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Simple Summary: Glyoxalase domain-containing protein 4 (GLOD4), a member of the glyoxalase gene family, is widely expressed in Leydig cells and its primary function within the Leydig cells remains unknown. GLOD4 expression in other species is often associated with functions such as cell proliferation, cell cycle, and detoxification. We therefore explored the relevant elements of Leydig cells. We speculate that GLOD4 may regulate testicular development and spermatogenesis by increasing the number of Leydig cells and regulation of testosterone secretion. The expression pattern of GLOD4 in the testis and its regulatory effect on testicular cells was explored in goats to enhance our understanding of spermatogenesis and improve reproduction in breeding rams. In this study, we demonstrated the localization of GLOD4 in testicular cells using immunohistochemistry and subcellular localization analyses. Subsequently, we analyzed the GLOD4 expression pattern in four age-based groups (0, 6, 12, and 18 months old) using real-time quantitative polymerase chain reaction (qRT-PCR) and protein blotting. Finally, we performed GLOD4 silencing and overexpression studies in Leydig cells (LCs) and explored the effects on cell proliferation, the cell cycle, steroid hormone secretion and the expression of candidate testosterone hormone-regulated genes. GLOD4 was mainly expressed in Leydig cells, and the subcellular localization results showed that the GLOD4 protein was mainly localized in the cytoplasm and nucleus. Silencing of GLOD4 significantly suppressed the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3β-HSD, and CYP17A1 and the mRNA expression levels of cell cycle-related genes CDK6, PCNA, and Cyclin E. Moreover, the cell cycle was blocked at the G2/M phase after GLOD4 silencing, which significantly suppressed testosterone secretion. In contrast, GLOD4 overexpression significantly increased the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3β-HSD, and CYP17A1 and increased the expression of the cell cycle-related genes CDK6, PCNA, and Cyclin E. Moreover, GLOD4 overexpression promoted the cell cycle from G0/G1 phases to enter the S phase and G2/M phases, promoted the secretion of testosterone. Taken together, our experimental results indicate that GLOD4 may affect the development of cells in Qianbei Ma goats of different ages by influencing the cell cycle, cell proliferation, and testosterone hormone synthesis. These findings enhance our understanding of the functions of GLOD4 in goats. [ABSTRACT FROM AUTHOR]

The efficacy of cancer immunotherapy is greatly restricted by insufficient infiltration of cytotoxic T lymphocytes and immunosuppressive microenvironment in tumor tissue. Here a potent strategy to address the limitations by combination therapy of chemokine (CXCL9) with BRD4‐PROTAC (dBET6) using the unique mixed‐shell polymeric micelle (MSPM)‐based nanochaperone (nChap) delivery platform is reported. CXCL9 significantly enhances the intratumoral infiltration of CD8+ T cells while dBET6 induces tumor cell immunogenic cell death (ICD) and downregulates the interferon‐γ (IFNγ)‐triggered programmed death ligand 1 (PD‐L1) expression, synergizing to boost robust T cell‐dependent antitumor immunity responses to enhance cancer immunotherapy is demonstrated. Moreover, this nano‐CXCL9/dBET6 exhibits reduced systemic toxicity, prolonged half‐life, and enhanced tumor accumulation in comparison to free drugs. This study provides a promising strategy for efficient cancer immunotherapy. [ABSTRACT FROM AUTHOR]

The effect of La2O3 and FexO on the viscosity and structure of CaO–MgO–Al2O3–SiO2 (CMAS) melt was investigated. The viscosity of CaO–MgO–Al2O3–SiO2 melts with La2O3 and FexO was measured by a rotating cylindrical method from 1375 °C to 1550 °C, and the structures of the melts were analyzed via Raman spectroscopy. The results indicated that the viscosity decreased with increasing temperature and the activation energy decreased from 111.53 to 99.25 kJ/mol with the mole ratio of La2O3/FexO decreased from 2/0 to 0/2. The structural analysis revealed that the weaker chemical bonds or non-chemical bonds between the network structures of the glass were broken with the temperature increases, and both La2O3 and FexO acted as network modifiers to simplify the Si–O–Si tetrahedral structural unit. When the mole ratio of La2O3/FexO decreased from 2:0 to 0:2, the relative fraction of QSi3 and QSi4 decreased and the relative fraction of QSi0, QSi1 and QSi2 increased. Therefore, the degree of polymerization (DOP) of CMAS melt decreased, as well as the viscosity decreased with the addition of FexO and La2O3. FexO has more effective on the decrement in CMAS melt viscosity than that of La2O3 due to the structure modification ability of La3+ being smaller than that of Fe2+. Moreover, the number of non-bridging oxygen atoms per tetrahedrally coordinated atom (NBO/T) was used to characterize the melt structure, the quantitative relationship among the viscosity, temperature and microstructure of the melt was given. [ABSTRACT FROM AUTHOR]

This study aimed to explore the effectiveness of school‐based mindfulness training on learning burnout of Chinese middle school students and the mediating role of psychological resilience between dispositional mindfulness and learning burnout. A cluster randomized controlled trial was conducted with repeated measurement analysis, in which 62 Chinese middle school students in the experimental group received a 10‐week school‐based mindfulness training. In comparison, 63 students in the control group were randomized to receive no intervention. Learning burnout, dispositional mindfulness, and psychological resilience were measured by Adolescent Student Burnout Inventory, Five Facet Mindfulness Questionnaire, and Resilience Scale for Chinese Adolescents, respectively. The results showed: (1) Compared with the experimental group's pre‐test scores and the control group's pretest and posttest scores, the posttest scores of learning burnout in the experimental group significantly decreased. In contrast, the posttest scores of dispositional mindfulness and psychological resilience in the experimental group significantly increased. Meanwhile, the control group gained no significant changes between the pre‐and posttest in learning burnout, dispositional mindfulness, and psychological resilience. (2) Dispositional mindfulness was positively related to psychological resilience, while dispositional mindfulness and psychological resilience were negatively associated with learning burnout. (3) The direct effect of dispositional mindfulness on learning burnout and the mediating effect of psychological resilience between dispositional mindfulness and learning burnout were significant. This study suggested that school‐based mindfulness training distinctly improves dispositional mindfulness and psychological resilience and alleviates learning burnout in Chinese middle school students. Furthermore, psychological resilience plays a mediating role between dispositional mindfulness and learning burnout. Practitioner Points: School‐based mindfulness training is an effective intervention method to alleviate learning burnout of Chinese middle school students.Dispositional mindfulness is a protective factor of learning burnout, and psychological resilience plays a mediating role between dispositional mindfulness and learning burnout.School‐based mindfulness training alleviates learning burnout by improving dispositional mindfulness and psychological resilience. [ABSTRACT FROM AUTHOR]

Background and Objectives: Comorbidity of substance use disorders and depression is a common phenomenon. It is well known that opioid addiction is neurobiologically distinct from psychostimulant addiction. However, direct comparisons of comorbid depressive symptoms in patients with methamphetamine (METH) use disorder (MAUD) and heroin use disorders (HUD) have been lacking until now. Methods: A total of 353 patients with methamphetamine use disorder, 76 patients with HUD, and 203 healthy controls were recruited. The Beck Depression Inventory (BDI‐SF), the Desires for Drug Questionnaire (DDQ) and the short form of the Childhood Trauma Questionnaire (CTQ‐SF) were used to measure participants' depressive symptoms, drug craving, and childhood abuse or neglect, respectively. Results: The prevalence of depressive symptoms was 35.41% (125/353) in MAUD and 56.57% (43/76) in MAUD, significantly higher than the 22.66% (46/203) in healthy controls. Furthermore, there was a significant difference in the total BDI score between the MAUD and HUD groups (F = 5.02, df = 1, 372, p =.026). Among MAUD, years of education, history of incarceration, month of abstinence and negative reinforcement scores were associated with depressive symptoms (all p <.05). Among HUD, duration of drug use, childhood emotional abuse and sexual abuse were associated with depressive symptoms (all p <.05). Conclusions and Scientific Significance: The prevalence and correlates of depressive symptoms differ between MAUD and HUD, adding to the existing literature. Therefore, treatment and intervention programs should be designed to address these unique correlates in HUD and MAUD patients. [ABSTRACT FROM AUTHOR]