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.

In recent years, with the in-depth study of PD-1/PD-L1 related pathways, great progress has been made in cancer immunotherapy. However, the immunotherapy regimen for mccRCC is still controversial in clinical practice. A 50-year-old man with mccRCC complicated with renal venous tumor thrombus from 2019 to present, including surgical treatment, targeted therapy and the combined treatment regimen of "Tislelizumab combined with Sunitinib". Although he experienced a roller coaster of adverse reactions during treatment, the patient's prognosis was good. Tislelizumab combined with Sunitinib is safe and effective in the Treatment of mccRCC.

The testis is vulnerable to ionizing radiation, sexual dysfunction and male infertility are common problems after local radiation or whole-body exposure. Currently, there are no approved drugs for the prevention or treatment of radiation testicular injury. Sulforaphane (SFN) is an indirect antioxidant that induces phase II detoxification enzymes and antioxidant genes. Herein, we investigated the radiation protective effect of SFN on testicular injury in mice and its potential mechanism. Mice were randomly divided into blank control group (Ctrl), radiation + no pretreatment group (IR), and radiation + SFN groups (IRS). In the radiation + SFN groups, starting from 72 h before radiation, SFN solution was intraperitoneally injected once a day until they were sacrificed. Mice in the blank control group and the radiation + no pretreatment group were simultaneously injected intraperitoneally with an equal volume of the solvent used to dissolve SFN (PBS with a final concentration of 0.1%DMSO) until they were sacrificed. They were subjected to 6Mev-ray radiation to the lower abdominal testis area (total dose 2Gy). Twenty-four hours after radiation, six mice in each group were randomly sacrificed. Seventy-two hours after radiation, the remaining mice were sacrificed. The results showed that the harmful effects of ionizing radiation on testes were manifested as damage to histoarchitecture, increased oxidative stress, and apoptosis, and thus impaired male fertility. SFN injections can reverse these symptoms. The results showed that SFN can improve the damage of mouse testis caused by irradiation. Furthermore, SFN prevents spermatogenesis dysfunction caused by ionizing radiation by activating Nrf2 and its downstream antioxidant gene.

Fbxo2 is part of the SKP1-Cullin-F-box (SCF) E3 ubiquitin ligase complex. While increasing evidence indicates that Fbxo2 influences tumorigenesis and progression in various human malignancies, its biological importance and molecular mechanisms in renal cell carcinoma (RCC) are poorly understood. Bioinformatic analysis of publicly available datasets was utilized to determine the association between Fbxo2 expression and survival in RCC patients. CCK8, colony-formation, and EdU assays were carried out to measure cell proliferation after Fbxo2 modulation in RCC cells. Coimmunoprecipitation, mass spectrometry, Western blotting, and ubiquitin assays were performed to explore the molecular mechanism of Fbxo2-involved tumorigenesis in RCC. Fbxo2 suppresses RCC cell growth. Moreover, higher Fbxo2 expression was positively associated with improved overall survival in RCC patients. In RCC, Fbxo2 inhibition increased cell motility and proliferation and inhibited cell apoptosis. WEE1 was identified as a novel substrate of Fbxo2 in RCC. Fbxo2 binds to the kinase domain of WEE1 through its FBA domain. Consistently, in xenograft mouse models, Fbxo2 knockdown increased tumor growth, whereas WEE1 depletion partially abolishes the tumorigenic effects caused by Fbxo2 silencing in vivo. Our research revealed that Fbxo2 impedes the progression of RCC by interacting with WEE1, promoting its ubiquitination and degradation. Therefore, targeting the Fbxo2/WEE1 axis may represent a promising therapeutic strategy for treating RCC.

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.