An integrative prediction model of successful sperm retrieval for men with non-obstructive azoospermia.

Microdissection testicular sperm extraction (micro-TESE) is an efficient method for obtaining spermatozoa from patients with non-obstructive azoospermia, but the overall success rate of this surgery is only approximately one-third. This study aimed to construct an integrative prediction model for andrologists to assess the preoperative success retrieval rate. A total of 217 patients diagnosed with non-obstructive azoospermia at the First Affiliated Hospital of Nanjing Medical University were included, in whom sperm was successfully retrieved in 71 patients. We retrospectively analyzed their clinical characteristics and pathological features. Single factor analysis and logistic regression analysis were utilized to validate the predictive performance, and the area under the curve (AUC) analysis was conducted to further assess the clinical diagnostic value of the model. The results showed that a history of Klinefelter syndrome or cryptorchidism, FSH (Follicle Stimulating Hormone) levels, and testicular pathology contributed differently to the nomogram prediction model. Relatively normal FSH levels, a history of Klinefelter syndrome or cryptorchidism, and favorable testicular pathological types were assigned higher scores, with higher scores often accompanying a preferable success rate of sperm retrieval. The integrated model showed good prediction performance, with an AUC (Area Under the Curve) of 0.781 (95% CI (confidence interval) 0.713-0.849). Overall, our integrative model demonstrates excellent prediction performance and may assist andrologists in balancing the benefits of surgery preoperatively.

The changes of peripheral blood hub genes in 24-week-old APP/PS1/Tau triple transgenic mouse model based on weighted gene co-expression network analysis.

Peripheral regulation emerges as a promising intervention in the early stages of Alzheimer's disease (AD). The hub genes in the peripheral blood of MCI patients from GEO database (GSE63060, GSE63061) were screened using weighted gene co-expression analysis (WGCNA). Meanwhile, behavioral tests, HE staining and Nissl staining were used to detect the memory impairment and histopathological changes in 24-week-old male 3×Tg-AD mice. Thioflavin-S and immunohistochemical staining were used to determine the Aß deposition in both intracellular and extracellular neurons. Subsequently, the MCI-hub genes were verified by quantitative real-time PCR (qRT-PCR) in the peripheral blood of 3×Tg-AD mice. The research revealed ten hub genes associated with MCI were identified WGCNA. Short-term memory loss, intracellular Aß deposition and limited of extracellular amyloid plaques in 3×Tg-AD mice. The qRT-PCR analysis of peripheral blood from these mice revealed significantly down-regulation in the expression levels of ATP5C1, ITGB2, EFTUD2 and RPS27A genes; whereas the expression level of VCP gene was significantly up-regulated. These findings confirmed that 24-week-old male 3×Tg-AD mice were a valuable animal model for simulating the early symptomatic stages of AD. Additionally, the peripheral blood MCI-hub genes related to immune response, energy metabolism and ribosomal coding efficiency provide potential biomarkers for this stage.

Study on Preclinical Safety and Toxic Mechanism of Human Umbilical Cord Mesenchymal Stem Cells in F344RG Rats.

Mesenchymal stem cells have made remarkable progress in recent years. Many studies have reported that human umbilical cord mesenchymal stem cells (hUC-MSCs) have no toxicity, but thromboembolism appeared in patients treated with hUC-MSCs. Therefore, people are still worried about the safety of clinical application. The study aims to determine the safety, potential toxic mechanism and biodistribution of hUC-MSCs. F344RG rats were given 5 or 50 million cells/kg of hUC-MSCs by single administration in compliance with Good Laboratory Practice standards. Standard toxicity was performed. RNA sequencing was then performed to explore the potential toxic mechanisms. In parallel, the biodistribution of hUC-MSCs was examined. The dose of 5 million cells/kg hUC-MSCs had no obvious toxicity on symptom, weight, food intake, hematology, serum biochemistry, urine biochemistry, cytokines, and histopathology. However, blood-tinged secretions in the urethral orifice and 20% mortality occurred at 50 million cells/kg. Disseminated intravascular coagulopathy (DIC) is the leading cause of death. hUC-MSCs significantly upregulated complement and coagulation cascade pathways gene expression, resulting in DIC. Besides, hUC-MSCs upregulated fibrinolytic system suppressor genes A2m, Serping1 and Serpinf2. hUC-MSCs survived in rats for less than 28 days, no hUC-MSC was detected in tissues outside the lungs. There was no toxicity in F344RG rats at 5 million cells/kg, but some toxicities were detected at 50 million cells/kg. hUC-MSCs significantly upregulated complement and coagulation cascade pathways, upregulated the expression of fibrinolytic system suppressor genes A2m, Serping1 and Serpinf2, to inhibit fibrinolytic system, caused DIC, which provided a new insight into the toxic mechanism of hUC-MSCs.

Messaging to Reduce Booster Hesitancy among the Fully Vaccinated.

Vaccine hesitancy was a serious problem in the United States throughout the COVID-19 pandemic, due in part to the reduction in public trust in science that accompanied the pandemic. Now we are facing a new, similar but more extensive problem: booster hesitancy. Even fewer Americans are current on the mRNA booster. We present the results of an experiment with residents of the US who received all initial doses of the mRNA vaccine but who were not up to date on the booster. Participants read a scientific explanation describing either the safety or the effectiveness of the boosters or nothing in the control group. The explanations significantly increased (compared to the control) participants' perceptions of the safety and effectiveness of the mRNA booster, as well as their willingness to get boosted. Explanations also improved emotions and attitudes toward the booster. Furthermore, although liberals were significantly more willing to get boosted than were conservatives, improvement due to the explanations was similar across political ideology groups. However, when interactions were observed, conservatives increased to a greater degree. Importantly, the explanations increased participants' perception of scientists' expertise and knowledge, as well as participants' trust in scientists and the vaccine technology.

Molecular mechanism of immunotoxicity: Binding interaction between perfluorinated compounds and human immunoglobulin G.

Perfluorinated compounds (PFCs) can induce immunotoxicity effect via binding with proteins. Immunoglobulin G (IgG) is a common four chain monomer protein in serum, and plays an important role in long-term body fluid immunity. Whether PFCs can bind with IgG and further induce immunotoxicity is not clear. Herein, fluorescence quenching assay was used to verify the PFCs-IgG binding interactions. The occurrence of fluorescence quenching phenomenon suggested that PFCs could bind to IgG. Linear fitting curves demonstrated that the binding constants (KA) for perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) were 2.51 × 106 L/mol and 1.58 × 105 L/mol, respectively. UV-vis spectral analysis results showed that the PFCs-IgG interactions mainly proceeded via the intercalation binding mode. Fourier transform infrared spectroscopy results revealed that PFCs preferentially bound to the C=O/N-H of IgG structure. Circular dichroism results revealed that PFCs-IgG binding induced the decrease of α-helix. Moreover, hydrogen bonds and van der Waals force dominated PFCs-IgG binding interactions. This binding process was a stable process, and its stability depended on the number of hydrogen bonds formation. This study reveals the mechanism of interaction between PFCs and IgG at the molecular level, providing a theoretical basis for the immunotoxic mechanism of PFCs.

Single-cell transcriptomic landscape reveals the role of intermediate monocytes in aneurysmal subarachnoid hemorrhage.

Objective: Neuroinflammation is associated with brain injury and poor outcomes after aneurysmal subarachnoid hemorrhage (SAH). In this study, we performed single-cell RNA sequencing (scRNA-seq) to analyze monocytes and explore the mechanisms of neuroinflammation after SAH. Methods: We recruited two male patients with SAH and collected paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples from each patient. Mononuclear cells from the CSF and PB samples were sequenced using 10x Genomics scRNA-seq. Additionally, scRNA-seq data for CSF from eight healthy individuals were obtained from the Gene Expression Omnibus database, serving as healthy controls (HC). We employed various R packages to comprehensively study the heterogeneity of transcriptome and phenotype of monocytes, including monocyte subset identification, function pathways, development and differentiation, and communication interaction. Results: (1) A total of 17,242 cells were obtained in this study, including 7,224 cells from CSF and 10,018 cells from PB, mainly identified as monocytes, T cells, B cells, and NK cells. (2) Monocytes were divided into three subsets based on the expression of CD14 and CD16: classical monocytes (CM), intermediate monocytes (IM), and nonclassical monocytes (NCM). Differentially expressed gene modules regulated the differentiation and biological function in monocyte subsets. (3) Compared with healthy controls, both the toll-like receptor (TLR) and nod-like receptor (NLR) pathways were significantly activated and upregulated in IM from CSF after SAH. The biological processes related to neuroinflammation, such as leukocyte migration and immune response regulation, were also enriched in IM. These findings revealed that IM may play a key role in neuroinflammation by mediating the TLR and NLR pathways after SAH. Interpretation: In conclusion, we establish a single-cell transcriptomic landscape of immune cells and uncover the heterogeneity of monocyte subsets in SAH. These findings offer new insights into the underlying mechanisms of neuroinflammation and therapeutic targets for SAH.

Microbiome and Microbial Pure Culture Study Reveal Commensal Microorganisms Alleviate Salmonella enterica Serovar Pullorum Infection in Chickens.

Pullorum disease, an intestinal disease in chickens caused by Salmonella enterica serovar pullorum (S. Pullorum), is a significant threat to the poultry industry and results in substantial economic losses. The bacteria's transmission, both vertical and horizontal, makes it difficult to completely eliminate it. Control strategies for pullorum disease primarily involve stringent eradication programs that cull infected birds and employ antibiotics for treatment. However, eradication programs are costly, and antibiotic use is restricted. Therefore, developing alternative control strategies is essential. Increasingly, studies are focusing on modulating the gut microbiota to control intestinal diseases. Modulating the chicken gut microbiota may offer a novel strategy for preventing and controlling pullorum disease in poultry. However, the impact of S. Pullorum on the chicken gut microbiota has not been well established, prompting our exploration of the relationship between S. Pullorum and the chicken gut microbiota in this study. In this study, we initially analyzed the dynamic distribution of the gut microbiota in chickens infected with S. Pullorum. Alpha diversity analysis revealed a decrease in observed OTUs and the Shannon diversity index in the infected group, suggesting a reduction in the richness of the chicken gut microbiota due to S. Pullorum infection. Principal coordinate analysis (PCoA) showed distinct clusters between the gut microbiota of infected and uninfected groups, indicating S. Pullorum infection changed the chicken gut microbiota structure. Specifically, S. Pullorum infection enriched the relative abundance of the genera Escherichia-Shigella (65% in infected vs. 40.6% in uninfected groups) and Enterococcus (10.8% vs. 3.7%) while reducing the abundance of Lactobacillus (9.9% vs. 32%) in the chicken microbiota. Additionally, based on the observed changes in the chicken gut microbiota, we isolated microorganisms, including Bifidobacterium pseudolongum, Streptococcus equi and Lacticaseibacillus paracasei (L. paracasei), which were decreased by S. Pullorum infection. Notably, the L. paracasei Lp02 strain was found to effectively inhibit S. Pullorum proliferation in vitro and alleviate its infection in vivo. We found that S. Pullorum infection reduced the richness of the chicken gut microbiota and enriched the relative abundance of the genera Escherichia-Shigella and Enterococcus while decreasing the abundance of the anaerobic genus Lactobacillus. Furthermore, microbiota analysis enabled the isolation of several antimicrobial microorganisms from healthy chicken feces, with a L. paracasei strain notably inhibiting S. Pullorum proliferation in vitro and alleviating its infection in vivo. Overall, this research enhances our understanding of the interaction between gut microbiota and pathogen infection, as well as offers new perspectives and strategies for modulating the chicken gut microbiota to control pullorum disease.

Micro-interfacial behavior of antibiotic-resistant bacteria and antibiotic resistance genes in the soil environment: A review.

Overutilization and misuse of antibiotics in recent decades markedly intensified the rapid proliferation and diffusion of antibiotic resistance genes (ARGs) within the environment, thereby elevating ARGs to the status of a global public health crisis. Recognizing that soil acts as a critical reservoir for ARGs, environmental researchers have made great progress in exploring the sources, distribution, and spread of ARGs in soil. However, the microscopic state and micro-interfacial behavior of ARGs in soil remains inadequately understood. In this study, we reviewed the micro-interfacial behaviors of antibiotic-resistant bacteria (ARB) in soil and porous media, predominantly including migration-deposition, adsorption, and biofilm formation. Meanwhile, adsorption, proliferation, and degradation were identified as the primary micro-interfacial behaviors of ARGs in the soil, with component of soil serving as significant determinant. Our work contributes to the further comprehension of the microstates and processes of ARB and ARGs in the soil environments and offers a theoretical foundation for managing and mitigating the risks associated with ARG contamination.

One-Step Genetic Modification by Embryonic Doral Aorta Injection of Adenoviral CRISPR/Cas9 Vector in Chicken.

In the avian species, genetic modification by cell nuclear transfer is infeasible due to its unique reproductive system. The in vitro primordial germ cell modification approach is difficult and cumbersome, although it is the main method of genetic modification in chickens. In the present study, the adenoviral CRISPR/Cas9 vector was directly microinjected into the dorsal aorta of chicken embryos to achieve in vivo genetic modification. The results demonstrated that keratin 75-like 4 (KRT75L4), a candidate gene crucial for feather development, was widely knocked out, and an 8bp deletion was the predominant mutation that occurred in multiple tissues in chimeras, particularly in the gonad (2.63-11.57%). As we expected, significant modification was detected in the sperm of G0 (0.16-4.85%), confirming the potential to generate homozygous chickens and establishing this vector as a simple and effective method for genetic modification in avian species.

Long-term efficacy of lobectomy for stage T1 papillary thyroid carcinoma with varying degrees of lymph node metastasis.

Background: The presence of lymph node metastasis (LNM) is frequently observed in papillary thyroid carcinoma (PTC), and most clinical guidelines recommend total thyroidectomy. However, the impact of LNM on specific types of locoregional recurrence remains uncertain, particularly for stage T1 PTC. Methods: The present retrospective cohort study enrolled patients diagnosed with stage T1 PTC between 2008 and 2015. Propensity score matching was performed in patients with lobectomy accompanied by varying degrees of LNM. Logistic regression analysis was performed to compare the effect of LNM on relapse types, and Kaplan-Meier method was utilized to calculate recurrence-free survival. Results: The study cohort comprised 2,785 patients who were followed up for an average duration of 69 months. After controlling follow-up time and potential prognostic factors, we include a total of 362 patients in each group. Recurrence rates in the N0, N1a, and N1b groups were found to be 2.5%, 9.7%, and 10.2% respectively. Notably, group N1a versus group N0 (P=0.803), N1b group versus N0 group (P=0.465), and group N1b versus group N1a (P=0.344) had no difference in residual thyroid recurrence. However, when considering lymph node recurrence, both N1a(P=0.003) and N1b(P=0.009) groups showed a higher risk than N0 group. In addition, there was no difference in lymph node recurrence between N1b group and N1a group (P=0.364), but positive lymph node (PLN) and lymph node positive rate (LNPR) demonstrated a strong discriminatory effect (P<0.001). Conclusion: Lobectomy may be more appropriate for patients with unilateral stage T1 PTC in the low LNPR group.

The Role of Long Noncoding RNAs in Vascular Smooth Muscle Cell Phenotype and the Pathogenesis of Cardiovascular and Cerebrovascular Aneurysms.

ABSTRACT: Aneurysms are localized dilations of blood vessels, which can expand to 50% of the original diameter. They are more common in cardiovascular and cerebrovascular vessels. Rupture is one of the most dangerous complications. The pathophysiology of aneurysms is complex and diverse, often associated with progressive vessel wall dysfunction resulting from vascular smooth muscle cell death and abnormal extracellular matrix synthesis and degradation. Multiple studies have shown that long noncoding RNAs (lncRNAs) play a significant role in the progression of cardiovascular and cerebrovascular diseases. Therefore, it is necessary to find and summarize them. LncRNAs control gene expression and disease progression by regulating target mRNA or miRNA and are biomarkers for the diagnosis and prognosis of aneurysmal cardiovascular and cerebrovascular diseases. This review explores the role, mechanism, and clinical value of lncRNAs in aneurysms, providing new insights for a deeper understanding of the pathogenesis of cardiovascular and cerebrovascular aneurysms.

Constrained motion of self-propelling eccentric disks linked by a spring.

It has been supposed that the interplay of elasticity and activity plays a key role in triggering the non-equilibrium behaviors in biological systems. However, the experimental model system is missing to investigate the spatiotemporally dynamical phenomena. Here, a model system of an active chain, where active eccentric-disks are linked by a spring, is designed to study the interplay of activity, elasticity, and friction. Individual active chain exhibits longitudinal and transverse motions; however, it starts to self-rotate when pinning one end and self-beat when clamping one end. In addition, our eccentric-disk model can qualitatively reproduce such behaviors and explain the unusual self-rotation of the first disk around its geometric center. Furthermore, the structure and dynamics of long chains were studied via simulations without steric interactions. It was found that a hairpin conformation emerges in free motion, while in the constrained motions, the rotational and beating frequencies scale with the flexure number (the ratio of self-propelling force to bending rigidity), χ, as ∼(χ)4/3. Scaling analysis suggests that it results from the balance between activity and energy dissipation. Our findings show that topological constraints play a vital role in non-equilibrium synergy behaviors.

Secretory Nogo-B regulates Th2 differentiation in the lung cancer microenvironment.

Nogo-B, a ubiquitously expressed member of the reticulon family, plays an important role in maintaining endoplasmic reticulum (ER) structure, regulating protein folding, and calcium homeostasis. In this study, we demonstrate that Nogo-B expression and secretion are upregulated in lung cancer and correlate to overall survival. Nogo-B is secreted by various cells, particularly lung cancer cells. ER stress and phosphorylation at serine 107 can induce Nogo-B secretion. Secretory Nogo-B suppresses the differentiation of Th2 cells and the release of type 2 cytokines, thus influencing the anti-tumor effects of Th2-related immune cells, including IgE+B cell class switching and eosinophil activation.

Association of Lymph Nodes Positive Rate With the Risk of Recurrence in Patients With Stage T1 Papillary Thyroid Cancer.

The incidence of lymph node metastasis in papillary thyroid carcinoma (PTC) is common and a significant risk factor for local recurrence; however, its impact on recurrence patterns among low-risk patients remains uncertain. We aimed to elucidate the effect of metastatic lymph node on recurrence type. The medical records of 1209 patients with stage T1 PTC who underwent unilateral thyroidectomy with ipsilateral central lymph node dissection were retrospectively analyzed. The study first identified risk factors for different types of recurrence and then categorized patients as high or low risk based on their lymph node positive ratio (LNPR). The diagnostic accuracy of LNPR in predicting recurrence was compared using receiver operating characteristic (ROC) curve analysis, while differences in recurrence-free survival were assessed using the Kaplan-Meier method. During follow-up, a total of 502 (41.5%) patients had central lymph node metastasis and 52 (4.3%) patients experienced recurrence. Notably, LNPR was significantly higher in relapsed patients compared to nonrelapsed patients, with mean values of 0.45 and 0.23, respectively (P < .001). The recurrence rate of residual thyroid did not differ significantly across different T stages (P = .679), N stages (P = .415), or LNPR risk groups (P = .175). However, the recurrence rate of lymph nodes showed a significant correlation with LNPR (P < .001). The area under the ROC curves for LNPR risk stratification at 5 and 10 years were approximately 0.691 and 0.634, respectively, both of which outperformed N stage. The findings underscore the significance of LNPR's reliability as a prognostic indicator for local lymph node recurrence in patients diagnosed with T1 stage PTC.

HIF-1 Transcriptionally Regulates Basal Expression of STING to Maintain Cellular Innate Immunity.

Stimulator of IFN genes (STING) is a critical component of the innate immune system, playing an essential role in defending against DNA virus infections. However, the mechanisms governing basal STING regulation remain poorly understood. In this study, we demonstrate that the basal level of STING is critically maintained by hypoxia-inducible factor 1 (HIF-1)α through transcription. Under normal conditions, HIF-1α binds constitutively to the promoter region of STING, actively promoting its transcription. Knocking down HIF-1α results in a decrease in STING expression in multiple cell lines and zebrafish, which in turn reduces cellular responses to synthetic dsDNAs, including cell signaling and IFN production. Moreover, this decrease in STING levels leads to an increase in cellular susceptibility to DNA viruses HSV-1 and pseudorabies virus. These findings unveil a (to our knowledge) novel role of HIF-1α in maintaining basal STING levels and provide valuable insights into STING-mediated antiviral activities and associated diseases.

Identification of novel drug targets for multiple sclerosis by integrating plasma genetics and proteomes.

BACKGROUND: Genome-wide association studies (GWAS) have revealed numerous loci associated with multiple sclerosis (MS). However, the challenge lies in deciphering the mechanisms by which these loci influence the target traits. Here, we employed an integrative analytical pipeline to efficiently transform genetic associations to identify novel proteins for MS. METHODS: We systematically integrated MS GWAS data (N = 115,803) with human plasma proteome data (N = 7213) and conducted proteome-wide association studies (PWAS) to identify MS-associated pathogenic proteins. Following this, we employed Mendelian randomization and Bayesian colocalization analyses to verify the causal relationship between these significant plasma proteins and MS. Lastly, we utilized the Drug-Gene Interaction Database (DGIdb) to identify potential drug targets for MS. RESULTS: The PWAS identified 25 statistically significant cis-regulated plasma proteins associated with MS at a false discovery rate of P < 0.05. Further analysis revealed that the abundance of 7 of these proteins (PLEK, TNXB, CASP3, CD59, CR1, TAPBPL, ATXN3) was causally related to the incidence of MS. Our findings indicated that genetically predicted higher levels of TNXB and CD59 were associated with a lower risk of MS, whereas higher levels of PLEK, CASP3, CR1, TAPBPL, and ATXN3 were associated with an increased risk of MS. Three plasma proteins (PLEK, CR1, CD59) were validated by colocalization analysis. Among these, CR1 was prioritized as a target for Eculizumab due to its significant association with MS risk. Additionally, PLEK, CR1, and CD59 were identified as druggable target genes. CONCLUSIONS: Our proteomic analysis has identified PLEK, CR1, and CD59 as potential drug targets for MS treatment. Developing pharmacological inducers or inhibitors for these proteins could pave the way for new therapeutic approaches, potentially improving outcomes for MS patients.

Two High-Nuclear Wheel-Hub-Shaped Transition-Metal-Doped Polyoxovanadates.

The first two unprecedented high-nuclear wheel-hub-shaped transition-metal-doped polyoxovanadates, [M8Mo4W4V20P20] [M = Ni (1), Co (2)], have been assembled under solvothermal conditions. The center of the cluster consists of two {Ni4(oa)4} rings as the center hole, four {MoO4} units acting as the spokes, and four {WV5(PPOA)5} molecular building blocks serving as the tire. Compound 1 exhibits good catalytic properties and recyclability in oxidative desulfurization reactions.

Role of FMRP in AKT/mTOR pathway-mediated hippocampal autophagy in fragile X syndrome.

Fragile X syndrome (FXS) is caused by epigenetic silencing of the Fmr1 gene, leading to the deletion of the coding protein FMRP. FXS induces abnormal hippocampal autophagy and mTOR overactivation. However, it remains unclear whether FMRP regulates hippocampal autophagy through the AKT/mTOR pathway, which influences the neural behavior of FXS. Our study revealed that FMRP deficiency increased the protein levels of p-ULK-1 and p62 and decreased LC3II/LC3I level in Fmr1 knockout (KO) mice. The mouse hippocampal neuronal cell line HT22 with knockdown of Fmr1 by lentivirus showed that the protein levels of p-ULK-1 and p62 were increased, whereas LC3II/LC3I was unchanged. Further observations revealed that FMRP deficiency obstructed autophagic flow in HT22 cells. Therefore, FMRP deficiency inhibited autophagy in the mouse hippocampus and HT22 cells. Moreover, FMRP deficiency increased reactive oxygen species (ROS) level, decreased the co-localization between the mitochondrial outer membrane proteins TOM20 and LC3 in HT22 cells, and caused a decrease in the mitochondrial autophagy protein PINK1 in HT22 cells and Fmr1 KO mice, indicating that FMRP deficiency caused mitochondrial autophagy disorder in HT22 cells and Fmr1 KO mice. To explore the mechanism by which FMRP deficiency inhibits autophagy, we examined the AKT/mTOR signaling pathway in the hippocampus of Fmr1 KO mice, found that FMRP deficiency caused overactivation of the AKT/mTOR pathway. Rapamycin-mediated mTOR inhibition activated and enhanced mitochondrial autophagy. Finally, we examined whether rapamycin affected the neurobehavior of Fmr1 KO mice. The Fmr1 KO mice exhibited stereotypical behavior, impaired social ability, and learning and memory impairment, while rapamycin treatment improved behavioral disorders in Fmr1 KO mice. Thus, our study revealed the molecular mechanism by which FMRP regulates autophagy function, clarifying the role of hippocampal neuron mitochondrial autophagy in the pathogenesis of FXS, and providing novel insights into potential therapeutic targets of FXS.