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Peroxiredoxin 4 (Prdx4) in the endoplasmic reticulum (ER) is the only secretory member of the antioxidant Prdx family. Our previous studies demonstrated that Prdx4 in cumulus cells (CCs) ameliorated the maturation of oocytes in vitro and enhanced oocyte developmental competence by preventing CCs apoptosis caused by oxidative stress (OS) through gap junctions. In this study, we aimed to determine whether Prdx4 released by CCs can repair meiotic defects in mouse oocytes by co-culturing immature (germinal vesicle) oocytes with CCs from mature oocytes in the absence of gap junctions. The OS-induced meiotic defects in mouse oocytes were impeded by co-culture with CCs, as evidenced by the increased first polar body (PB1) extrusion rate and decreased ROS level. CCs increased Prdx4 expression and lowered IRE1α, Bip expression in H 2 O 2 -treated oocytes. After knockdown of Prdx4 expression in CCs, the rate of PB1 extrusion in the oocytes was significantly reduced to the level detected in H 2 O 2 group, and ER stress was not alleviated. CO-IP and immunofluorescence co-localization experiments demonstrated that Prdx4 interacted with PDIA6 in the oocytes and the Pearson's R value was 0.69 calculated using ImageJ. Cumulus cells can promote the maturation of oocytes in vitro by secreting Prdx4 in a paracrine manner and serve as a promising therapeutic antioxidant for improving the quality of oocytes, especially aging oocytes, in clinical in vitro maturation (IVM). • Cumulus cells could secrete Prdx4 in a paracrine manner. • Prdx4 interacts with PDIA6 to ameliorate the release of ROS, rectify misfolded protein. • Prdx4 supplementation might improve the oocyte quality. [ABSTRACT FROM AUTHOR]

Objective To analyse the treatment outcomes of isoniazid-resistant tuberculosis (Hr-TB) in Shenzhen, and we provide scientific evidences for the optimization of therapeutic regimen and control measure of Hr-TB in the future. Methods Data of registration records of Hr-TB patients which were enrolled in Shenzhen's drug-resistant TB project for treatment from January 2016 to January 2019, and the treatment outcome of patients with completed treatment course of Hr-TB patients and the reasons for unsuccessful treatment before February 2020 were analyzed. Results In 144 Hr-TB patients treated with the project, 102 cases were successful treatment (70.83%), 42 cases without successful treatment (29.17%). There were no significant difference in different gender, household registration and the successful treatment rate between the treatment regimen containing Levofloxacin (Lfx) and without Lfx (P>0.05). 37 cases with treatment unsuccessfully (88.10%) were due to the subjective factors (loss of follow-up/self discontinuation/return home/drop out), and 5 cases with treatment unsuccessfully (11.90%) were due to non-subjective factors (death/withdrawal for the adverse reactions/convert to multidrug resistance). In terms of non-subjective factors or subjective factors leading to unsuccessful treatment, there were no statistically significant differences between patients of different genders, household registration and treatment regimen (including Lfx and without Lfx) (P>0.05). Conclusion Lfx in the therapeutic regimen of Hr-TB patients had no difference in the rate of successful treatment in Shenzhen, loss of follow-up, self-discontinuation and drop out were the main reasons of treatment unsuccessfully in patients with Hr-TB in Shenzhen. To optimize the appropriate control measures for them could achieve better therapeutic effect. [ABSTRACT FROM AUTHOR]

Focus on the problem or high demand on prior knowledge and weak timeliness or traditional algorithm for emergency communication network planning, a topology planning method for emergency communication network based on deep reinforcement learning is proposed. Developing a method or sample data generation using Monte Carlo tree search and self-game, the policy network and value network based on residual network is designed. On this basis, Tensorflow is used to build and train the model. Simulation results show that the proposed planning method can effectively realize the intelligent planning of network topology, and has high timeliness and feasibility. [ABSTRACT FROM AUTHOR]

Ovarian aging, a complex and challenging concern within the realm of reproductive medicine, is associated with reduced fertility, menopausal symptoms and long-term health risks. Our previous investigation revealed a correlation between Peroxiredoxin 4 (PRDX4) and human ovarian aging. The purpose of this research was to substantiate the protective role of PRDX4 against ovarian aging and elucidate the underlying molecular mechanism in mice. In this study, a Prdx4 -/- mouse model was established and it was observed that the deficiency of PRDX4 led to only an accelerated decline of ovarian function in comparison to wild-type (WT) mice. The impaired ovarian function observed in this study can be attributed to an imbalance in protein homeostasis, an exacerbation of endoplasmic reticulum stress (ER stress), and ultimately an increase in apoptosis of granulosa cells. Furthermore, our research reveals a noteworthy decline in the expression of Follicle-stimulating hormone receptor (FSHR) in aging Prdx4 -/- mice, especially the functional trimer, due to impaired disulfide bond formation. Contrarily, the overexpression of PRDX4 facilitated the maintenance of protein homeostasis, mitigated ER stress, and consequently elevated E2 levels in a simulated KGN cell aging model. Additionally, the overexpression of PRDX4 restored the expression of the correct spatial conformation of FSHR, the functional trimer. In summary, our research reveals the significant contribution of PRDX4 in delaying ovarian aging, presenting a novel and promising therapeutic target for ovarian aging from the perspective of endoplasmic reticulum protein homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)