Transcriptomics-based identification of TYROBP and TLR8 as novel macrophage-related biomarkers for the diagnosis of acute rejection after kidney transplantation.

Macrophages play an important role in the development and progression of acute rejection after kidney transplantation. The study aims to investigate the biological role and significance of macrophage-associated genes (MAG) in acute rejection after kidney transplantation. We utilized transcriptome sequencing results from public databases related to acute rejection of kidney transplantation for comprehensive analysis and validation in animal experiments. We found that a large number of immune-related signaling pathways are activated in acute rejection. PPI protein interaction networks and machine learning were used to establish a Hub gene consisting of TYROBP and TLR8 for the diagnosis of acute rejection. The single-gene GSEA enrichment analysis and immune cell correlation analysis revealed a close correlation between the expression of Hub genes and immune-related biological pathways as well as the expression of multiple immune cells. In addition, the study of TF, miRNAs, and drugs provided a theoretical basis for regulating and treating the Hub genes in acute rejection. Finally, the animal experiments demonstrated once again that acute rejection can aggravate kidney tissue damage, apoptosis level, and increase the release of inflammatory factors. We established and validated a macrophage-associated diagnostic model for acute rejection after kidney transplantation, which can accurately diagnose the biological alterations in acute rejection after kidney transplantation.

Exosomes From Human Umbilical Cord Stem Cells Suppress Macrophage-to-myofibroblast Transition, Alleviating Renal Fibrosis.

Renal fibrosis, a progressive scarring of the kidney, lacks effective treatment. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Exos) hold promise for treating kidney diseases due to their anti-inflammatory properties. This study investigates their potential to lessen renal fibrosis by targeting macrophage-to-myofibroblast transformation (MMT), a key driver of fibrosis. We employed a mouse model of unilateral ureteral obstruction (UUO) and cultured cells exposed to transforming growth factor-ß (TGF-ß) to mimic MMT. HucMSC-Exos were administered to UUO mice, and their effects on kidney function and fibrosis were assessed. Additionally, RNA sequencing and cellular analysis were performed to elucidate the mechanisms by which HucMSC-Exos inhibit MMT. HucMSC-Exos treatment significantly reduced kidney damage and fibrosis in UUO mice. They downregulated markers of fibrosis (Collagen I, vimentin, alpha-smooth muscle actin) and suppressed MMT (α-SMA + F4/80 + cells). Furthermore, ARNTL, a specific molecule, emerged as a potential target of HucMSC-Exos in hindering MMT and consequently preventing fibrosis. HucMSC-Exos effectively lessen renal fibrosis by suppressing MMT, suggesting a novel therapeutic strategy for managing kidney damage and fibrosis.

The necroptosis-mediated imbalance of mitochondrial dynamics is involved in DEHP-induced toxicity to immature testes via the PGAM5-DRP1 interaction.

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that has been shown to impair male reproduction, but the potential mechanism underlying testicular injury caused by DEHP remains unclear. In vivo, rats were gavaged consecutively from postnatal day (PND) 21 to PND 31 with 0, 250, or 500 mg/kg DEHP for 10 days, and impaired mitochondria and increased necroptosis were observed in immature testes. In vitro, the GC-1 and GC-2 cell lines were exposed to monoethylhexyl phthalate (MEHP) at 100, 200 and 400 µM for 24 h, and this exposure induced oxidative stress damage, necroptosis and mitochondrial injury. Necroptosis and mitochondrial fission were inhibited by the reactive oxygen species (ROS) inhibitor acetylcysteine, and the imbalanced mitochondrial dynamics were rescued by the RIPK1 inhibitor necrostatin-1. Colocalization and co-IP analyses confirmed an interaction between dynamin-related protein 1 (DRP1) and phosphoglycerate mutase 5 (PGAM5), indicating that PGAM5 dephosphorylates DRP1 at serine 637 to induce mitochondrial fragmentation and thereby induces germ cell damage. Drug prediction with Connectivity Map (cMap) identified sulforaphane as a therapeutic drug. In summary, our findings indicate that DEHP triggers necroptosis and mitochondrial injury via a ROS storm in immature testes and that the PGAM5-DRP1 interaction is involved in this process.

Rab25 is involved in hypospadias via the ß1 integrin/EGFR pathway.

BACKGROUND: Hypospadias is a common congenital abnormality of the penile. Abnormal regulation of critical genes involved in urethral development leads to hypospadias. We used the Rab25-/- mice and foreskin fibroblasts transfected with lentivirus in vitro and in vivo to investigate the role of Rab25 in hypospadias. METHODS: The expression levels of various molecules in tissue samples and foreskin fibroblasts were confirmed using molecular biology methods (western blotting, PCR, immunohistochemistry, etc.). A scanning electron microscope (SEM) was used to visualize the external morphology of genital tubercles (GTs) of gestation day (GD) 18.5 male wild-type (WT) and Rab25-/- mice. RESULTS: An expanded distal cleft and V-shaped urethral opening were observed in GD 18.5 Rab25-/- mice. We demonstrated that Rab25 mediated hypospadias through the ß1 integrin/EGFR pathway. In addition, silencing Rab25 inhibited cell proliferation and migration and promoted apoptosis in the foreskin fibroblasts; Ki-67- and TUNEL-positive cells were mainly concentrated near the urethral seam. CONCLUSION: These findings suggest that Rab25 plays an essential role in hypospadias by activation of ß1 integrin/EGFR pathway, and Rab25 is a critical mediator of urethral seam formation in GD18.5 male fetal mice.

Differentiation Potential of Hypodifferentiated Subsets of Nephrogenic Rests and Its Relationship to Prognosis in Wilms Tumor.

Background Wilms tumor (WT) is highly curable, although anaplastic histology or relapse imparts a worse prognosis. Nephrogenic rests (NR) associated with a high risk of developing WT are abnormally retained embryonic kidney precursor cells. Methods After pseudo-time analysis using single-cell RNA sequencing (scRNA-seq) data, we generated and validated a WT differentiation-related gene (WTDRG) signature to predict overall survival (OS) in children with a poor OS. Results A differentiation trajectory from NR to WT was identified and showed that hypodifferentiated subsets of NR could differentiate into WT. Classification of WT children with anaplastic histology or relapse based on the expression patterns of WTDRGs suggested that patients with relatively high levels of hypodifferentiated NR presented a poorer prognosis. A WTDRG-based risk model and a clinically applicable nomogram was developed. Conclusions These findings may inform oncogenesis of WT and interventions directed toward poor prognosis in WT children of anaplastic histology or relapse.

Maternal Diabetes and Risk of Hypospadias: A Systemic Review and Meta-Analysis.

INTRODUCTION: This study aimed to investigate the association between maternal diabetes and the risk of hypospadias in male infants, as the relationship between them remains uncertain. METHODS: To comprehensively evaluate the association between pregestational diabetes mellitus and gestational diabetes mellitus with hypospadias, we conducted a systematic review and meta-analysis. A thorough literature search was conducted, encompassing relevant publications published prior to January 2023. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Our meta-analysis comprised a total of 13 studies, 11 of which investigated the relationship between pregestational diabetes mellitus and hypospadias, while 9 studies explored the association between gestational diabetes mellitus and hypospadias. Notably, these investigations yielded compelling evidence of significant positive associations between pregestational diabetes mellitus and hypospadias (OR = 1.51, 95% CI = 1.13-2.03), as well as between gestational diabetes mellitus and hypospadias (OR = 1.18, 95% CI = 1.04-1.35). CONCLUSION: Our findings suggest that both pregestational diabetes mellitus and gestational diabetes mellitus are associated with an increased risk of hypospadias in offspring. Further investigations are needed to explore the optimal range of blood glucose during pregnancy that minimizes the risk of congenital malformation in the fetus, as well as to develop more effective measures for glycemic control in pregnant women.

Automatedly identify dryland threatened species at large scale by using deep learning.

Dryland biodiversity is decreasing at an alarming rate. Advanced intelligent tools are urgently needed to rapidly, automatedly, and precisely detect dryland threatened species on a large scale for biological conservation. Here, we explored the performance of three deep convolutional neural networks (Deeplabv3+, Unet, and Pspnet models) on the intelligent recognition of rare species based on high-resolution (0.3 m) satellite images taken by an unmanned aerial vehicle (UAV). We focused on a threatened species, Populus euphratica, in the Tarim River Basin (China), where there has been a severe population decline in the 1970s and restoration has been carried out since 2000. The testing results showed that Unet outperforms Deeplabv3+ and Pspnet when the training samples are lower, while Deeplabv3+ performs best as the dataset increases. Overall, when training samples are 80, Deeplabv3+ had the best overall performance for Populus euphratica identification, with mean pixel accuracy (MPA) between 87.31 % and 90.2 %, which, on average is 3.74 % and 11.29 % higher than Unet and Pspnet, respectively. Deeplabv3+ can accurately detect the boundaries of Populus euphratica even in areas of dense vegetation, with lower identification uncertainty for each pixel than other models. This study developed a UAV imagery-based identification framework using deep learning with high resolution in large-scale regions. This approach can accurately capture the variation in dryland threatened species, especially those in inaccessible areas, thereby fostering rapid and efficient conservation actions.

IL-13 alleviates acute kidney injury and promotes regeneration via activating the JAK-STAT signaling pathway in a rat kidney transplantation model.

AIMS: To identify whether and how a younger systemic internal milieu alleviates acute kidney injury (AKI) in grafts after kidney transplantation. MATERIALS AND METHODS: We conducted an allogenic heterotopic rat kidney transplantation model with young and adult recipients receiving similar donor kidneys. We evaluated the renal function, histological damage, apoptosis, dedifferentiation, proliferation, hub regulating cytokines, and signaling pathways involved in young and adult recipients based on transcriptomics, proteomics, and experimental validation. We also validated the protective effect and mechanism of interleukin-13 (IL-13) on tubular epithelial cell injury induced by transplantation in vivo and by cisplatin in vitro. KEY FINDINGS: Compared with adult recipients, the young recipients had lower levels of renal histological damage and apoptosis, while had higher levels of dedifferentiation and proliferation. Serum IL-13 levels were higher in young recipients both before and after surgery. Pretreating with IL-13 decreased apoptosis and promoted regeneration in injured rat tubular epithelial cells induced by cisplatin, while this effect can be counteracted by a JAK2 and STAT3 specific inhibitor, AG490. Recipients pretreated with IL-13 also had lower levels of histological damage and improved renal function. SIGNIFICANCE: Higher levels of IL-13 in young recipients ameliorates tubular epithelial cell apoptosis and promotes regeneration via activating the JAK-STAT signaling pathway both in vivo and in vitro. Our results suggest that IL-13 is a promising therapeutic strategy for alleviating AKI. The therapeutic potential of IL-13 in injury repair and immune regulation deserves further evaluation and clinical consideration.

Protective effects of melatonin on DEHP-induced apoptosis and oxidative stress in prepubertal testes via the PI3K/AKT pathway.

Di(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, is one of the most common plasticizers and is widely used in various plastic products. DEHP induces apoptosis and oxidative stress and has been shown to have androgenic toxicity. However, the methods to combat DEHP-induced testicular damage and the mechanisms involved remain to be elucidated. In the present study, we used melatonin, which has strong antioxidant properties, to intervene in prepubertal mice and mouse Leydig cells (TM3) treated with DEHP or its metabolite mono(2-ethylhexyl) phthalate (MEHP). The results showed that melatonin protected against DEHP-induced testicular damage in prepubertal mice, mainly by protecting against DEHP-induced structural destruction of the germinal tubules and by attenuating the DEHP-induced decrease in testicular organ coefficients and testosterone levels. Transcriptomic analysis found that melatonin may attenuate DEHP-induced oxidative stress and apoptosis in prepubertal testes. In vitro studies further revealed that MEHP induces oxidative stress injury and increases apoptosis in TM3 cells, while melatonin reversed this damage. In vitro studies also found that MEHP exposure inhibited the expression levels of molecules related to the PI3K/AKT signaling pathway, and melatonin reversed this change. In conclusion, these findings suggest that melatonin protects against DEHP-induced prepubertal testicular injury via the PI3K/AKT signaling pathway, and provide a theoretical basis and experimental rationale for combating male reproductive dysfunction.

Vitamin D levels and the risk of overactive bladder: a systematic review and meta-analysis.

CONTEXT: Overactive bladder is treated mainly with behavioral and drug therapy, and symptoms of urinary frequency and incontinence are challenging to eliminate. There is thus a continuous unmet need for new drugs with a substitution effect mechanism. OBJECTIVE: It not known whether vitamin D deficiency can lead to overactive bladder or urinary incontinence or whether vitamin D supplementation alleviates bladder symptoms. This comprehensive systematic review with meta-analysis was conducted to determine whether overactive bladder is associated with vitamin D deficiency. DATA SOURCES: The PubMed and Cochrane Library databases were searched systematically up to July 3, 2022. DATA EXTRACTION: Initially, 706 articles were identified in the literature search, of which 13 were included in the systematic review: 4 randomized controlled trials, 3 cohort studies, 3 cross-sectional studies, and 3 case-control studies. DATA ANALYSIS: An increased risk of overactive bladder and urinary incontinence was observed with vitamin D deficiency (odds ratio [OR] = 4.46; 95%CI, 1.03-19.33; P = 0.046 and OR = 1.30; 95%CI, 1.01-1.66; P = 0.036, respectively). Vitamin D levels were relatively low in patients with overactive bladder or urinary incontinence (SMD = -0.33; 95%CI, -0.61 to -0.06, P = 0.019). On the basis of existing data, the risk of urinary incontinence was reduced by 66% after vitamin D supplementation (OR = 0.34; 95%CI, 0.18-0.66; P = 0.001). Egger test was conducted to assess publication bias, and the results were tested for robustness using a sensitivity analysis. CONCLUSIONS: Vitamin D deficiency increases the risk of overactive bladder and urinary incontinence, and vitamin D supplementation reduces the risk of urinary incontinence. The development of new strategies to prevent or alleviate bladder symptoms is crucial. Vitamin D supplementation may be gaining recognition as an effective strategy for prevention or alleviation of bladder symptoms such as overactive bladder and incontinence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022351443.

Di-(2-ethylhexyl) phthalate induces ferroptosis in prepubertal mouse testes via the lipid metabolism pathway.

Di-(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, has been shown to cause reproductive toxicity, but the precise mechanism remains unclear. This study aimed to investigate the possible molecular mechanism of DEHP-induced testicular damage. In vivo study, we administered different doses of DEHP (0, 250, and 500 mg/kg/day) to male C57BL/6 mice from 22 and 35 days after birth. We found that DEHP exposure induced histopathological alterations in prepubertal testes, and testicular lipidomics indicated notable alterations in lipid metabolism and significant enrichment of ferroptosis. Further tests showed that ferrous iron (Fe2+ ) and malondialdehyde (MDA) levels significantly increased after DEHP exposure. Western blotting revealed that DEHP exposure reduced glutathione peroxidase 4 (GPX4) expression, and elevated acyl coenzyme A synthetase long-chain member 4 (ACSL4) and lysophosphatidylcholine acyltransferase 3 (LPCAT3) expression. The in vitro results were consistent with the in vivo results. When Leydig cells and Sertoli cells were treated with ferrostatin-1 and monoethylhexyl phthalate (MEHP), MEHP-induced increases in Fe2+ and MDA levels, accumulation of lipid reactive oxygen species, downregulation of GPX4, and upregulation of ACSL4 and LPCAT3 were reversed. Collectively, our findings suggested that aberrant lipid metabolism and ferroptosis may be involved in prepubertal DEHP exposure-induced testicular damage.

Risk factors and timing of complication presentation following primary hypospadias repair in adolescents.

OBJECTIVES: To evaluate the risk factors for postoperative complications in adolescents who undergo primary hypospadias repair and determine the time required for complication detection. METHODS: Our study included patients classified as Tanner stages three to five who underwent primary hypospadias repairs at our hospital from January 2015 to August 2022. The patients' baseline information, clinical characteristics, postoperative complications, and time to complication detection were collected. Cox regression analysis, ROC curves, Kaplan-Meier survival analyses, and the Mann-Whitney U test were used. RESULTS: The study comprised 143 patients, with a median age of 12.58 years. Postoperative complications were experienced by 66 patients. The length of the urethral defect was identified as an independent risk factor for postoperative complications. The ROC curve analysis identified 3 cm as the optimal cutoff value for the length of the urethral defect. The median time to complication detection was 30.5 days (IQR 23 to 209.25). 89.4% of the complications were identified within the first year. Patients with a urethral defect of <3 cm experienced a significantly longer time for the detection of urethral fistula compared to those with a urethral defect of ≥3 cm (p = 0.047). CONCLUSIONS: Our data indicate that adolescents with a urethral defect ≥3 cm have a higher risk of postoperative complications. Although most complications were identified within the first year, conducting long-term follow-ups for adolescents is recommended to identify potential subsequent complications that may arise from persistent urethral alterations.

Efficacy and Safety of High-Dose Vitamin D Supplementation vs Solifenacin or Standard Urotherapy for Overactive Bladder Dry in Children: A Randomized Clinical Trial.

PURPOSE: We investigated the efficacy and safety of high-dose vitamin D supplementation (VDS) plus standard urotherapy (SU) in managing overactive bladder dry in children. MATERIALS AND METHODS: A 3-arm, randomized clinical trial was performed at an academic center in China between January 2023 and June 2023. Eligible patients (n=303) were randomized to receive 8 weeks of high-dose VDS (vitamin D3 drops encapsulated as soft capsules, 2400 IU/d) plus SU (VDS + SU group; n=100), solifenacin (5-10 mg/d) plus SU (SOL + SU group; n=102), or SU alone (SU group; n=101). Reduction in voiding frequency was the primary outcome. Secondary outcomes encompassed improvement in urgency, nocturia, quality of life score, pediatric lower urinary tract symptom score, and participant satisfaction. Treatment-emergent adverse events were recorded within each group. RESULTS: Participants had a median age of 82.0 months and their baseline mean vitamin D level was 22.64 ng/mL. The VDS + SU group showed greater improvements in voids/d than the SOL + SU group (median difference 3.0; 95% CI, 2.0 to 3.5; P < .001) and the SU group (median difference 4.0; 95% CI, 3.0 to 5.0; P < .001) after intervention. The VDS + SU group also showed the greatest improvement in quality of life and pediatric lower urinary tract symptom scores. Patient satisfaction was similar between the SOL + SU and SU groups. The VDS + SU group did not exhibit a heightened risk of treatment-emergent adverse events compared to the other groups. CONCLUSIONS: High-dose VDS plus SU was effective and well-tolerated in managing overactive bladder dry in children, suggesting its potential as a novel therapeutic option for this population.

Acute renal injury after aortic arch reconstruction with cardiopulmonary bypass for children: prediction models by machine learning of a retrospective cohort study.

BACKGROUND: Acute renal injury (AKI) after aortic arch reconstruction with cardiopulmonary bypass leads to injury of multiple organs and increases perioperative mortality. The study was performed to explore risk factors for AKI. We aim to develop a prediction model that can be used to accurately predict AKI through machine learning (ML). METHODS: A retrospective analysis was performed on 134 patients with aortic arch reconstruction with cardiopulmonary bypass who were treated at our hospital from January 2002 to January 2022. Risk factors for AKI were compositive and were evaluated with comprehensive analyses. Six artificial intelligence (AI) models were used for machine learning to build prediction models and to screen out the best model to predict AKI. RESULTS: Weight, eGFR, cyanosis, PDA, newborn birth and duration of renal ischemia were closely related to AKI. By integrating the results of the training cohort and validation cohort, we finally confirmed that the logistic regression model was the most stable model among all the models, and the logistic regression model showed good discrimination, calibration and clinical practicability. Based on 6 independent factors, the dynamic nomogram can be used as a predictive tool for clinical application. CONCLUSIONS: DHCA could be considered in aortic arch reconstruction if additional perfusion of lower body were not performed especially when renal ischemia is greater than 30 min. Machine Learning models should be developed for early recognition of AKI. TRIAL REGISTRATION: ChiCTR, ChiCTR2200060552. Registered 4 june 2022.

Efficacy of Body Wash and Povidone-Iodine in Skin Preparation in Reducing Surgical Site Infections After Hypospadias Repair Among Adolescents: A Prospective Cohort Study With Retrospective Controls.

Background: Surgical site infections (SSIs) that occur after hypospadias repair frequently result in incision healing complications, especially during puberty. This study aimed to evaluate the efficacy of twice-daily pre-operative skin preparation using body wash and povidone-iodine within 48 hours before hypospadias repair with regard to infection rates in adolescents. Patients and Methods: Prospective recruitment included patients in Tanner stages 3 to 5 undergoing hypospadias repair from January 2015 to January 2021. The experimental group comprised patients who performed twice-daily skin preparation with body wash and povidone-iodine within 48 hours before surgery. Surgeons selected either 0.5% or 5% povidone-iodine for skin preparation. The control group comprised a retrospective cohort of hypospadias repair conducted in the preceding five years, where patients performed pre-surgery evening showers using a body wash. Complications were collected over a six-month follow-up period. Results: The study included 90 patients in the 0.5% povidone-iodine group, 92 patients in the 5% povidone-iodine group, and 84 patients in the control group. Differences were observed among the groups in terms of SSI (p = 0.030) and urethral fistula (p = 0.019). In post hoc tests, only the 5% povidone-iodine group demonstrated a diminished incidence of SSI (p = 0.009) and urethral fistula (p = 0.005) in comparison to the control group. Conclusions: Using body wash and 5% povidone-iodine for skin preparation was associated with a reduction in the incidence of SSI and urethral fistula following hypospadias repair in adolescents and may be considered to improve outcomes.

Transcriptome-based exploration of potential molecular targets and mechanisms of selenomethionine in alleviating renal ischemia-reperfusion injury.

Renal ischemia-reperfusion injuries (IRIs) are one of the leading causes of acute kidney injuries (AKIs). Selenium, as an essential trace element, is able to antioxidant stress and reduces inflammatory responses. The regulation mechanism of selenomethionine, one of the major forms of selenium intake by humans, is not yet clear in renal IRIs. Therefore, we aimed to explore the key targets and related mechanisms of selenomethionine regulation in renal IRIs and provide new ideas for the treatment of selenomethionine with renal IRIs. We used transcriptome sequencing data from public databases as well as animal experiments to explore the key target genes and related mechanisms regulated by selenomethionine in renal IRI. We found that selenomethionine can effectively alleviate renal IRI by a mechanism that may be achieved by inhibiting the MAPK signaling pathway. Meanwhile, we also found that the key target of selenomethionine regulation in renal IRI might be selenoprotein GPX3 based on the PPI protein interaction network and machine learning. Through a comprehensive analysis of bioinformatic techniques and animal experiments, we found that Gpx3 might serve as a key gene for the regulation of selenomethionine in renal IRIs. Selenomethionine may exert a protective effect against renal IRI by up-regulating GPX3, inhibiting the MAPK signaling pathway, increased production of antioxidants, decreasing inflammation levels, mitigation of apoptosis in renal tubular epithelial cells, this reduces renal histopathological damage and protects renal function. Providing a theoretical basis for the mechanism of selenomethionine actions in renal IRIs.

CCNB1 is a novel prognostic biomarker and promotes proliferation, migration and invasion in Wilms tumor.

BACKGROUND: Wilms tumour (WT) is a mixed type of embryonal tumour that usually occurs in early childhood. However, our knowledge of the pathogenesis or progression mechanism of WT is inadequate, and there is a scarcity of beneficial therapeutic strategies. METHODS: High-throughput RNA sequencing was employed in this study to identify differentially expressed genes (DEGs) in clinical tumor samples and matching normal tissues. The STRING database was utilized to build a protein-protein interaction (PPI) network, and the Cytohubba method was used to identify the top 10 highly related HUB genes. Then, the key genes were further screened by univariate COX survival analysis. Subsequently, the XCELL algorithm was used to evaluate the tumour immune infiltration. RT-PCR, WB, and IF were used to verify the expression level of key genes in clinical tissues and tumour cell lines. Finally, the function of the key gene was further verified by loss-of-function experiments. RESULTS: We initially screened 1612 DEGs, of which 1030 were up-regulated and 582 were down-regulated. The GO and KEGG enrichment analysis suggested these genes were associated with 'cell cycle', 'DNA replication'. Subsequently, we identified 10 key HUB genes, among them CCNB1 was strongly related to WT patients' overall survival. Multiple survival analyses showed that CCNB1 was an independent indicator of WT prognosis. Thus, we constructed a nomogram of CCNB1 combined with other clinical indicators. Single gene GSEA and immune infiltration analysis revealed that CCNB1 was associated with the degree of infiltration or activation status of multiple immune cells. TIDE analysis indicated that this gene was correlated with multiple key immune checkpoint molecules and TIDE scores. Finally, we validated the differential expression level of CCNB1 in an external gene set, the pan-cancer, clinical samples, and cell lines. CCNB1 silencing significantly inhibited the proliferation, migration, and invasive capabilities of WIT-49 cells, also, promoted apoptosis, and in turn induced G2 phase cell cycle arrest in loss-of-function assays. CONCLUSION: Our study suggests that CCNB1 is closely related to WT progression and prognosis, and serves as a potential target.

Adverse effects of microplastics and nanoplastics on the reproductive system: A comprehensive review of fertility and potential harmful interactions.

In recent years, microplastics (MPs) and nanoplastics (NPs) have caused ubiquitous environmental pollution and raised widespread concern about their potential toxicity to human health, especially in the reproductive system. Moreover, infertility affects >15 % of couples worldwide, and the birth rate is decreasing. Environmental factors are some of the most important causes of infertility. However, little is known about the effects of MPs and NPs on the testes and ovaries. These particles can enter the body primarily via ingestion, inhalation, and skin contact, target the reproductive system in a size-dependent manner and disturb germ cell and other somatic cell development. Our study systematically reviewed the adverse effects of plastic particles on reproductive function and offers valuable insights into the different stages of germ cells and the potential mechanisms. Moreover, the synergistic reproductive toxicity of these particles and carried contaminants was summarized. Given the limited research scale, a shift toward innovative technologies and the adoption of multiple omics are recommended for advancing related studies. Further study is needed to explore the reproductive toxicity of MPs and NPs based on their size, polymer type, shape, and carried toxins, establish effective protective measures, and develop precision medicine for targeted reproductive damage.