Computer-aided mining of a psychrophilic cellobiose 2-epimerase from the Qinghai-Tibet Plateau gene catalogue.

Cellobiose 2-epimerase (CE) catalyzes the conversion of the lactose into its high-value derivatives, epilactose and lactulose, which has great prospects in food applications. In this study, CE sequences from the Qinghai-Tibet Plateau gene catalogue, we screened these for structural flexibility through molecular dynamics simulation to identify potential psychrophilic CE candidates. One such psychrophilic CE we termed psyCE demonstrated exceptional epimerization activity, achieving an optimum activity of 122.2 ± 1.6 U/mg. Its kinetic parameters (Kcat and Km) for epimerization activity were 219.9 ± 5.6 s-1 and 261.9 ± 18.1 mM, respectively, representing the highest Kcat recorded among known cold-active CEs. Notably, this is the first report of a psychrophilic CE. The psyCE can effectively produce epilactose at 8 °C, converting 20.3 % of 200 mM lactose into epilactose within four hours. These findings suggest that psyCE is highly suitable for cryogenic food processing, and glaciers may serve as a valuable repository of psychrophilic enzymes.

PGE2 synthesis and signaling in the liver physiology and pathophysiology: An update.

The liver plays a central role in systemic metabolism and drug degradation. However, it is highly susceptible to damage due to various factors, including metabolic imbalances, excessive alcohol consumption, viral infections, and drug influences. These factors often result in conditions such as fatty liver, hepatitis, and acute or chronic liver injury. Failure to address these injuries could promptly lead to the development of liver cirrhosis and potentially hepatocellular carcinoma (HCC). Prostaglandin E2 (PGE2) is a metabolite of arachidonic acid that belongs to the class of polyunsaturated fatty acids (PUFA) and is synthesized via the cyclooxygenase (COX) pathway. By binding to its G protein coupled receptors (i.e., EP1, EP2, EP3 and EP4), PGE2 has a wide range of physiological and pathophysiology effects, including pain, inflammation, fever, cardiovascular homeostasis, etc. Recently, emerging studies showed that PGE2 plays an indispensable role in liver health and disease. This review focus on the research progress of the role of PGE2 synthase and its receptors in liver physiological and pathophysiological processes and discuss the possibility of developing liver protective drugs targeting the COXs/PGESs/PGE2/EPs axis.

Cucurbitacins mitigate vascular neointimal hyperplasia by suppressing cyclin A2 expression and inhibiting VSMC proliferation.

BACKGROUND: Restenosis frequently occurs after percutaneous angioplasty in patients with vascular occlusion and seriously threatens their health. Substantial evidence has revealed that preventing vascular smooth muscle cell proliferation using a drug-eluting stent is an effective approach to improve restenosis. Cucurbitacins have been demonstrated to exert an anti-proliferation effect in various tumors and a hypotensive effect. This study aims to investigate the role of cucurbitacins extracted from Cucumis melo L. (CuECs) and cucurbitacin B (CuB) on restenosis. METHODS: C57BL/6 mice were subjected to left carotid artery ligation and subcutaneously injected with CuECs or CuB for 4 weeks. Hematoxylin-Eosin, immunofluorescence and immunohistochemistry staining were used to evaluate the effect of CuECs and CuB on neointimal hyperplasia. Western blot, real-time PCR, flow cytometry analysis, EdU staining and cellular immunofluorescence assay were employed to measure the effects of CuECs and CuB on cell proliferation and the cell cycle in vitro. The potential interactions of CuECs with cyclin A2 were performed by molecular docking. RESULTS: The results demonstrated that both CuECs and CuB exhibited significant inhibitory effects on neointimal hyperplasia and proliferation of vascular smooth muscle cells. Furthermore, CuECs and CuB mediated cell cycle arrest at the S phase. Autodocking analysis demonstrated that CuB, CuD, CuE and CuI had high binding energy for cyclin A2. Our study also showed that CuECs and CuB dramatically inhibited FBS-induced cyclin A2 expression. Moreover, the expression of cyclin A2 in CuEC- and CuB-treated neointima was downregulated. CONCLUSIONS: CuECs, especially CuB, exert an anti-proliferation effect in VSMCs and may be potential drugs to prevent restenosis.

Elevated TyG index is associated with increased risk of vitamin D deficiency among elderly patients with type 2 diabetes.

Vitamin D deficiency (VDD) is associated with increased risk of type 2 diabetes mellitus (T2DM) and insulin resistance (IR). We aimed to investigate the association between the triglyceride-glucose (TyG) index that represents IR and VDD in elderly patients with T2DM. We enrolled 572 elderly participants with T2DM in this study. TyG index was calculated as ln [fasting triglyceride (TG, mg/dL) × fasting blood glucose (mg/dL)/2]. Serum 25-hydroxyvitamin D [25(OH)D] level below 50 nmol/L was defined as VDD. The association between the TyG index and the VDD risk was evaluated by multivariate logistic regression analysis. We observed a significant decreased 25(OH)D level with the increase of the TyG index in elderly diabetic patients, and a negative correlation between the TyG index and 25(OH)D level. The participants in the highest TyG quartile had a 2.40-fold higher risk of VDD than those in the lowest TyG index quartile [OR 2.40; 95% CI 1.47-3.92; P < 0.001]. The association persisted after adjustments for age, sex, smoking, obesity, insulin therapy, hypoglycemic agents' medication, and some biochemical parameters. TyG index may be involved in the pathophysiology of VDD, which could be a predictor for VDD in elderly diabetic patients.

The potential roles of PKM2 in cerebrovascular diseases.

Pyruvate kinase M2 (PKM2), a key enzyme involved in glycolysis,plays an important role in regulating cell metabolism and growth under different physiological conditions. PKM2 has been intensively investigated in multiple cancer diseases. Recent years, many studies have found its pivotal role in cerebrovascular diseases (CeVDs), the disturbances in intracranial blood circulation. CeVDs has been confirmed to be closely associated with oxidative stress (OS), mitochondrial dynamics, systemic inflammation, and local neuroinflammation in the brain. It has further been revealed that PKM2 exerts various biological functions in the regulation of energy supply, OS, inflammatory responses, and mitochondrial dysfunction. The roles of PKM2 are closely related to its different isoforms, expression levels in subcellular localization, and post-translational modifications. Therefore, summarizing the roles of PKM2 in CeVDs will help further understanding the molecular mechanisms of CeVDs. In this review, we illustrate the characteristics of PKM2, the regulated PKM2 expression, and the biological roles of PKM2 in CeVDs.

Denosumab ameliorates osteoarthritis by protecting cartilage against degradation and modulating subchondral bone remodeling.

Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. Effective management for early-stage OA is crucial. Denosumab (DS) has been widely used to treat osteoporosis (OP) and rheumatoid arthritis, but its potential for managing OA remains clear. We assessed the effects of DS on osteoclast activity and chondrocyte apoptosis using tartrate-resistant acid phosphatase (TRAP) assay, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, and TUNEL staining. To assess the impact of DS on the NF-κB pathway, we performed Western blot and immunofluorescence staining. Additionally, we used an OA model to explore the influence of DS on subchondral bone remodeling and cartilage degeneration in vivo. We found that DS hindered receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis by inhibiting the activity of the NF-κB pathway. Besides, DS alleviated reactive oxygen species (ROS)-induced apoptosis in chondrocytes by regulating the expression of genes related to apoptosis. Moreover, we observed an attenuation of OA-related subchondral bone remodeling and cartilage degeneration in vivo. Our findings indicate that DS could effectively suppress osteoclast activity and chondrocyte apoptosis, thereby mitigating OA-related subchondral bone remodeling and cartilage degeneration. These results provide a mechanistic basis for using DS to treat OA.

Enhancing the electrochemical properties of TiNb2O7 anodes with SP-CNT binary conductive agents for both liquid and solid state lithium ion batteries.

A high performance oxide composite electrode is obtained with a two-step solid state calcined titanium niobium oxide TiNb2O7 (TNO) anode and super P-carbon nanotube (SP-CNT) binary conductive agents. The solid state synthesized TNO-0.2C (the proportion of CNTs in the binary conductive agent is 20% wt) anode exhibits a high reversible discharge capacity of 278.6 mA h g-1 at 0.5C, a competitive rate capability with reported works that employed wet chemical methods at moderate rates (178.1 mA h g-1 at 10C), and an excellent capacity retention of 92.2% after 200 cycles at 1.5C/1.5C. The enhancement in electrochemical properties of the TNO-0.2C anode is mainly attributed to the combination of the short range and long range conductive agents in the SP-CNT binary conductive system, which guarantees an efficient electronic conductive network. The Li|Li1.3Al0.3Ti1.7(PO4)3 composite polymer electrolyte (LATPCPEs)|TNO-0.2C solid state batteries are also assembled, which deliver a high initial reversible discharge capacity of 241.3 mA h g-1 at 1C and a good capacity retention rate of 93% after 50 cycles. This work provides an efficient way to improve the electrochemical properties of TNO anodes in lithium ion batteries, especially for solid state batteries.

The NF-κB/FXR/TonEBP pathway protects renal medullary interstitial cells against hypertonic stress.

Farnesoid X receptor (FXR), a ligand-activated transcription factor, plays an important role in maintaining water homeostasis by up-regulating aquaporin 2 (AQP2) expression in renal medullary collecting ducts; however, its role in the survival of renal medullary interstitial cells (RMICs) under hypertonic conditions remains unclear. We cultured primary mouse RMICs and found that the FXR was expressed constitutively in RMICs, and that its expression was significantly up-regulated at both mRNA and protein levels by hypertonic stress. Using luciferase and ChIP assays, we found a potential binding site of nuclear factor kappa-B (NF-κB) located in the FXR gene promoter which can be bound and activated by NF-κB. Moreover, hypertonic stress-induced cell death in RMICs was significantly attenuated by FXR activation but worsened by FXR inhibition. Furthermore, FXR increased the expression and nuclear translocation of hypertonicity-induced tonicity-responsive enhance-binding protein (TonEBP), the expressions of its downstream target gene sodium myo-inositol transporter (SMIT), and heat shock protein 70 (HSP70). The present study demonstrates that the NF-κB/FXR/TonEBP pathway protects RMICs against hypertonic stress.

Functionalized MBenes as promising anode materials for high-performance alkali-ion batteries: a first-principles study.

The discovery of novel electrode materials based on two-dimensional (2D) structures is critical for alkali metal-ion batteries. Herein, we performed first-principles computations to investigate functionalized MXenes, Mo2BT2(T = O, S), which are also regarded as B-based MXenes, or named as MBenes, as potential anode materials for Li-ion batteries and beyond. The pristine and T-terminated Mo2BT2(T = O, S) monolayers reveal metallic character with higher electronic conductivity and are thermodynamically stable with an intrinsic dipole moment. Both Mo2BO2and Mo2BS2monolayers exhibit high theoretical Li/Na/K storage capacity and low ion diffusion barriers. These findings suggest that functionalized Mo2BT2(T = O, S) monolayers are promising for designing viable anode materials for high-performance alkali-ion batteries.

Manure replacing synthetic fertilizer improves crop yield sustainability and reduces carbon footprint under winter wheat-summer maize cropping system.

Manure replacing synthetic fertilizer is a viable practice to ensure crop yield and increase soil organic carbon (SOC), but its impact on greenhouse gas (GHG) emissions is inconsistent, thus remains its effect on CF unclear. In this study, a 7-year field experiment was conducted to assess the impact of replacing synthetic fertilizer with manure on crop productivity, SOC sequestration, GHG emissions and crop CF under winter wheat-summer maize cropping system. Five treatments were involved: synthetic nitrogen, phosphorus, and potassium fertilizer (NPK) and 25%, 50%, 75%, and 100% of manure replacing synthetic N (25%M, 50%M, 75%M, and 100%M). Compared with NPK treatment, 25%M and 50%M treatments maintained annual yield (winter wheat plus summer maize) and sustainable yield index (SYI), but 75%M and 100%M treatments significantly decreased annual yield, and 100%M treatment also significantly reduced annual SYI. The SOC content exhibited a significant increasing trend over years in all treatments. After 7 years, SOC storage in manure treatments increased by 3.06-11.82 Mg ha-1 relative to NPK treatment. Manure treatments reduced annual GHG emissions by 14%-60% over NPK treatment. The CF of the cropping system ranged from 0.16 to 0.39 kg CO2 eq kg-1 of grain without considering SOC sequestration, in which the CF of manure treatments lowered by 18%-58% relative to NPK treatment. When SOC sequestration was involved in, the CF varied from -0.39 to 0.37 kg CO2 eq kg-1 of grain, manure treatments significantly reduced the CF by 22%-208% over NPK treatment. It was concluded that replacing 50% of synthetic fertilizer with manure was a sound option for achieving high crop yield and SYI but low CF under the tested cropping system.

Visual interpretable MRI fine grading of meniscus injury for intelligent assisted diagnosis and treatment.

Meniscal injury represents a common type of knee injury, accounting for over 50% of all knee injuries. The clinical diagnosis and treatment of meniscal injury heavily rely on magnetic resonance imaging (MRI). However, accurately diagnosing the meniscus from a comprehensive knee MRI is challenging due to its limited and weak signal, significantly impeding the precise grading of meniscal injuries. In this study, a visual interpretable fine grading (VIFG) diagnosis model has been developed to facilitate intelligent and quantified grading of meniscal injuries. Leveraging a multilevel transfer learning framework, it extracts comprehensive features and incorporates an attributional attention module to precisely locate the injured positions. Moreover, the attention-enhancing feedback module effectively concentrates on and distinguishes regions with similar grades of injury. The proposed method underwent validation on FastMRI_Knee and Xijing_Knee dataset, achieving mean grading accuracies of 0.8631 and 0.8502, surpassing the state-of-the-art grading methods notably in error-prone Grade 1 and Grade 2 cases. Additionally, the visually interpretable heatmaps generated by VIFG provide accurate depictions of actual or potential meniscus injury areas beyond human visual capability. Building upon this, a novel fine grading criterion was introduced for subtypes of meniscal injury, further classifying Grade 2 into 2a, 2b, and 2c, aligning with the anatomical knowledge of meniscal blood supply. It can provide enhanced injury-specific details, facilitating the development of more precise surgical strategies. The efficacy of this subtype classification was evidenced in 20 arthroscopic cases, underscoring the potential enhancement brought by intelligent-assisted diagnosis and treatment for meniscal injuries.

Development and application of a blocking ELISA based on a N protein monoclonal antibody for the antibody detection against porcine reproductive and respiratory syndrome virus 2.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most widespread illnesses in the world's swine business. To detect the antibodies against PRRSV-2, a blocking enzyme-linked immunosorbent assay (B-ELISA) was developed, utilizing a PRRSV-2 N protein monoclonal antibody as the detection antibody. A checkerboard titration test was used to determine the optimal detection antibody dilution, tested pig serum dilution and purified PRRSV coated antigen concentration. After analyzing 174 negative pig sera and 451 positive pig sera, a cutoff value of 40 % was selected to distinguish between positive and negative sera using receiver operating characteristic curve analysis. The specificity and sensitivity of the assay were evaluated to equal 99.8 % and 96 %, respectively. The method had no cross-reaction with PCV2, PRV, PPV, CSFV, PEDV, TGEV, and PRRSV-1 serum antibodies, and the coefficients of variation of intra-batch and inter-batch repeatability experiments were both <10 %. A total of 215 clinical serum samples were tested, and the relative coincidence rate with commercial ELISA kit was 99.06 %, and the kappa value was 0.989, indicating that these two detection results exhibited high consistency. Overall, the B-ELISA should serve as an ideal method for large-scale serological investigation of PRRSV-2 antibodies in domestic pigs.

Regulating Excess Electrons in Reducible Metal Oxides for Enhanced Oxygen Evolution Reaction Activity: A Mini-Review.

Identifying a universal activity descriptor for metal oxides, akin to the d-band center for transition metals, remains a significant challenge in catalyst design, largely due to the intricate electronic structures of metal oxides. This review highlights a major advancement in formulating the number of excess electrons (NEE) as an activity descriptor for oxygen evolution reaction (OER) on reducible metal oxide surfaces. We elaborate on the quantitative relationship between NEE and the adsorption properties of OER intermediates, and unveil the decisive role of the octet rule on the OER performance of these oxides. This insight provides a robust theoretical basis for designing effective OER catalysts. Moreover, we discuss critical experimental evidence supporting this theory and summarize recent advances in employing NEE as a guiding principle for developing highly efficient OER catalysts experimentally.

A global dataset of biochar application effects on crop yield, soil properties, and greenhouse gas emissions.

Biochar application is widely studied to mitigate the threats of soil degradation to food security and climate change. However, there are big variations in the effects of biochar application on crops, soils, and the atmosphere during crop production. This study provides a global dataset of biochar application effects on crop yield, soil properties, and greenhouse emissions. The dataset is extracted and integrated from 367 peer-reviewed studies with 891 independent field, laboratory, and incubation experiments across 37 countries. This dataset includes 21 variables before and after biochar application (including soil properties, crop yield, greenhouse gas emissions, etc.) of 2438 items, focusing on two main biochar application types: biochar application alone and combined with fertilizers. Background information on climate conditions, initial soil properties, management practices, and characteristics of biochar sources and production is also contained in the dataset. This dataset facilitates a comprehensive understanding of the impact of biochar application, supports the utilization of agricultural wastes for biochar production, and assists researchers in refining experimental protocols for further studies.

Molecular Biology Applications of Psychrophilic Enzymes: Adaptations, Advantages, Expression, and Prospective.

Psychrophilic enzymes are primarily produced by microorganisms from extremely low-temperature environments which are known as psychrophiles. Their high efficiency at low temperatures and easy heat inactivation property have attracted extensive attention from various food and industrial bioprocesses. However, the application of these enzymes in molecular biology is still limited. In a previous review, the applications of psychrophilic enzymes in industries such as the detergent additives, the food additives, the bioremediation, and the pharmaceutical medicine, and cosmetics have been discussed. In this review, we discuss the main cold adaptation characteristics of psychrophiles and psychrophilic enzymes, as well as the relevant information on different psychrophilic enzymes in molecular biology. We summarize the mining and screening methods of psychrophilic enzymes. We finally recap the expression of psychrophilic enzymes. We aim to provide a reference process for the exploration and expression of new generation of psychrophilic enzymes.

Prevalence and genetic evolution of porcine reproductive and respiratory syndrome virus in commercial fattening pig farms in China.

BACKGROUND: To investigate the prevalence and evolution of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) at commercial fattening pig farms, a total of 1397 clinical samples were collected from a single fattening cycle at seven pig farms in five provinces of China from 2020 to 2021. RESULTS: The RT‒PCR results revealed that PRRSV was present on all seven farms, and the percentage of PRRSV-positive individuals was 17.54-53.33%. A total of 344 partial NSP2 gene sequences and 334 complete ORF5 gene sequences were obtained from the positive samples. The statistical results showed that PRRSV-2 was present on all seven commercial fattening farms, and PRRSV-1 was present on only one commercial fattening farm. A total of six PRRSV-2 subtypes were detected, and five of the seven farms had two or more PRRSV-2 subtypes. L1.8 (L1C) PRRSV was the dominant epidemic strain on five of the seven pig farms. Sequence analysis of L1.8 (L1C) PRRSV from different commercial fattening pig farms revealed that its consistency across farms varied substantially. The amino acid alignment results demonstrated that there were 131 aa discontinuous deletions in NSP2 between different L1.8 (L1C) PRRSV strains and that the GP5 mutation in L1.8 (L1C) PRRSV was mainly concentrated in the peptide signal region and T-cell epitopes. Selection pressure analysis of GP5 revealed that the use of the PRRSV MLV vaccine had no significant episodic diversifying effect on L1.8 (L1C) PRRSV. CONCLUSION: PRRSV infection is common at commercial fattening pig farms in China, and the percentage of positive individuals is high. There are multiple PRRSV subtypes of infection at commercial fattening pig farms in China. L1.8 (L1C) is the main circulating PRRSV strain on commercial fattening pig farms. L1.8 (L1C) PRRSV detected at different commercial fattening pig farms exhibited substantial differences in consistency but similar molecular characteristics. The pressure on the GP5 of L1.8 (L1C) PRRSV may not be directly related to the use of the vaccines.

Effects of fecal microbial transplantation on police performance and transportation stress in Kunming police dogs.

Fecal microbiota transplantation (FMT) has been shown to improve gut dysbiosis in dogs; however, it has not completely been understood in police dogs. This study aimed to investigate the effects of FMT on performance and gut microflora in Kunming police dogs. Twenty Wolf Cyan dogs were randomly assigned to receive physiological saline or fecal suspension at low, medium, or high doses through oral gavage for 14 days. Growth performance, police performance, serum biochemical profiling, and gut microflora were determined 2-week post-FMT. Dogs after FMT treatment were also subjected to an hour road transportation and then were evaluated for serum stress indicators. Overall, FMT enhanced the growth performance and alleviated diarrhea rate in Kunming dogs with the greatest effects occurring in the low dose FMT (KML) group. The improvement of FMT on police performance was also determined. These above alterations were accompanied by changed serum biochemical parameters as indicated by elevated total protein and albumin and reduced total cholesterol and glycerol. Furthermore, the serum stress indicators after road transportation in dog post-FMT significantly decreased. Increased bacterial diversity and modified bacterial composition were found in the feces of dogs receiving FMT. The fecal samples from FMT dogs were characterized by higher abundances of the genera Lactobacillus, Prevotella, and Fusobacterium and lower concentrations of Cetobacterium, Allobaculum, Bifidobacterium, and Streptococcus. The present study supports a potential benefit of FMT on police performance in Kunming dogs. KEY POINTS: • FMT improves the growth performance and reduces diarrhea rates in Kunming police dogs. • FMT alleviates the serum stress profiles after road transportation in Kunming police dogs. • FMT modifies the gut microbiota composition of Kunming police dogs.

Improved detection sensitivity of anti-PRV variant antibodies through preparation of anti-gB and anti-gE monoclonal antibodies and development of blocking ELISAs.

Since 2011, PRV has resurged in China and is characterized by a mutated strain with significant alterations in antigenicity and virulence. Therefore, we hypothesized that antibody detection kits based on classic PRV strains may have limitations in detecting PRV variants. For more sensitive antibody detection of PRV variants, two MABs targeting the gB and gE proteins were developed. IFA revealed that these MABs exhibited strong reactivity toward both classic and variant PRV strains. MAB-gE recognizes a novel conserved linear B-cell epitope (41PSAEVWD47), while MAB-gB recognizes a conformational B-cell epitope. The binding of both MABs was effectively inhibited in the PRV-positive pig blood samples. Accordingly, we established blocking-ELISAs to detect anti-PRV gB and gE antibodies, which achieved higher sensitivity than commercial kits. Moreover, the clinical serum samples results of our method and that of IFA were in high agreement, and our test results had a higher coincidence rate than that of a commercial kit. Assessing antibody levels by our methods at various times following immunization and challenge accurately reflected the trend of antibody-level changes and revealed the conversion to positive antibody status before the commercial kit. Our method is crucial for monitoring PRV infections, assessing immune responses, and controlling disease.

Role and mechanism of esketamine in improving postoperative cognitive dysfunction in aged mice through the TLR4/MyD88/p38 MAPK pathway.

Postoperative cognitive dysfunction (POCD) is a significant concern for the elderly population worldwide. This study explored the effects of esketamine on aged mice with POCD and investigate its mechanism of action involving the TLR4/MyD88/MAPK pathway. We administrated esketamine, along with lipopolysaccharide or anisomycin, to the aged POCD mouse models. We assessed their cognitive function using the Morris water maze test. Additionally, we evaluated histopathological changes/neuronal apoptosis in the mouse hippocampal CA1 area through HE/TUNEL stainings. Furthermore, we measured IL-1ß/IL-6/TNF-α/TLR4/MyD88/MAPK (p-p38/p38) levels in mouse hippocampal tissues using ELISA/RT-qPCR/Western blotting. Lastly, we analyzed the interaction between TLR4 and MyD88 using a co-immunoprecipitation assay. Our findings showed that esketamine effectively mitigated POCD in aged mice. This was evident from the improved cognitive performance observed in the Morris water maze test, characterized by reduced escape latency/increased number of platform crossing/a higher percentage of time spent in the target quadrant. Furthermore, esketamine exhibited a protective effect against neuronal apoptosis and reduced the levels of inflammatory factors. These findings suggest that esketamine exerts an anti-inflammatory effect by downregulating TLR4/MyD88, thereby attenuating the inflammatory response associated with POCD. Additionally, esketamine suppressed the p38 MAPK pathway by inhibiting the TLR4/MyD88 signaling cascade. Esketamine demonstrated its efficacy in improving postoperative inflammation and cognitive impairment in aged mice by inhibiting the TLR4/MyD88 pathway. The activation of p38 MAPK signaling diminished the beneficial effects of esketamine in aged POCD mice. Collectively, the underlying mechanism of esketamine in mitigating POCD in aged mice involves the suppression of the TLR4/MyD88/p38 MAPK pathway.