Immunogenicity-masking delivery of uricase against hyperuricemia and gout.

Improving the activity of uricase and lowering its immunogenicity remain significant challenges in the enzyme replacement management of hyperuricemia and related inflammatory diseases. Herein, an immunogenicity-masking strategy based on engineered red blood cells (RBCs) was developed for effective uricase delivery against both hyperuricemia and gout. The dynamic membrane of RBCs enabled high resistance to protease inactivation and hydrogen peroxide accumulation. Benefiting from these advantages, a single infusion of RBC-loaded uricase (Uri@RBC) performed prolonged blood circulation and sustained hyperuricemia management. Importantly, RBCs masked the immunogenicity of uricase, leading to the maintenance of UA-lowering performance after repeated infusion through reduced antibody-mediated macrophage clearance. In an acute gout model, Uri@RBC profoundly alleviated joint edema and inflammation with minimal systemic toxicity. This study supports the employment of immunogenicity-masking tools for efficient and safe enzyme delivery, and this strategy may be leveraged to improve the usefulness of enzyme replacement therapies for managing a wide range of inflammatory diseases.

Extensive photochemical restructuring of molecule-metal surfaces under room light.

The molecule-metal interface is of paramount importance for many devices and processes, and directly involved in photocatalysis, molecular electronics, nanophotonics, and molecular (bio-)sensing. Here the photostability of this interface is shown to be sensitive even to room light levels for specific molecules and metals. Optical spectroscopy is used to track photoinduced migration of gold atoms when functionalised with different thiolated molecules that form uniform monolayers on Au. Nucleation and growth of characteristic surface metal nanostructures is observed from the light-driven adatoms. By watching the spectral shifts of optical modes from nanoparticles used to precoat these surfaces, we identify processes involved in the photo-migration mechanism and the chemical groups that facilitate it. This photosensitivity of the molecule-metal interface highlights the significance of optically induced surface reconstruction. In some catalytic contexts this can enhance activity, especially utilising atomically dispersed gold. Conversely, in electronic device applications such reconstructions introduce problematic aging effects.

Exercise training modalities in prediabetes: a systematic review and network meta-analysis.

Background: Lifestyle modification based on exercise intervention is still the primary way to delay or reverse the development of diabetes in patients with prediabetes. However, there are still challenges in setting up a detailed exercise prescription for people with prediabetes. This study mainly ranks exercise prescriptions by comparing the improvement of glucose and lipid metabolism and the level of weight loss in patients. Method: All studies on exercise intervention in prediabetes were identified by searching five electronic databases. Risk assessment and meta-analysis were performed on eligible studies. Results: Twenty-four studies involving 1946 patients with prediabetes and seven exercise intervention models were included in the final analysis. The meta-analysis showed that exercise of any type was more effective for glycemic control in prediabetes than no exercise. However, the changes in blood glucose were moderate. In prediabetes, combining moderate-intensity aerobic exercise with low-to moderate-load resistance training showed the most significant improvements in glycosylated hemoglobin (HbA1c), body mass index (BMI), body weight (BW), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL) (P-score=0.82; 0.70; 0.87; 1; 0.99), low-to moderate-load resistance training showed the most significant improvements in fasting blood glucose (FBG) (P-score=0.98), the vigorous-intensity aerobic exercise showed the most significant improvements in 2-hour post-meal blood glucose (2hPG) and systolic blood pressure (SBP) (P-score=0.79; 0.78), and moderate-intensity aerobic exercise showed the most significant improvements in diastolic blood pressure (DBP) (P-score=0.78). Conclusion: In summary, moderate-intensity aerobic exercise, low-to moderate-load resistance training and the combination of both have beneficial effects on glycemic control, weight loss, and cardiovascular health in patients with prediabetes. These findings provide valuable guidance for rehabilitation clinicians and patients alike to follow. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD 42021284922.

Enhanced Photocurrent and Electrically Pumped Quantum Dot Emission from Single Plasmonic Nanoantennas.

Integrating cavity-enhanced colloidal quantum dots (QDs) into photonic chip devices would be transformative for advancing room-temperature optoelectronic and quantum photonic technologies. However, issues with efficiency, stability, and cost remain formidable challenges to reach the single antenna limit. Here, we present a bottom-up approach that delivers single QD-plasmonic nanoantennas with electrical addressability. These QD nanojunctions exhibit robust photoresponse characteristics, with plasmonically enhanced photocurrent spectra matching the QD solution absorption. We demonstrate electroluminescence from individual plasmonic nanoantennas, extending the device lifetime beyond 40 min by utilizing a 3 nm electron-blocking polymer layer. In addition, we reveal a giant voltage-dependent redshift of up to 62 meV due to the quantum-confined Stark effect and determine the exciton polarizability of the CdSe QD monolayer to be 4 × 10-5 meV/(kV/cm)2. These developments provide a foundation for accessing scalable quantum light sources and high-speed, tunable optoelectronic systems operating under ambient conditions.

The important role of whole-process computed tomography guidance for percutaneous gastrostomy in esophageal cancer patients who are unsuitable for or have had unsuccessful attempts with endoscopic and fluoroscopic gastrostomy.

PURPOSE: To explore the value of clinical application with the whole process computed tomography (CT) guided percutaneous gastrostomy in esophageal tumor patients. MATERIALS AND METHODS: A consecutive series of 32 esophageal tumor patients in whom endoscopic gastrostomy or fluoroscopy guided gastrostomy were considered too dangerous or impossible due to the esophagus complete obstruction, complicate esophageal mediastinal fistula, esophageal trachea fistula or severe heart disease. All of the 32 patients were included in this study from 2 medical center and underwent the gastrostomy under whole process CT guided. RESULTS: All of the gastrostomy procedure was finished successfully under whole process CT guided and the technical success rate was 100%. The average time for each operation was 27 min. No serious complications occurred and the minor complications occurred in 3 patients, including local infection, severe hyperplasia of granulation tissue and tube dislodgment. There were no procedure related deaths. CONCLUSION: The technical success rate of whole process CT guided percutaneous gastrostomy is high and the complication is low. This technique can be used feasible and effectively in some special patients.

Observation of the Fluctuation Spin Hall Effect in a Low-Resistivity Antiferromagnet.

The spin Hall effect (SHE) can generate a pure spin current by an electric current, which is promisingly used to electrically control magnetization. To reduce the power consumption of this control, a giant spin Hall angle (SHA) in the SHE is desired in low-resistivity systems for practical applications. Here, critical spin fluctuation near the antiferromagnetic (AFM) phase transition in chromium (Cr) is proven to be an effective mechanism for creating an additional part of the SHE, named the fluctuation spin Hall effect. The SHA is significantly enhanced when the temperature approaches the Néel temperature (TN) of Cr and has a peak value of -0.36 near TN. This value is higher than the room-temperature value by 153% and leads to a low normalized power consumption among known spin-orbit torque materials. This study demonstrates the critical spin fluctuation as a prospective way to increase the SHA and enriches the AFM material candidates for spin-orbitronic devices.

Room temperature field-free switching of perpendicular magnetization through spin-orbit torque originating from low-symmetry type II Weyl semimetal.

Spin-orbit torque (SOT) is a promising strategy to deterministically switch the perpendicular magnetization, but usually requires an in-plane magnetic field for breaking the mirror symmetry, which is not suitable for most advanced industrial applications. Van der Waals (vdW) materials with low crystalline symmetry and topological band structures, e.g., Weyl semimetals (WSMs), potentially serve as an outstanding system that may simultaneously realize field-free switching and high energy efficiency. Yet, the demonstration of these superiorities at room temperature has not been realized. Here, we achieve a field-free switching of perpendicular magnetization by using a layered type II WSM, TaIrTe4, in a TaIrTe4/Ti/CoFeB system at room temperature with the critical switching current density ~2.4 × 106 A cm-2. The field-free switching is ascribed to the out-of-plane SOT allowed by the low crystal symmetry. Our work suggests that using low-symmetry materials to generate SOT is a promising route for the manipulation of perpendicular magnetization at room temperature.

Prophylactic Effects of Hemp Seed Oil on Perimenopausal Depression: A Role of HPA Axis.

Hemp seed, the dried fruit of Cannabis sativa L. (Moraceae), has been extensively documented as a folk source of food due to its nutritional and functional value. This study evaluated the antidepressant effect of hemp seed oil (HSO) during its estrogen-like effect in Perimenopausal depression (PMD) rats induced by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS). Female SD rats (SPF, 10 weeks, sham operated group, ovariectomy (OVX) model group, ovariectomy - chronic unpredictable mild stress (OVX-CUMS) group, HSO + OVX-CUMS group, fluoxetine (FLU) + OVX-CUMS group, n=8) were subjected to treatment with HSO (4.32 g/kg) or fluoxetine (10 mg/kg) for 28 days (20 mL/kg by ig). Sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), estrogen receptor α (ERα) and estrogen receptor ß (ERß) expression, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol (CORT), adrenocorticotropic hormone (ACTH), corticotropin releasing hormone (CRH), norepinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5HIAA) levels are measured to evaluate the function of the hypothalamic-pituitary-ovarian (HPO) and hypothalamic-pituitary-adrenal (HPA) axis. The results showed that OVX-CUMS significantly decrease sucrose preference rate in SPT, increase immobility time in FST and OFT, and decrease movement distance and stand-up times in OFT. HSO treatment significantly improves depression-like behaviors, upregulates the expression of ERα and ERß, improves HPO axis function by increasing E2 levels and decreasing FSH and LH levels, reverses HPA axis hyperactivation by decreasing CORT, ACTH, and CRH levels, and upregulates NE, 5-HT, and 5HIAA levels in model rats. The findings suggested that HSO could improve depression-like behavior in OVX-CUMS rats by regulating HPO/HPA axis function and neurotransmitter disturbance.

Circulating Cell-Free DNAs as a Biomarker and Therapeutic Target for Acetaminophen-Induced Liver Injury.

Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury and acute liver failure, while the detection, prognosis prediction, and therapy for APAP-induced liver injury (AILI) remain improved. Here, it is determined that the temporal pattern of circulating cell-free DNA (cfDNA) is strongly associated with damage and inflammation parameters in AILI. CfDNA is comparable to alanine aminotransferase (ALT) in predicting mortality and outperformed ALT when combined with ALT in AILI. The depletion of cfDNA or neutrophils alleviates liver damage, while the addition of cfDNA or adoptive transfer of neutrophils exacerbates the damage. The combination of DNase I and N-acetylcysteine attenuates AILI significantly. This study establishes that cfDNA is a mechanistic biomarker to predict mortality in AILI mice. The combination of scavenging cfDNA and reducing oxidative damage provides a promising treatment for AILI.

Extracellular Vesicles Secreted by TGF-ß1-Treated Mesenchymal Stem Cells Promote Fracture Healing by SCD1-Regulated Transference of LRP5.

Bone fracture repair is a multiphased regenerative process requiring paracrine intervention throughout the healing process. Mesenchymal stem cells (MSCs) play a crucial role in cell-to-cell communication and the regeneration of tissue, but their transplantation is difficult to regulate. The paracrine processes that occur in MSC-derived extracellular vesicles (MSC-EVs) have been exploited for this study. The primary goal was to determine whether EVs secreted by TGF-ß1-stimulated MSCs (MSCTGF-ß1-EVs) exhibit greater effects on bone fracture healing than EVs secreted by PBS-treated MSCs (MSCPBS-EVs). Our research was conducted using an in vivo bone fracture model and in vitro experiments, which included assays to measure cell proliferation, migration, and angiogenesis, as well as in vivo and in vitro gain/loss of function studies. In this study, we were able to confirm that SCD1 expression and MSC-EVs can be induced by TGF-ß1. After MSCTGF-ß1-EVs are transplanted in mice, bone fracture repair is accelerated. MSCTGF-ß1-EV administration stimulates human umbilical vein endothelial cell (HUVEC) angiogenesis, proliferation, and migration in vitro. Furthermore, we were able to demonstrate that SCD1 plays a functional role in the process of MSCTGF-ß1-EV-mediated bone fracture healing and HUVEC angiogenesis, proliferation, and migration. Additionally, using a luciferase reporter assay and chromatin immunoprecipitation studies, we discovered that SREBP-1 targets the promoter of the SCD1 gene specifically. We also discovered that the EV-SCD1 protein could stimulate proliferation, angiogenesis, and migration in HUVECs through interactions with LRP5. Our findings provide evidence of a mechanism whereby MSCTGF-ß1-EVs enhance bone fracture repair by regulating the expression of SCD1. The use of TGF-ß1 preconditioning has the potential to maximize the therapeutic effects of MSC-EVs in the treatment of bone fractures.

Full Control of Plasmonic Nanocavities Using Gold Decahedra-on-Mirror Constructs with Monodisperse Facets.

Bottom-up assembly of nanoparticle-on-mirror (NPoM) nanocavities enables precise inter-metal gap control down to ≈ 0.4 nm for confining light to sub-nanometer scales, thereby opening opportunities for developing innovative nanophotonic devices. However limited understanding, prediction, and optimization of light coupling and the difficulty of controlling nanoparticle facet shapes restricts the use of such building blocks. Here, an ultraprecise symmetry-breaking plasmonic nanocavity based on gold nanodecahedra is presented, to form the nanodecahedron-on-mirror (NDoM) which shows highly consistent cavity modes and fields. By characterizing > 20 000 individual NDoMs, the variability of light in/output coupling is thoroughly explored and a set of robust higher-order plasmonic whispering gallery modes uniquely localized at the edges of the triangular facet in contact with the metallic substrate is found. Assisted by quasinormal mode simulations, systematic elaboration of NDoMs is proposed to give nanocavities with near hundred-fold enhanced radiative efficiencies. Such systematically designed and precisely-assembled metallic nanocavities will find broad application in nanophotonic devices, optomechanics, and surface science.

Withdrawn: 'Downregulation of circPPFIA1 elevates radiosensitivity via miR-1299-mediated TXNRD1 inhibition in oesophageal squamous cell carcinoma', Weihui Yu, Ke Ning, Jincheng Xiao, Qiwen Bai and Chenyang Guo. (https://onlinelibrary.wiley.com/doi/10.1111/1440-1681.13751).

The above article, published online on 16 February 2023 in Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the journal Editor in Chief, Yang Yang, and John Wiley & Sons Ltd. The withdrawal has been agreed following no response from the authors to requests to sign the journal's publishing license agreement.

Downstaging and Conversation Strategy for Advanced Hepatocellular Carcinoma with Portal Vein Branch Tumor Thrombus: TACE, 125I Seed Implantation, and RFA for Hepatocellular Carcinoma with Portal Vein Branch Tumor Thrombus.

Background and Objectives: Trans-arterial chemoembolization (TACE) combined with 125I seed implantation is an effective treatment modality for hepatocellular carcinoma (HCC) with a portal vein tumor thrombus (PVTT). However, there are no reports on the effectiveness of radiofrequency ablation (RFA) after downstaging in such patients. This study aimed to investigate the efficacy and safety of TACE in combination with 125I seed implantation and RFA for the treatment of HCC complicated by PVTT. Methods: 49 patients diagnosed with HCC with PVTT between February 2015 and December 2016 were included. All patients were clinically or pathologically diagnosed with advanced HCC, intrahepatic lesions ≤3, and a single tumor diameter ≤70 mm, total diameter ≤100 mm. PVTT was limited to the unilateral portal vein branches. All the patients were treated with TACE combined with PVTT 125I seed implantation. The size and activity of intrahepatic lesions and PVTT were evaluated using enhanced magnetic resonance imaging 3 months after treatment, and other indicators were combined to determine the success of downstaging. Results: A total of 31 patients were successfully downstaged, while 18 patients did not achieve downstaging owing to the progression of intrahepatic lesions or PVTT activity/progression, the success rate of the downstaging was 63.27%. All 31 patients with successful downstaging underwent RFA for intrahepatic lesions. The 1-, 2-, and 3-year survival rates were 90.3%, 80.6%, and 48.4%, respectively. The median overall survival was 36 months (95% CI: 24.7-47.3). Conclusion: 125I seed implantation in combination with TACE can effectively inactivate PVTT and achieve downstaging. Furthermore, the addition of RFA can significantly improve patient survival.

Boosting Optical Nanocavity Coupling by Retardation Matching to Dark Modes.

Plasmonic nanoantennas can focus light at nanometer length scales providing intense field enhancements. For the tightest optical confinements (0.5-5 nm) achieved in plasmonic gaps, the gap spacing, refractive index, and facet width play a dominant role in determining the optical properties making tuning through antenna shape challenging. We show here that controlling the surrounding refractive index instead allows both efficient frequency tuning and enhanced in-/output coupling through retardation matching as this allows dark modes to become optically active, improving widespread functionalities.

Hsa_circ_0007380 silencing restrains the growth and enhances radiosensitivity in esophagus cancer by miR-644a/Spindlin 1 axis.

Circular RNAs are frequently dysregulated and show important regulatory function of tumorigenesis in cancers. Hsa_circ_0007380 was found to be elevated in human radioresistant esophageal cancer cells. Here, this study aimed to investigate the action and mechanism of hsa_circ_0007380 in esophageal cancer carcinogenesis and radiosensitivity. Quantitative real-time PCR and western blotting were performed to detect levels of genes and proteins. Functional experiments were conducted using MTT assay, EdU assay, clonogenic survival assay, flow cytometry and murine xenograft model assay, respectively. The binding between miR-644a and hsa_circ_0007380 or spindlin1 (SPIN1) was validated using dual-luciferase activity assay. Hsa_circ_0007380 was highly expressed in esophagus cancer tissues and cells, knockdown of hsa_circ_0007380 suppressed esophagus cancer cell proliferation, induced apoptosis and enhanced radiosensitivity in vitro, and the same effects were also confirmed in nude mice. Mechanistically, hsa_circ_0007380 sequestered miR-644a to release SPIN1 expression, implying the hsa_circ_0007380/miR-644a/SPIN1 competing endogenous RNA network esophagus cancer cells. miR-644a was decreased in esophagus cancer, re-expression of miR-644a restrained cell growth and conferred radiosensitivity in esophagus cancer, which were reversed by SPIN1 overexpression. Besides that, inhibition of miR-644a abolished the promoting action of hsa_circ_0007380 knockdown on esophagus cancer apoptosis and radiosensitivity. Hsa_circ_0007380 silencing impedes cell growth and reinforces radiosensitivity in esophagus cancer by miR-644a/SPIN1 axis, suggesting a promising therapeutic target for esophagus cancer combined treatment.

Transarterial chemoembolization combined with apatinib with or without PD-1 inhibitors in BCLC stage C hepatocellular carcinoma: A multicenter retrospective study.

Objective: We evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib plus PD-1 inhibitors (TACE-AP) compared with TACE combined with apatinib (TACE-A) in patients with advanced hepatocellular carcinoma (HCC) and to explore the prognostic factors affecting patient survival. Methods: Data from patients with unresectable HCC who received TACE-AP or TACE-A from December 2018 to June 2021 were collected retrospectively. The main outcome of the study was overall survival (OS) and prognostic factors affecting survival, while the secondary outcomes were progression-free survival (PFS), the objective response rate (ORR), and treatment-related adverse events (TRAEs). Propensity score matching (PSM) analysis was used to reduce patient selection bias, and the random survival forest (RF) model was employed to explore prognostic factors affecting patient survival. Results: We enrolled 216 patients, including 148 and 68 patients in the TACE-A and TACE-AP groups, respectively. A total of 59 pairs of patients were matched using PSM analysis. Before and after PSM, the OS, PFS, and ORR in the TACE-AP group were significantly higher than in the TACE-A group (before, OS: 22.5 months vs. 12.8 months, P < 0.001; PFS: 6.7 months vs. 4.3 months, P < 0.001; ORR: 63.2% vs. 34.5%, P < 0.001; after, OS: 22.5 months vs. 12.0 months, P < 0.001; PFS: 6.7 months vs. 4.3 months, P < 0.001; ORR: 62.7% vs. 30.5%, P = 0.003). Multivariate Cox regression and RF models before and after PSM analysis revealed that the main prognostic factors affecting survival were tumor number, portal vein tumor thrombus (PVTT) invasion, alpha-fetoprotein (AFP) levels, total bilirubin (TBIL) level, and treatment. There was no significant difference in TRAEs between the two groups (P > 0.05). Conclusion: Compared with TACE-A, TACE-AP significantly improved OS, PFS, and ORR in patients with advanced HCC. The number of tumors, PVTT invasion, AFP levels, TBIL level, and treatment were significant prognostic factors associated with patient survival. All observed TRAEs were mild and controllable.

Prospective study of TACE combined with sorafenib vs TACE combined with 125I seed implantation in the treatment of hepatocellular carcinoma with portal vein tumor thrombus and arterioportal fistulas.

Purpose: To compare the efficacy of TACE combined with sorafenib and TACE combined with 125I seed implantation in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) combined with arterioportal fistulas (APFs), and discuss the efficacy and safety of TACE combined with 125I seed implantation. Patients and methods: Between January 2017 and December 2018, the clinical data of patients with HCC complicated with PVTT and APFs who were admitted to the Affiliated Cancer Hospital of Zhengzhou University, First Affiliated Hospital of Zhengzhou University, and Henan Provincial People's Hospital were prospectively collected. The patients were divided into the TACE+sorafenib (TACE-S) group based on their treatment willingness. There were 26 and 32 patients in the TACE-S and TACE-125I groups, respectively. Both groups of patients underwent APFs occlusion during TACE therapy. The embolization effect of APFs was observed and recorded in the two groups, the efficacy of intrahepatic lesions and PVTT was evaluated, and the effects of different treatment methods on the efficacy were analysed. Results: All patients completed the 3 months follow-up. The improvement rates of APFs in TACE-S and TACE-125I groups were 30.77% (8/26) and 68.75% (22/32), respectively, and difference was statistically significant (χ2 = 8.287, P=0.004). The median survival time of TACE-S and TACE-125I groups was 8.00 months and 12.8 months, respectively (χ2 = 7.106, P=0.008). Multivariate analysis showed that the PVTT subtype (IIa/IIb) and treatment method (TACE-S or TACE-125I) were independent factors affecting the recanalization of APFs in patients (P<0.05). Conclusion: For patients with HCC with PVTT and APFs, TACE combined with 125I seed implantation can effectively treat portal vein tumor thrombus, thereby reducing the recanalization of APFs and prolonging the survival time of patients.

Plasma arginase-1 as a predictive marker for early transarterial chemoembolization refractoriness in unresectable hepatocellular carcinoma.

Objective: To explore the relationship between plasma arginase-1 (ARG1) and early transarterial chemoembolization (TACE) refractoriness in patients with hepatocellular carcinoma (HCC) and develop nomograms for predicting early TACE refractoriness. Methods: A total of 200 patients with HCC, treated with TACE, were included in the study, including 120 in the training set and 80 in the validation set. Pre-treatment enzyme-linked immunosorbent assay was used to detected the plasma ARG1 levels of the patient, and independent predictors of early TACE refractoriness were determined using a multivariate logistic regression model, based on which a predictive model was developed using a nomogram. Results: Risk of early TACE refractoriness was negatively correlated with plasma ARG1 levels, and multivariate logistic analysis showed tumour size (OR = 1.138, 95% CI = 1.006-1.288, P = 0.041), multiple tumors (OR=4.374, 95% CI = 1.189-16.089, P = 0.026), platelet count (OR = 0.990, 95% CI = 0.980-0.999, P = 0.036), and plasma ARG1 levels (OR = 0.209, 95% CI = 0.079-0.551, P = 0.002) to be independent prognostic factors for early TACE refractoriness.The AUC value for the nomogram of the training cohort was 0.786 (95% CI = 0.702-0.870), and the validation set AUC value was 0.833 (95% CI = 0.791-0.875).The decision curve analysis suggested that the nomogram had good clinical utility. Conclusion: High plasma ARG1 expression was associated with a lower incidence of early TACE refractoriness. The nomogram constructed based on four independent prognostic factors could facilitate an individualised prediction of the incidence of early TACE refractoriness.

Exercise improves choroid plexus epithelial cells metabolism to prevent glial cell-associated neurodegeneration.

Recent studies have shown that physical activities can prevent aging-related neurodegeneration. Exercise improves the metabolic landscape of the body. However, the role of these differential metabolites in preventing neurovascular unit degeneration (NVU) is still unclear. Here, we performed single-cell analysis of brain tissue from young and old mice. Normalized mutual information (NMI) was used to measure heterogeneity between each pair of cells using the non-negative Matrix Factorization (NMF) method. Astrocytes and choroid plexus epithelial cells (CPC), two types of CNS glial cells, differed significantly in heterogeneity depending on their aging status and intercellular interactions. The MetaboAnalyst 5.0 database and the scMetabolism package were used to analyze and calculate the differential metabolic pathways associated with aging in the CPC. These mRNAs and corresponding proteins were involved in the metabolites (R)-3-Hydroxybutyric acid, 2-Hydroxyglutarate, 2-Ketobutyric acid, 3-Hydroxyanthranilic acid, Fumaric acid, L-Leucine, and Oxidized glutathione pathways in CPC. Our results showed that CPC age heterogeneity-associated proteins (ECHS1, GSTT1, HSD17B10, LDHA, and LDHB) might be directly targeted by the metabolite of oxidized glutathione (GSSG). Further molecular dynamics and free-energy simulations confirmed the insight into GSSG's targeting function and free-energy barrier on these CPC age heterogeneity-associated proteins. By inhibiting these proteins in CPC, GSSG inhibits brain energy metabolism, whereas exercise improves the metabolic pathway activity of CPC in NVU by regulating GSSG homeostasis. In order to develop drugs targeting neurodegenerative diseases, further studies are needed to understand how physical exercise enhances NVU function and metabolism by modulating CPC-glial cell interactions.