Duplication and sub-functionalization of flavonoid biosynthesis genes plays important role in Leguminosae root nodule symbiosis evolution.

Gene innovation plays an essential role in trait evolution. Rhizobial symbioses, the most important N2-fixing agent in agricultural systems that exists mainly in Leguminosae, is one of the most attractive evolution events. However, the gene innovations underlying Leguminosae root nodule symbiosis (RNS) remain largely unknown. Here, we investigated the gene gain event in Leguminosae RNS evolution through comprehensive phylogenomic analyses. We revealed that Leguminosae-gain genes were acquired by gene duplication and underwent a strong purifying selection. Kyoto Encyclopedia of Genes and Genomes analyses showed that the innovated genes were enriched in flavonoid biosynthesis pathways, particular downstream of chalcone synthase (CHS). Among them, Leguminosae-gain type Ⅱ chalcone isomerase (CHI) could be further divided into CHI1A and CHI1B clades, which resulted from the products of tandem duplication. Furthermore, the duplicated CHI genes exhibited exon-intron structural divergences evolved through exon/intron gain/loss and insertion/deletion. Knocking down CHI1B significantly reduced nodulation in Glycine max (soybean) and Medicago truncatula; whereas, knocking down its duplication gene CHI1A had no effect on nodulation. Therefore, Leguminosae-gain type Ⅱ CHI participated in RNS and the duplicated CHI1A and CHI1B genes exhibited RNS functional divergence. This study provides functional insights into Leguminosae-gain genetic innovation and sub-functionalization after gene duplication that contribute to the evolution and adaptation of RNS in Leguminosae.

Percutaneous Endoscope-assisted Visualized Implantation of Puncture Cylindrical Electrodes for Spinal Cord Stimulation: A Cadaveric Feasibility Study.

BACKGROUND: Spinal cord stimulation is an established technique wherein diverse electrode types are strategically implanted within the spinal epidural space for neuromodulation. Traditional percutaneous puncture cylindrical electrodes (PEs) are predominantly implanted by interventionalists utilizing a percutaneous technique under the monitor of radiation, which is a nonvisualized procedure. OBJECTIVE: Our study aimed to assess the feasibility of percutaneous endoscope-assisted visualized implantation approach for PEs, delineating its specific merits and demerits compared to the traditional method. STUDY DESIGN: Laboratory study with Institutional Review Board Number B2023-056SETTING: Clinical Anatomy Research Center, Fudan University. METHODS: Eight freshly procured adult cadavers (4 women and 4 men) were operated on in this study. They were divided into either Group A or Group B, each encompassing 4 cadavers. Group A was subjected to endoscope-assisted PEs implantation, whereas Group B followed the conventional PEs implantation route.In both groups the operative time of introducer needles placement (OTNP), total operative time (TOT), fluoroscopy time of introducer needles placement (FTNP), and total fluoroscopy time (TFT) were documented and analyzed. Furthermore, the precise positioning of the PEs and any ensuing complications were systematically examined. RESULTS: Both Group A and Group B successfully executed all predetermined surgical steps. A total of 16 PEs were implanted (dual electrodes in each cadaver): 8 using the percutaneous endoscope-assisted visualized approach (Group A) and 8 via the traditional methodology (Group B). Group A's mean ± SD durations for OTNP, TOT, FTNP, and TFT were 10.25 ± 1.03 minutes, 31.63 ± 5.87 minutes, 4.58 ± 1.35 seconds, and 43.73 ± 14.46 seconds, respectively. In contrast, Group B exhibited mean ± SD times of 11.55 ± 2.81 minutes, 44.75 ± 7.85 minutes, 23.53 ± 4.16 seconds, and 66.30 ± 6.35 seconds for the same metrics. No discernible statistical difference in OTNP and TOT emerged between the groups. However, Group A demonstrated reduced durations for both FTNP and TFT compared to Group B. The optimal position of the PEs was verified via fluoroscopy, with no recorded instances of dura rupture. These outcomes suggest that this endoscope-assisted technique neither increases surgical time nor compromises efficacy. Instead, it leads to a marked reduction in fluoroscopic duration relative to the traditional methodology. LIMITATIONS: Anatomical study on a human cadaver, the quantity of cadavers, and the procedure's steep learning curve. CONCLUSION: With the assistance of percutaneous spinal endoscopy, introducer needles can be punctured through the ligamentum flavum at the anticipated interlaminar window locus under direct visualization, improving the convenience of the puncture and reducing fluoroscopic exposure. It is a viable alternative for surgeons from diverse training backgrounds to implant PEs, particularly benefiting those well-versed in endoscopic spine surgery techniques.

Step-by-Step Description of Percutaneous Full-Endoscopic C2 Ganglionectomy: An Anatomic Feasibility Study in Human Cadavers.

BACKGROUND AND OBJECTIVES: The percutaneous full-endoscopic C2 ganglionectomy (PEC2G), an innovative procedure developed for the surgical treatment of intractable occipital neuralgia, was firstly reported by us in 2021. However, a universally accepted and well-articulated protocol modality remains elusive. The primary objective of this anatomic investigation was to meticulously elucidate the standard procedural steps of PEC2G and assess the anatomic features supporting the safe implementation of PEC2G. METHODS: Eighteen fresh adult cadavers were incorporated into this study. From this sample, 3 cadavers were subjected to bilateral PEC2G. Each procedure was documented and assessed, leading to the formulation of standard procedure criteria for PEC2G. Subsequently, 10 sets of anatomic parameters pertinent to this procedure were identified, quantified, and analyzed in 15 cadavers after complete bilateral endoscopic exposure of the C2 ganglion. An assessment of the technical feasibility and potential constraints associated with PEC2G was conducted, providing invaluable insights into the procedure's anatomic considerations. RESULTS: All 3 cadavers successfully underwent the PEC2G without any observed complications, such as dura tears or vertebral artery injuries. The C2 inferior articular process emerged as the optimal bony target for puncture, with the C2 pedicle serving as the standard guiding landmark en route to the C2 ganglion. In the 15 cadavers subjected to the planned procedure, 10 sets of anatomic parameters were quantified, establishing a foundational understanding of the anatomy in the context of PEC2G procedure. The results demonstrated that the characteristic of anatomic data pertinent to surgical site supported the safe implementation of PEC2G. CONCLUSION: This study contributes the standard surgical steps and crucial anatomic parameters relevant to PEC2G. The characteristic of anatomic data bolsters the safety credentials of this technique, which offers a reliable approach to achieve C2 ganglionectomy. These insights undeniably establish a robust foundation for the ongoing refinement and broader adoption of PEC2G.

Neutrophil Extracellular Traps-Inspired Bismuth-Based Polypeptide Nanonets for Synergetic Treatment of Bacterial Infections.

Excessive use of antibiotics and the formation of bacterial biofilms can lead to persistent infections caused by drug-resistant bacteria, rendering ineffective immune responses and even life-threatening. There is an urgent need to explore synergistic antibacterial therapies across all stages of infection. Drawing inspiration from the antibacterial properties of neutrophil extracellular traps (NETs) and integrating the bacterial biofilm dispersal mechanism involving boronic acid-catechol interaction, the multifunctional bismuth-based polypeptide nanonets (PLBA-Bi-Fe-TA) are developed. These nanonets are designed to capture bacteria through a coordination complex involving cationic polypeptides (PLBA) with boronic acid-functionalized side chains, alongside metal ions (bismuth (Bi) and iron (Fe)), and tannic acid (TA). Leveraging the nanoconfinement-enhanced high-contact network-driven multiple efficiency, PLBA-Bi-Fe-TA demonstrates the excellent ability to swiftly capture bacteria and their extracellular polysaccharides. This interaction culminates in the formation of a highly hydrophilic complex, effectively enabling the rapid inhibition and dispersion of antibiotic-resistant bacterial biofilms, while Fe-TA shows mild photothermal ability to further assist fluffy mature biofilm. In addition, Bi is beneficial to regulate the polarization of macrophages to pro-inflammatory phenotype to further kill escaping biofilm bacteria. In summary, this novel approach offers a promising bionic optimization strategy for treating bacterial-associated infections at all stages through synergetic treatment.

Components, Formulations, Deliveries, and Combinations of Tumor Vaccines.

Tumor vaccines, an important part of immunotherapy, prevent cancer or kill existing tumor cells by activating or restoring the body's own immune system. Currently, various formulations of tumor vaccines have been developed, including cell vaccines, tumor cell membrane vaccines, tumor DNA vaccines, tumor mRNA vaccines, tumor polypeptide vaccines, virus-vectored tumor vaccines, and tumor-in-situ vaccines. There are also multiple delivery systems for tumor vaccines, such as liposomes, cell membrane vesicles, viruses, exosomes, and emulsions. In addition, to decrease the risk of tumor immune escape and immune tolerance that may exist with a single tumor vaccine, combination therapy of tumor vaccines with radiotherapy, chemotherapy, immune checkpoint inhibitors, cytokines, CAR-T therapy, or photoimmunotherapy is an effective strategy. Given the critical role of tumor vaccines in immunotherapy, here, we look back to the history of tumor vaccines, and we discuss the antigens, adjuvants, formulations, delivery systems, mechanisms, combination therapy, and future directions of tumor vaccines.

Cell Membrane Engineered Polypeptide Nanonets Mimicking Macrophage Aggregates for Enhanced Antibacterial Treatment.

Drug-resistant bacterial infections and their lipopolysaccharide-related inflammatory complications continue to pose significant challenges in traditional treatments. Inspired by the rapid initiation of resident macrophages to form aggregates for efficient antibacterial action, this study proposes a multifunctional and enhanced antibacterial strategy through the construction of novel biomimetic cell membrane polypeptide nanonets (R-DPB-TA-Ce). The design involves the fusion of end-terminal lipidated polypeptides containing side-chain cationic boronic acid groups (DNPLBA) with cell membrane intercalation engineering (R-DPB), followed by coordination with the tannic acid-cerium complex (TA-Ce) to assemble into a biomimetic nanonet through boronic acid-polyphenol-metal ion interactions. In addition to the ability of RAW 264.7 macrophages cell membrane components' (R) ability to neutralize lipopolysaccharide (LPS), R-DPB-TA-Ce demonstrated enhanced capture of bacteria and its LPS, leveraging nanoconfinement-enhanced multiple interactions based on the boronic acid-polyphenol nanonets skeleton combined with polysaccharide. Utilizing these advantages, indocyanine green (ICG) is further employed as a model drug for delivery, showcasing the exceptional treatment effect of R-DPB-TA-Ce as a new biomimetic assembled drug delivery system in antibacterial, anti-inflammatory, and wound healing promotion. Thus, this strategy of mimicking macrophage aggregates is anticipated to be further applicable to various types of cell membrane engineering for enhanced antibacterial treatment.

Polycyclic Aromatic Hydrocarbons' Impact on Crops and Occurrence, Sources, and Detection Methods in Food: A Review.

Polycyclic aromatic hydrocarbons (PAHs) represent a category of persistent organic pollutants that pose a global concern in the realm of food safety due to their recognized carcinogenic properties in humans. Food can be contaminated with PAHs that are present in water, air, or soil, or during food processing and cooking. The wide and varied sources of PAHs contribute to their persistent contamination of food, leading to their accumulation within these products. As a result, monitoring of the levels of PAHs in food is necessary to guarantee the safety of food products as well as the public health. This review paper attempts to give its readers an overview of the impact of PAHs on crops, their occurrence and sources, and the methodologies employed for the sample preparation and detection of PAHs in food. In addition, possible directions for future research are proposed. The objective is to provide references for the monitoring, prevention, and in-depth exploration of PAHs in food.

E3 ubiquitin ligase TRIM31 alleviates dopaminergic neurodegeneration by promoting proteasomal degradation of VDAC1 in Parkinson's Disease model.

Mitochondrial dysfunction plays a pivotal role in the pathogenesis of Parkinson's disease (PD). As a mitochondrial governor, voltage-dependent anion channel 1 (VDAC1) is critical for cell survival and death signals and implicated in neurodegenerative diseases. However, the mechanisms of VDAC1 regulation are poorly understood and the role of tripartite motif-containing protein 31 (TRIM31), an E3 ubiquitin ligase which is enriched in mitochondria, in PD remains unclear. In this study, we found that TRIM31-/- mice developed age associated motor defects and dopaminergic (DA) neurodegeneration spontaneously. In addition, TRIM31 was markedly reduced both in nigrostriatal region of PD mice induced by MPTP and in SH-SY5Y cells stimulated by MPP+. TRIM31 deficiency significantly aggravated DA neurotoxicity induced by MPTP. Mechanistically, TRIM31 interacted with VDAC1 and catalyzed the K48-linked polyubiquitination to degrade it through its E3 ubiquitin ligase activity. In conclusion, we demonstrated for the first time that TRIM31 served as an important regulator in DA neuronal homeostasis by facilitating VDAC1 degradation through the ubiquitin-proteasome pathway. Our study identified TRIM31 as a novel potential therapeutic target and pharmaceutical intervention to the interaction between TRIM31 and VDAC1 may provide a promising strategy for PD.

MADE: Multicurvature Adaptive Embedding for Temporal Knowledge Graph Completion.

Temporal knowledge graphs (TKGs) are receiving increased attention due to their time-dependent properties and the evolving nature of knowledge over time. TKGs typically contain complex geometric structures, such as hierarchical, ring, and chain structures, which can often be mixed together. However, embedding TKGs into Euclidean space, as is typically done with TKG completion (TKGC) models, presents a challenge when dealing with high-dimensional nonlinear data and complex geometric structures. To address this issue, we propose a novel TKGC model called multicurvature adaptive embedding (MADE). MADE models TKGs in multicurvature spaces, including flat Euclidean space (zero curvature), hyperbolic space (negative curvature), and hyperspherical space (positive curvature), to handle multiple geometric structures. We assign different weights to different curvature spaces in a data-driven manner to strengthen the ideal curvature spaces for modeling and weaken the inappropriate ones. Additionally, we introduce the quadruplet distributor (QD) to assist the information interaction in each geometric space. Ultimately, we develop an innovative temporal regularization to enhance the smoothness of timestamp embeddings by strengthening the correlation of neighboring timestamps. Experimental results show that MADE outperforms the existing state-of-the-art TKGC models.

Deciphering the progression of fine-needle aspiration: A bibliometric analysis of thyroid nodule research.

This study aims to dissect the evolution and pivotal shifts in Fine-Needle Aspiration (FNA) research for thyroid nodules over the past 2 decades, focusing on delineating key technological advancements and their impact on clinical practice. A comprehensive bibliometric analysis was conducted on 5418 publications from the Web of Science Core Collection database (2000-2023). Publications were rigorously selected based on their contributions to the advancement of FNA techniques and their influence on thyroid nodule management practices. Our analysis uncovered significant breakthroughs, most notably the incorporation of ultrasound and molecular diagnostics in FNA, which have markedly elevated diagnostic accuracy. A pivotal shift was identified towards minimally invasive post-FNA treatments, such as Radiofrequency Ablation, attributable to these diagnostic advancements. Additionally, the emergence of AI-assisted cytology represents a frontier in precision diagnostics, promising enhanced disease identification. The geographical analysis pinpointed the United States, Italy, and China as key contributors, with the United States leading in both publication volume and citation impact. This bibliometric analysis sheds light on the transformative progression in FNA practices for thyroid nodules, characterized by innovative diagnostic technologies and a trend towards patient-centric treatment approaches. The findings underscore the need for further research into AI integration and global practice standardization. Future explorations should focus on the practical application of these advancements in diverse healthcare settings and their implications for global thyroid nodule management.

Predictive value of positive lymph node ratio in patients with locally advanced gastric remnant cancer.

BACKGROUND: Traditional lymph node stage (N stage) has limitations in advanced gastric remnant cancer (GRC) patients; therefore, establishing a new predictive stage is necessary. AIM: To explore the predictive value of positive lymph node ratio (LNR) according to clinicopathological characteristics and prognosis of locally advanced GRC. METHODS: Seventy-four patients who underwent radical gastrectomy and lymphadenectomy for locally advanced GRC were retrospectively reviewed. The relationship between LNR and clinicopathological characteristics was analyzed. The survival analysis was performed using Kaplan-Meier survival curves and Cox regression model. RESULTS: Number of metastatic LNs, tumor diameter, depth of tumor invasion, Borrmann type, serum tumor biomarkers, and tumor-node-metastasis (TNM) stage were correlated with LNR stage and N stage. Univariate analysis revealed that the factors affecting survival included tumor diameter, anemia, serum tumor biomarkers, vascular or neural invasion, combined resection, LNR stage, N stage, and TNM stage (all P < 0.05). The median survival time for those with LNR0, LNR1, LNR2 and LNR3 stage were 61, 31, 23 and 17 mo, respectively, and the differences were significant (P = 0.000). Anemia, tumor biomarkers and LNR stage were independent prognostic factors for survival in multivariable analysis (all P < 0.05). CONCLUSION: The new LNR stage is uniquely based on number of metastatic LNs, with significant prognostic value for locally advanced GRC, and could better differentiate overall survival, compared with N stage.

Enantioselective Formal 1,2-Diamination of Ketenes with Iminosulfinamides: Asymmetric Synthesis of Unnatural α,α-Disubstituted α-Amino Acid Derivatives.

A method was developed for the enantioselective formal 1,2-diamination of disubstituted ketenes using iminosulfinamides as nitrogen sources. The protocol involves the addition of lithium iminosulfinamides to ketenes to form N-iminosulfinyl amide metalloenolates. These metalloenolates then undergo a [2,3]-sigmatropic rearrangement to yield unnatural α,α-disubstituted α-amino acid derivatives with high enantiopurity. The chirality present at the sulfur atom in the iminosulfinamides is effectively transferred to α carbon of the resulting products, facilitating the highly enantioselective amination of ketenes.

Fractional Amplitude of Low-Frequency Fluctuation and Voxel-Mirrored Homotopic Connectivity in Patients with Persistent Postural-Perceptual Dizziness: Resting-State Functional Magnetic Resonance Imaging Study.

Purpose: Persistent postural-perception dizziness (PPPD) is a chronic subjective form of dizziness characterized by the exacerbation of dizziness with active or passive movement, complex visual stimuli, and upright posture. Therefore, we aimed to analyze the resting-state functional magnetic resonance imaging (fMRI) in patients with PPPD using fractional amplitude of low-frequency fluctuation (fALFF) and voxel-mirrored homotopic connectivity (VMHC) and evaluate the correlation between abnormal regions in the brain and clinical features to investigate the pathogenesis of PPPD. Methods: Thirty patients with PPPD (19 females and 11 males) and 30 healthy controls (HCs; 18 females and 12 males) were closely matched for age and sex. The fALFF and VMHC methods were used to investigate differences in fMRI (BOLD sequences) between the PPPD and HC groups and to explore the associations between areas of functional abnormality and clinical characteristics (dizziness, anxiety, depression, and duration). Result: Compared to the HC group, patients with PPPD displayed different functional change patterns, with increased fALFF in the right precuneus and decreased VMHC in the bilateral precuneus. In addition, patients with PPPD had a positive correlation between precuneus fALFF values and dizziness handicap inventory (DHI) scores, and a negative correlation between VMHC values and the disease duration. Conclusions: Precuneus dysfunction was observed in patients with PPPD. The fALFF values correlated with the degree of dizziness in PPPD, and changes in VMHC values were associated with the duration of dizziness, suggesting that fMRI changes in the precuneus of patients could be used as a potential imaging marker for PPPD.

Evolution and Antigenic Differentiation of Avian Influenza A(H7N9) Virus, China.

We characterized the evolution and molecular characteristics of avian influenza A(H7N9) viruses isolated in China during 2021-2023. We systematically analyzed the 10-year evolution of the hemagglutinin gene to determine the evolutionary branch. Our results showed recent antigenic drift, providing crucial clues for updating the H7N9 vaccine and disease prevention and control.

Multi-modal long document classification based on Hierarchical Prompt and Multi-modal Transformer.

In the realm of long document classification (LDC), previous research has predominantly focused on modeling unimodal texts, overlooking the potential of multi-modal documents incorporating images. To address this gap, we introduce an innovative approach for multi-modal long document classification based on the Hierarchical Prompt and Multi-modal Transformer (HPMT). The proposed HPMT method facilitates multi-modal interactions at both the section and sentence levels, enabling a comprehensive capture of hierarchical structural features and complex multi-modal associations of long documents. Specifically, a Multi-scale Multi-modal Transformer (MsMMT) is tailored to capture the multi-granularity correlations between sentences and images. This is achieved through the incorporation of multi-scale convolutional kernels on sentence features, enhancing the model's ability to discern intricate patterns. Furthermore, to facilitate cross-level information interaction and promote learning of specific features at different levels, we introduce a Hierarchical Prompt (HierPrompt) block. This block incorporates section-level prompts and sentence-level prompts, both derived from a global prompt via distinct projection networks. Extensive experiments are conducted on four challenging multi-modal long document datasets. The results conclusively demonstrate the superiority of our proposed method, showcasing its performance advantages over existing techniques.

Assimilation of phthalate esters in bacteria.

The massive usage of phthalate esters (PAEs) has caused serious pollution. Bacterial degradation is a potential strategy to remove PAE contamination. So far, an increasing number of PAE-degrading strains have been isolated, and the catabolism of PAEs has been extensively studied and reviewed. However, the investigation into the bacterial PAE uptake process has received limited attention and remains preliminary. PAEs can interact spontaneously with compounds like peptidoglycan, lipopolysaccharides, and lipids on the bacterial cell envelope to migrate inside. However, this process compromises the structural integrity of the cells and causes disruptions. Thus, membrane protein-facilitated transport seems to be the main assimilation strategy in bacteria. So far, only an ATP-binding-cassette transporter PatDABC was proven to transport PAEs across the cytomembrane in a Gram-positive bacterium Rhodococcus jostii RHA1. Other cytomembrane proteins like major facilitator superfamily (MFS) proteins and outer membrane proteins in cell walls like FadL family channels, TonB-dependent transporters, and OmpW family proteins were only reported to facilitate the transport of PAEs analogs such as monoaromatic and polyaromatic hydrocarbons. The functions of these proteins in the intracellular transport of PAEs in bacteria await characterization and it is a promising avenue for future research on enhancing bacterial degradation of PAEs. KEY POINTS: • Membrane proteins on the bacterial cell envelope may be PAE transporters. • Most potential transporters need experimental validation.

Endoscopic Supracerebellar Infratentorial Transpineal Approach for Posterior-Medial Thalamic Lesions: Surgical Technique and Clinical Experience.

BACKGROUND AND OBJECTIVES: Accessing lesions in the posterior-medial thalamus can be challenging because of their deep location and intricate neurovascular anatomy. This study aims to describe the techniques and feasibility of the endoscopic supracerebellar infratentorial transpineal approach for treating posterior-medial thalamus lesions. METHODS: We reviewed and analyzed the clinical outcomes and endoscopic surgical experience of 11 patients with posterior-medial thalamic lesions. The first 4 cases used the endoscopic midline supracerebellar infratentorial transpineal approach, whereas the subsequent 7 cases used the endoscopic contralateral paramedian supracerebellar infratentorial transpineal approach. All cases involved the upward transposition of the pineal gland to access the posterior-medial thalamus. The extent of resection and the endoscopic techniques were the main focus of analysis. Neurological examinations and MRI/computed tomography follow-up were conducted for 3-12 months after surgery. RESULTS: The pathology of the group included 6 gliomas, 1 cavernous malformation, 1 inflammation, 1 melanoma, and 2 hematomas. All 11 patients achieved gross total resection (6 patients, 54.5%) or subtotal resection (5 patients, 45.5%) with no new neurological deficits. Most patients (9 patients, 81.8%) experienced improvement in Karnofsky Performance Status after surgery. Postoperative hydrocephalus occurred in 2 patients (18.2%) and was relieved by endoscopic third ventriculostomy. CONCLUSION: The endoscopic supracerebellar infratentorial transpineal approach is an effective approach for removing posterior-medial thalamic lesions that require access through the third ventricle surfaces of the thalamus. The endoscopic contralateral paramedian supracerebellar infratentorial transpineal approach provides a more superior and lateral view of the posterior-medial thalamic lesions.

MiR129-5p-loaded exosomes suppress seizure-associated neurodegeneration in status epilepticus model mice by inhibiting HMGB1/TLR4-mediated neuroinflammation.

BACKGROUND: Neuroinflammation contributes to both epileptogenesis and the associated neurodegeneration, so regulation of inflammatory signaling is a potential strategy for suppressing epilepsy development and pathological progression. Exosomes are enriched in microRNAs (miRNAs), considered as vital communication tools between cells, which have been proven as potential therapeutic method for neurological disease. Here, we investigated the role of miR129-5p-loaded mesenchymal stem cell (MSC)-derived exosomes in status epilepticus (SE) mice model. METHODS: Mice were divided into four groups: untreated control (CON group), kainic acid (KA)-induced SE groups (KA group), control exosome injection (KA + Exo-con group), miR129-5p-loaded exosome injection (KA + Exo-miR129-5p group). Hippocampal expression levels of miR129-5p, HMGB1, and TLR4 were compared among groups. Nissl and Fluoro-jade B staining were conducted to evaluate neuronal damage. In addition, immunofluorescence staining for IBA-1 and GFAP was performed to assess glial cell activation, and inflammatory factor content was determined by ELISA. Hippocampal neurogenesis was assessed by BrdU staining. RESULTS: The expression of HMGB1 was increased after KA-induced SE and peaking at 48 h, while hippocampal miR129-5p expression decreased in SE mice. Exo-miR129-5p injection reversed KA-induced upregulation of hippocampal HMGB1 and TLR4, alleviated neuronal damage in the hippocampal CA3, reduced IBA-1 + and GFAP + staining intensity, suppressed SE-associated increases in inflammatory factors, and decreased BrdU + cell number in dentate gyrus. CONCLUSIONS: Exosomes loaded with miR129-5p can protect neurons against SE-mediated degeneration by inhibiting the pro-inflammatory HMGB1/TLR4 signaling axis.