduates during the COVID-19 pandemic. The purpose of the present study was to examine the potential association between mobile phone addiction and insomnia, as well as the mediating role of social anxiety and the moderating role of physical activity.MethodsUsing the Mobile Phone Addiction Tendency Scale, Social Phobia Inventory, Physical Activity Rating Scale and Insomnia Severity Index, 301 eligible college students in China were investigated. For data analysis, descriptive analysis, correlation analysis, moderating effect test, moderating effect test were carried out in turn.ResultsThe findings revealed a favorable correlation between mobile phone addiction, social anxiety and insomnia, as well as between social anxiety and insomnia. But physical activity was negatively correlated with social anxiety and mobile phone addiction, and social anxiety partially mediated the relationship between mobile phone addiction and insomnia. Additionally, physical activity played a significant moderating effect between mobile phone addiction and social anxiety.ConclusionThis study advances the knowledge of how mobile phone addiction raises the likelihood of experiencing insomnia symptoms, and also implies that upping physical activity level could lessen the harmful impacts from mobile phone addiction.

ObjectiveSmartphone addiction, as a key topic in the current field of behavioral addictions and public health, has brought many negative impacts on the physical, psychological, interpersonal communication, and even academic performance among contemporary college students. Therefore, the purpose of this study is to offer ideas for solving smartphone addiction among college students through investigating the potential mediating effect of self-esteem in the relationship between physical activity and smartphone addiction.MethodsBy the quota sampling, a cross-sectional study was conducted to investigate 650 college students from 10 colleges in Guangzhou Higher Mega Center, and several self-reported instruments including physical activity rating scale-3 (PARS-3), mobile phone addiction tendency scale (MPATS), self-esteem scale (SES) were used to collect the related data needed for the present study. The descriptive analysis, correlation analysis, hierarchical regression analysis, and mediating effect analysis in this study were performed in turn.ResultsThe results showed that physical activity (r = −0.124, p < 0.01) and self-esteem (r = −0.360, p < 0.01) were all negatively correlated with smartphone addiction, and both could also significantly and negatively predict smartphone addiction. There was a positive correlation between physical activity and self-esteem (r = 0.084, p < 0.05), and self-esteem could be significantly predicted by physical activity. And more important, the relationship between physical activity and smartphone addiction could be partially mediated by self-esteem, and the indirect effect value was −0.346 (95% Boot CI = −0.695; −0.023), along with the mediating effect accounted for 24% of the total effect between physical activity and smartphone addiction.ConclusionThe current study shows that physical activity could not only directly reduce smartphone addiction, but also decrease smartphone addiction by indirectly improving self-esteem, which is important in practice for solving this troublesome issue and then gradually developing a healthy behavior in daily life for college students in China, and even across the world in near future.

ABSTRACT Purpose Targeted biopsy (TB) combined with systematic biopsy (SB) is an optimized mode of prostate biopsy but can often lead to oversampling and overdiagnosis accompanied by potential biopsy-related complications and patient discomfort. Here, we attempted to reasonably stratify the patient population based on multi-parameter indicators with the aim of avoiding unnecessary SB. Methods In total, 340 biopsy-naïve men with suspected lesions, prostate-specific antigen (PSA) < 20 ng/mL and prostate imaging-reporting and data system (PI-RADS) ≥ 3 enrolled for study underwent both TB and SB. The primary outcome was to determine independent predictors for a valid diagnosis, assuming that only TB was performed and SB omitted (defined as mono-TB), taking TB + SB as the reference standard. The secondary outcomes were exploration of the predictive factors of mono-TB and TB + SB in detection of prostate cancer (PCa) and clinically significant PCa (csPCa). Results The mean PSA density (PSAD) of patient group was 0.27 ng/mL/mL. Multiparametric MRI PI-RADS scores were 3-5 in 146 (42.94%), 105 (30.88%), and 89 (26.18%) cases, respectively. PCa and csPCa were detected in 178/340 (52.35%) and 162/340 (47.65%) patients, respectively. Overall, 116/178 (65.17%) patients diagnosed with PCa displayed pathological consistencies between mono-TB and TB + SB modes. PSAD and PI-RADS were independent predictors of valid diagnosis using mono-TB. Conclusions PSAD combined with PI-RADS showed utility in guiding optimization of the prostate biopsy mode. Higher PSAD and PI-RADS values were associated with greater confidence in implementing mono-TB and safely omitting SB, thus effectively balancing the benefits and risks.

Abstract This paper analyzes the media frames adopted by the official WeChat and Sina Weibo accounts of the People’s Daily between January 1 and December 31, 2020, for reports about female medical personnel involved in pandemic prevention and control. Although the number of female medical personnel involved in pandemic prevention and control far exceeded that of their male counterparts, the extent of media reports on the former was far less than that of the latter. The human interest frame about female medical personnel was mainly applied, while the use of the action frame was less frequent, which highlighted the gender identity and family role of these women but weakened their professional identity. This was not conducive to praising the contributions of female medical personnel in fighting the pandemic. The media frames of reporting medical personnel in WeChat and Sina Weibo accounts of the People’s Daily are not always the same. After Wuhan’s lockdown ended on April 8, the proportion of the human interest frame of the report text of female medical personnel decreased, and the proportion of the action frame increased, while the proportion of the human interest frame of the report text of male medical personnel increased and the proportion of the action frame decreased. Previous studies mainly analyzed the use of the media frames of female news personalities, but few studies focused on whether women had the possibility of breaking away from the gender media frames. This study shows that some female medical personnel with exceptional professional competence are likely to transcend the gender media frames and receive similar coverage to that of male medical professionals, like Li Lanjuan and Chen Wei.

Ischemic acute kidney injury (AKI) is a prevalent disorder among hospitalized patients worldwide. Astragaloside IV (AS-IV) has been shown to protect against ischemic AKI. However, the specific effects and mechanisms of AS-IV on alleviating kidney ischemia-reperfusion (I/R) injury remain unclear. The objective of this research was to elucidate the regulatory targets and mechanisms through which AS-IV protects kidney I/R injury. A combination of network pharmacology, molecular docking, molecular dynamics (MD) simulation, pharmacodynamic study and Western blot were employed to explore the underlying mechanisms. Network pharmacology revealed that ferroptosis was a potential mechanism of AS-IV against kidney I/R injury. Molecular docking and MD simulations demonstrated strong binding affinity between the GPX4/SLC7A11 and AS-IV. The experimental verification demonstrated that AS-IV improved cell proliferation, decreased the level of ROS and Fe2+, and increased the expressions of GPX4 and SLC7A11 as same as Ferrostatin-1 in OGD/R-injured HUVECs. In conclusion, AS-IV had a significant inhibition on ferroptosis in kidney I/R injury, providing a new perspective for drug development on kidney I/R injury. Definitely, further exploration in vivo is necessary to fully understand whether AS-IV alleviates kidney I/R injury through inhibiting endothelial ferroptosis.

The Notch signaling pathway plays an important role in otic neurogenesis by regulating the differentiation of inner ear hair cells and supporting cells. Notch-regulated differentiation is required for the regeneration of hair cells in the inner ear. The temporal expression pattern of Notch ligands and receptors during in vitro hair cell-like cell differentiation from human embryonic stem cells (hESCs) was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Subsequently, pAJ-U6-shRNA-CMV-Puro/GFP recombinant lentiviral vectors encoding short hairpin RNAs were used to silence JAG-1, JAG-2, and DLL-1, according to the temporal expression pattern of Notch ligands. Then, the effect of each ligand on the in vitro differentiation of hair cells was examined by RT-PCR, immunofluorescence, and scanning electron microscopy (SEM). The results showed that the individual deletion of JAG-2 or DLL-1 had no significant effect on the differentiation of hair cell-like cells. However, the simultaneous inhibition of both DLL-1 and JAG-2 increased the number of hair cell-like cells and decreased the number of supporting cells. JAG-2 and DLL-1 may have a synergistic role in in vitro hair cell differentiation.