Black phosphorus, an advanced versatile nanoparticles of antitumor, antibacterial and bone regeneration for OS therapy.

Osteosarcoma (OS) is the most common primary malignant bone tumor. In the clinic, usual strategies for OS treatment include surgery, chemotherapy, and radiation. However, all of these therapies have complications that cannot be ignored. Therefore, the search for better OS treatments is urgent. Black phosphorus (BP), a rising star of 2D inorganic nanoparticles, has shown excellent results in OS therapy due to its outstanding photothermal, photodynamic, biodegradable and biocompatible properties. This review aims to present current advances in the use of BP nanoparticles in OS therapy, including the synthesis of BP nanoparticles, properties of BP nanoparticles, types of BP nanoparticles, and modification strategies for BP nanoparticles. In addition, we have discussed comprehensively the application of BP in OS therapy, including single, dual, and multimodal synergistic OS therapies, as well as studies about bone regeneration and antibacterial properties. Finally, we have summarized the conclusions, limitations and perspectives of BP nanoparticles for OS therapy.

Finite element analysis of the effect of tibial osteotomy on the stress of polyethylene liner in total knee arthroplasty.

AIM: To explore the effects of tibial osteotomy varus angle combined with posterior tibial slope (PTS) on the stress of polyethylene liner in total knee arthroplasty (TKA) by building finite element model (FEM). METHODS: Established the FEM of standard TKA with tibial osteotomy varus angle 0° to 9° were established and divided into 10 groups. Next, each group was created 10 FEMs with 0° to 9° PTS separately. Calculated the stress on polyethylene liner in each group in Abaqus. Finally, the relevancy between tibial osteotomy angle and polyethylene liner stress was statistically analyzed using multiple regression analysis. RESULTS: As the varus angle increased, the area of maximum stress gradually shifted medially on the polyethylene liner. As the PTS increases, the percentage of surface contact forces on the medial and lateral compartmental of the polyethylene liner gradually converge to the same. When the varus angle is between 0° and 3°, the maximum stress of the medial compartmental surfaces of polyethylene liner rises smoothly with the increase of the PTS. When the varus angle is between 4° and 9°, as the increase of the PTS, the maximum stress of polyethylene liner rises first and then falls, forming a trough at PTS 5° and then rises again. Compared to the PTS, the varus angle has a large effect on the maximum stress of the polyethylene liner (p < .001). CONCLUSION: When the varus angle is 0° to 3°, PTS 0° is recommended, which will result in a more equalized stress distribution of the polyethylene liner in TKA.

A carbon nanotube metamaterial sensor showing slow light properties based on double plasmon-induced transparency.

In this study, we proposed a bifunctional sensor of high sensitivity and slow light based on carbon nanotubes (CNTs). An array of left semicircular ring (LSR), right semicircular ring (RSR), and circular ring (CR) resonators are utilized to form the proposed metamaterial. The proposed structure can achieve double plasmon-induced transparency (PIT) effects under the excitation of a TM-polarization wave. The double PIT originated from the destructive interference between two bright modes and a dark mode. A coupled harmonic oscillator model is used to describe the destructive interference between the two bright modes and a dark mode, and the simulation results agree well with the calculated results. Moreover, we investigate the influence of the coupling distance, period, and flare angle on the PIT spectra. The relationship between the resonant frequencies, full width at half maximum (FWHM), amplitudes, quality factors (Q), and the coupling distance is also studied. Finally, a high sensitivity of 1.02 THz RIU-1 is obtained, and the transmission performance can be maintained at a good level when the incident angle is less than 40°. Thus, the sensor can cope with situations where electromagnetic waves are not perpendicular to the structure's surface. The maximum figure of merit (FOM) can reach about 8.26 RIU-1; to verify the slow light property of the device, the slow light performance of the proposed structure is investigated, and a maximum time delay (TD) of 22.26 ps is obtained. The proposed CNT-based metamaterial can be used in electromagnetically induced transparency applications, such as sensors, optical memory devices, and flexible terahertz functional devices.

Spatial-temporal changes of landscape and habitat quality in typical ecologically fragile areas of western China over the past 40 years: A case study of the Ningxia Hui Autonomous Region.

In this paper, we use the InVEST model and five periods of land use data from 1980 to 2020 to assess the habitat quality of the Ningxia Hui Autonomous Region in Western China, which has characteristics of a typical fragile ecosystem. We further analyse the spatial and temporal characteristics of habitat quality evolution and its relationship with land use and landscape pattern indices to explore the close relationship between regional habitat quality changes and human natural resource conservation and utilization. The research results show that the overall habitat quality of Ningxia Hui Autonomous Region was stable and at a moderate level (0.57-0.60) during the 40 years from 1980 to 2020; Habitat patches (2020) with low (24.89%), high (22.45%) and very high (29.81%) quality occupy a larger proportion of the area, followed by very low (13.31%) and moderate levels (9.54%). Over the past 40 years, there have been 275 sample sites in Ningxia where habitat quality has deteriorated, 1593 sample sites where the habitat quality has remained stable, and 184 sample sites where the habitat quality has increased. From 1980 to 2020, the Mean Patch Area of landscape types in Ningxia decreased by 25.9 hm2. The Patch Density increased by 0.06 /hm2. The Largest Patch Index decreased by 15.69%. The Edge Density increased by 2.5 m/hm2. The Contagion Index decreased by 2.99%. The Area-Weighted Mean Patch Fractal Dimension remained basically unchanged (0.01). The Landscape Shape Index showed a trend of first increasing and then decreasing, increasing by 13.94. The Area-Weighted Mean Shape Index has been reduced by 9.45. The Shannon Diversity Index and Shannon Evenness Index both show an increasing trend, but the amplitude is relatively small, with 0.09 and 0.04, respectively. There was a significant spatial aggregation of high and low habitat quality in Ningxia, with high values usually distributed in the northern and southern areas with good natural conditions and low values distributed in areas with frequent human activities and poor natural conditions. The decrease in habitat quality in Ningxia was mainly due to the expansion of cultivated land and construction land, the increase in landscape fragmentation and the resulting decrease in connectivity. On the other hand, due to the implementation of ecological protection measures, such as the project of returning farmland to pasture and grass to forest, the quality of habitats in Ningxia increased. The conclusions of this study support the idea that the conservation of habitat quality in ecologically fragile areas should fully preserve the original natural habitats and reduce the interference of human activities to increase the habitat suitability of the landscape and the habitat connectivity between patches. At the same time, targeted ecological protection policies should be developed to restore the areas where the habitat quality has been damaged and ultimately maintain the stability of biodiversity and ecosystems in ecologically fragile areas. Meanwhile, for ecologically fragile areas with similar ecological characteristics to those of Ningxia, our research supports the idea of increasing the protection of the stability of the original habitats, increasing the proportion of ecological restoration projects, financial investment and seeking cooperation with local community managers and residents will help to improve the quality of the regional habitats and the enrichment of the biodiversity, and ultimately promote the harmonious coexistence of human beings and nature in the modernized sense of the word.

A new perspective on anthropogenic nitrogen loss mitigation strategies: Integrated control via sustainable regional integration.

Unregulated regional integrated development disrupts the reactive nitrogen (Nr) cycle, adding complexity to anthropogenic Nr environmental losses. The objective of this study was to establish a framework for mitigating anthropogenic Nr loss through a new regional integration perspective by analyzing anthropogenic Nr loss and integrated control strategies in the Yangtze River Delta (YRD) region from 2011 to 2020. The results revealed that the total Nr loss in the YRD ranged from 1780.7 to 1972.0 Gg N yr-1. Re-linking cropland and livestock is crucial for reducing Nr loss, as they act as the main sources of Nr loss. Spatial analysis at the regional scale revealed that regional integration has led to a dispersion of Nr loss, while uneven development among cities has resulted in a westward shift of 8.6 km in the Nr loss centroid, suggesting the need for the implementation of collaborative governance and integrated environmental regulation in the YRD. At the city scale, 27 cities were clustered into six types based on the similarity of Nr loss structural characteristics, allowing for the development of targeted reduction policies based on the specific Nr structural characteristics of each city. The results of driver and mitigation potential analysis indicated the feasibility of achieving the shared goal of sustainable regional integration and the application of optimal mitigation strategies in different cities and the YRD. Overall, the new-perspective framework established in this study provides valuable references for sustainable Nr management in the context of regional integration.

Collagen-Based Hydrogels for Cartilage Regeneration.

Cartilage regeneration remains difficult due to a lack of blood vessels. Degradation of the extracellular matrix (ECM) causes cartilage defects, and the ECM provides the natural environment and nutrition for cartilage regeneration. Until now, collagen hydrogels are considered to be excellent material for cartilage regeneration due to the similar structure to ECM and good biocompatibility. However, collagen hydrogels also have several drawbacks, such as low mechanical strength, limited ability to induce stem cell differentiation, and rapid degradation. Thus, there is a demanding need to optimize collagen hydrogels for cartilage regeneration. In this review, we will first briefly introduce the structure of articular cartilage and cartilage defect classification and collagen, then provide an overview of the progress made in research on collagen hydrogels with chondrocytes or stem cells, comprehensively expound the research progress and clinical applications of collagen-based hydrogels that integrate inorganic or organic materials, and finally present challenges for further clinical translation.

ABCE1 selectively promotes HIF-1α transactivation of angiogenic gene expression.

BACKGROUND: Copper (Cu), by inhibiting the factor inhibiting HIF-1 (FIH-1), promotes the transcriptional activity of hypoxia-inducible factor-1 (HIF-1). OBJECTIVE: The present study was undertaken to understand the molecular mechanism by which Cu inhibits FIH-1. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with dimethyloxalylglycine (DMOG) resulting in HIF-1α accumulation and the FIH-1 protein complexes were pulled down for candidate protein analysis. The metal binding sites were predicted by both MetalDetector V2.0 and Metal Ion-Binding Site Prediction Server, and then the actual ability to bind to Cu in vitro was tested by both Copper-Immobilized metal affinity chromatography (Cu-IMAC) and Isothermal Titration Calorimetry (ITC). Subsequently, subcellular localization was monitored by immunocytochemistry, GFP-fusion protein expression plasmid and Western blotting in the nuclear extract. The interaction of candidate protein with HIF-1α and FIH-1 was validated by Co-Immunoprecipitation (Co-IP). Finally, the effect of candidate protein on the FIH-1 structure and HIF-1α transcriptional activity was analyzed by the InterEvDock3 web server and real-time quantitative RT-PCR. RESULTS: ATP-binding cassette E1 (ABCE1) was present in the FIH-1 complexes and identified as a leading Cu-binding protein as indicated by a number of possible Cu binding sites. The ability of ABCE1 to bind Cu was demonstrated in vitro. ABCE1 entered the nucleus along with FIH-1 under hypoxic conditions. Protein interaction analysis revealed that ABCE1 prevented FIH-1 to bind iron ions, inhibiting FIH-1 enzymatic activity. ABCE1 silencing suppressed the expression of Cu-dependent HIF-1 target gene BNIP3, not that of Cu-independent IGF-2. CONCLUSION: The results demonstrate that ABCE1, as a Cu-binding protein, enters the nucleus under hypoxic conditions and inhibits FIH-1degradation of HIF-1α, thus promoting HIF-1 transactivation of angiogenic gene expression.

TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5.

To investigate the specific role of TRIM29 in colon cancer progression, bioinformatic analysis was performed on TRIM29. Colon cancer tissues were collected and colon cancer cells were cultured for further experiments. Cell viability and proliferation were determined using CCK-8, colony formation, and EDU staining assays. The mRNA and protein levels of TRIM29 and KRT5 were determined using quantitative real-time PCR and western blotting, respectively. The interaction between TRIM29 and KRT5 was detected using a co-immunoprecipitation (CO-IP) assay. Cycloheximide treatment was performed to analyse the stability of KRT5. TRIM29 was upregulated in colon cancer tissues and cells. TRIM29 knockdown decreased the cell viability and proliferation and ubiquitination levels of KRT5 and enhanced the protein stability and expression of KRT5. The CO-IP assay confirmed that TRIM29 and KRT5 binded to each other. KRT5 knockdown neutralises the inhibitory effect of sh-TRIM29 on colon cancer cell growth and TRIM29 knockdown prevented the proliferation of colon cancer cells by decreasing ubiquitination of KRT5, which enhanced the protein stability and expression of KRT5 in cancer cells. Thus, targeting TRIM29-mediated ubiquitination levels of KRT5 might be a new direction for colon cancer therapy.

Molecular mechanism of Cuscutae semen-radix rehmanniae praeparata in relieving reproductive injury of male rats induced with tripterygium wilfordii multiglycosides: A tandem mass tag-based proteomics analysis.

Background: We determined the effects of Cuscutae semen (Cuscuta chinensis Lam. or Cuscuta australis R. Br.)-Radix rehmanniae praeparata (Rehjnannia glutinosa Libosch.) on the protein levels in testicular tissues of rats gavaged with tripterygium wilfordii multiglycosides (GTW) and elucidated the molecular mechanism underlying Cuscutae semen-Radix rehmanniae praeparata for relieving GTW-induced reproductive injury. Methods: A total of 21 male Sprague-Dawley rats were randomly divided into the control group, model group, and Cuscutae semen-Radix rehmanniae praeparata group based on their body weights. The control group was given 10 mLkg-1 of 0.9% normal saline by gavage daily. The model group (GTW group) was administered with 12 mg kg-1 GTW by gavage daily. Cuscutae semen-Radix rehmanniae praeparata group (the TSZSDH group) was administered with 1.56 gkg-1 of Cuscutae semen-Radix rehmanniae praeparata granules daily according to their model group dosing. The serum levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and testosterone were measured after 12 weeks of continuous gavage, and the pathological lesion of testicular tissues was observed. Differentially expressed proteins were evaluated by quantitative proteomics and verified by western blotting (WB) and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). Results: Cuscutae semen-Radix rehmanniae praeparata can effectively relieve pathological lesions of GTW-induced testicular tissues. A total of 216 differentially expressed proteins were identified in the TSZSDH group and model group. High-throughput proteomics revealed that differentially expressed proteins are closely associated with the peroxisome proliferator-activated receptor (PPAR) signaling pathway, protein digestion and absorption, and protein glycan pathway in cancer. Cuscutae semen-Radix rehmanniae praeparata can significantly upregulate the protein expressions of Acsl1, Plin1, Dbil5, Plin4, Col12a1, Col1a1, Col5a3, Col1a2, Dcn, so as to play a protective role on testicular tissues. Acsl1, Plin1, and PPARγ on the PPAR signaling pathway were verified by WB and RT-qPCR experiments, which were found to be consistent with the results of proteomics analysis. Conclusion: Cuscutae semen and Radix rehmanniae praeparata may regulate the PPAR signaling pathway mediated Acsl1, Plin1 and PPARγ to reduce the testicular tissue damage of male rats caused by GTW.

Recent advances on bioactive compounds, biosynthesis mechanism, and physiological functions of Nelumbo nucifera.

Nelumbo nucifera Gaertn, commonly known as lotus, is a genus comprising perennial and rhizomatous aquatic plants, found throughout Asia and Australia. This review aimed to cover the biosynthesis of flavonoids, alkaloids, and lipids in plants and their types in different parts of lotus. This review also examined the physiological functions of bioactive compounds in lotus and the extracts from different organs of the lotus plant. The structures and identities of flavonoids, alkaloids, and lipids in different parts of lotus as well as their biosynthesis were illustrated and updated. In the traditional medicine systems and previous scientific studies, bioactive compounds and the extracts of lotus have been applied for treating inflammation, cancer, liver disease, Alzheimer's disease, etc. We suggest future studies to be focused on standardization of the extract of lotus, and their pharmacological mechanisms as drugs or functional foods. This review is important for the lotus-based food processing and application.

Developing pre-service teachers' computational thinking: a systematic literature review.

Recently, computational thinking (CT) has gained importance in education systems worldwide, specifically the CT training of pre-service teachers. This study conducted a systematic literature analysis (2011-2021) of 38 works on pre-service teachers' CT based on Web of Science, Science Direct, and Google Scholar databases. The results were as follows: (1) Six training methods were found, (2) CT training effectively improved pre-service teachers' CT, (3) A positive relationship was found between pre-service teachers' CT ability and the five factors affecting the ability, (4) A mode of training to improve CT ability of pre-service teachers and the relationship between CT ability and teaching methods were considered. This study suggested ideas for designing training modules of CT ability and a reference for realizing the best training effect. Finally, future research trends and a general model of training were presented as references for researchers, instructors, and policy makers to promote the CT of pre-service teachers.

Zoning method of aquatic ecosystem functional management fourth-level region in the Daqing River Basin, China.

Watershed management needs more information on ecological function and services in large regions. Spatial units are particularly important for the watershed management. Zoning of aquatic ecosystem functional management region refers to the zoning of terrestrial ecosystems as per the characteristics of aquatic ecosystems, providing an ecological background and basic spatial units for water environment management in basins. Although basin water environment management based on aquatic ecosystem functional management region and control unit is highly effective in practice, the current need for refined management of water environments cannot be met by existing zoning schemes of aquatic ecosystem functional management regions and control units. In response to the need to protect basin water environments, which is raised in the 14th Five-Year plan, a zoning method of aquatic ecosystem functional management fourth-level region for basins is proposed in this study. It features an effective integration of aquatic ecosystem functional management regions and control units and township-level administrative divisions, thus contributing to the implementation of a basin water environment management system that fulfils the zoning, grading, classification and period goals of aquatic ecosystem functional management. In this way, it can satisfy the business application of administrative management and refined management of water environments, which features coupling terrestrial and aquatic ecosystems and unification of water resources, water environments and aquatic ecology. The feasibility and effectiveness of the proposed zoning method were verified by using the Daqing River Basin, Beijing-Tianjin-Hebei region, China, as a case study. The results were accepted by the Ministry of Ecology and Environment and the Haihe River Water Conservancy Commission of the Ministry of Water Resources, which can provide scientific rationale and technical support for the accurate and differentiated watershed water environments management and ecological restoration of coastal wetlands in the Haihe River Basin based on aquatic ecosystem functional management fourth-level region with clear responsibility for the local government during the period of the 14th Five-Year plan.

Degradation Characteristics of Cellulose Acetate in Different Aqueous Conditions.

Cellulose acetate (CA) is widely used in cigarette filters and packaging films, but due to its acetylation, it is difficult to degrade in the natural environment, and the problem of pollution has become a serious challenge. Understanding the degradation behavior and performance of CA in different environments is the basis and prerequisite for achieving its comprehensive utilization and developing efficient degradation methods. In this study, we investigated the degradation performance of CA in different aqueous environments to evaluate the effects of pH, salinity and microorganisms on CA degradation. The CA tows and films were immersed in HCl, NaOH solution, river water, seawater or homemade seawater for 16 weeks and the degradation mechanism was investigated by the changes in weight loss rate, degree of substitution, hydrophilicity, molecular structure and surface morphology. The results showed that the degradation of CA tow and film were the fastest in NaOH solution; the weight loss rates after 16 weeks were 40.29% and 39.63%, respectively, followed by HCl solution, and the degradation performance of CA tow was better than that of film. After 16 weeks of degradation in river water, seawater and homemade seawater, all the weight loss rates were less than 3%. In summary, this study illustrated that the environmental acidity, basicity and high concentration of inorganic salts had a critical promotion effect on the non-enzymatic hydrolysis of CA, whereas the number and type of microorganisms were the key factors affecting the biodegradation of CA.

Enhancement of Optomechanical Squeezing of Light Using the Optical Coherent Feedback.

A coherent feedback scheme is used to enhance the degree of squeezing of the output field in a cavity optomechanical system. In the feedback loop, a beam splitter (BS) plays the roles of both a feedback controller and an input-output port. To realize effective enhancement, the output quadrature should take the same form as the input quadrature, and the system should operate at the deamplification situation in the meantime. This can be realized by choosing an appropriate frequency-dependent phase angle for the generalized quadrature. Additionally, both the transmissivity of the BS and the phase factor induced by time delays in the loop affect optical squeezing. For the fixed frequency, the optimal values of transmissivity and phase factor can be used to achieve the enhanced optical squeezing. The effect of optical losses on squeezing is also discussed. Optical squeezing is degraded by the introduced vacuum noise owing to the inefficient transmission in the loop. We show that the enhancement of squeezing is achievable with the parameters of the current experiments.

Gut brain interaction theory reveals gut microbiota mediated neurogenesis and traditional Chinese medicine research strategies.

Adult neurogenesis is the process of differentiation of neural stem cells (NSCs) into neurons and glial cells in certain areas of the adult brain. Defects in neurogenesis can lead to neurodegenerative diseases, mental disorders, and other maladies. This process is directionally regulated by transcription factors, the Wnt and Notch pathway, the extracellular matrix, and various growth factors. External factors like stress, physical exercise, diet, medications, etc., affect neurogenesis and the gut microbiota. The gut microbiota may affect NSCs through vagal, immune and chemical pathways, and other pathways. Traditional Chinese medicine (TCM) has been proven to affect NSCs proliferation and differentiation and can regulate the abundance and metabolites produced by intestinal microorganisms. However, the underlying mechanisms by which these factors regulate neurogenesis through the gut microbiota are not fully understood. In this review, we describe the recent evidence on the role of the gut microbiota in neurogenesis. Moreover, we hypothesize on the characteristics of the microbiota-gut-brain axis based on bacterial phyla, including microbiota's metabolites, and neuronal and immune pathways while providing an outlook on TCM's potential effects on adult neurogenesis by regulating gut microbiota.

Microstructure Evolution and Mechanical Properties of Ferrite-Austenite Duplex Fe-Mn-Al-(Cu)-C Steel under Different Annealing Temperatures.

The effect of Cu addition and the intercritical annealing (IA) temperature on the microstructural evolution and mechanical properties of Fe-0.4C-7Mn-4Al (wt%) was investigated via scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), X-ray diffraction (XRD) and nanoindentation tests. The results showed that the volume fraction and the average grain size of austenite, and the fraction of high angle grain boundaries, increased with IA temperature increase in the range of 650 °C to 710 °C. The addition of Cu facilitates the formation of Cu-rich nanoparticles, raises the volume fraction of austenite, and delays the recrystallization of austenite. As IA temperature increased, the yield strength (YS), ultimate tensile strength (UTS), and Lüders bands strain (LBS) decreased in both experimental steels. The Cu addition not only increases the YS of medium Mn steel but also benefits the decrease of LBS. The best comprehensive mechanical properties were obtained at the IA temperature of 690 °C in the studied steel, with Cu addition. According to nanoindentation experiments, the Cu addition raises the hardness of ferrite and austenite from 4.7 GPa to 6.3 GPa and 7.4 GPa to 8.5 GPa, respectively, contributing to the increase of YS of medium-Mn steel.

Systemic immune effects of anesthetics and their intracellular targets in tumors.

According to the result released by the World Health Organization (WHO), non-communicable diseases have occupied four of the top 10 current causes for death in the world. Cancer is one of the significant factors that trigger complications and deaths; more than 80% cancer patients require surgical or palliative treatment. In this case, anesthetic treatment is indispensable. Since cancer is a heterogeneous disease, various types of interventions can activate oncogenes or mutate tumor suppressor genes. More and more researchers believe that anesthetics have a certain effect on the long-term recurrence and metastasis of tumors, but it is still controversial whether they promote or inhibit the progression of cancer. On this basis, a series of retrospective or prospective randomized clinical trials have been conducted, but it seems to be difficult to reach a conclusion within 5 years or longer. This article focuses on the effects of anesthetic drugs on immune function and cancer and reviews their latest targets on the tumor cells, in order to provide a theoretical basis for optimizing the selection of anesthetic drugs, exploring therapeutic targets, and improving the prognosis of cancer patients.

The Origin and Evolution of Bladder Cancer Stem Cells.

Bladder cancer is the most common malignant tumor of the urinary system. Bladder cancer stem cells (BCSCs) play key roles in tumor initiation, metastasis, relapse and drug-resistance. Investigation of BCSCs is of great value. On the basis of a review of normal bladder stem cells and universal cancer stem cells (CSCs), we summarize the origin of BCSCs, isolation and identification of CSCs from bladder cancer, signaling pathway of BCSCs, BCSCs targeted therapy, and relationship of BCSCs with non-muscle invasiveness and muscle invasiveness. This review aims to provide better elucidation about BCSCs, and provide constructive data for classification, prognosis, treatment and early intervention of bladder cancer.

Proteomic Study on the Reproductive Toxicity of Tripterygium Glycosides in Rats.

Tripterygium glycoside tablet (TGT) is a common clinically used and effective non-steroidal immunosuppressant. However, its reproductive toxicity limits its application in pediatric immune diseases, warranting the study of the molecular mechanism behind its reproductive toxicity. In the present study, 4-week-old male Sprague Dawley (SD) rats were provided TGT through continuous gavage with a clinically equivalent dose of 12 mg/kg for 12 weeks. The reproductive toxicity of TGT was recorded, and its toxicity mechanism was verified through experimental validation and proteomics analyses. Our results demonstrated that TGT could significantly reduce the testosterone level in the serum as well as the concentration and survival rate of sperms. Pathological sections of the testis revealed that TGT could reduce spermatocytes at different levels and make the convoluted meridians vacuolated. Based on tandem mass tag (TMT)-labeled quantitative rats testicular tissue proteomics, 34 differential proteins were screened, involving protein digestion and absorption, PPAR signaling pathway, PI3K-Akt, and other pathways, among which PI3K-Akt plays an important role in the study of reproductive injury. Western blotting results revealed that TGT could significantly downregulate the Col1A1, Col1A2, p-PI3K, and p-Akt expressions and inhibit the expression of proteins related to the PI3K-Akt signaling pathway. In summary, the clinically equivalent dose of TGT induced reproductive toxicity of 4-week-old male SD rats, possibly in relation to the inhibition of the PI3K-Akt pathway expression.