Trps1 predicts poor prognosis in advanced high grade serous ovarian carcinoma.

TRPS1 is aberrantly expressed in a variety of tumors, including breast, prostate, and gastric cancers, and is strongly associated with tumorigenesis or prognosis. However, the role of TRPS1 in high grade serous ovarian carcinoma (HGSC) is unknown. We investigated the relationship between TRPS1 expression and clinicopathology in HGSC patients. The tumor-related regulatory mechanisms of TRPS1 was explored through in vivo and vitro experiments. The results showed that TRPS1 was highly expressed in HGSC compared to normal tissues. It was also linked to the cell proliferation index Ki67 and poor prognosis. In vivo experiments showed that knockdown of TRPS1 could inhibit tumor growth. In vitro experiments, knockdown of TRPS1 inhibited the proliferation of ovarian cancer cells. TRPS1 exerted its regulatory role as a transcription factor, binding to the PSAT1 promoter and promoting the expression of PSAT1 gene. Meanwhile, PSAT1 was positively correlated with CCND1 expression. These results suggest that TRPS1 affects HGSC proliferation and cell cycle by regulating PSAT1 and thus CCND1 expression.

Trps1 acts as a regulator of Sf-1 transcription and testosterone synthesis in mouse Leydig cells.

Infertility has attracted global concern, and disruption of testosterone is a common cause of male infertility. Exploring the critical factors in testosterone biosynthesis may provide new insights for disease research and clinical therapy. Research on trichorhinophalangeal syndrome-1 (Trps1) gene has recently been focus on cancers; it is yet unknown whether Trps1 produces a marked effect in the male reproductive system. In the current study, single-cell RNA sequencing analysis of trichorhinophalangeal syndrome-1 gene (Trps1) expression in mouse testes and cleavage under targets and tagmentation and RNA sequencing were utilized to investigate the functionality of Trps1 in mouse Leydig cells. Knockdown of Trps1 increased testosterone synthesis in vitro and vivo using adeno-associated viral delivery and conditional knockout models. The results showed that Trps1 was abundantly expressed in Leydig cells. The expression levels of both steroidogenic factor-1 (Sf-1) and steroidogenic enzymes (Cyp11a1, Hsd3b, Cyp17a1, and Hsd17b3) as well as testosterone secretion were increased after Trps1 deficiency in vivo and vitro. Furthermore, disruption of Trps1 reduced histone deacetylase 1/2 activity and increased histone H3 acetylation in the Sf-1 promoter, thereby promoting testosterone secretion. Interestingly, Sf-1 also regulated the transcription of Trps1 through activating transcription factor 2. These results indicate that Trps1 targets Sf-1 to affect steroidogenesis through histone acetylation and shed light on the critical role of Trps1 functioning in the mouse Leydig cells.

Sub-terahertz scanning near-field optical microscope using a quartz tuning fork based probe.

We report a sub-terahertz scattering-type scanning near-field microscope (sub-THz s-SNOM) which uses a 6 mm long metallic tip driven by a quartz tuning fork as the near-field probe. Under continuous-wave illumination by a 94 GHz Gunn diode oscillator, terahertz near-field images are obtained by demodulating the scattered wave at both the fundamental and the second harmonic of the tuning fork oscillation frequency together with the atomic-force-microscope (AFM) image. The terahertz near-field image of a gold grating with a period of 2.3 µm obtained at the fundamental modulation frequency agrees well with the AFM image. The experimental relationship between the signal demodulated at the fundamental frequency and the tip-sample distance is well fitted with the coupled dipole model indicating that the scattered signal from the long probe is mainly contributed by the near-field interaction between the tip and the sample. This near-filed probe scheme using quartz tuning fork can adjust the tip length flexibly to match the wavelength over the entire terahertz frequency range and allows for operation in cryogenic environment.

0.2-4.0 THz broadband terahertz detector based on antenna-coupled AlGaN/GaN HEMTs arrayed in a bow-tie pattern.

To satisfy the demand for broadband and high-sensitivity terahertz detectors, we designed and verified a broadband terahertz detector built with antenna-coupled AlGaN/GaN high-electron-mobility transistors (HEMTs). Eighteen pairs of dipole antennas with different center frequency from 0.24 to 7.4 THz are arrayed into a bow-tie pattern. The corresponding eighteen transistors have common a source and a drain but different gated channels coupled by the corresponding antennas. The photocurrents generated by each gated channel are combined in the drain as the output port. With incoherent terahertz radiation from a hot blackbody in a Fourier-transform spectrometer (FTS), the detector exhibits a continuous response spectrum from 0.2 to 2.0 THz at 298 K and from 0.2 to 4.0 THz at 77 K, respectively. The results agree well with simulations taking into account the silicon lens, antenna and blackbody radiation law. The sensitivity is characterized under coherent terahertz irradiation, the average noise-equivalent power (NEP) is about 188 p W/H z at 298 K and 19 p W/H z at 77 K from 0.2 to 1.1 THz, respectively. A maximum optical responsivity of 0.56 A/W and a minimum NEP of 7.0 p W/H z at 0.74 THz are achieved at 77 K. The blackbody response spectrum is divided by the blackbody radiation intensity to obtain a performance spectrum, which is calibrated by measuring coherence performance from 0.2 to 1.1 THz to evaluate detector performance at frequencies above 1.1 THz. At 298 K, the NEP is about 1.7 n W/H z at 2.0 THz. At 77 K, the NEP is about 3 n W/H z at 4.0 THz. For further improvements in sensitivity and bandwidth, high-bandwidth coupling components, smaller series resistance, smaller gate lengths and high-mobility materials need to be considered.

UBE3A deficiency-induced autophagy is associated with activation of AMPK-ULK1 and p53 pathways.

Angelman Syndrome (AS) is a neurodevelopmental disorder caused by deficiency of the maternally expressed UBE3A gene. The UBE3A proteins functions both as an E3 ligase in the ubiquitin-proteasome system (UPS), and as a transcriptional co-activator for steroid hormone receptors. Here we investigated the effects of UBE3A deficiency on autophagy in the cerebellum of AS mice and in COS1 cells. Numbers and size of LC3- and LAMP2-immunopositive puncta were increased in cerebellar Purkinje cells of AS mice, as compared to wildtype mice. Western blot analysis showed an increase in the conversion of LC3I to LC3II in AS mice, as expected from increased autophagy. Levels of active AMPK and of one of its substrates, ULK1, a factor involved in autophagy initiation, were also increased. Colocalization of LC3 with LAMP2 was increased and p62 levels were decreased, indicating an increase in autophagy flux. UBE3A deficiency was also associated with reduced levels of phosphorylated p53 in the cytosol and increased levels in nuclei, which favors autophagy induction. UBE3A siRNA knockdown in COS-1 cells resulted in increased size and intensity of LC3-immunopositive puncta and increased the LC3 II/I ratio, as compared to control siRNA-treated cells, confirming the results found in the cerebellum of AS mice. These results indicate that UBE3A deficiency enhances autophagic activity through activation of the AMPK-ULK1 pathway and alterations in p53.

Analysis of the Dust-Concentration Distribution Law in an Open-Pit Mine and Its Influencing Factors.

In this study, a solar-powered multipoint network monitoring method was used to record dust-particle concentrations and meteorological indicators in the Anjialing open-pit coal mine in the Pingshuo mining area. The factors influencing the concentrations of particulate matter of different maximum diameters (PM2.5, PM10, and total suspended particulates; TSPs) and the regularity of the spatial distribution were examined. The results show that the highest dust concentration and thus the most serious dust pollution occur in winter, and the lowest dust concentration is found in summer. There are peaks in dust concentration in December and January to February, and the pollution is more serious at these times. On a given day, the pollution is higher between 11:00 and 13:00, but it does not exceed the 24 h air concentration limits specified in the Chinese Ambient Air Quality Standard (GB3095-2012). It was found that the PM2.5 and PM10 concentrations are positively correlated with humidity and air pressure, and they are negatively correlated with wind speed, temperature, and noise. The TSP concentration is positively correlated with temperature and negatively correlated with humidity. The results of this study provide theoretical guidance and a reference for the distribution law of dust concentration in open-pit coal mines.

Terahertz direct polarization detector based on integrated antenna-coupled AlGaN/GaN high-electron-mobility transistors.

The foundation for polarization-based terahertz applications is the acquisition of polarization information. To develop an all-electronic terahertz straightforward polarization detection system, in this paper, a terahertz polarization detector based on three antenna-coupled AlGaN/GaN high-electron-mobility transistors (HEMTs) on a single chip is designed and fabricated. The function of the direct polarization detector is proven by measuring the polarization angle of linearly polarized continuous-wave terahertz radiation at 216 GHz. The average deviation and maximum deviation of the measured polarization angle are 3.7 degrees and 10 degrees, respectively. The error comes mainly from the disturbance of the local terahertz field by the interference effect. Simulations locate the sources of interference and guide the further device design and packaging of such kind of direct polarization detectors.

Ultraviolet Radiation Promoted Hypoxia-Induced Apoptosis in HL-60 Human Promyelocytic Leukemia Cell Line.

Minimal residual disease (MRD) is an important reason for the failure of autologous hematopoietic stem cell transplantation (auto-HSCT). Reducing MRD in grafts is particularly important to improve the efficacy of auto-HSCT. Previously, we reported that ultraviolet light-emitting diode (UV LED) suppressed the expression of Bcl-2 to induce apoptosis in HL-60 cells. Leukemia can lead to severe hypoxia of the bone marrow. Therefore, this study aimed to investigate the effect of UV LED on leukemia cells under hypoxia. HL-60 cells were irradiated with a UV LED (30 J/m2) and simulated under hypoxia with cobalt chloride. We found that UV LED irradiation or CoCl2 inhibited proliferation, induced apoptosis, decreased the Bcl-2/Bax ratio, and increased the levels of caspase 3, cleaved-caspase 3, and caspase 9 in HL-60 cells. In particular, the combined application of UV and CoCl2 significantly enhanced the apoptosis of HL-60 cells. In conclusion, UV LED in hypoxia exacerbated the inhibition of proliferation and induction of apoptosis and necrosis in HL-60 cells via the regulation of caspase 3/9 and the Bcl-2/Bax ratio-dependent pathway. The application of UV LEDs in hypoxia conditions may be a promising approach to kill residual drug-resistant leukemia cells in autologous grafts.

Lack of UBE3A-Mediated Regulation of Synaptic SK2 Channels Contributes to Learning and Memory Impairment in the Female Mouse Model of Angelman Syndrome.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe developmental delay, motor impairment, language and cognition deficits, and often with increased seizure activity. AS is caused by deficiency of UBE3A, which is both an E3 ligase and a cofactor for transcriptional regulation. We previously showed that the small conductance potassium channel protein SK2 is a UBE3A substrate, and that increased synaptic SK2 levels contribute to impairments in synaptic plasticity and fear-conditioning memory, as inhibition of SK2 channels significantly improved both synaptic plasticity and fear memory in male AS mice. In the present study, we investigated UBE3a-mediated regulation of synaptic plasticity and fear-conditioning in female AS mice. Results from both western blot and immunofluorescence analyses showed that synaptic SK2 levels were significantly increased in hippocampus of female AS mice, as compared to wild-type (WT) littermates. Like in male AS mice, long-term potentiation (LTP) was significantly reduced while long-term depression (LTD) was enhanced at hippocampal CA3-CA1 synapses of female AS mice, as compared to female WT mice. Both alterations were significantly reduced by treatment with the SK2 inhibitor, apamin. The shunting effect of SK2 channels on NMDA receptor was significantly larger in female AS mice as compared to female WT mice. Female AS mice also showed impairment in both contextual and tone memory recall, and this impairment was significantly reduced by apamin treatment. Our results indicate that like male AS mice, female AS mice showed significant impairment in both synaptic plasticity and fear-conditioning memory due to increased levels of synaptic SK2 channels. Any therapeutic strategy to reduce SK2-mediated inhibition of NMDAR should be beneficial to both male and female patients.

Real-world evaluation of sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors for managing type 2 diabetes mellitus: a retrospective multi-ethnic cohort study.

Purpose: Sodium-glucose co-transporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors are increasingly used as second-line therapies in patients with type 2 diabetes. The aim of this study was to assess the real-world effects of SGLT2 inhibitors in a multi-ethnic population in Singapore. Methods: This retrospective cohort study examined patients diagnosed with and treated for diabetes from the Ministry of Health's administrative database. Differences in outcomes between treatment groups were assessed using Poisson regression. Demographics, clinical characteristics, previous diagnoses and hospitalisations, and diabetes medication history were used for propensity score matching. Subgroup analyses by ethnicity were performed. Effect size was estimated using risk ratios (RRs) with 95% confidence intervals (CIs). Results: Patients initiating SGLT2 inhibitors were more likely to achieve glycaemic control target than DPP4 inhibitor-treated patients (RR 1.09; 95% CI 1.04, 1.14). This was observed only in patients of Chinese ethnicity. A higher risk of diabetic ketoacidosis in SGLT2 inhibitor initiators was not observed. SGLT2 inhibitors were associated with reduced risk of hypoglycaemia (RR 0.69; 95% CI 0.59, 0.82) and urinary tract infection (RR 0.52; 95% CI 0.43, 0.63) but was not statistically significant for hypoglycaemia in Malay patients. Compared to DPP4 inhibitors, SGLT2 inhibitors were associated with 12% and 34% reduction in any-cause hospitalisation and all-cause mortality, respectively, potentially resulting in more than $50 million savings over 10 years. Conclusion: SGLT2 inhibitors were associated with improvements in glycaemic control, reduced risk of complications, and was well tolerated. Ethnicity also plays a role and should be considered in future studies.

Icariin promotes mouse Leydig cell testosterone synthesis via the Esr1/Src/Akt/Creb/Sf-1 pathway.

Icariin (ICA), extracted from Epimedium, is a flavonoid used in traditional Chinese medicine. Di(2-ethylhexyl) phthalate (DEHP) is a phthalate used in commercial products as a plasticizer that can influence the human endocrine and reproduction system. We previously found that ICA reversed DEHP-induced damage through the prevention of reactive oxygen species accumulation and promotion of testosterone secretion. Here we investigated the mechanisms of ICA in promoting testosterone secretion from murine Leydig cells. We used ICA, DEHP, the Akt agonist SC-79, the Akt inhibitor MK2206, and the Creb inhibitor KG501 to determine the effect of these treatments on the expression levels of the steroidogenic enzymes, Cyp11a1 and Hsd3b, which play critical roles in androgen production, in Leydig cells. Bioinformatic analysis was used to search for ICA-targeted proteins and their associated pathways. We found that icariin interacted with estrogen receptor on the cell membrane, leading to increased phosphorylation levels of Akt and Creb proteins and enhanced transcription of genes encoding steroidogenic enzymes and testosterone synthesis. We further investigated ICA activity in vivo using male mice pretreated with 100 mg/kg ICA and then treated with 750 mg/kg DEHP. ICA pretreatment reversed the reduced protein expression levels of Cyp11a1 and Hsd3b induced by DEHP in Leydig cells in vivo. Furthermore, while the phosphorylation levels of Akt and Creb were decreased in testes of mice exposed to DEHP alone, these effects were reversed by ICA pretreatment. These findings indicate that ICA promotes testosterone synthesis via the Esr1/Src/Akt/Creb/Sf-1 signaling pathway.

LAMTOR1 inhibition of TRPML1-dependent lysosomal calcium release regulates dendritic lysosome trafficking and hippocampal neuronal function.

Lysosomes function not only as degradatory compartments but also as dynamic intracellular calcium ion stores. The transient receptor potential mucolipin 1 (TRPML1) channel mediates lysosomal Ca2+ release, thereby participating in multiple cellular functions. The pentameric Ragulator complex, which plays a critical role in the activation of mTORC1, is also involved in lysosomal trafficking and is anchored to lysosomes through its LAMTOR1 subunit. Here, we report that the Ragulator restricts lysosomal trafficking in dendrites of hippocampal neurons via LAMTOR1-mediated tonic inhibition of TRPML1 activity, independently of mTORC1. LAMTOR1 directly interacts with TRPML1 through its N-terminal domain. Eliminating this inhibition in hippocampal neurons by LAMTOR1 deletion or by disrupting LAMTOR1-TRPML1 binding increases TRPML1-mediated Ca2+ release and facilitates dendritic lysosomal trafficking powered by dynein. LAMTOR1 deletion in the hippocampal CA1 region of adult mice results in alterations in synaptic plasticity, and in impaired object-recognition memory and contextual fear conditioning, due to TRPML1 activation. Mechanistically, changes in synaptic plasticity are associated with increased GluA1 dephosphorylation by calcineurin and lysosomal degradation. Thus, LAMTOR1-mediated inhibition of TRPML1 is critical for regulating dendritic lysosomal motility, synaptic plasticity, and learning.

Long noncoding RNA EIF1AX-AS1 promotes endometrial cancer cell apoptosis by affecting EIF1AX mRNA stabilization.

Long noncoding RNAs (lncRNAs) have been found to play an important role in the occurrence and development of endometrial carcinoma (EC). Here, using RNA sequencing analysis, we systemically screened and identified the lncRNA eukaryotic translation initiation factor 1A, X-linked (EIF1AX)-AS1, which is aberrantly downregulated in clinical EC tissues and closely correlated with tumor type. EIF1AX-AS1 markedly inhibited EC cell proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, EIF1AX-AS1 interacts with EIF1AX mRNA and poly C binding protein 1 (PCBP1), which promote EIF1AX mRNA degradation. Intriguingly, by interacting with internal ribosome entry site-related protein Y-box binding protein 1 (YBX-1), EIF1AX promotes c-Myc translation through the internal ribosome entry site pathway. c-Myc promotes EIF1AX transcription and thus forms a feed-forward loop to regulate EC cell proliferation. Taken together, these data reveal new insights into the biology driving EC proliferation and highlights the potential of lncRNAs as biomarkers for prognosis and future therapeutic targets for cancer.

XPO1-Mediated EIF1AX Cytoplasmic Relocation Promotes Tumor Migration and Invasion in Endometrial Carcinoma.

Dysregulation of eukaryotic translation initiation factor 1A, X-linked (EIF1AX), has been implicated in the pathogenesis of some cancers. However, the role of EIF1AX in endometrial carcinoma (EC) remains unknown. We investigated the EIF1AX expression in EC patients and assessed its tumorigenesis-associated function and nucleocytoplasmic transport mechanism in vitro and in vivo. The results indicated that the cytoplasmic EIF1AX expression showed a gradual increase when going from endometrium normal tissue, simple endometrial hyperplasia, complex endometrial hyperplasia, and endometrial atypical hyperplasia to EC, while vice versa for the nuclear EIF1AX expression. In addition, the cytoplasmic EIF1AX expression was positively correlated with histologic type, high International Federation of Gynecology and Obstetrics (FIGO) grade, advanced FIGO stage, deeper infiltration, high Ki67 index, and shorter recurrence-free survival in EC patients. In vitro, short hairpin RNA-mediated EIF1AX depletion or SV40NLS-mediated EIF1AX import into the nucleus in multiple human EC cells potently suppressed cell migration and invasion, epithelial-mesenchymal transition, and lung metastasis. Moreover, exportin 1 induced the transport of EIF1AX from the nucleus to the cytoplasm that could be inhibited by leptomycin B treatment or the mutation in the EIF1AX location sequence. These results demonstrate that cytoplasmic EIF1AX may play a key role in the incidence and promotion of EC, and thus, targeting EIF1AX or its nucleocytoplasmic transport process may offer an effective new therapeutic approach to EC.

High production of d-psicose from d-fructose by immobilized whole recombinant Bacillus subtilis cells expressing d-psicose 3-epimerase from Agrobacterium tumefaciens.

d-Psicose 3-epimerase (DPEase) can catalyze the isomerization of d-fructose to be rare sugar d-psicose, which has wide application prospects in the food and medical fields. In this study, the DPEase gene from Agrobacterium tumefaciens was constructed into plasmid pMA5, and was successfully expressed in the host Bacillus subtilis WB600 (B. subtilis). After optimization of the fermentation conditions, whole recombinant B. subtilis WB600/pMA5-At-DEPase(O) cells produced d-psicose from d-fructose with a conversion rate of 29.01 ± 0.19%, which could be used for the efficient synthesis of d-psicose. To further improve the whole recombinant B. subtilis application, B. subtilis cells were immobilized onto a gel bead biocatalyst by Ca-alginate. After optimization of the biotransformation conditions, the conversion rate of the immobilized biocatalyst reached 20.74 ± 0.39%, which was lower than the free cells. However, the results showed that the immobilized biocatalyst had higher thermal/pH stability and storability, and the gel beads could be recycled for at least six batches. The results showed that the amount of d-psicose generated reached 32.83 ± 2.56 g/L with the immobilized biocatalyst after six times biotransformation, whereas the free cells produced only approximately 10.44 ± 0.07 g/L. The results showed that immobilized recombinant B. subtilis cells are promising to use for the efficient synthesis of d-psicose.

Research on Recognition of Faces with Masks Based on Improved Neural Network.

Background: At present, the new crown virus is spreading around the world, causing all people in the world to wear masks to prevent the spread of the virus. Problem. People with masks have found a lot of trouble for face recognition. Finding a feasible method to recognize faces wearing masks is a problem that needs to be solved urgently. Method: This paper proposes a mask recognition algorithm based on improved YOLO-V4 neural network and the integrated SE-Net and DenseNet network and introduces deformable convolution. Conclusion: Compared with other target detection networks, the improved YOLO-V4 neural network used in this paper improves the accuracy of face recognition and detection with masks to a certain extent.

Nuclear-localized eukaryotic translation initiation factor 1A is involved in mouse preimplantation embryo development.

Preimplantation embryo development is characterized by drastic nuclear reprogramming and dynamic stage-specific gene expression. Key regulators of this earliest developmental stage have not been revealed. In the present study, a "non-classical" nuclear-localization pattern of eIF1A was observed during early developmental stages of mouse preimplantation embryo before late-morula. In particular, eIF1A is most highly expressed in the nuclear of 2-cell embryo. Knockdown eIF1A by siRNA microinjection affected the development of mouse preimplantation embryo, resulted in decreased blastocyst formation rate. CDX2 protein expression level significantly down-regulated after eIF1A knockdown in morula stage. In addition, the mRNA expression level of Hsp70.1 was also decreased in 2-cell embryo. The results indicate an indispensable role of eIF1A in mouse preimplantation embryos.

Role of Calpain-1 in Neurogenesis.

While calpains have been implicated in neurogenesis for a long time, there is still little information regarding the specific contributions of various isoforms in this process. We took advantage of the availability of mutant mice with complete deletion of calpain-1 to analyze its contribution to neurogenesis. We first used the incorporation of BrdU in newly-generated cells in the subgranular zone of the dentate gyrus to determine the role of calpain-1 deletion in neuronal proliferation. Our results showed that the lack of calpain-1 decreased the rate of cell proliferation in adult hippocampus. As previously shown, it also decreased the long-term survival of newly-generated neurons. We also used data from previously reported RNA and miRNA sequencing analyses to identify differentially expressed genes in brain of calpain-1 knock-out mice related to cell division, cell migration, cell proliferation and cell survival. A number of differentially expressed genes were identified, which could play a significant role in the changes in neurogenesis in calpain-1 knock out mice. The results provide new information regarding the role of calpain-1 in neurogenesis and have implications for better understanding the pathologies associated with calpain-1 mutations in humans.

Trps1 targets Ccnd1 to regulate mouse Leydig cell proliferation.

BACKGROUND: The tricho-rhino-phalangeal syndrome-1 gene (Trps1) is an atypical GATA family member. Although current studies of Trps1 mainly focus on tumors, whether Trps1 plays a role in the male reproductive system remains unknown. OBJECTIVES: The purpose of this study was to elucidate the function of Trps1 in Leydig cells, indicating its regulatory mechanism on the cell cycle. METHODS: Gene-silencing technology, RNA-seq, RT-qPCR, and western blotting were used to evaluate the function of Trps1 in mouse primary Leydig cells and MLTC-1 cells. In addition, ChIP-base sets and ChIP-qPCR were employed to further assess the regulatory mechanism of Trps1 in MLTC-1 cells. RESULTS: Knockdown of Trps1 in Leydig cells significantly suppressed phosphorylation of Src and Akt and expression of Ccnd1, which was accompanied by impairment of cell proliferative ability. Trps1 may affect the cell cycle through the Src/Akt/Ccnd1 signaling pathway. In addition, Trps1 may bind to the promoter of Srcin1 to regulate its transcription, thus influencing Src phosphorylation levels and the proliferation of Leydig cells. DISCUSSION AND CONCLUSION: Src increases in Leydig cells during pubertal development, suggesting its functional involvement in differentiated adult Leydig cells. Inhibition of the Src/Akt pathway would reduce Ccnd1 expression. In the present study, we found that Trps1 may regulate the phosphorylation level of Src and Akt through Srcin1, targeting Ccnd1 to influence mouse Leydig cell proliferation. These findings shed light on the regulation of Trps1 on cell proliferation and differentiation of mouse Leydig cells.