CCR7 and CD48 as Predicted Targets in Acute Rejection Related to M1 Macrophage after Pediatric Kidney Transplantation.

Background: Kidney transplantation (KT) is the best treatment for end-stage renal disease. Although long and short-term survival rates for the graft have improved significantly with the development of immunosuppressants, acute rejection (AR) remains a major risk factor attacking the graft and patients. The innate immune response plays an important role in rejection. Therefore, our objective is to determine the biomarkers of congenital immunity associated with AR after KT and provide support for future research. Materials and Methods: A differential expression genes (DEGs) analysis was performed based on the dataset GSE174020 from the NCBI gene Expression Synthesis Database (GEO) and then combined with the GSE5099 M1 macrophage-related gene identified in the Molecular Signatures Database. We then identified genes in DEGs associated with M1 macrophages defined as DEM1Gs and performed gene ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Cibersort was used to analyze the immune cell infiltration during AR. At the same time, we used the protein-protein interaction (PPI) network and Cytoscape software to determine the key genes. Dataset, GSE14328 derived from pediatric patients, GSE138043 and GSE9493 derived from adult patients, were used to verify Hub genes. Additional verification was the rat KT model, which was used to perform HE staining, immunohistochemical staining, and Western Blot. Hub genes were searched in the HPA database to confirm their expression. Finally, we construct the interaction network of transcription factor (TF)-Hub genes and miRNA-Hub genes. Results: Compared to the normal group, 366 genes were upregulated, and 423 genes were downregulated in the AR group. Then, 106 genes related to M1 macrophages were found among these genes. GO and KEGG enrichment analysis showed that these genes are mainly involved in cytokine binding, antigen binding, NK cell-mediated cytotoxicity, activation of immune receptors and immune response, and activation of the inflammatory NF-κB signaling pathway. Two Hub genes, namely CCR7 and CD48, were identified by PPI and Cytoscape analysis. They have been verified in external validation sets, originated from both pediatric patients and adult patients, and animal experiments. In the HPA database, CCR7 and CD48 are mainly expressed in T cells, B cells, macrophages, and tissues where these immune cells are distributed. In addition to immunoinfiltration, CD4+T, CD8+T, NK cells, NKT cells, and monocytes increased significantly in the AR group, which was highly consistent with the results of Hub gene screening. Finally, we predicted that 19 TFs and 32 miRNAs might interact with the Hub gene. Conclusions: Through a comprehensive bioinformatic analysis, our findings may provide predictive and therapeutic targets for AR after KT.

Transcriptomics-based exploration of shared M1-type macrophage-related biomarker in acute kidney injury after kidney transplantation and acute rejection after kidney transplantation.

BACKGROUND: Macrophage type 1 (M1) cells are associated with both acute kidney injury (AKI) during kidney transplantation and acute rejection (AR) after kidney transplantation. Our study explored M1-related biomarkers involved in both AKI and AR and their potential biological functions. METHODS: Based on the Gene Expression Omnibus (GEO) database, the immune cell infiltration levels and differentially expressed genes were examined in AKI and AR in the kidney transplantation; M1-related genes shared in AKI and AR were identified using weighted gene co-expression analysis (WGCNA) system. Subsequently, protein-protein interaction (PPI) networks and machine learning methods to identify Hub genes and construct diagnostic models. Both AKI model and AR rat models were built to validate the expressions of Hub genes and test the injury phenotype, oxidative stress markers, and inflammatory factors. Finally, the transcription factor (TF)-Hub gene and micro-RNA (miRNA)-Hub gene regulatory networks were constructed based on identified Hub genes. RESULTS: Out of 2167 differential expression genes (DEGs) in AKI and 2100 DEGs in AR, four M1-related Hub genes were obtained by PPI networks and machine learning methods, namely GBP2, TYROBP, CCR5, and TLR8. The calibration curves in the nomogram diagnostic model for these four Hub genes suggested the same predictive probability as an ideal model for AKI and AR after kidney transplantation (AUC values of the area under the ROC curve were all >0.7). The same observations were confirmed in ischemia reperfusion injury (IRI) and AR rat models by identifying common four Hub genes (GBP2, TYROBP, TLR8, and CCR5). Western blots showed that these four Hub genes were significantly different in rat models of IRI and AR (all p<0.05). Compared with the control group, IRI and AR groups showed aggravated histopathological damage and increased secretion of oxidative stress markers and inflammatory factors in rat kidneys (all p<0.05). Finally, TF-Hub and miRNA-Hub gene regulatory networks were constructed to provide a theoretical basis for the regulation of Hub genes. CONCLUSION: We identified four macrophage M1-related Hub genes shared among AKI and AR after kidney transplantation. These genes may be considered for diagnosis of AKI and AR after kidney transplantation.

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.

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.

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.

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.

The efficacy of robotic-assisted laparoscopic pyeloplasty for pediatric ureteropelvic junction obstruction: a systematic review and meta-analysis.

To evaluate the safety and effectiveness of robotic-assisted laparoscopic pyeloplasty (RALP) for treating pediatric ureteropelvic junction obstruction through an extensive comparison of RALP, open pyeloplasty (OP) and laparoscopic pyeloplasty (LP). We conducted a comprehensive search of the following databases: PubMed, Excerpta Medica Database, Cochrane Library, Web of Science database, China National Knowledge Infrastructure, WanFang Data, and China Biology Medical Disc. Baseline data were compared, the sources of heterogeneity were assessed, and publication biases were detected. This study was registered with PROSPERO (CRD42023415667). 26 studies with 6074 cases performing pyeloplasty were included, and the overall data are comparable. Our analysis showed no significant difference in success rate and postoperative complications between RALP and OP, and RALP is associated with a shorter length of stay (LOS) (MD - 1.00 95%CI - 1.45 to - 0.55, p < 0.0001). In addition, compared to LP, RALP was associated with a shorter anastomosis time (MD - 18.35 95%CI - 29.88 to - 6.82, p = 0.002) and fewer postoperative analgesics (MD - 0.09 95% CI - 0.18 to - 0.01, p = 0.03); however, RALP has a longer operative time (OT) (MD 52.39, 95% CI 39.75-65.03, p < 0.00001) and higher cost. The heterogeneity of OT may be influenced by factors, such as age and region, while the heterogeneity of LOS primarily stems from regional differences. No significant publication bias was detected. Our meta-analysis shows that RALP can be an alternative to OP and LP with a high success rate, minimal postoperative complications, and shorter LOS. In addition, RALP contributes to reduce anastomosis time and postoperative analgesic drugs. However, further well-designed, large-scale, randomized controlled trials with additional parameters are needed to conduct a more comprehensive analysis of heterogeneity.

Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis.

Most children with a neurogenic bladder (NB) have bladder fibrosis, which causes irreversible bladder dysfunction and damage to the upper urinary tract. However, the mechanism of bladder fibrosis remains unclear. This study aimed to investigate the underlying causes of bladder fibrosis. Here, the lumbar 6 (L6) and sacral 1 (S1) spinal nerves of Sprague Dawley rats were severed bilaterally to establish NB models. Using RNA-seq, we discovered that the NF-κB signaling pathway and inflammation were upregulated in spinal cord injury (SCI)-induced bladder fibrosis. Subsequent Western blotting, enzyme-linked immunosorbent assays, immunohistochemical staining, and immunofluorescence staining verified the RNA-seq findings. To further clarify whether the NF-κB signaling pathway and pyroptosis were involved in bladder fibrosis, a TGF-ß1-treated urinary epithelial cell line (SV-HUC-1 cells) was used as an in vitro model. Based on the results of RNA-seq, we consistently found that the NF-κB signaling pathway and pyroptosis might play important roles in TGF-ß1-treated cells. Further experiments also confirmed the RNA-seq findings in vitro. Moreover, using the NLRP3 inhibitor MCC950 rescued TGF-ß1-induced fibrosis, and the NF-κB signaling pathway inhibitor BAY 11-7082 effectively rescued TGF-ß1-induced pyroptosis and the deposition of extracellular matrix by SV-HUC-1 cells. In summary, our research demonstrated for the first time that the NF-κB signaling pathway inhibition rescued bladder epithelial cells pyroptosis and fibrosis in neurogenic bladders.

Wnt10a downregulation contributes to MEHP-induced disruption of self-renewal and differentiation balance and proliferation inhibition in GC-1 cells: Insights from multiple transcriptomic profiling.

Di (2-ethylhexyl) phthalate (DEHP), one of phthalic acid esters, has been widely used in daily products. Its main metabolite, mono (2-ethylhexyl) phthalate (MEHP) was reported to possess higher testicular toxicity than DEHP. To explore the precise mechanism in MEHP-induced testis damage, multiple transcriptomic sequencing was employed in spermatogonia cell line GC-1 cells treated with MEHP (0, 100, and 200 µM) for 24 h. Integrative omics analysis and empirical validation revealed that Wnt signaling pathway was downregulated and wnt10a, one of hub genes, may be the key player in this process. Similar results were observed in DEHP-exposed rats. MEHP-induced disturbance of self-renewal and differentiation was dose-dependent. Moreover, self-renewal proteins were downregulated; the differentiation level was stimulated. Meanwhile, GC-1 proliferation was decreased. Stable transformation strain of wnt10a overexpression GC-1 cell line constructed from lentivirus was utilized in this study. The upregulation of Wnt10a significantly reversed the dysfunction of self-renewal and differentiation and promoted the cell proliferation. Finally, retinol, predicted to be useful in CONNECTIVITY MAP (cMAP), failed to rescue the damage caused by MEHP. Cumulatively, our findings revealed that the downregulation of Wnt10a induced the imbalance of self-renew and differentiation, and inhibition of cell proliferation in GC-1 cells after MEHP exposure.

Inhibition of inflammatory factor TNF-α by ferrostatin-1 in microglia regulates necroptosis of oligodendrocyte precursor cells.

OBJECTIVE: Inflammation of the surrounding environment is a major reason causing loss or injury of oligodendrocyte precursor cells (OPCs) in myelin-associated diseases. Lipopolysaccharide-activated microglia can release various inflammatory factors such as tumor necrosis factor-α (TNF-α). One of the ways of OPC death is necroptosis, which can be triggered by TNF-α, a death receptor ligand, by activating receptor-interacting protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling pathway. This study investigated whether inhibiting microglia ferroptosis can decrease TNF-α release to alleviate OPC necroptosis. METHODS: Lipopolysaccharide and Fer-1 stimulate BV2 cells. The expressions of GPX4 and TNF-α were detected by western blot and quantitative real-time PCR; malondialdehyde, glutathione, iron, and reactive oxygen species were measured by the assay kits. After lipopolysaccharide stimulation of BV2 cells, the supernatant was taken to culture OPC. The protein expression levels of RIPK1, p-RIPK1, RIPK3, p-RIPK3, MLKL, and p-MLKL were detected by western blot. RESULTS: Lipopolysaccharide administration could induce ferroptosis in microglia by decreasing ferroptosis marker GPX4, while ferroptosis inhibitor Fer-1 could significantly increase GPX4 level. Fer-1 prevented oxidative stress and iron concentration elevation and alleviated mitochondrial damage in lipopolysaccharide-induced BV2 cells. The results revealed that Fer-1 downregulated the release of lipopolysaccharide-induced TNF-α in microglia and attenuated OPC necroptosis by significantly decreasing the expression levels of RIPK1, p-RIPK1, MLKL, p-MLKL, RIPK3, and p-RIPK3. CONCLUSION: Fer-1 may be a potential agent for inhibiting inflammation and treating myelin-related diseases.

Human umbilical cord mesenchymal stem cell exosomes alleviate acute kidney injury by inhibiting pyroptosis in rats and NRK-52E cells.

Human umbilical cord mesenchymal stem cells (hucMSCs) have been shown to improve kidney injury. Exosomes have been indicated to be important mediators of renal protection in MSC therapy. In spite of this, the mechanism remains unclear. Our study investigated how exosomes derived from hucMSCs (hucMSC-Ex) improve acute kidney injury (AKI). Exosomes were extracted by using an ultracentrifugation technique and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. Twenty-four male SD rats were randomly divided into four groups: sham group, sham + hucMSC-Ex group, ischemia-reperfusion injury (IRI) group, and IRI + hucMSC-Ex group. In vitro, we treated rat proximal renal tubular epithelial cell line (NRK-52E) with cisplatin to mimic in vivo models of AKI. The NRK-52E cells were treated with or without 160 µg/mL hucMSC-Ex, and 1 µg/mL cisplatin was added after 9 h. Cells were harvested after 24 h. In the IRI group, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were increased; renal tubules were dilated, epithelial cells were vacuolated, and collagen fibers were deposited in the renal interstitium. After treatment with cisplatin, the NRK-52E cells displayed pyroptotic morphology characterized by pyroptotic bodies. The protein expression levels of fibronectin, α-smooth muscle actin (α-SMA), vimentin, gasdermin D (GSDMD), caspase-1, interleukin-1 (IL-1ß) and NLRP3 in IRI tissues and in cisplatin treatment NRK-52E cells were significantly upregulated. However, after the hucMSC-Ex intervention, kidney injury was effectively improved in vivo and in vitro. The current study shows that pyroptosis is involved in AKI and that hucMSC-Ex improves AKI by inhibiting pyroptosis.

GPX3 and GSTT1 as biomarkers related to oxidative stress during renal ischemia reperfusion injuries and their relationship with immune infiltration.

Background: Renal ischemia reperfusion injuries (IRIs) are very common in clinical diagnoses and treatments, which are a common cause of impaired renal functions, worsening pathological damage, affecting disease progression and hindering recovery. Renal IRIs are an inflammatory disease mediated by the adaptive and innate immune system. There is a complex interaction between oxidative stress and immune cell infiltration. Therefore, we aimed to determine biomarkers associated with oxidative stress during renal IRIs and their relationship with immune cell infiltration. Method: A differential gene expression analysis was made based on the GSE148420 dataset from the NCBI Gene Expression Comprehensive Database (GEO) combined with 92 oxidative-stress (OS)-related genes identified in the Molecular Signatures Database. Then we identified differentially-expressed genes (DEOSGs) associated with oxidative stress, which were used for gene ontology (GO) and a Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. At the same time, we used PPI protein interaction networks and Lasso regression analysis to identify key genes, which were verified by the validation sets GSE58438 and GSE71647, as well as Western Blot detection on rat renal IRI models. At the same time, PAS staining, HE staining and immunohistochemistry were used to detect tissue damage and expression of markers related to oxidative stress during renal ischemia-reperfusion. Single-gene enrichment analysis (GSEA) was used to further clarify the underlying biological functions of key genes. Cibersort was used to analyze the immune cell infiltration during renal IRI and the correlation of key genes with immune cells. At the same time, we constructed a network of transcription-factor (TF)-Hub genes and miRNA-Hub genes. DGIDB was used to predict drugs and molecular compounds that might interact with the Hub genes. Results: Compared with the control group, a total of 5456 differential genes (DEGs) were measured in the renal IRI group, 2486 of which were upregulated and 2970 were down-regulated. Among them, we found 30 DEGs (DEOSGs) associated with oxidative stress. The results of GO and KEGG enrichment analysis showed that these DEOSGs were mainly enriched in glutathione metabolism, the response to oxidative stress stimulation, the regulation of T cell activation and apoptosis signaling pathways. Through a protein interaction network (PPI) and a LASSO regression analysis, a total of two Hub genes were identified, namely GPX3 and GSTT1, which were validated through external validation sets and animal experiments. Through pathological methods, we found that the pathological damage of renal tissue and the expression of oxidative stress markers increased after renal ischemia-reperfusion. The results of GSEA showed that the Hub genes were related to oxidative stress pathways, apoptosis signaling pathways and immune-response-related signaling pathways. An immunoinfiltration correlation analysis showed that genes GPX3 and GSTT1 were significantly positively correlated with plasma cells and macrophage M0, while were negatively correlated with monocytes and macrophages M1 and M2. Using the Strust, Starbase and DGIDB database, we predicted that 81 transcription factors, 49 miRNAs and 13 drug or molecular compounds might interact with the Hub genes. Conclusion: Through a comprehensive analysis of gene expression, our findings may provide new potential biomarkers for the pathogenesis of renal IRIs and a reliable basis for its early diagnosis as well as treatment.

Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes.

Difenoconazole (DFZ) is a broad-spectrum triazole fungicide that is widely utilized in agriculture. Although DFZ has been demonstrated to induce reproductive toxicity in aquatic species, its toxic effects on the mammalian reproductive system have yet to be fully elucidated. In vivo, male mice were administered 0, 20 or 40 mg/kg/d of DFZ via oral gavage for 35 days. Consequently, DFZ significantly decreased testicular organ coefficient, sperm count and testosterone levels, augmented sperm malformation rates, and elicited histopathological alterations in testes. TUNEL assay showed increased apoptosis in testis. Western blotting results suggested abnormally high expression of the sperm meiosis-associated proteins STRA8 and SCP3. The concentrations of retinoic acid (RA), retinaldehyde (RE), and retinol (ROL) were increased in the testicular tissues of DFZ-treated groups. The mRNA expression level of genes implicated in RA synthesis significantly increased while genes involved in RA catabolism significantly decreased. In vitro, DFZ reduced cell viability and increased RA, RE, and ROL levels in GC-2 cells. Transcriptome analysis revealed a significant enrichment of numerous terms associated with the RA pathway and apoptosis. The qPCR experiment verified the transcriptome results. In conclusion, our results indicate that DFZ exposure can disrupt RA signaling pathway homeostasis, and induce testicular injury in mice testes.

Exploring the role of Hmox1 in ferroptosis and immune infiltration during renal ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) is inevitable in kidney transplantations and, as a complex pathophysiological process, it can be greatly impacted by ferroptosis and immune inflammation. Our study aimed to identify the biomarkers of renal IRI (RIRI) and elucidate their relationship with immune infiltration. In this study, the GSE148420 database was used as a training set to analyze differential genes and overlap them with ferroptosis-related genes to identify hub genes using a protein-protein interaction (PPI) network, the least absolute shrinkage and selection operator (LASSO), and random forest algorithm (RFA). We verified the hub gene and ferroptosis-related phenotypes in a verification set and animal experiments involving unilateral IRI with contralateral nephrectomy in rats. Gene set enrichment analysis (GSEA) of single genes was conducted according to the hub gene to predict related endogenous RNAs (ceRNAs) and drugs to establish a network. Finally, we used the Cibersort to analyze immunological infiltration and conducted Spearman's correlation analysis. We identified 5456 differential genes and obtained 26 ferroptosis-related differentially expressed genes. Through PPI, LASSO, and RFA, Hmox1 was identified as the only hub gene and its expression levels were verified using verification sets. In animal experiments, Hmox1 was verified as a key biomarker. GSEA of single genes revealed the seven most related pathways, and the ceRNAs network included 138 mRNAs and miRNAs. We predicted 11 related drugs and their three-dimensional structural maps. Thus, Hmox1 was identified as a key biomarker and regulator of ferroptosis in RIRI and its regulation of ferroptosis was closely related to immune infiltration.

Research on Chengdu Ma Goat Recognition Based on Computer Vison.

The Chengdu ma goat is an excellent local breed in China. As one of the breeds listed in the National List of Livestock and Poultry Genetic Resources Protection, the protection of its germplasm resources is particularly important. However, the existing breeding and protection methods for them are relatively simple, due to the weak technical force and lack of intelligent means to assist. Most livestock farmers still conduct small-scale breeding in primitive ways, which is not conducive to the breeding and protection of Chengdu ma goats. In this paper, an automatic individual recognition method for Chengdu ma goats is proposed, which saves labor costs and does not depend on large-scale mechanized facilities. The main contributions of our work are as follows: (1) a new Chengdu ma goat dataset is built, which forms the basis for object detection and classification tasks; (2) an improved detection algorithm for Chengdu ma goats based on TPH-YOLOv5 is proposed, which is able to accurately localize goats in high-density scenes with severe scale variance of targets; (3) a classifier incorporating a self-supervised learning module is implemented to improve the classification performance without increasing the labeled data and inference computation overhead. Experiments show that our method is able to accurately recognize Chengdu ma goats in the actual indoor barn breeding environment, which lays the foundation for precision feeding based on sex and age.

An Integrated Goat Head Detection and Automatic Counting Method Based on Deep Learning.

Goat farming is one of the pillar industries for sustainable development of national economies in some countries and plays an active role in social and economic development. In order to realize the precision and intelligence of goat breeding, this paper describes an integrated goat detection and counting method based on deep learning. First, we constructed a new dataset of video images of goats for the object tracking task. Then, we took YOLOv5 as the baseline of the object detector and improved it using a series of advanced methods, including: using RandAugment to explore suitable data augmentation strategies in a real goat barn environment, using AF-FPN to improve the network's ability to represent multi-scale objects, and using the Dynamic Head framework to unify the attention mechanism with the detector's heads to improve its performance. The improved detector achieved 92.19% mAP, a significant improvement compared to the 84.26% mAP of the original YOLOv5. In addition, we also input the information obtained by the detector into DeepSORT for goat tracking and counting. The average overlap rate of our proposed method is 89.69%, which is significantly higher than the 82.78% of the original combination of YOLOv5 and DeepSORT. In order to avoid double counting as much as possible, goats were counted using the single-line counting based on the results of goat head tracking, which can support practical applications.

Maternal phthalate exposure during pregnancy and male reproductive disorders: a systematic review and metaanalysis.

BACKGROUND: Phthalates are ubiquitous in the environment and they can penetrate the human body via multiple routes. However, the impact of phthalates on human male reproductive disorders remains unclear. METHODS: A critical review of published studies was conducted to clarify the association of phthalates and male reproductive disorders and to highlight future research needs. PubMed, Cochrane Library, and Web of Science Database were systematically searched for relevant articles written in English, independent of region and time period. If more than one paper overlapped in study design or participants included, the most recent manuscript was included in our review. Due to limited homogeneous statistical data, observed trends were summarized to draw approximate conclusions. RESULTS: Nineteen manuscripts were included in our final analysis. Exposure to di-(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), diethyl phthalate (DEP), and/or benzyl butyl phthalate (BBP) is associated with a shorter anogenital distance (AGD). Meanwhile, exposure to DEHP and/or di-isodecyl phthalate (DIDP) is associated with higher risks for cryptorchidism and hypospadias. CONCLUSIONS: Generic exposure to phthalates has an adverse effect on human reproductive development, especially exposure to DEHP, DBP, DEP, BBP, and DIDP. A critical time for exposure sensitivity is during early pregnancy. Due to the lack of significant statistical power in this study, the conclusions drawn should be cautiously interpreted and they remain to be validated. Thus, additional well-designed studies, as well as propaganda and education regarding phthalate exposure and safer substitutes for these compounds, are greatly needed.

Clinical and Microbial Etiology Characteristics in Pediatric Urinary Tract Infection.

Background: Urinary tract infection (UTI) is a common occurrence in children. UTI and urological malformations are intimately linked. However, whether urinary tract malformations affect the clinical features of pediatric UTI remains unclear. The purpose of this study was to characterize the clinical features and microbial etiology of UTI in children. Methods: We retrospectively reviewed the records of 741 patients with UTI treated at the Chongqing Medical University Affiliated Children's Hospital between 2015 and 2020. Patients with and without urological malformations were compared using propensity score matching (PSM). Results: Escherichia coli was the most common causative microorganism of UTI, accounting for 40.5% of infections. One hundred twenty-two patients (16.5%) had urological malformations. PSM identified 122 matched pairs of patients with or without urological malformations. The proportion of patients with UTI caused by atypical microorganisms was significantly higher in patients with urological malformations (P = 0.048). Children with urological malformations showed longer duration of intravenous antibiotic treatment (P = 0.010), higher cost of treatment (P < 0.001), and higher prevalence of recurrence (23.8 vs. 10.7%, P < 0.001), compared with the normal group. Conclusion: Children with urological malformations are more likely to develop UTI with atypical microorganisms. Appropriate imaging examination and urine culture are strongly recommended for the diagnosis and management of pediatric UTI.

Comparison of Single-Incision Scrotal Orchiopexy and Traditional Two-Incision Inguinal Orchiopexy for Primary Palpable Undescended Testis in Children: A Systematic Review and Meta-Analysis.

Purpose: To compare the safety, efficacy, and cosmetic results of single-incision scrotal orchiopexy (SISO) and traditional two-incision inguinal orchiopexy (TTIO) for primary palpable undescended testes (PUDTs) in children. Materials and Methods: A systematic literature search of all relevant studies published on PubMed, Embase, Medline, Cochrane Library, Web of Science database, and Wanfang data until July 2021 was conducted. The operative time, hospitalization duration, conversion rate, wound infection or dehiscence, scrotal hematoma or swelling, testicular atrophy, reascent, hernia or hydrocele, analgesics needs, and cosmetic results were compared between SISO and TTIO using the Mantel-Haenszel or inverse-variance method. Results: A total of 17 studies involving 2,627 children (1,362 SISOs and 1,265 TTIOs) were included in the final analysis. The conversion rate of SISO was 3.6%. The SISO approach had a statistically significant shorter operative time than the TTIO approach for PUDT (weighted mean difference-11.96, 95% confidence interval -14.33 to -9.59, I2 = 79%, P < 0.00001) and a shorter hospital stay (weighted mean difference-1.05, 95% confidence interval -2.07 to -0.03, P = 0.04). SISO needed fewer analgesics and had better cosmetic results than TTIO. SISO had a similar total, short-term, or long-term complication rate with TTIO. Conclusion: Compared with TTIO, SISO has the advantages of shorter operative time, shorter hospitalization duration, less postoperative pain, and better cosmetic appealing results. SISO is a safe, effective, promising, and potential minimal invasive surgical approach for PUDT. SISO is an alternative to TTIO in selected cryptorchid patients, especially for lower positioned ones. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021268562.