In-depth analysis of prognostic markers associated with the tumor immune microenvironment and genetic mutations in breast cancer based on an NK cell-related risk model.

The natural killer (NK) cell population is unique because it consists of innate lymphocytes capable of detecting and eliminating tumors and virus-infected cells. This research aims to identify a new prognostic signal in breast cancer (BRCA) based on NK-cell-related genes (NKRGs). A variety of sequencing and gene mutation data, along with clinical information, were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Database (GEO). COX regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were conducted to identify prognostic genes. In addition, the immune-related analysis was performed to evaluate the association between the immune microenvironment and clusters and risk model. The Edu assay, colony assay, wound healing assay, and transwell assay were performed to evaluate the cell proliferative and invasive abilities. A 4-NKRG-based prognostic model was constructed. Patients in high-risk groups were associated with poorer OS in TCGA and GSE42568. Further, a nomogram was constructed for better prediction of the prognosis of patients with BRCA. Finally, it was discovered that the over-expression of IFNE could suppress the proliferative and invasive abilities of BRCA cells, which might be a promising biomarker for patients with BRCA. As a result, we developed a novel 4-NKRG signal and nomogram capable of predicting the prognosis of patients with BRCA. Additionally, this model was closely associated with the immune microenvironment, which opened new therapeutic avenues for the treatment of cancer in the future.

Dynamic-group-aware networks for multi-agent trajectory prediction with relational reasoning.

Demystifying the interactions among multiple agents from their past trajectories is fundamental to precise and interpretable trajectory prediction. However, previous works mainly consider static, pairwise interactions with limited relational reasoning. To more comprehensively model interactions and reason relations, we propose DynGroupNet, a dynamic-group-aware network, which (i) models time-varying interactions in highly dynamic scenes; (ii) captures both pairwise and group-wise interactions; and (iii) reasons both interaction strength and category without direct supervision. Based on DynGroupNet, we further design a prediction system to forecast socially plausible trajectories with dynamic relational reasoning. The proposed prediction system leverages the Gaussian mixture model, multiple sampling and prediction refinement to promote prediction diversity for multiple future possibilities capturing, training stability for efficient model learning and trajectory smoothness for more realistic predictions, respectively. The proposed complex interaction modeling of DynGroupNet, future diversity capturing, efficient model training and trajectory smoothing of prediction system together to promote more accurate and plausible future predictions. Extensive experiments show that: (1) DynGroupNet can capture time-varying group behaviors, infer time-varying interaction category and interaction strength during prediction; (2) DynGroupNet significantly outperforms the state-of-the-art trajectory prediction methods by 28.0%, 34.9%, 13.0% in FDE on the NBA, NFL and SDD datasets.

Bioactive Peptides from Ruditapes philippinarum Attenuate Hypertension and Cardiorenal Damage in Deoxycorticosterone Acetate-Salt Hypertensive Rats.

Hypertension is a common disease that affects human health and can lead to damage to the heart, kidneys, and other important organs. In this study, we investigated the regulatory effects of bioactive peptides derived from Ruditapes philippinarum (RPP) on hypertension and organ protection in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We found that RPPs exhibited significant blood pressure-lowering properties. Furthermore, the results showed that RPPs positively influenced vascular remodeling and effectively maintained a balanced water-sodium equilibrium. Meanwhile, RPPs demonstrated anti-inflammatory potential by reducing the serum levels of inflammatory cytokines (TNF-α, IL-2, and IL-6). Moreover, we observed the strong antioxidant activity of RPPs, which played a critical role in reducing oxidative stress and alleviating hypertension-induced damage to the aorta, heart, and kidneys. Additionally, our study explored the regulatory effects of RPPs on the gut microbiota, suggesting a possible correlation between their antihypertensive effects and the modulation of gut microbiota. Our previous studies have demonstrated that RPPs can significantly reduce blood pressure in SHR rats. This suggests that RPPs can significantly improve both essential hypertension and DOAC-salt-induced secondary hypertension and can ameliorate cardiorenal damage caused by hypertension. These findings further support the possibility of RPPs as an active ingredient in functional anti-hypertensive foods.

Knowledge graph and CBR-based approach for automated analysis of bridge operational accidents: Case representation and retrieval.

Bridge operational accident analysis is a critical process in bridge operational risk management. It provides valuable knowledge support for responding to newly occurring accidents. However, there are three issues: (1) research specifically focused on the past bridge operational accidents is relatively scarce; (2) there is a lack of mature research findings regarding the bridge operational accidents knowledge representation; and (3) in similar case retrieval, while case-based reasoning (CBR) is a valuable approach, there are still some challenges and limitations associated with its usage. To tackle these problems, this research proposed an automated analysis approach for bridge operational accidents based on a knowledge graph and CBR. The approach includes case representation and case retrieval, leveraging advancements in computer science and artificial intelligence. In the proposed approach, the case representation involves the adoption of a knowledge graph to construct multi-dimensional networks. The knowledge graph captures the relationships between various factors and entities, allowing for a comprehensive representation of accidents domain knowledge. In the case retrieval, a multi-circle layer retrieval strategy was innovatively proposed to enhance retrieval efficiency. Three target cases were randomly selected to verify the validity of the proposed methodology. The combination of a knowledge graph and CBR can indeed provide useful tools for the automated analysis of bridge operational accidents. Additionally, the proposed methodology can serve as a reference for intelligent risk management in other types of infrastructures.

Afforestation changed the fungal functional community of paddy fields and dry farmlands differently.

Afforestation currently makes a great contribution to carbon uptake in terrestrial ecosystems, while dramatically affects soil ecosystem functions too. Little is known, however, about the changes in soil fungal functional groups and their interactions following afforestation. Here, based on high-throughput sequencing and FUNGuild annotation, we investigated the functional characteristics of soil fungi as well as environmental factors in a watershed where paddy field and dry farmland were changed to eucalyptus plantation. The results showed that afforestation on paddy field resulted in greater changes in diversity, community structure and taxon interactions of fungal functional groups than afforestation on dry farmland. The most complex and distinctive community structure was found in eucalyptus plantation, as well as the greatest taxon interactions, and the lowest alpha-diversity of functional guilds of symbiotrophic fungi because of the dominant ectomycorrhizal fungi. Paddy field exhibited the highest proportion of saprotrophic fungi, but the lowest taxonomic diversity of saprotrophic and pathotrophic fungi. The taxonomic diversity of undefined saprotrophic fungi shaped the differences in community structure and network complexity between eucalyptus plantation and cropland. Limited cooperation within dominant fungi was the main reason for the establishment of a loose co-occurrence network in paddy field. From croplands to artificial forests, reduced soil pH boosted the taxonomic diversity of fungal functional groups. All of these findings suggested that afforestation may lead to an increase in the taxonomic diversity of soil fungal functional groups, which would further intensify the taxon interactions.

Molecular subtypes and prognostic models for predicting prognosis of lung adenocarcinoma based on miRNA-related genes.

BACKGROUND: MicroRNAs (miRNAs) are crucial in cancer development and progression, and therapies targeting miRNAs demonstrate great therapeutic promise. AIM: We sought to predict the prognosis and therapeutic response of lung adenocarcinoma (LUAD) by classifying molecular subtypes and constructing a prognostic model based on miRNA-related genes. METHOD: This study was based on miRNA-mRNA action pairs and ceRNA networks in the Cancer Genome Atlas (TCGA) database. Three molecular subtypes were determined based on 64 miRNA-associated target genes identified in the ceRNA network. The S3 subtype had the best prognosis, and the S2 subtype had the worst prognosis. The S2 subtype had a higher tumor mutational load (TMB) and a lower immune score. The S2 subtype was more suitable for immunotherapy and sensitive to chemotherapy. The least absolute shrinkage and selection operator (LASSO) algorithm was performed to determine eight miRNA-associated target genes for the construction of prognostic models. RESULT: High-risk patients had a poorer prognosis, lower immune score, and lower response to immunotherapy. Robustness was confirmed in the Gene-Expression Omnibus (GEO) database cohort (GSE31210, GSE50081, and GSE37745 datasets). Overall, our study deepened the understanding of the mechanism of miRNA-related target genes in LUAD and provided new ideas for classification. CONCLUSION: Such miRNA-associated target gene characterization could be useful for prognostic prediction and contribute to therapeutic decision-making in LUAD.

Characterization, health benefits, and food applications of enzymatic digestion- resistant dextrin: A review.

Resistant dextrin or resistant maltodextrin (RD), a short-chain glucose polymer that is highly resistant to hydrolysis by human digestive enzymes, has shown broad developmental prospects in the food industry and has gained substantial attention owing to its lack of undesirable effects on the sensory features of food or the digestive system. However, comprehensive fundamental and application information on RD and how RD improves anti-diabetes and obesity have not yet been received. Therefore, the characterization, health benefits and application of RD in various fields are summarized and discussed in the current study. Typically, RD is prepared by the acid thermal method and possesses excellent physicochemical properties, including low viscosity, high solubility, storage stability, and low retro-gradation, which are correlated with its low molecular weight (Mw) and non-digestible glycosidic linkages. In contrast, RD prepared by the simultaneous debranching and crystallization method has low solubility and high crystallinity. The ingestion of RD can positively affect metabolic diseases (diabetes and obesity) in animals and humans by producing short-chain fatty acids (SCFAs), and facilitating the inflammatory response. Moreover, RD has been widely used in the beverage, dairy products, and dessert industries due to its nutritional value and textural properties without unacceptable quality loss. More studies are required to further explore RD application potential in the food industry and its role in the management of different chronic metabolic disorders.

Immune Enhancement of Clam Peptides on Immunosuppressed Mice Induced by Hydrocortisone.

Clam peptides, marine-derived biological peptides, have been broadly investigated and applied as health foods, among which immunomodulation is one of their biological activities that cannot be ignored in vivo. In this study, we concentrated on exploring the effects of Ruditapes philippinarum peptides (RPPs) on immunomodulation and the balance of intestinal microbiota in hydrocortisone (HC)-induced immunosuppressed mice. The results revealed that RPPs could increase the thymus and spleen indices and number of white blood cells, promote the secretion level of cytokines (IL-2, IL-6, TNF-α, and INF-γ), repair the morphology of the spleen and thymus, and enhance the proliferation of T-lymphocyte subsets in immunosuppressed mice. Moreover, RPPs improved the abundance of beneficial bacteria and preserved the ecological equilibrium of the gut microbiota. In conclusion, RPPs have significant immunomodulatory effects on immunosuppressed mice and may be developed as immunomodulators or immune adjuvants in functional foods and drugs; they are also beneficial to the utilization of the high value of marine shellfish.

The sharp structural switch of covalent cages mediated by subtle variation of directing groups.

It is considered a more formidable task to precisely control the self-assembled products containing purely covalent components, due to a lack of intrinsic templates such as transition metals to suppress entropy loss during self-assembly. Here, we attempt to tackle this challenge by using directing groups. That is, the self-assembly products of condensing a 1:2 mixture of a tetraformyl and a biamine can be precisely controlled by slightly changing the substituent groups in the aldehyde precursor. This is because different directing groups provide hydrogen bonds with different modes to the adjacent imine units, so that the building blocks are endowed with totally different conformations. Each conformation favors the formation of a specific product that is thus produced selectively, including chiral and achiral cages. These results of using a specific directing group to favor a target product pave the way for accomplishing atom economy in synthesizing purely covalent molecules without relying on toxic transition metal templates.

Ameliorative effect of mussel-derived ACE inhibitory peptides on spontaneous hypertension rats.

PURPOSE: The purpose of this study was to prepare the novel mussel-derived ACE inhibitory peptides (MEPs) by enzymatic hydrolysis of Mytilus edulis and investigate their antihypertensive effects in vivo. METHODS: After assessing the stability of MEPs in vitro, we investigated the effect of MEPs on hypertension using spontaneously hypertensive rats (SHRs). Subsequently, MEPs were purified and identified by ultrafiltration, gel filtration chromatography and liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Our study demonstrated that MEPs could keep stable ACE inhibitory activity after treatment with heat, acid, alkali, metal ions and simulated gastrointestinal digestive fluid. Additionally, the animal experiments showed that both short-term and long-term treatment with MEPs resulted in a significant reduction in systolic and diastolic blood pressure in SHRs. Mechanistically, the results suggested that MEPs could reduce vascular remodeling, regulate renin-angiotensin system (RAS), and inhibit kidney and myocardial fibrosis. Finally, we isolated and identified five peptides from MEPs, with the peptide Ile-Leu-Thr-Glu-Arg showed the highest ACE inhibition rate. CONCLUSION: Our findings demonstrate the potential use of MEPs as active components in functional foods designed to lower blood pressure.

Subcritical low temperature extraction of bioactive ingredients from foods and food by-products and its applications in the agro-food industry.

Bioactive ingredients are part of the food chain and are responsible for numerous health benefits. Subcritical low temperature extraction has been employed to acquire bioactive ingredients because of its excellent properties, such as energy conservation, low temperature, elimination of residual solvent, and high extraction yield and quality. This review aims to provide a clear picture of the basics of subcritical-temperature extraction, its bioactive ingredient extraction efficiency, and possible applications in the agro-food industry. This review suggested that the extraction temperature, time, co-solvents, solid-fluid ratio, and pressure impacted the extraction efficiency of bioactive ingredients from foods and food by-products. Subcritical solvents are appropriate for extracting low polar ingredients, while the inclusion of co-solvents could extract medium and high polar substances. Bioactive ingredients from foods and food by-products can be used as antioxidants, colorants, and nutritional supplements. Additionally, this technology could remove pesticide residues in tea, concentrate edible proteins, and reduce cigarette tar. A new trend toward using subcritical low temperature extraction in extracting bioactive ingredients will acquire momentum.

Immune checkpoint inhibitors for the treatment of non-small cell lung cancer brain metastases.

ABSTRACT: Lung cancer has the highest risk of brain metastasis (BM) among all solid carcinomas. The emergence of BM has a significant impact on the selection of oncologic treatment for patients. Immune checkpoint inhibitors (ICIs) are the most promising treatment option for patients without druggable mutations and have been shown to improve survival in patients with non-small cell lung cancer (NSCLC) BM in clinical trials with good safety. Moreover, ICI has shown certain effects in NSCLC BM, and the overall intracranial efficacy is comparable to extracranial efficacy. However, a proportion of patients showed discordant responses in primary and metastatic lesions, suggesting that multiple mechanisms may exist underlying ICI activity in BM. According to studies pertaining to tumor immune microenvironments, ICIs may be capable of provoking immunity in situ . Meanwhile, systematic immune cells activated by ICIs can migrate into the central nervous system and exert antitumor effects. This review summarizes the present evidence for ICI treatment efficacy in NSCLC BM and proposes the possible mechanisms of ICI treatment for NSCLC BMs based on existing evidence.

Performance enhancement of electrochemiluminescence magnetic microbiosensors by using double magnetic field actuation for cancer biomarkers and exosomes.

This work reports the performance enhancement strategies on magnetic beads (MBs)-based electrochemiluminescence (ECL) platforms by using double magnetic field actuation of the ECL magnetic microbiosensors (MMbiosensors) for highly sensitive determination of cancer biomarker and exosomes. To obtain the high sensitivity and reproducibility of the ECL MMbiosensors, a series of strategies have been developed including replacing a conventional photomultiplier tube (PMT) with a diamagnetic PMT, replacing the stacked ring-disc magnets with circular-disc magnets lain-in glassy carbon electrode, adding a pre-concentration process of MBs using external magnet actuation. For fundamental research, the ECL MBs taken as the substitute of ECL MMbiosensors were prepared by binding biotinylated DNA tagged with Ru(bpy)32+ derivative (Ru1) to streptavidin-coated MB(MB@SA) were which showed that the developed strategies can enhance 45-fold sensitivity. Importantly, the developed MBs-based ECL platform was estimated by determination of prostate specific antigen (PSA) and exosomes. For PSA, MB@SA•biotin-Ab1(PSA) was taken as the capture probe and Ru1-labeled Ab2 (PSA) was done as ECL probe, while for exosomes, MB@SA•biotin-aptamer (CD63) was taken as the capture probe and Ru1-labeled Ab (CD9) was done as the ECL probe. The experiment results showed that the developed strategies can enhance 33-fold sensitivity of ECL MMbiosensors for PSA and exosomes. The detection limit is 0.28 ng mL-1 for PSA and 4.9 × 102 particle mL-1 for exosomes. This work demonstrated that a series of proposed magnetic field actuation strategies greatly increase the sensitivity of the ECL MMbiosensors. The developed strategies can be expanded to MBs-based ECL and electrochemical biosensors for clinical analysis with greater sensitivity.

Washing-free electrogenerated chemiluminescence magnetic microbiosensors based on target assistant proximity hybridization for multiple protein biomarkers.

This work reports washing-free electrogenerated chemiluminescence (ECL) magnetic microbiosensors based on target assistant proximity hybridization (TAPH) for multiple protein biomarkers for the first time. As a principle-of-proof, alpha-fetoprotein (AFP) was chosen as a model analyte, and biotin-DNA1 bound streptavidin-coated magnetic microbeads (MMB@SA⋅biotin-DNA1) were designed as the universal capture MMB, while the corresponding two antibodies tagged with DNA2 or DNA3 were utilized as hybrid recognition probes, and ruthenium complex-tagged DNA4-10A was designed as a universal ECL signal probe. When the capture MMB was added into the mixture solution (containing the analyte, hybrid recognition probes, signal probe and tri-n-propylamine), biocomplexes were formed on the MMB. After the resulting MMB was efficiently brought to the surface of a magnetic glassy carbon electrode (MGCE), ECL measurement was performed without a washing step, resulting in an increase in the ECL intensity. A model for ECL measuring the second-order rate constants of hybridization reactions on MMB was derived. It was found that the rate constants for hybridization reactions on MMB in rotating mode are 1.6-fold higher than those in shaking mode, and a suitable DNA length of the signal probe can improve the signal-to-noise ratio. The washing-free ECL method was developed for the determination of AFP with a much lower detection limit (LOD) of 0.04 ng mL-1. The developed flexible strategy has been extended to determine D-dimer with an LOD of 0.1 ng mL-1 and myoglobinglobin with an LOD of 1.1 ng mL-1. This work demonstrated that the proposed strategy of ECL TAPH on MMB at MGCE is a washing-free and flexible promising strategy, and can be extended to qualify other multiple protein biomarkers in real clinical assays.

Recent advances and challenges in developing electrochemiluminescence biosensors for health analysis.

This Feature Article simply introduces principles and mechanisms of electrochemiluminescence (ECL) biosensors for the determination of biomarkers and highlights recent advances of ECL biosensors on key aspects including new ECL reagents and materials, new biological recognition elements, and emerging construction biointerfacial strategies with illustrative examples and a critical eye on pitfalls and discusses challenges and perspectives of ECL biosensors for health analysis.

Effects of total hip arthroplasty and hemiarthroplasty on hip function in patients with traumatic femoral neck fracture.

OBJECTIVE: Traumatic femoral neck fracture is a common disease that can be treated by hip arthroplasty, which is divided into hemiarthroplasty (HA) and total hip arthroplasty (THA). The difference between HA and THA are incompletely understood. The objective of this study was to investigate the effect of hip arthroplasty on hip function in patients with traumatic femoral neck fracture. METHODS: A total of 132 patients with traumatic femoral neck fracture admitted to our hospital from January 2019 to January 2021 were selected and divided into control group (HA group) and study group (THA group) with 66 cases in each group by random number table method. The duration of operation, intraoperative blood loss, postoperative drainage and length of hospital stay were compared between the two groups. The degree of pain before operation, 3 days after operation and 7 days after operation were observed, the hip joint function before operation, 6 months after operation and 12 months after operation was analyzed, and the occurrence of short-term and long-term complications was compared between the two groups. RESULT: Compared with the HA group, the operative time, intraoperative blood loss, postoperative drainage and hospital stay were higher in the THA group. The degree of pain in THA group was higher than that in HA group on 3 and 7 days after operation; At 6 and 12 months after surgery, the scores of pain, range of motion, joint function and deformity in the THA group were higher than those in the HA group with statistically significant. Compared with HA group, IGF-1 and Leptin in THA group were increased significantly, while inflammatory cytokines TNF-α was decreased in THA group. The total incidence of short-term and long-term complications was lower in THA group. CONCLUSION: Total hip arthroplasty can effectively restore hip joint function in patients with traumatic femoral neck fracture, with low incidence of short-term and long-term complications, high safety, and worthy of clinical application.

Extraction, characterization, and biological activities of exopolysaccharides from plant root soil fungus Fusarium merismoides A6.

The exploration of polysaccharides from microorganisms is of great importance. In this study, a new type of exopolysaccharide excreted by Fusarium merismoides A6 (FM-EPS) was isolated, and the extraction conditions were optimized using a response surface methodology (RSM). The extraction temperature at 0 °C, a precipitation time of 7.83 h, and an ethanol precipitation concentration of 77.64% were predicted and proved to be the best extraction conditions with the maximum extraction yield of 0.74 g/mL. Then, two fractions of F. merismoides A6 exopolysaccharides (FM-EPS1 and FM-EPS2) were obtained through DEAE Sepharose fast flow column chromatography. As indicated by monosaccharide composition analysis, both fractions mainly consisted of mannose, glucose, galactose, and ribose, with an average molecular weight of 5.14 × 104 and 6.50 × 104 g/mol, respectively. FT-IR and NMR spectroscopy indicated the FM-EPSs had both α- and ß-glycosidic bonds. Moreover, the determination of antioxidant and antiproliferative activities in vitro proved that FM-EPSs had good antioxidant activities and antiproliferation activities. FM-EPS1 showed stronger antioxidant activities than FM-EPS2. FM-EPS2 showed antiproliferation activities on HeLa and HepG2 cells, while FM-EPS1 had no obvious antiproliferative activity. Therefore, FM-EPSs could be explored as potential antioxidant and anticancer agent applied in food, feed, nutraceutical, pharmaceutical, cosmetics, and chemical industries.

The Ameliorative Effect and Mechanisms of Ruditapes philippinarum Bioactive Peptides on Obesity and Hyperlipidemia Induced by a High-Fat Diet in Mice.

In this study, bioactive peptides (RBPs) from Ruditapes philippinarum were prepared by fermentation with Bacillus natto and the effect and mechanisms of RBPs on obesity and hyperlipidemia were explored in mice. We found that RBPs significantly reduced body weight, adipose tissue weight, accumulation of hepatic lipids, and serum levels of total cholesterol (CHO), triglyceride (TG), and low-density lipoprotein (LDL). Mechanistic studies showed that RBPs up-regulated the hepatic expression of genes related to lipolysis, such as hormone-sensitive lipase (HSL), phosphorylated AMP-activated protein kinase (p-AMPK), and peroxisome proliferator-activated receptors α (PPARα), and down-regulated the expression of peroxisome proliferator-activated receptors γ (PPARγ) which is related to lipid synthesis. In addition, RBPs could attenuate obesity and hyperlipidemia by regulating disordered gut microbiota composition, such as increasing the abundance of microflora related to the synthesis of short chain fatty acids (SCFAs) (Bacteroidetes, Prevotellaceas_UCG_001, norank_f_Muribaculaceae, and Odoribacter) and controlling those related to intestinal inflammation (reduced abundance of Deferribacteres and increased abundance of Alistipes and ASF356) to exert anti-obesity and lipid-lowering activities. Our findings laid the foundation for the development and utilization of RBPs as a functional food to ameliorate obesity and hyperlipidemia.

Positive Effect of a Pea-Clam Two-Peptide Composite on Hypertension and Organ Protection in Spontaneously Hypertensive Rats.

In the present study, we prepared pea peptides with high angiotensin-converting enzyme (ACE) inhibitory activity in vitro using an enzymatic hydrolysis of pea protein and compounded them with clam peptides to obtain a pea-clam double peptide. The effects of the two-peptide composite and pea peptides on hypertension and the damage-repair of corresponding organs were studied in spontaneously hypertensive rats (SHRs). We found that both pea peptides and the two-peptide composite significantly reduced the blood pressure upon a single or long-term intragastric administration, with the two-peptide composite being more effective. Mechanistically, we found that the two-peptide composite could regulate the renal renin-angiotensin system (RAS), rebalance gut microbial dysbiosis, decrease renal and myocardial fibrosis, and improve renal and cardiac function and vascular remodeling. Additionally, hippocampal lesions caused by hypertension were also eliminated after two-peptide composite administration. Our research provides a scientific basis for the use of this two-peptide composite as a safe antihypertension ingredient in functional foods.

Magnolol effectively ameliorates diabetic peripheral neuropathy in mice.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes lacking efficient treatment. Magnolol (MG), a peroxisome proliferator-activated receptor γ (PPARγ) agonist, is a natural product derived from Magnolia officinalis and widely used to treat a variety of diseases as a traditional Chinese medicine and Japanese Kampo medicine. PURPOSE: Here, we aimed to investigate the potential of MG in ameliorating DPN-like pathology in mice and decipher the mechanism of MG in treating DPN. MATERIALS AND METHODS: 12-week-old male streptozotocin (STZ)-induced type 1 diabetic (T1DM) mice and 15-week-old male BKS Cg-m+/+Lepr db/J (db/db) type 2 diabetic mice (T2DM) were used as DPN mice. MG was administrated (i.p) daily for 4 weeks. Peripheral nerve functions of mice were evaluated by measuring mechanical response latency, thermal response latency and motor nerve conduction velocity (MNCV). The mechanisms underlying the amelioration of MG on DPN-like pathology were examined by qRT-PCR, western blot and immunohistochemistry assays, and verified in the DPN mice with PPARγ-specific knockdown in dorsal root ganglia (DRG) neuron and sciatic nerve tissues by injecting adeno-associated virus (AAV)8-PPARγ-RNAi. RESULTS: MG promoted DRG neuronal neurite outgrowth and effectively ameliorated neurological dysfunctions in both T1DM and T2DM diabetic mice, including improvement of paw withdrawal threshold, thermal response latency and MNCV. Additionally, MG promoted neurite outgrowth of DRG neurons, protected sciatic nerve myelin sheath structure, and ameliorated foot skin intraepidermal nerve fiber (IENF) density in DPN mice by targeting PPARγ. Mechanism research results indicated that MG improved mitochondrial dysfunction involving PPARγ/MKP-7/JNK/SIRT1/LKB1/AMPK/PGC-1α pathway in DRG neurons, repressed inflammation via PPARγ/NF-κB signaling and inhibited apoptosis through regulation of PPARγ-mediated Bcl-2 family proteins in DRG neurons and sciatic nerves. CONCLUSIONS: Our work has detailed the mechanism underlying the amelioration of PPARγ agonist on DPN-like pathology in mice with MG as a probe, and highlighted the potential of MG in the treatment of DPN.