Ionizing radiation poses a significant risk to male fertility by inducing testicular damage, yet effective protective strategies remain limited. The tripeptide Met-Ser-Arg (MSA) has demonstrated potential in alleviating radiation-induced oxidative stress and lipid metabolic disorders, prompting investigation into its protective effects on the male reproductive system. Male BALB/c mice were exposed to X-ray irradiation (0.5 Gy/day for 5 days) to establish a testicular injury model, followed by MSA treatment. Testicular structure and function were evaluated through histology, electron microscopy, computer-assisted sperm analysis, and quantitative PCR. MSA significantly alleviated radiation-induced testicular damage, restoring the structural integrity and function of spermatogenesis tubules while increasing both the height of the spermatogenic epithelium and germ cell number. Sperm quality and motility were markedly improved, and the expression of several sperm cell molecular markers was favorably adjusted. Mechanistic investigations revealed that MSA regulated lipid metabolism by upregulating fatty acid β-oxidation enzymes, including acyl-CoA synthetase long-chain family member 3 (ACSL3)and carnitine palmitoyl transferase 1A (CPT1A), while downregulating the lipid synthase diacylglycerol O-acyltransferase 2 (DGAT2), thereby reducing lipid droplet accumulation. MSA also attenuated radiation-induced reactive oxygen species and malondialdehyde levels, enhanced antioxidant capacity through upregulation of nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase 1 (HO-1), and preserved mitochondrial structure and function via upregulation of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1A). Furthermore, MSA reduced apoptosis by lowering the levels of Cleaved-caspase 3 and γH2AX. Collectively, these findings demonstrate that MSA ameliorates radiation-induced testicular injury and improves sperm quality through coordinated regulation of lipid metabolism, antioxidant pathway activation, mitochondrial protection, and apoptosis inhibition, providing a theoretical basis for its potential clinical application in the context of radiotherapy.

Metabolically unhealthy obesity (MUO) poses significant health risks, including increased susceptibility to type 2 diabetes and cardiovascular diseases. Hesperetin is a key bioactive compound found in citrus fruits. Previous studies have shown that hesperetin can correct metabolic abnormalities and mitigate the progression of various metabolic disorders, but the underlying mechanisms remain unclear. Here, we explored the impact of hesperetin on MUO using ob/ob mice and investigated its potential pharmacological mechanisms. The present data indicated that administration of hesperetin for 12 weeks led to notable improvements in metabolic parameters, including reduced fasting blood glucose, fasting insulin levels, and the HOMA-IR index in ob/ob mice. Glucose and insulin tolerance tests demonstrated that hesperetin effectively enhanced insulin sensitivity, with high-dose effects comparable to metformin. Hesperetin treatment decreased inguinal white adipose tissue (iWAT) weight and improved insulin signaling by increasing AKT phosphorylation. Additionally, it reduced the expression of pro-inflammatory cytokines (Il-6 and Il-1β), chemokine Ccl2 and its receptor Ccr2, and macrophage activation markers Nos2 and Ptgs2 within iWAT of ob/ob mice, likely by inhibiting NF-κB activation and macrophage-mediated inflammation. In vitro studies further confirmed hesperetin's anti-inflammatory effects in LPS-stimulated macrophages, where it suppressed cytokine production and NF-κB signaling. Hesperetin also impaired CCL2-induced macrophage chemotaxis, reducing migration velocity and distance. Mechanistically, hesperetin directly interacts with and inhibits IKKβ kinase activity by binding to key residues (LEU21, VAL465, CYS99, and GLU97) and stabilizing the complex, as demonstrated by molecular docking and molecular dynamics simulations. These findings underscore hesperetin's therapeutic potential in mitigating metabolically unhealthy obesity, obesity-induced insulin resistance, and inflammation through direct modulation of the IKKβ and NF-κB pathways.

OBJECTIVE:This study was designed to explore the toxic effects of Transferrin a(tfa)-mediated uranium exposure on the hematopoietic system. METHODS:Zebrafish embryos were subjected to uranium nitrate solutions at concentrations of 50, 100, 250, and 500 μg/L for a defined period, followed by sample collection. The impact of uranium on hematopoietic system development in zebrafish was evaluated through hemoglobin staining, qRT-PCR, and in situ hybridization. RNA-Seq was utilized to detect differentially expressed genes (DEGs) in embryos exposed to 100 μg/L uranium, with subsequent bioinformatics analysis to confirm these DEGs. Furthermore, blood samples from patients with hematological disorders and impaired hematopoietic function were collected, and RNA-Seq was applied to identify DEGs. RESULTS:Uranium exposure in zebrafish embryos led to reduced hemoglobin expression, with key transcription factors for primitive and definitive hematopoiesis being significantly downregulated at 100 μg/L uranium exposure. Overexpression of tfa resulted in a marked increase in hemoglobin content and upregulation of GATA1, a key factor in primitive hematopoiesis. Patients with hematopoietic dysfunction exhibited abnormalities in the tfa signaling pathway. CONCLUSION:tfa plays a role in mediating the inhibitory effects of uranium on hematopoietic function.

As immune cells, neutrophils serve as the first line of defense against infections; however, the mechanism by which neutrophils regulate lipid metabolism is unknown. The neutrophil depletion group was treated with 100 μg InVivoMAb anti-mouse Ly6G 6 times, whereas the control group mice were intraperitoneally injected with the same quantity of InVivoMAb rat IgG2a. Body fat content, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) in the jejunum and ileum, as well as 9 long-chain fatty acids (LCFAs) in the intestinal contents were significantly decreased. Furthermore, genes involved in the absorption of lipids in each segment of the intestine also showed decreased expression. Neutrophil-depletion and control models were administered 25 μCi of 3H-cholesterol by gavage. The distribution of 3H cholesterol in the intestinal segment, heart, liver, serum, and feces was not altered by anti-Ly6G antibodies. Metagenomics was applied to investigate uncultured microorganisms in the intestinal contents to identify bacteria containing lipid metabolism genes. At the species level, 12 bacteria were involved in unsaturated LCFA synthesis, among which 2 increased and 10 decreased. The overall relative abundance of these bacteria decreased from 3.102% to 0.734%. Many genes involved in lipid metabolism were also reduced as a result, such as fatty acid synthase and peroxisome proliferator-activated receptor γ. In conclusion, neutrophil depletion does not affect intestinal lipid absorption in the diet but leads to a decrease in the overall relative abundance of gut bacteria involved in unsaturated LCFA synthesis. Consequently, intestinal lipid synthesis and absorption are reduced.

OBJECTIVE:To investigate the impact of ionizing radiation (IR) on the structure and function of the testis and provide some strategies for the prevention and treatment of IR-induced damage (IRD). METHODS:Using radiation dose simulation, semen analysis, hormone testing, electron microscopy and single-cell transcriptome sequencing, we assessed and analyzed a case of IRD. We established a mouse model of IRD to validate the results of single-cell sequencing, and investigated the specific biological mechanisms of IRD and potential strategies for its intervention. RESULTS:IR at 1－2 Gy significantly reduced sperm concentration and motility, which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low. It also caused imbalanced levels of various steroid hormones, decreased testosterone and dehydroepiandrosterone sulfate, increased progesterone, prolactin, luteinizing hormone, and follicle-stimulating hormone. Electron microscopy revealed damages to the testis structure, including loss of germ cells, atrophy of the seminiferous tubules, nuclear membrane depression of the spermatocytes, mitochondrial atrophy and deformation, and reduction of mitochondrial cristae. Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD. Administration of L-carnitine to the mouse model improved lipid metabolism disorders and partially alleviated IRD to the germ cells. CONCLUSION:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages. Improving lipid metabolism can alleviate IRD to germ cells.

BACKGROUND:Testicular macrophages (TM) have long been recognized for their role in immune response within the testicular environment. However, their involvement in steroid hormone synthesis, particularly testosterone, has not been fully elucidated. This study aims to explore the capability of TM to synthesize and secrete testosterone de novo and to investigate the regulatory mechanisms involved. RESULTS:Transcriptomic analysis revealed significant expression of Cyp11a1, Cyp17a1, Hsd3b1, and Hsd17b3 in TM, which are key enzymes in the testosterone synthesis pathway. qPCR analysis and immunofluorescence validation confirmed the autonomous capability of TM to synthesize testosterone. Ablation of TM in mice resulted in decreased physiological testosterone levels, underscoring the significance of TM in maintaining testicular testosterone levels. Additionally, the study also demonstrated that Cebpb regulates the expression of these crucial genes, thereby modulating testosterone synthesis. CONCLUSIONS:This research establishes that TM possess the autonomous capacity to synthesize and secrete testosterone, contributing significantly to testicular testosterone levels. The transcription factor Cebpb plays a crucial role in this process by regulating the expression of key genes involved in testosterone synthesis.

BACKGROUND:We aim to investigate the potential causal link between blood pressure (BP) levels and cerebral artery dissection (CAD) risk by employing a 2-sample Mendelian randomization (TSMR) framework. METHODS:Utilizing large-scale genome-wide association studies-retrieved data, we employed various Mendelian randomization (MR) techniques, including inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode, to ascertain BP's causal impact on CAD. The MR-Egger intercept was calculated to assess pleiotropy presence, determining heterogeneity by Cochran's Q statistic. RESULTS:The findings highlighted a significant association between elevated systolic BP (SBP; IVW: OR = 3.09, 95% CI: 1.11-8.61, P = 0.031) and increased diastolic BP (DBP; IVW: OR = 2.17, 95% CI: 1.14-6.21, P = 0.023) with CAD risk. Sensitivity analyses reinforced the robustness and reliability of these results. CONCLUSIONS:The results from this TSMR study suggest a causal link between high SBP and DBP and the increased likelihood of CAD, which provides genetic evidence for a reduced risk of CAD under BP control.

Radionuclide-contaminated wounds face clinical dilemmas such as repeated erosion and ulceration and are difficult to heal. In this work, we aimed to develop a biodegradable hydrogel with a beneficial effect on radionuclide-contaminated wounds and initially investigated the mechanism of action of the hydrogel. The hydrogel was produced through the ring-opening polymerization of polycaprolactone (PCL) triggered by polyethylene glycol (PEG), and its physicochemical properties were characterized by gel permeation chromatography, nuclear magnetic resonance, rheological properties testing, and other techniques. The low critical solution temperatures were 30 degrees C and 46 degrees C, which are suitable for the human body to realize the degradable properties of the hydrogel. A radionuclide-contaminated wound model was established, which proved that the biodegradable hydrogel had good healing properties and did not form secondary lesions. The effect was better than clinically used EGF or VB12. Pathological results showed that mature granulation tissue formed on the 7th day after the injury, and by the 10th day after the injury, the scab had completely fallen off, the epithelial coverage had reached over 70% and the wound was essentially completely healed. Additionally, the hydrogel affects immune metabolism, regulates immune cell function, promotes the formation of new blood vessels and granular tissue, and effectively accelerates the healing process of radionuclide-contaminated wounds. We developed a biodegradable hydrogel that benefits radionuclide-contaminated wounds, modulates immune cell function, and promotes vascularization and granulation.

After decades of research, the biological effects of tritium have been basically clear. Compared with many studies on tritium biology and RBE value, the research on the toxicity mechanism is relatively lacking. Previous research on the mechanism of tritiated water toxicity focused on oxidative stress, cell apoptosis, and DNA damage, but the specific molecular mechanism is lacking. With the development of molecular biology technology, it has become possible to elucidate the molecular mechanism of internal tritium radiation damage at multiple levels. In this paper, we reviewed our studies over the past ten years to clarify the mechanism of tritium toxicity from different aspects such as miRNA, DNA methylation, and gene expression changes. Some key target molecules were found and tried to be used to evaluate the tritium toxicity.

Abstract Background: The intestine is sensitive to radiation. After irradiation, the DNA of intestinal cells breaks and leaks, resulting in collagen deposition. Macrophages in the intestine perform cleaning and repair functions. However, the specific mechanism between cleaning and repairhas not yet been clarified. Methods and Results: Here, we found that after macrophages engulf DNA, the signal is transmitted to the CCAAT/enhancer binding protein beta (CEBPB) nuclear transcription factor through DEAD-box helicase 5 (DDX5) found by a coimmunoprecipitation assay. Next, a chromatinimmunoprecipitation assay showed that CEBPB bound to the promoter of the bone morphogenetic protein (BMP) inhibitory molecule Gremlin2 (GREM2) to increase GREM2 mRNA. Simultaneously, macrophages swallow collagen, and collagen inhibits HSP90AB1 (heat shock protein 90 kDa alphaB1) and CEBPB. Next, CEBPB suppresses the transforming growth factor (TGF) β inhibitory molecules latent transforming growth factor beta binding protein 1 (LTBP1) and decorin (DCN), leading to increased expression of LTBP1 and DCN in irradiated macrophages. In the presence of estrogen and prolactin, the expression of GREM2, LTBP1, and DCN in irradiated macrophages significantly increased. GREM2 dose-dependently promoted crypt proliferation. Therefore, after depleting macrophages, the intestinal damage of female mice was significantly more severe than that of male mice after irradiation. Conclusions: The data here showed that irradiated intestinal macrophages engulfed DNA and secreted GREM2 (positively regulated by CEBPB), while phagocytic collagen stimulated macrophages to secrete LTBP1 and DCN (negatively regulated by CEBPB). Estrogen will greatly amplify this mixed phenotype to promote intestinalrepair post ionizing radiation. These results suggest that there should be differences in the dosage of radiation therapy between male and female cancer patients.

This study aimed to develop an exosome-coated polydatin (PD) nanoparticles (exo-PD) for improving the water solubility and bioavailability of polydatin and explore its salutary effects on intestinal radiation injury. Exosomes (exo) were extracted from the medium of human amniotic fluid stem cells (hAFSc). Mice were divided into control group, irradiation (IR) group, irradiation+PD (IR+PD) group, irradiation+exo (IR+exo) group and irradiation+exo-PD (IR+exo-PD) group. The results of characterization of protein markers, particle size, morphology and cellular uptake ability confirmed that exosomes were effectively isolated using ultracentrifugation. Compared with the IR group, exo-PD improved cell viability, prolonged survival of mice, improved leukocyte count and reduced diarrhea rate. Histological results showed that the exo-PD group had significant improvements in small intestinal villus length and crypt number and less crypt cell damage. exo-PD could reduce IL-1α and IL-6 levels, reduced γ-H2AX expression, increased mitochondrial membrane potential, enhanced oxidative phosphorylation, and delayed cellular senescence. exo-PD could alleviate intestinal injury by improving mitochondrial function through PI3K-AKT pathway. The exo-PD was able to reduce radiation damage to intestinal cells and could be a potential candidate for salvage of intestinal radiation damage.

The effect of autophagy on the radiation-induced bystander effect (RIBE) in vivo is unclear. Here, the whole brains of microtubule-associated protein 1A/1B-light chain 3 (LC3) and C57BL/6 (B6) mice were irradiated once (10 Gy)(IR1), given 3 fractions in three weeks (IR3), or 6 fractions in six weeks (IR6). The median survival of LC3 mice was 56.5 days, and that of B6 mice was 65 days after IR6. LC3 mice showed more congestion and fibrosis in the lung after the IR3 and IR6 irradiation protocols than B6 mice. Quantitative proteomics of serum samples and lung RNA sequencing of the LC3 group showed that the common most clustered pathway of the IR3 group was the elastic fiber formation pathway, which contained Periostin (POSTN). POSTN in the motoneurons increased with increasing number of radiation fractions in LC3 mice. A 1 lg/g POSTN neutralizing antibody reduced the lung fibrosis of LC3 mice exposed to IR3 by one-third, and significantly prolonged the survival time of LC3 mice exposed to IR6. LDN-214117 and LRRK2-in-1 were the best two of sixteen transforming growth factor-beta1 (TGF-beta) receptor and autophagy mediators to decrease Postn mRNA. These data led us to conclude that LC3 accelerated motoneuron secretion of POSTN and aggravated the RIBE in the lung after brain irradiation. (c) 2023 by Radiation Research Society

Male infertility is a hot problem worldwide, but there are few treatments, especially male infertility caused by irradiation is difficult to treat. The aim of this study was to investigate and evaluate novel drugs for the treatment of male infertility caused by irradiation. we randomly divided 18 male BALB/c mice into 3 groups: control, irradiated, and telmisartan. Both irradiated and telmisartan group completed whole-body 0.5 Gy five times irradiation, and the telmisartan group received intraperitoneal injection of telmisartan (1.2 mg/kg) daily on the next day after irradiation, and all groups were sampled on day 25 after irradiation. Sperm motility results show that total sperm motility of irradiated group was significantly lower compared with control group, and testicular HE results showed that testis in irradiated group were severely damaged. Compared with irradiated group, the total sperm motility, sperm concentration, testicular index, Johnsen score, and the seminiferous tubule layer numbers were higher in telmisartan group (P < 0.05). The immunohistochemical staining showed γ-H2AX expression is higher in telmisartan group compared with irradiated group. And the relative mRNA expression of PLZF, GFRA1, STRA8, DMRT1, SPO11, SYCP2, OVOL2, CCNA1, TJP3, RUNX2, TXNDC2 TNP1, and PRM3 in telmisartan group was all significantly higher than irradiated group (P < 0.05). In conclusion, in vivo experiments confirmed that telmisartan ameliorated the spermatogenic disorder in mice caused by fractionated low-dose irradiation via promoting spermatogenesis.

Objective:To study the differential expressions of piRNAs in the seminal plasma of men and the role of piRNAs in spermatogenesis.Methods:We sequenced the seminal plasma samples collected from 187 male infertility patients and 58 normal healthy men,obtained differentially expressed piRNAs,and detected the relative expressions of piRNAs in different types of sperm by RT-qPCR to explore their significance in the diagnosis of male infertility.Using histopathology,RNA-protein pull-down and Western blot,we investigated the action mechanism of piRNAs in spermatogenesis in the mouse model.Results:RT-qPCR of the seminal plasma samples revealed a high expression of hsa_piR_000478 in teratozoospermia and ROC curve analysis showed an auxiliary signifi-cance of hsa_piR_000478 in the diagnosis of the disease(AUC=0.7549).Transfection of hsa_piR_000478 and its homologous se-quence piR_mmu_54800729 into the seminiferous tubules of the mouse model significantly decreased sperm motility,increased the per-centage of morphologically abnormal sperm and destroyed the testicular structure.Molecular biological experiments exhibited a close correlation between piRNAs and the energy metabolism-related pathway,which elevated the level of cell glycolysis and interfered with normal spermatogenesis.Conclusion:hsa_piR_000478 has an auxiliary significance in the diagnosis of male infertility,and piRNAs may interfere with spermatogenesis by affecting the glycolysis-related pathway in the spermatogenic microenvironment of the testis.

Objective:To investigate the differences in small intestinal toxicity and taxonomic composition,diversity,and functional pathways of gut microbiome and metabolome after different radiotherapies in mouse colorectal cancer(CRC)model.Methods:Azoxymethane/dextran sodium sulfate(AOM/DSS)-induced mouse CRC model was treated with single pulse FLASH-RT(dose rate 100 Gy/s)or CONV-RT(dose rate 2 Gy/min)at whole abdomen.At 12 d after radiotherapy,sections of small intestinal tract tissue were dissected for hematoxylin and eosin(HE)staining and the fresh feces were collected for 16S ribosomal RNA(rRNA)microbiome sequencing and liquid chromatography and mass spectrometry(LC-MS)metabolomics sequencing to assess changes in the gut microbiota and metabo-lites.Microbial high-throughput 16S rRNA data was analyzed with QIIME2 and LEfSe softwares.ProteoWizard,XCMS and Ropls softwares were used for LC-MS analysis.Results:HE staining showed that FLASH-RT maintained small intestinal integrity and reduced the radiotherapy-induced injury.Sequencing analysis of gut fecal microbiome showed that phylum Bacteroidetes and genera Prevotella and Lactobacillus of microbial community were increased after FLASH-RT.Metabolomics sequencing analysis revealed that the metabolites after FLASH-RT were enriched in amino acid metabolism,while cholesterol metabolism was top enriched after CONV-RT.Conclusions:FLASH-RT significantly mitigates the small intestine tissue damage compared with CONV-RT.FLASH-RT and CONV-RT have different impact on gut microbiota and its metabolites.Our results provide a theoretical basis for the early evaluation,prediction and individualized treatment of the irradiation effect after novel FLASH-RT on tumors through the evaluation of intestinal microbiota and metabolites.

Non-obstructive azoospermia (NOA) is a common cause of male infertility, and no specific diagnostic indicators exist. In this study, we used human testis datasets GSE45885, GSE45887, and GSE108886 from GEO database as training datasets, and screened 6 signature genes (all lowly expressed in the NOA group) using Boruta algorithm and Lasso regression: C12orf54, TSSK6, OR2H1, FER1L5, C9orf153, XKR3. The diagnostic efficacy of the above genes was examined by constructing models with LightGBM algorithm: the AUC (Area Under Curve) of both ROC and Precision-Recall curves for internal validation was 1.0 (p < 0.05). For the external validation dataset GSE145467 (human testis), the AUC of its ROC curve was 0.9 and that of its Precision-Recall curve was 0.833 (p < 0.05). Next, we confirmed the cellular localization of the above genes using human testis single-cell RNA sequencing dataset GSE149512, which were all located in spermatid. Besides, the downstream regulatory mechanisms of the above genes in spermatid were inferred by GSEA algorithm: C12orf54 may be involved in the repression of E2F-related and MYC-related pathways, TSSK6 and C9orf153 may be involved in the repression of MYC-related pathways, while FER1L5 may be involved in the repression of spermatogenesis pathway. Finally, we constructed a NOA model in mice using X-ray irradiation, and quantitative Real-time PCR results showed that C12orf54, TSSK6, OR2H1, FER1L5, and C9orf153 were all lowly expressed in NOA group. In summary, we have identified novel signature genes of NOA using machine learning methods and complete experimental validation, which will be helpful for its early diagnosis.

Background: Male infertility is a worldwide problem but few treatments, especially irradiation-induced testicular injury. The aim of this research was to investigate novel drugs for the treatment of irradiation-induced testicular injury. Methods: We administered dibucaine (0.8 mg/kg) intraperitoneally to male mice (6 mice per group) after five consecutive daily 0.5 Gy whole-body irradiation, and evaluated its ameliorating efficacy by testicular HE staining and morphological measurements. Drug affinity responsive target stability assay (Darts) were used to find target protein and pathway; mouse primary Leydig cells were isolated and to explore the mechanism (Flow cytometry, Western blot, and Seahorse palmitate oxidative stress assays); finally rescue experiments were completed by combining dibucaine with fatty acid oxidative pathway inhibitors and activators. Results: The testicular HE staining and morphological measurements in dibucaine treatment group was significantly better than that in irradiation group (P < 0.05); sperm motility and mRNA levels of spermatogenic cell markers were also higher than those in the latter (P < 0.05). Darts and Western blot results showed that dibucaine targets CPT1A and downregulate fatty acid oxidation. Flow cytometry, Western blot, and Palmitate oxidative stress assays of primary Leydig cells demonstrated that dibucaine inhibits fatty acid oxidation in Leydig cells. Dibucaine combined with etomoxir/baicalin confirmed that its inhibition of fatty acid oxidation was beneficial in ameliorating irradiation-induced testicular injury. Conclusions: In conclusion, our data suggest that dibucaine ameliorates irradiation-induced testicular injury in mice by inhibiting fatty acid oxidation in Leydig cells. This will provide novel ideas for the treatment of irradiation-induced testicular injury.

Objective This study aimed to investigate the expression levels of T cell immunoglobulin and mucin domain-3 (Tim-3) on CD4+ T cells in children diagnosed with infectious mononucleosis (IM), a condition caused by the Epstein Barr virus (EBV). Additionally, we examined which transcription factors could regulate the expression of interleukin 17 (IL-17). Methods We collected peripheral blood from two groups: 10 children with infectious mononucleosis (the IM group) and 5 healthy volunteers (the control group). Using magnetic beads, we sorted the CD4+T cells. The IL-17 levels were measured using an enzyme-linked immunosorbent assay (ELISA), while the proportion of Tim3+ T cells was determined through flow cytometry. We employed the Cleavage Under Targets and Tagmentation (CUT&Tag) method to digest near the IL-17 transcription start site. The resulting product was then extracted and amplified using Quantitative Real-time PCR (qPCR). Results The IL-17 expression in the IM group was significantly higher than in the control group (79.79±23.78ng/ml vs 45.46±17.53ng/ml). Similarly, the expression of Tim-3 on CD4+T cells was higher in the IM group compared to the control group (2.84±0.25 vs 0.06 ±0.04). The level of PU.1 transcription factor binding fragments in the IM group was higher than that in the control group (1.24±0.45 vs 0.07±0.19). Conclusion The EBV can trigger the expression of the Tim-3 molecule on CD4+ T cells. The high expression of Tim-3 can upregulate IL-17 transcription via the PU.1 transcription factor, which is associated with the body's antiviral response and inflammatory damage.

Water pollution and control are important issues of our lasting concern. Environmental media often contains a variety of compounds. Tritium is widely present in nature due to human activities. As an endocrine disruptor, genistein is widely found in water body. Will it cause damage when combined with tritiated water and genistein? In this study, Zebrafish embryos were randomly divided into 4 groups: blank control group (simple E3 medium), tritiated water exposure group (tritiated water with a final concentration of 3.7*102Bq/mL in the medium), and genistein exposure group (the final concentration of 1.4 mg/L genistein in the medium) and the combined exposure group of tritiated water and genistein (3.7*102 Bq/mL tritium water +1.4 mg/L genistein). The results show that tritiated water with 3.7*102 Bq/ml exposure alone did not affect the development of zebrafish embryos. However, the survival rate, hatching rate and heart rate of zebrafish larvae decreased combined exposure with genistein, and the abnormality rate and apoptotic cells in the embryos and the level of oxidative stress increased. The results of RNA sequencing showed that the combined exposure of tritiated water and genistein affected the gene expression of zebrafish embryos. Differential genes were mainly enriched in many pathways, such as p53 signaling pathway, steroid hormone biosynthesis, PPAR signaling pathway, metabolism of xenobiotics by cytochrome P450. The results of qRT-PCR and gene knockout experiment showed that cyp19a1b gene may plays an important role in the toxic effects of combined exposure.