A tactile sensing system capable of recognizing objects based on bioinspired self-sensing soft pneumatic actuator.

Tactile sensors play an important role when robots perform contact tasks, such as physical information collection, force or displacement control to avoid collision. For these manipulations, excessive contact may cause damage while poor contact cause information loss between robotic end-effector and objects. Inspired by skin structure and signal transmission method, this paper proposes a tactile sensing system based on the self-sensing soft pneumatic actuator (S-SPA) capable of providing tactile sensing capability for robots. Based on the adjustable height and compliance characteristics of the S-SPA, contact is safe and accurate tactile information can be collected. And to demonstrate the feasibility and advantage of this system, a robotic hand with S-SPAs could recognize different textures and stiffness of objects by touching and pinching behaviours to collect physical information of the various objects under the positive work states of the S-SPA. The result shows the recognition accuracy of the fifteen texture plates reaches 99.4%, and the recognition accuracy of the four stiffness cuboid reaches 100% by training a KNN model. This safe and simple tactile sensing system with high recognition accuracies based on S-SPA shows great potential in robotic manipulations and beneficial to applications in domestic and industrial fields.

Primate-Specific DAZ Regulates Translation of Cell Proliferation-Related mRNAs and is Essential for Maintenance of Spermatogonia.

Primate-specific DAZ (deleted in azoospermia) has evolved in the azoospermia factor c (AZFc) locus on the Y chromosome. Loss of DAZ is associated with azoospermia in patients with deletion of the AZFc region (AZFc_del). However, the molecular mechanisms of DAZ in spermatogenesis remain uncertain. In this study, the molecular mechanism of DAZ is identified, which is unknown since it is identified 40 years ago because of the lack of a suitable model. Using clinical samples and cell models, it is shown that DAZ plays an important role in spermatogenesis and that loss of DAZ is associated with defective proliferation of c-KIT-positive spermatogonia in patients with AZFc_del. Mechanistically, it is shown that knockdown of DAZ significantly downregulated global translation and subsequently decreased cell proliferation. Furthermore, DAZ interacted with PABPC1 via the DAZ repeat domain to regulate global translation. DAZ targeted mRNAs that are involved in cell proliferation and cell cycle phase transition. These findings indicate that DAZ is a master translational regulator and essential for the maintenance of spermatogonia. Loss of DAZ may result in defective proliferation of c-KIT-positive spermatogonia and spermatogenic failure.

Association between physical activity and adolescent mental health in the post COVID-19: The chain mediating effect of self-esteem and social anxiety.

BACKGROUND: In order to gain a deeper understanding of the relationship between physical activity and adolescent mental health in the post COVID-19 pandemic era, self-esteem and social anxiety were used as mediating variables to explore the potential mechanisms by which physical activity affects adolescent mental health. METHODS: The study used the HELP-II Health Promoting Lifestyle Scale, the SPIN Social Phobia Scale, the Self-Esteem Scale, and the 10-item Kessler Psychological Distress Scale to administer questionnaires to 400 Chinese secondary school students, and SPSS 26.0 and PROCESS 3.3 were used to process the data. RESULTS: The findings showed that (1) physical activity was significantly and positively associated with mental health; (2) self-esteem and social anxiety played a fully mediating role between physical activity and adolescent mental health respectively; (3) self-esteem and social anxiety played a chain mediating role between physical activity and adolescent mental health. CONCLUSION: This study reveals the relationship and influencing mechanism between physical activity and adolescent mental health in the post COVID-19 pandemic era. Appropriate interventions for physical activity, self-esteem, and social anxiety may be beneficial to adolescent mental health. The protective role of self-esteem in adolescent mental health should be the focus of future studies, and further investigations into the association between the COVID-19 and adolescent mental health are warranted.

Targeting dysregulated phago-/auto-lysosomes in Sertoli cells to ameliorate late-onset hypogonadism.

Age-related changes in testicular function can impact health and well-being. The mechanisms underlying age-related testicular dysfunction, such as late-onset hypogonadism (LOH), remain incompletely understood. Using single-cell RNA sequencing on human testes with LOH, we delineated Sertoli cells (SCs) as pivotal metabolic coordinators within the testicular microenvironment. In particular, lysosomal acidity probing revealed compromised degradative capacity in aged SCs, hindering autophagy and phagocytic flux. Consequently, SCs accumulated metabolites, including cholesterol, and have increased inflammatory gene expression; thus, we termed these cells as phago-/auto-lysosomal deregulated SCs. Exposure to a high-fat diet-induced phago-/auto-lysosomal dysregulated-like SCs, recapitulating LOH features in mice. Notably, efferent ductular injection and systemic TRPML1 agonist administration restored lysosomal function, normalizing testosterone deficiency and associated abnormalities in high-fat diet-induced LOH mice. Our findings underscore the central role of SCs in testis aging, presenting a promising therapeutic avenue for LOH.

Investigation of supplementation with a combination of fermented bean dregs and wheat bran for improving the growth performance of the sow.

To investigate the effect of dietary supplementation with a fermented mixture of bean dregs and wheat bran (FBW) on sow performance. FBW was given to sows during late gestation and lactation; in total, 24 sows were randomly assigned to 4 groups (control diet; 3% FBW diet; 6% FBW diet; 9% FBW diet, n = 6). The weight ratio of bean dregs (wet) to wheat bran was 4:6. Sows were fed different diets from 85 d of gestation until weaning. The results showed that supplementation with FBW increased average daily feed intake (ADFI) during lactation (p < 0.05). FBW supplementation also increased litter weight and milk yield (p < 0.05). The contents of Escherichia coli in the feces of the treatment groups were significantly reduced by FBW supplementation (p < 0.01). FBW supplementation significantly improved the fecal morphology (p < 0.05), alleviating sows' constipation. In conclusion, FBW could increase the ADFI, improve lactation and piglet litter weight in sows and reduce the pathogenic bacterial content in sow feces and constipation.

Social participation and health in middle-aged and older empty nesters: A study on gender differences.

Background: The growing population of middle-aged and older empty nesters is characterized by poorer health, and social participation (SP) has been shown to improve this situation. However, few studies have investigated specific performance and gender differences between SP and health. The present study aims to address these issues. Methods: A total of 1207 middle-aged and older empty nesters over 45 years old were selected from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2018). Random-effects analyses were used to explore the association between changes in SP (diversity, frequency, type) and changes in health status. Health status include physical health, mental health, self-reported health (SRH). Results: Female middle-aged and olderly empty nesters have significantly poorer health and participate in SP more frequently. The higher the diversity of SP, the better the health of middle-aged and olderly empty nesters, while higher frequency is beneficial to SRH. Female's participation in sports and Internet had better mental health and SRH, and mahjong helped female's mental health. Clubs are helpful for male's SRH. Conclusions: This study reveals the specifics of the association between SP and health status of middle-aged and older empty nesters. Therefore, all aspects of SP and gender differences should be taken into account when predicting and improving the health status. Help the government to better formulate policies to better cope with the increasing empty nest phenomenon and build a harmonious and stable society.

The association between physical activity, self-efficacy, stress self-management and mental health among adolescents.

This study aimed to explore the interplay between physical activity, self-efficacy, stress self-management and mental health among adolescents. The study gathered data from an online survey conducted among 400 Chinese middle school students (mean age = 13.74 years). The collected data were analyzed using SPSS 27.0 and PROCESS 4.1. The findings indicated a positive and significant relationship between physical activity, self-efficacy, stress self-management, and mental health. Notably, the association between physical activity and mental health was entirely mediated by self-efficacy and stress self-management. Moreover, self-efficacy and stress self-management exhibited a chain mediation effect on the relationship between physical activity and mental health. It is suggested that interventions focusing on physical activity should prioritize strategies for enhancing students' self-efficacy and stress self-management skills as integral components of promoting adolescents' mental health. Future research should delve into identifying specific types of physical activities that have a greater potential to enhance self-efficacy and stress self-management abilities.

Control strategies for inverted pendulum: A comparative analysis of linear, nonlinear, and artificial intelligence approaches.

An inverted pendulum is a challenging underactuated system characterized by nonlinear behavior. Defining an effective control strategy for such a system is challenging. This paper presents an overview of the IP control system augmented by a comparative analysis of multiple control strategies. Linear techniques such as linear quadratic regulators (LQR) and progressing to nonlinear methods such as Sliding Mode Control (SMC) and back-stepping (BS), as well as artificial intelligence (AI) methods such as Fuzzy Logic Controllers (FLC) and SMC based Neural Networks (SMCNN). These strategies are studied and analyzed based on multiple parameters. Nonlinear techniques and AI-based approaches play key roles in mitigating IP nonlinearity and stabilizing its unbalanced form. The aforementioned algorithms are simulated and compared by conducting a comprehensive literature study. The results demonstrate that the SMCNN controller outperforms the LQR, SMC, FLC, and BS in terms of settling time, overshoot, and steady-state error. Furthermore, SMCNN exhibit superior performance for IP systems, albeit with a complexity trade-off compared to other techniques. This comparative analysis sheds light on the complexity involved in controlling the IP while also providing insights into the optimal performance achieved by the SMCNN controller and the potential of neural network for inverted pendulum stabilization.

Age-Related Changes in Urethral Structure and Responds to Injury: Single-Cell Atlas of a Rat Model of Vaginal Birth Injury induced Stress Urinary Incontinence.

Stress urinary incontinence (SUI) greatly affects the daily life of numerous women and is closely related to a history of vaginal delivery and aging. We used vaginal balloon dilation to simulate vaginal birth injury in young and middle-aged rats to produce a SUI animal model, and found that young rats restored urethral structure and function well, but not the middle-aged rats. To identify the characteristics of cellular and molecular changes in the urethral microenvironment during the repair process of SUI. We profiled 51,690 individual female rat urethra cells from 24 and 48 weeks old, with or without simulated vaginal birth injury. Cell interaction analysis showed that signal networks during repair process changed from resting to active, and aging altered the distribution but not the overall level of cell interaction in the repair process. Similarity analysis showed that muscle, fibroblasts, and immune cells underwent large transcriptional changes during aging and repair. In middle-aged rats, cell senescence occurs mainly in the superficial and middle urothelium due to cellular death and shedding, and the basal urothelium expressed many Senescence-Associated Secretory Phenotype (SASP) genes. In conclusion, we established the aging and vaginal balloon dilation (VBD) model of female urethral cell anatomy and the signal network landscape, which provides an insight into the normal or disordered urethra repair process and the scientific basis for developing novel SUI therapies.

A hybrid neural network-based intelligent body posture estimation system in sports scenes.

Body posture estimation has been a hot branch in the field of computer vision. This work focuses on one of its typical applications: recognition of various body postures in sports scenes. Existing technical methods were mostly established on the basis of convolution neural network (CNN) structures, due to their strong visual information sensing ability. However, sports scenes are highly dynamic, and many valuable contextual features can be extracted from multimedia frame sequences. To handle the current challenge, this paper proposes a hybrid neural network-based intelligent body posture estimation system for sports scenes. Specifically, a CNN unit and a long short-term memory (LSTM) unit are employed as the backbone network in order to extract key-point information and temporal information from video frames, respectively. Then, a semi-supervised learning-based computing framework is developed to output estimation results. It can make training procedures using limited labeled samples. Finally, through extensive experiments, it is proved that the proposed body posture estimation method in this paper can achieve proper estimation effect in real-world frame samples of sports scenes.

Artificial cavernosa-like tissue based on multibubble Matrigel and a human corpus cavernous fibroblast scaffold.

Ex vivo tissue culture of the human corpus cavernosum (CC) can be used to explore the tissue structural changes and complex signaling networks. At present, artificial CC-like tissues based on acellular or three-dimensional (3D)-printed scaffolds are used to solve the scarcity of primary penis tissue samples. However, inconvenience and high costs limit the wide application of such methods. Here, we describe a simple, fast, and economical method of constructing artificial CC-like tissue. Human CC fibroblasts (FBs), endothelial cells (ECs), and smooth muscle cells (SMCs) were expanded in vitro and mixed with Matrigel in specific proportions. A large number of bubbles were formed in the mixture by vortexing combined with pipette blowing, creating a porous, spongy, and spatial structure. The CC FBs produced a variety of signaling factors, showed multidirectional differentiation potential, and grew in a 3D grid in Matrigel, which is necessary for CC-like tissue to maintain a porous structure as a cell scaffold. Within the CC-like tissue, ECs covered the surface of the lumen, and SMCs were located inside the trabeculae, similar to the structure of the primary CC. Various cell components remained stable for 3 days in vitro, but the EC content decreased on the 7th day. Wingless/integrated (WNT) signaling activation led to lumen atrophy and increased tissue fibrosis in CC-like tissue, inducing the same changes in characteristics as in the primary CC. This study describes a preparation method for human artificial CC-like tissue that may provide an improved experimental platform for exploring the function and structure of the CC and conducting drug screening for erectile dysfunction therapy.

Removal of tetracycline by ultraviolet/sodium percarbonate (UV/SPC)advanced oxidation process in water.

Tetracycline (TC) was widely used and frequently detected in various water bodies, where the presence of TC posed a significant threat to the health of aquatic organisms. Furthermore, antibiotics were hardly degraded by biological treatment. Thus, in order to enhance the removal of TC, we proposed the use of a novel ultraviolet/sodium percarbonate (UV/SPC) advanced oxidation process and initiated an in-depth study. The study investigated the influence of oxidant dosage, initial pH, UV intensity, and TC concentration on the removal of TC. The results demonstrated that the UV/SPC system efficiently removed TC, with removal efficiency increasing as the SPC concentration increased. Within the pH range of 3-11, TC degradation exhibited minimal variation, indicating the UV/SPC system's strong adaptability to pH variations. The research on the impact of the water matrix on TC removal revealed that HCO3- had an inhibitory effect on TC degradation, while NO3- promoted TC degradation. Additionally, the presence of free radical species (·OH, ·CO3-, ·O2-) were detected and rate constants for the secondary reactions (k·OH,TC = 6.3 × 109 L mol-1·s-1, k·CO3-,TC = 3.4 × 108 L mol-1·s-1) were calculated, indicating that ·OH exhibited a stronger oxidative performance compared to ·CO3-. This study did not only present a novel strategy via UV/SPC to remove TC but also uncovered the unique role of ·CO3- for contaminant removal.

scRNA-seq reveals that origin recognition complex subunit 6 regulates mouse spermatogonial cell proliferation and apoptosis via activation of Wnt/ß-catenin signaling.

ABSTRACT: The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ ß-catenin signaling. Western blot revealed that the expression of ß-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/ß-catenin signaling.

Relationship between perceived social support and mental health among Chinese college football athletes: a moderated mediation model.

Previous researches have confirmed that perceived social support has a profound effect on individuals' mental health. However, the effects and potential mechanisms of perceived social support on mental health of college athletes are still largely unknown, especially during and after the COVID-19 pandemic. Thus, the aim of this study was to explore the relationship between perceived social support and mental health in college football athletes, and to evaluate whether hopelessness and psychological pressure affected this relationship. A sample of 672 Chinese college football athletes (37.9% girls; Mage = 20.43 years; SDage = 1.68) were investigated with the Perceived Social Support Scale (PSSS), the Kessler Psychological Distress Scale (K10), the Beck Hopelessness Scale (BHS) and the Perceived Stress Scale (PSS). Surveys were voluntary and anonymous. The findings revealed that, after adjusting for demographic factors, hopelessness mediated the relationship between Chinese college football athletes' perceived social support and their mental health. Furthermore, psychological pressure moderated the negative association between perceived social support and hopelessness, and the association was stronger for them with high-level psychological pressure. These results underline the need for focused strategies in the prevention and treatment of mental health issues among Chinese college football athletes.

Knockdown of NR3C1 inhibits the proliferation and migration of clear cell renal cell carcinoma through activating endoplasmic reticulum stress-mitophagy.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is closely associated with steroid hormones and their receptors affected by lipid metabolism. Recently, there has been growing interest in the carcinogenic role of NR3C1, the sole gene responsible for encoding glucocorticoid receptor. However, the specific role of NR3C1 in ccRCC remains unclear. The present study was thus developed to explore the underlying mechanism of NR3C1's carcinogenic effects in ccRCC. METHODS: Expression of NR3C1 was verified by various tumor databases and assessed using RT-qPCR and western blot. Stable transfected cell lines of ccRCC with NR3C1 knockdown were constructed, and a range of in vitro and in vivo experiments were performed to examine the effects of NR3C1 on ccRCC proliferation and migration. Transcriptomics and lipidomics sequencing were then conducted on ACHN cells, which were divided into control and sh-NR3C1 group. Finally, the sequencing results were validated using transmission electron microscopy, mitochondrial membrane potential assay, immunofluorescence co-localization, cell immunofluorescent staining, and Western blot. The rescue experiments were designed to investigate the relationship between endoplasmic reticulum stress (ER stress) and mitophagy in ccRCC cells after NR3C1 knockdown, as well as the regulation of their intrinsic signaling pathways. RESULTS: The expression of NR3C1 in ccRCC cells and tissues was significantly elevated. The sh-NR3C1 group, which had lower levels of NR3C1, exhibited a lower proliferation and migration capacity of ccRCC than that of the control group (P < 0.05). Then, lipidomic and transcriptomic sequencing showed that lipid metabolism disorders, ER stress, and mitophagy genes were enriched in the sh-NR3C1 group. Finally, compared to the control group, ER stress and mitophagy were observed in the sh-NR3C1 group, while the expression of ATF6, CHOP, PINK1, and BNIP3 was also up-regulated (P < 0.05). Furthermore, Ceapin-A7, an inhibitor of ATF6, significantly down-regulated the expression of PINK1 and BNIP3 (P < 0.05), and significantly increased the proliferation and migration of ccRCC cells (P < 0.05). CONCLUSIONS: This study confirms that knockdown of NR3C1 activates ER stress and induces mitophagy through the ATF6-PINK1/BNIP3 pathway, resulting in reduced proliferation and migration of ccRCC. These findings indicate potential novel targets for clinical treatment of ccRCC.

Association of Public Sports Space Perception with Health-Related Quality of Life in Middle-Aged and Older Adults-Evidence from a Survey in Shandong, China.

Creating a healthy living environment for middle-aged and older adults is a key strategy for countries to address the aging challenge, but the effects of such an environment on the health-related quality of life (HRQoL) of middle-aged and older adults remain underexplored. This study aimed to examine the link between public sports facilities and the HRQoL of middle-aged and older adult residents in communities. A total of 1169 respondents (average age: 66.84; male: 46.19%) were selected from the Shandong, China. This study measured respondents 'physical activity (PA) using the International Physical Activity Questionnaire, the HRQoL of respondents using the 36-item Short Form Health Survey, and the Public Sports Space Perception Scale for respondents' public sports space perception. Correlation analysis and logistic regression analysis were employed to test the relationship among public sports space perception, physical activity (PA), and HRQoL. The mediating role of PA was conducted using the PROCESS macro for SPSS. The results revealed that public sports space perception only influenced the HRQoL of middle-aged and older adults through light-intensity PA (PCS: B = 0.09, 95% CI 0.01, 0.03; MCS: B = 0.02, 95% CI 0.01, 0.05) among light-intensity PA, moderate-intensity PA, vigorous-intensity PA., and this mediation model varied across different age groups of middle-aged and older adults. Moreover, digital inclusion only moderated the psychological aspect of HRQoL of middle-aged and older adults (p < 0.05). This study provided empirical evidence for enhancing the HRQoL of middle-aged and older adults and offered useful insights for the planning and design of public sports facilities and the formulation of health management policies for middle-aged and older adults.

Exploring the relationship between distress rumination, resilience, depression, and self-injurious behaviors among Chinese college athletes infected with COVID-19: a cross-sectional study.

Objectives: Distress rumination is a cause of suicidality and self-injurious behavior (SSIB) among individuals. Although previous studies have shown that distress rumination, SSIB, resilience, and depression are significantly related, the interaction mechanism remains unclear. This study aimed to evaluate resilience and depression as mediators of the relationship between distress rumination and SSIB among Chinese college athletes infected with COVID-19. Methods: Convenience sampling was used to recruit participants from the National College Football Championship in Guangxi City, China from January to February 2023. Participants completed the Ruminative Responses Scale (RRS), a subscale of the Health-Risk Behavior Inventory (HBI), the Mental Toughness Index (MTI) and the Patient Health Questionnaire (PHQ-9). We used the PROCESS macro for SPSS to determine the mediating effect of resilience and depression between distress rumination and SSIB. Results: A total of 350 Chinese college athletes participated in this study and completed the questionnaire survey. 289 (81.7% boys; Mage = 20.31 years, SD = 1.60) of them have been infected with COVID-19. 59.9% (n = 173) participants were from urban areas and 15.6% (n = 45) of participants have engaged in self-injurious behaviors or suicidal ideation. College athletes' distress rumination was significantly negatively correlated with resilience (r = - 0.28, p < 0.01), and was significantly positively correlated with depression (r = 0.49, p < 0.01) and SSIB (r = - 0.18, p < 0.01). Resilience was significantly negatively correlated with depression (r = - 0.35, p < 0.01) and SSIB (r = - 0.30, p < 0.01). Finally, depression was significantly positively correlated with SSIB (r = - 0.38, p < 0.01). Resilience and depression played a mediating role of the total effects of distress rumination and SSIB, respectively. Meanwhile, the chain mediating effect of resilience and depression was also significant. Conclusion: This study found that distress rumination can directly predict SSIB, and indirectly predict SSIB through the mediating effect of resilience and depression, and the chain mediating effect of resilience-depression. Therefore, reducing the degree of distress rumination of college athletes infected by COVID-19 and improving their resilience, as well as reducing their depression may help prevent SSIB.

Post-Traumatic Stress Disorder and Mental Health in Chinese College Athletes during and after the COVID-19 Pandemic: The Multiple Mediating Effects of Basic Psychological Needs and Generalized Anxiety Disorder.

Psychological issues have a complex and multidimensional impact on a college athlete's training and performance. As the reserve talent of competitive sports, it is very important to investigate the psychological health of athletes. This study aims to explore the association between generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), basic psychological needs (BPN), and mental health (MH) among Chinese college athletes. Chinese college athletes who were willing to participate in the study, had participated in national competitions, and had a Chinese athlete rating certificate were included in this study. Participants completed the Kessler Psychological Distress Scale (K10), the Generalized Anxiety Disorder Scale (GAD-7), the Impact of Event Scale-Revised (IES-R), and the Basic Needs Satisfaction in General Scale (BNSG-S). The study involved 665 college athletes (415 males and 250 females), with an average age of 20.43 years (SD = 1.68). We performed descriptive statistics, correlation analyses, and moderated chain mediation analyses using SPSS 22.0 and Hayes' PROCESS macro. The results of the final model showed that basic psychological needs were positively correlated with mental health (r = 0.443, p < 0.001), while PTSD (r = -0.346, p < 0.001) and generalized anxiety disorder (r = -0.527, p < 0.001) were negatively correlated with mental health among college athletes. There were significant indirect impacts. According to the bootstrapping results, basic psychological needs and generalized anxiety disorder played a mediating role in 22.54% and 50.29% of the total effects of PTSD on mental health, respectively. Meanwhile, the chain mediating effect of basic psychological needs and generalized anxiety disorder (7.23%) was also significant. The study's findings advance our understanding of the connections between PTSD and mental health and highlight the significant roles played by basic psychological needs and generalized anxiety disorder in that link among Chinese college athletes.

Ammonium tetrathiomolybdate relieves oxidative stress in cisplatin-induced acute kidney injury via NRF2 signaling pathway.

Cisplatin is an efficient chemotherapeutic agent for various solid tumors, but its usage is restricted by nephrotoxicity. A single dose of cisplatin can cause acute kidney injury (AKI), which is characterized by rapid reduction in kidney function. However, the current therapies, such as hydration, are limited. It is vital to develop novel therapeutic reagents that have both anticancer and renoprotective properties. The objective of this study was to determine whether ammonium tetrathiomolybdate (TM), a copper chelator used to treat cancer and disorders of copper metabolism, may offer protection against cisplatin-induced AKI. In this study, we demonstrated that TM treatment had antioxidative effects and mitigated cisplatin-induced AKI both in vivo and in vitro. Mechanically, TM inhibited NRF2 ubiquitination, which activated the NRF2 pathway in HK-2 cells and promoted the expression of target genes. It should be noted that the protective effect conferred by TM against cisplatin was compromised by the knockdown of the NRF2 gene. Furthermore, TM selectively activated the NRF2 pathways in the liver and kidney. The current study provided evidence for additional clinical applications of TM by showing that it activates NRF2 and has a favorable therapeutic impact on cisplatin-induced AKI.

Low XIST expression in Sertoli cells of Klinefelter syndrome patients causes high susceptibility of these cells to an extra X chromosome.

Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. However, the effect of the extra X chromosome on different testicular cell types remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals. Among the different somatic cells, Sertoli cells showed the greatest transcriptome changes in KS patients. Further analysis showed that X-inactive-specific transcript ( XIST ), a key factor that inactivates one X chromosome in female mammals, was widely expressed in each testicular somatic cell type but not in Sertoli cells. The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes, and further disrupts their transcription pattern and cellular function. This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells. These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia. Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.