Melatonin ameliorates 10-hydroxycamptothecin-induced oxidative stress and apoptosis via autophagy-regulated p62/Keap1/Nrf2 pathway in mouse testicular cells.

10-Hydroxycamptothecin (HCPT) is a widely used clinical anticancer drug but has a significant side effect profile. Melatonin has a beneficial impact on the chemotherapy of different cancer cells and reproductive processes, but the effect and underlying molecular mechanism of melatonin's involvement in the HCPT-induced side effects in cells, especially in the testicular cells, are poorly understood. In this study, we found that melatonin therapy significantly restored HCPT-induced testicular cell damage and did not affect the antitumor effect of HCPT. Further analysis found that melatonin therapy suppressed HCPT-induced DNA damage associated with ataxia-telangiectasia mutated- and Rad3-related and CHK1 phosphorylation levels in the testis. Changes in apoptosis-associated protein levels (Bax, Bcl-2, p53, and Cleaved caspase-3) and in reactive oxygen species-associated proteins (Nrf2 and Keap1) and index (malondialdehyde and glutathione) suggested that melatonin treatment relieved HCPT-induced cell apoptosis and oxidative damage, respectively. Mechanistically, melatonin-activated autophagy proteins (ATG7, Beclin1, and LC3bII/I) may induce p62-dependent autophagy to degrade Keap1, eliciting Nrf2 from Keap1-Nrf2 interaction to promote antioxidant enzyme expression such as HO-1, which would salvage HCPT-induced ROS production and mitochondrial dysfunction. Collectively, this study reveals that melatonin therapy may protect testicular cells from HCPT-induced damage via the activation of autophagy, which alleviates oxidative stress, mitochondrial dysfunction, and cell apoptosis.

Laser-activable murine ferritin nanocage for chemo-photothermal therapy of colorectal cancer.

Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects. Herein, we genetically engineered a thermal-responsive murine Ferritin (mHFn) to specifically deliver mitoxantrone (MTO, a chemotherapeutic and photothermal agent) to tumor tissue for the chemotherapy and photothermal combined therapy of colorectal cancer, thanks to the high affinity of mHFn to transferrin receptor that highly expressed on tumor cells. The thermal-sensitive channels on mHFn allowed the effective encapsulation of MTO in vitro and the laser-controlled release of MTO in vivo. Upon irradiation with a 660 nm laser, the raised temperature triggered the opening of the thermal-sensitive channel in mHFn nanocage, resulting in the controlled and rapid release of MTO. Consequently, a significant amount of reactive oxygen species was generated, causing mitochondrial collapse and tumor cell death. The photothermal-sensitive controlled release, low systemic cytotoxicity, and excellent synergistic tumor eradication ability in vivo made mHFn@MTO a promising candidate for chemo-photothermal combination therapy against colorectal cancer.

A single-molecule localization microscopy method for tissues reveals nonrandom nuclear pore distribution in Drosophila.

Single-molecule localization microscopy (SMLM) can provide nanoscale resolution in thin samples but has rarely been applied to tissues because of high background from out-of-focus emitters and optical aberrations. Here, we describe a line scanning microscope that provides optical sectioning for SMLM in tissues. Imaging endogenously-tagged nucleoporins and F-actin on this system using DNA- and peptide-point accumulation for imaging in nanoscale topography (PAINT) routinely gives 30 nm resolution or better at depths greater than 20 µm. This revealed that the nuclear pores are nonrandomly distributed in most Drosophila tissues, in contrast to what is seen in cultured cells. Lamin Dm0 shows a complementary localization to the nuclear pores, suggesting that it corrals the pores. Furthermore, ectopic expression of the tissue-specific Lamin C causes the nuclear pores to distribute more randomly, whereas lamin C mutants enhance nuclear pore clustering, particularly in muscle nuclei. Given that nucleoporins interact with specific chromatin domains, nuclear pore clustering could regulate local chromatin organization and contribute to the disease phenotypes caused by human lamin A/C laminopathies.

Melatonin prevents oocyte deterioration due to cotinine exposure in mice†.

Levels of cotinine, a major metabolite of nicotine, have been positively correlated with risks of cigarette smoking-related diseases. Melatonin is synthesized by the pineal gland and has been demonstrated to be beneficial to oocyte maturation due to its antioxidative activity. In this study, we investigated the effects of cotinine on mouse oocyte meiosis and the protective roles of melatonin in vitro and in vivo. The results showed that cotinine exposure caused defects in the first polar body extrusion and reduced parthenogenetic activation in in vitro-matured oocytes. Additionally, cotinine exposure increased the level of oxidative stress, which resulted in aberrant actin distribution, abnormal spindle morphology, chromosome misalignment, and even oocyte aneuploidy. Simultaneously, cotinine exposure decreased the mitochondrial membrane potential and antioxidant gene expression and increased apoptosis-related gene expression. However, all these toxic effects of cotinine could be reversed after the addition of melatonin, and the mechanism may be a decrease in reactive oxygen species production. In conclusion, cotinine causes poor oocyte quality, which could be rescued by melatonin supplementation during meiotic maturation in mouse oocytes.

Zinc-metal-organic frameworks with tunable UV diffuse-reflectance as sunscreens.

BACKGROUND: UV exposure continues to induce many health issues, though commercial sunscreens are available. Novel UV filters with high safety and efficacy are urgently needed. Metal-organic frameworks (MOFs) could be a suitable platform for UV filter development, due to their tunable optical, electrical, and photoelectric properties by precise controlled synthesis. RESULTS: Herein, four zinc-based MOFs with various bandgap energies were chose to investigate their optical behaviors and evaluate their possibility as sunscreens. Zeolitic imidazolate framework-8 (ZIF-8) was found to possess the highest and widest UV reflectance, thereby protecting against sunburn and DNA damage on mouse skin and even achieving a comparable or higher anti-UV efficacy relative to the commercially available UV filters, TiO2 or ZnO, on pig skin, a model that correlates well with human skin. Also, ZIF-8 exerted appealing characteristics for topical skin use with low radical production, low skin penetration, low toxicity, high transparency, and high stability. CONCLUSION: These results confirmed ZIF-8 could potentially be a safe and effective sunscreen surrogate for human, and MOFs could be a novel source to develop more effective and safe UV filters.

An exploration of the role of Sertoli cells on fetal testis development using cell ablation strategy.

Sertoli cells (SCs) are presumed to be the center of testis differentiation because they provide both structural support and biological regulation for spermatogenesis. Previous studies suggest that SCs control germ cell (GC) count and Leydig cell (LC) development in mouse testes. However, the regulatory role of SCs on peritubular myoid (PTM) cell fate in fetal testis has not been clearly reported. Here, we employed Amh-Cre; diphtheria toxin fragment A (DTA) mouse model to selectively ablate SCs from embryonic day (E) 14.5. Results found that SC ablation in the fetal stage caused the disruption of testis cords and the massive loss of GCs. Furthermore, the number of α-smooth muscle actin-labeled PTM cells was gradually decreased from E14.5 and almost lost at E18.5 in SC ablation testis. Interestingly, some Ki67 and 3ß-HSD double-positive fetal LCs could be observed in Amh-Cre; DTA testes at E16.5 and E18.5. Consistent with this phenomenon, the messenger RNA levels of Hsd3b1, Cyp11a1, Lhr, Star and the protein levels of 3ß-HSD and P450Scc were significantly elevated by SC ablation. SC ablation appears to induce ectopic proliferation of fetal LCs although the total LC number appeared reduced. Together, these findings bring us a better understanding of SCs' central role in fetal testis development.

Toxic effects of 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal on the maturation and subsequent development of murine oocyte.

Cigarette smoke can cause follicle destruction and oocyte dysfunction and increase the risks of spontaneous abortion, stillbirth, and tubal ectopic pregnancy, affecting female reproductive health. Third-hand smoke (THS) is residual tobacco smoke existing in the environment long after cigarettes are extinguished, which can react with other compounds in the environment to produce secondary pollutants. However, the effects of THS on the female reproductive system, particularly the maturation of the oocyte, remain unclear. 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA), a component of THS, is a logical biomarker of THS exposure. Thus, this study aims to investigate the toxic effects of NNA on the maturation of murine oocytes and subsequent developmental competence. Herein, murine oocytes were exposed to 0 (control group), 0.1, 1.0, 10, and 50 µM NNA for 24 h. Our results showed that NNA exposure reduced the polar body extrusion rate by causing 8-oxo-deoxyguanosine (8-OHdG) to increase and disrupting the meiotic spindle morphology by inhibiting ERK1/2 activation during in vitro maturation. Additionally, NNA exposure resulted in cleavage and blastocyst rate reduction by altering DNA and histone methylations by reducing 5 mC and H3K4me2 levels and by inducing apoptosis caused by mitochondrial dysfunction and reactive oxygen species accumulation, as shown by the increased superoxide dismutase mRNA level and by the decreased Bcl-x mRNA level. Collectively, our results demonstrate that NNA exposure reduces the maturation and developmental capability of murine oocytes by increasing the risk of DNA damage and abnormal spindle morphology, altering epigenetic modifications, and inducing apoptosis, suggesting the toxic effect of NNA on mammalian productive health.

Role of WNT signaling in epididymal sperm maturation.

PURPOSE: Spermatozoa maturation, a process required for spermatozoa to acquire progressive motility and the ability to fertilize ova, primarily occurs in the caput and corpus of the epididymis. Despite considerable efforts, the factor(s) promoting epididymal sperm maturation remains unclear. Recently, WNT signaling has been implicated in epididymal sperm maturation. METHODS: To further investigate WNT signaling function in epididymal sperm maturation, we generated Wntless conditional knockout mice (Wls cKO), Wls flox/flox ; Lcn5-Cre. RESULTS: In these mice, WNTLESS (WLS), a conserved membrane protein required for all WNT protein secretion, was specifically disrupted in the principal cells of the caput epididymidis. Immunoblot analysis showed that WLS was significantly reduced in the caput epididymidis of Wls cKO mice. In the caput epididymidis of Wls cKO mice, WNT 10A and WNT 2b, which are typically secreted by the principal cells of the caput epididymis, were not secreted. Interestingly, sperm motility analysis showed that the WLS deficiency in the caput epididymidis had no effect on sperm motility. Moreover, fertility tests showed that Wls cKO male mice had normal fertility. CONCLUSION: These results indicate that the disruption of WLS in principal cells of the caput epididymidis inhibits WNT protein secretion but has no effect on sperm motility and male fertility, suggesting that WNT signaling in the caput epididymidis may be dispensable for epididymal sperm maturation in mice.

Study on the Clinical Features and Prognosis of Penicilliosis marneffei Without Human Immunodeficiency Virus Infection.

OBJECTIVE: To improve the diagnosis and treatment of Penicilliosis marneffei without human immunodeficiency virus infection. METHODS: Analyze and review the clinical features, diagnosis and treatment of six cases of P. marneffei without human immunodeficiency virus infection at The First Affiliated Hospital of Fujian Medical University. RESULTS: Two cases were diagnosed in the ENT Department, three cases in the respiratory department and one case in the dermatological department. Penicillium marneffei infection was confirmed by sputum culture, blood culture and tissue biopsy. After definite diagnosis, one refused further treatment, and others showed significant improvement. CONCLUSION: Penicilliosis marneffei is insidious onset and easy to be escaped and misdiagnosed. To achieve early diagnosis and appropriate treatment, doubtful cases should be alerted for the diagnoses as P. marneffei.

EZH2 deletion promotes spermatogonial differentiation and apoptosis.

Spermatogenesis is crucial for male fertility and is therefore tightly controlled by a variety of epigenetic regulators. However, the function of enhancer of zeste homolog 2 (EZH2) in spermatogenesis and the molecular mechanisms underlying its activity remain poorly defined. Here, we demonstrate that deleting EZH2 promoted spermatogonial differentiation and apoptosis. EZH2 is expressed in spermatogonia, spermatocytes and round and elongated spermatids from stage 9 to 11 but not in leptotene and zygotene spermatocytes. Knocking down Ezh2 in vitro using a lentivirus impaired self-renewal in spermatogonial stem cells (SSCs), and the conditional knockout of Ezh2 in spermatogonial progenitors promoted precocious spermatogonial differentiation. EZH2 functions to balance self-renewal and differentiation in spermatogonia by suppressing NEUROG3 and KIT via a direct interaction that is independent of its histone methyltransferase activity. Moreover, deleting Ezh2 enhanced the activation of CASP3 in spermatids, resulting in reduced spermatozoa production. Collectively, these data demonstrate that EZH2 plays a nonclassical role in the regulation of spermatogonial differentiation and apoptosis in murine spermatogenesis.

Age-Related Loss of Cohesion: Causes and Effects.

Aneuploidy is a leading genetic cause of birth defects and lower implantation rates in humans. Most errors in chromosome number originate from oocytes. Aneuploidy in oocytes increases with advanced maternal age. Recent studies support the hypothesis that cohesion deterioration with advanced maternal age represents a leading cause of age-related aneuploidy. Cohesin generates cohesion, and is established only during the premeiotic S phase of fetal development without any replenishment throughout a female's period of fertility. Cohesion holds sister chromatids together until meiosis resumes at puberty, and then chromosome segregation requires the release of sister chromatid cohesion from chromosome arms and centromeres at anaphase I and anaphase II, respectively. The time of cohesion cleavage plays an important role in correct chromosome segregation. This review focuses specifically on the causes and effects of age-related cohesion deterioration in female meiosis.

Selective deletion of Smad4 in postnatal germ cells does not affect spermatogenesis or fertility in mice.

SMAD4 is the central component of canonical signaling in the transforming growth factor beta (TGFß) superfamily. Loss of Smad4 in Sertoli cells affects the expansion of the fetal testis cords, whereas selective deletion of Smad4 in Leydig cells alone does not appreciably alter fetal or adult testis development. Loss of Smad4 in Sertoli and Leydig cells, on the other hand, leads to testicular dysgenesis, and tumor formation in mice. Within the murine testes, Smad4 is also expressed in germ cells of the seminiferous tubules. We therefore, crossed Ngn3-Cre or Stra8-Cre transgenic mice with Smad4-flox mice to generate conditional knockout animals in which Smad4 was specifically deleted in postnatal germ cells to further uncover cell type-specific requirement of Smad4. Unexpectedly, these germ-cell-knockout mice were fertile and did not exhibit any detectable abnormalities in spermatogenesis, indicating that Smad4 is not required for the production of sperm; instead, these data indicate a cell type-specific requirement of Smad4 primarily during testis development. Mol. Reprod. Dev. 83: 615-623, 2016. © 2016 Wiley Periodicals, Inc.

Melatonin promotes development of haploid germ cells from early developing spermatogenic cells of Suffolk sheep under in vitro condition.

Promotion of spermatogonial stem cell (SSC) differentiation into functional sperms under in vitro conditions is a great challenge for reproductive physiologists. In this study, we observed that melatonin (10(-7) M) supplementation significantly enhanced the cultured SSCs differentiation into haploid germ cells. This was confirmed by the expression of sperm special protein, acrosin. The rate of SSCs differentiation into sperm with melatonin supplementation was 11.85 ± 0.93% which was twofold higher than that in the control. The level of testosterone, the transcriptions of luteinizing hormone receptor (LHR), and the steroidogenic acute regulatory protein (StAR) were upregulated with melatonin treatment. At the early stage of SSCs culture, melatonin suppressed the level of cAMP, while at the later stage, it promoted cAMP production. The similar pattern was observed in testosterone content. Expressions for marker genes of meiosis anaphase, Dnmt3a, and Bcl-2 were upregulated by melatonin. In contrast, Bax expression was downregulated. Importantly, the in vitro-generated sperms were functional and they were capable to fertilize oocytes. These fertilized oocytes have successfully developed to the blastula stage.

The association between the oocyte pool and aneuploidy: a comparative study of the reproductive potential of young and aged mice.

PURPOSE: The present study examined the effect of aging on female reproductive potential. METHODS: Six-week-old and 9-month-old CD1 mice were referred to as the 'young' and 'aged' groups, respectively. Oocytes were collected after superovulation, and their viability were compared using parthenogenetic activation. The aneuploidy of the oocytes (MII) was assessed using chromosome spread, and the whole ovarian follicle number was counted using an unbiased stereological method. Serum hormone levels were measured using the radio-immunity method, and the expression of the Cohesin subunit genes in the oocytes (GV) were assessed using RT-PCR. RESULTS: The mean number of recovered (25.8 vs. 16.2; P < 0.05) and live oocytes (24.0 vs. 11.73; P <0.01) per head in the young-mice group (6-week-old) was significantly higher than that of the aged group (9-month-old). The aneuploidy rate of the ovulated oocytes in the aged group was significantly higher than that of the young group (36.8% vs. 10%; P < 0.01), and the rate of blastocyst formation in the young group (85.23%) was significantly higher than that of the aged group (81.2%; P <0.05). The number of primordial follicles (the oocyte pool) per ovary in the aged group was significantly decreased compared with the young group (330 ± 33.51 vs. 2079.6 ± 420.70; P < 0.01), and the level of AMH in the aged group was significantly higher than that of the young group (4.66 ± 0.11 ng/ml vs. 4.07 ± 0.18 ng/ml; P < 0.01). CONCLUSIONS: We propose that maternal aging significantly reduces the oocyte pool, superovulation efficiency and developmental potential and increases the oocyte aneuploidy rate.

A Systematic Review and Meta-Analysis of MRI Radiomics for Predicting Microvascular Invasion in Patients with Hepatocellular Carcinoma.

BACKGROUND: The prediction power of MRI radiomics for microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) remains uncertain. OBJECTIVE: To investigate the prediction performance of MRI radiomics for MVI in HCC. METHODS: Original studies focusing on preoperative prediction performance of MRI radiomics for MVI in HCC, were systematically searched from databases of PubMed, Embase, Web of Science and Cochrane Library. Radiomics quality score (RQS) and risk of bias of involved studies were evaluated. Meta-analysis was carried out to demonstrate the value of MRI radiomics for MVI prediction in HCC. Influencing factors of the prediction performance of MRI radiomics were identified by subgroup analyses. RESULTS: 13 studies classified as type 2a or above according to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis statement were eligible for this systematic review and meta-analysis. The studies achieved an average RQS of 14 (ranging from 11 to 17), accounting for 38.9% of the total points. MRI radiomics achieved a pooled sensitivity of 0.82 (95%CI: 0.78 - 0.86), specificity of 0.79 (95%CI: 0.76 - 0.83) and area under the summary receiver operator characteristic curve (AUC) of 0.88 (95%CI: 0.84 - 0.91) to predict MVI in HCC. Radiomics models combined with clinical features achieved superior performances compared to models without the combination (AUC: 0.90 vs 0.85, P < 0.05). CONCLUSION: MRI radiomics has the potential for preoperative prediction of MVI in HCC. Further studies with high methodological quality should be designed to improve the reliability and reproducibility of the radiomics models for clinical application. The systematic review and meta-analysis was registered prospectively in the International Prospective Register of Systematic Reviews (No. CRD42022333822).

Nasopharyngeal angiofibroma: a concise classification system and appropriate treatment options.

OBJECTIVES: To describe a clear and simplified classification system for juvenile nasopharyngeal angiofibroma (JNA), and to describe suitable management options. STUDY DESIGN: Retrospective medical record review. METHODS: The clinical and imaging materials of 51 cases of JNA diagnosed at our hospital between 1981 and 2011 were collected and studied. Based on our experiences, we prefer to divide JNAs into three types. Type I includes JNAs fundamentally localized to the nasal cavity, paranasal sinus, nasopharynx, or pterygopalatine fossa. Type II is a JNA extending into the infratemporal fossa, cheek region, or orbital cavity, with anterior and/or minimal middle cranial fossa extension but intact dura mater. Type III is a calabash-like massive tumor lobe in the middle cranial fossa. The management and prognosis for the three types of JNA were compared and evaluated. RESULTS: Among cases of type I JNA (n=16), the entire mass was removed by the initial operation in 15 cases and by a repeat operation in 1 case. Among cases of type II JNA (n=29), the entire mass was removed by the first operation in 24 cases and by repeat operation in 5 cases. In cases of type III JNA (n=6), the huge calabash-like lobe in the middle cranial fossa could not be completely excised; 4 cases underwent radiotherapy and 2 cases were lost to follow-up. CONCLUSIONS: 1) The transnasal cavity approach with endoscopic guidance is suitable for type I JNA resection. 2) The transantral-infratemporal fossa-nasal cavity combined approach is reliable for resection of a type II JNA, which extends into the deep anterior cranial fossa and/or minimally into the middle cranial fossa, with intact dura mater. 3) The complete removal of a type III JNA is difficult, even through a combined extracranial and intracranial approach. Radiotherapy is useful for treating the residual intracranial tumor. The successful or failed experiences of 6 typical cases prove that this revised classification system is reasonable and reliable.

Elevated intracellular pH of zygotes during mouse aging causes mitochondrial dysfunction associated with poor embryo development.

The mortality of preimplantation embryos is positively correlated with maternal age. However, the underlying mechanism for the poor quality of embryos remains unclear. Here, we found that aging caused elevated intracellular pH (pHi) in zygotes, which could trigger aberrant mitochondrial membrane potential, increased reactive oxygen species (ROS) levels, and poor embryo development. Moreover, single-cell transcriptome sequencing of mouse zygotes identified 120 genes that were significantly differentially expressed (DE) between young and older zygotes. These include genes such as Slc14a1, Fxyd5, CD74, and Bst, which are related to cell division, ion transporter, and cell differentiation. Further analysis indicated that these DE genes were enriched in apoptosis, the NF-kappa B signaling pathway, and the chemokine signaling pathway, which might be the key regulatory pathway affecting the quality of zygotes and subsequent embryo development. Taken together, our study helps elucidate the poor quality and development of older preimplantation embryos.

Knockdown of disheveled-associated activator of morphogenesis 2 disrupts cytoskeletal organization and phagocytosis in rat Sertoli cells.

Disheveled-associated activator of morphogenesis 2 (DAAM2) regulates actin polymerization and cell motility. In this study, we investigated the role of DAAM2 in the cytoskeleton and phagocytosis of rat Sertoli cells in vitro and in vivo through siRNA transfection and intratesticular injection. We found that knockdown of DAAM2 significantly attenuated cytoskeletal and tight junction marker expression and reduced the integrity of the Sertoli cell monolayer. In rats, loss of DAAM2 induced disarrangement and deformation of sperms and promoted accumulation of apoptotic sperms in the testis, accompanied by morphological abnormalities in the blood-testis barrier. DAAM2 silencing also reduced the ability of Sertoli cells to engulf apoptotic spermatogenic cells and green fluorescence-labeled beads. RNA sequencing and bioinformatics analysis revealed that phagocytosis and cytoskeleton-related genes and pathways were significantly associated with DAAM2. Our study suggests that DAAM2 may be involved in spermatogenesis possibly by regulating cytoskeleton organization and phagocytosis of Sertoli cells.

Biomimetic Gold Nanostructure with a Virus-like Topological Surface for Enhanced Antigen Cross-Presentation and Antitumor Immune Response.

The internalization of antigens by dendritic cells (DCs) is the initial critical step for vaccines to activate the immune response; however, the systemic delivery of antigens into DCs is hampered by various technical challenges. Here we show that a virus-like gold nanostructure (AuNV) can effectively bind to and be internalized by DCs due to its biomimetic topological morphology, thereby significantly promoting the maturation of DCs and the cross-presentation of the model antigen ovalbumin (OVA). In vivo experiments demonstrate that AuNV efficiently delivers OVA to draining lymph nodes and significantly inhibits the growth of MC38-OVA tumors, generating a ∼80% decrease in tumor volume. Mechanistic studies reveal that the AuNV-OVA vaccine induces a remarkable increase in the rate of maturation of DCs, OVA presentation, and CD4+ and CD8+ T lymphocyte populations in both lymph node and tumor and an obvious decrease in myeloid-derived suppressor cells and regulatory T cell populations in spleen. The good biocompatibility, strong adjuvant activity, enhanced uptake of DCs, and improved T cell activation make AuNV a promising antigen delivery platform for vaccine development.

Renal ectopic lipid deposition in rats with early-stage diabetic nephropathy evaluated by the MR mDixon-Quant technique: association with the expression of SREBP-1 and PPARα in renal tissue.

Background: Renal ectopic lipid deposition (ELD) plays a significant role in the development of diabetic nephropathy (DN). This study aimed to use the magnetic resonance (MR) mDixon-Quant technique to evaluate renal ELD and its association with the expression of sterol regulatory element binding protein 1 (SREBP-1) and peroxisome proliferator-activated receptor alpha (PPARα) in renal tissue. Methods: Seventy male Sprague-Dawley (SD) rats were randomly divided into experimental (n=50) and control groups (n=20). A high-fat diet combined with low-dose streptozotocin (STZ) was administered to the experimental group to establish a type 2 diabetes mellitus (T2DM) model. The rats received renal mDixon-Quant scans and blood lipid and histopathological examinations in batches after the T2DM model was established. According to the histopathological findings, the included rats were stratified into control and early DN groups. Renal fat fraction (FF), blood lipid level, the ratio of the integrated optical density of intracellular lipid droplets and the total area of all the cells (IOD/TAC), and the expression of SREBP-1 and PPARɑ in renal tissue were analyzed. Results: Compared to the controls, renal FF, IOD/TAC, the expression of SREBP-1 in renal tissue, and serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) levels were higher in the early DN group, while the expression of PPARɑ in renal tissue and the high-density lipoprotein (HDL) level were lower (all P values <0.001). Renal FF gradually increased with the progression of disease [r=0.810 (95% CI: 0.675-0.928), P<0.001]. Positive correlations between renal FF and each of the following: TC, TG, LDL, IOD/TAC, and the expression of SREBP-1 [r=0.479 (95% CI: 0.353-0.640, P=0.012), 0.576 (95% CI: 0.283-0.842, P=0.002), 0.441 (95% CI: 0.305-0.606, P=0.021), 0.911 (95% CI: 0.809-0.964, P<0.001) and 0.800 (95% CI: 0.640-0.910, P<0.001), respectively] and negative correlations between renal FF and each of the following: HDL and the expression of PPARɑ [r=-0.611 (95% CI: -0.809 to -0.469, P=0.001) and -0.748 (95% CI: -0.886 to -0.585, P<0.001), respectively] were found. Conclusions: Renal lipid deposition evaluated by the MR mDixon-Quant technique is associated with the blood lipid level, histological fat quantification, and the expression of SREBP-1 and PPARɑ in renal tissue. The renal FF value might serve as a biomarker for better understanding of renal lipid metabolism in early-stage DN.