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Abstract Objective To explore the effects of tube voltage, radiation dose and adaptive statistical iterative reconstruction (ASiR-V) strength level on the detection and characterization of pulmonary nodules by an artificial intelligence (AI) software in ultra-low-dose chest CT (ULDCT). Materials and methods An anthropomorphic thorax phantom containing 12 spherical simulated nodules (Diameter: 12 mm, 10 mm, 8 mm, 5 mm; CT value: -800HU, -630HU, 100HU) was scanned with three ULDCT protocols: Dose-1 (70kVp:0.11mSv, 100kVp:0.10mSv), Dose-2 (70kVp:0.34mSv, 100kVp:0.32mSv), Dose-3 (70kVp:0.53mSv, 100kVp:0.51mSv). All scanning protocols were repeated five times. CT images were reconstructed using four different strength levels of ASiR-V (0%=FBP, 30%, 50%, 70%ASiR-V) with a slice thickness of 1.25 mm. The characteristics of the physical nodules were used as reference standards. All images were analyzed using a commercially available AI software to identify nodules for calculating nodule detection rate (DR) and to obtain their long diameter and short diameter, which were used to calculate the deformation coefficient (DC) and size measurement deviation percentage (SP) of nodules. DR, DC and SP of different imaging groups were statistically compared. Results Image noise decreased with the increase of ASiR-V strength level, and the 70 kV images had lower noise under the same strength level (mean-value 70 kV: 40.14 ± 7.05 (dose 1), 27.55 ± 7.38 (dose 2), 23.88 ± 6.98 (dose 3); 100 kV: 42.36 ± 7.62 (dose 1); 30.78 ± 6.87 (dose 2); 26.49 ± 6.61 (dose 3)). Under the same dose level, there were no differences in DR between 70 kV and 100 kV (dose 1: 58.76% vs. 58.33%; dose 2: 73.33% vs. 70.83%; dose 3: 75.42% vs. 75.42%, all p > 0.05). The DR of GGNs increased significantly at dose 2 and higher (70 kV: 38.12% (dose 1), 60.63% (dose 2), 64.38% (dose 3); 100 kV: 37.50% (dose 1), 59.38% (dose 2), 66.25% (dose 3)). In general, the use of ASiR-V at higher strength levels (> 50%) and 100 kV provided better (lower) DC and SP. Conclusion Detection rates are similar between 70 kV and 100 kV scans. The 70 kV images have better noise performance under the same ASiR-V level, while images of 100 kV and higher ASiR-V levels are better in preserving the nodule morphology (lower DC and SP); the dose levels above 0.33mSv provide high sensitivity for nodules detection, especially the simulated ground glass nodules.

Abstract Background Pancreatic cancer is one of the most lethal malignancies and the lack of treatment options makes it more deadly. Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has revolutionized cancer treatment and made great breakthroughs in treating hematological malignancies, however its success in treating solid cancers remains limited mainly due to the lack of tumor-specific antigens. On the other hand, the prolonged traditional manufacturing process poses challenges, taking 2 to 6 weeks and impacting patient outcomes. CD276 has recently emerged as a potential therapeutic target for anti-solid cancer therapy. Here, we investigated the efficacy of CD276 CAR-T and rapidly-manufactured CAR-T against pancreatic cancer. Methods In the present study, CD276 CAR-T was prepared by CAR structure carrying 376.96 scFv sequence, CD8 hinge and transmembrane domain, 4-1BB and CD3ζ intracellular domains. Additionally, CD276 rapidly-manufactured CAR-T (named CD276 Dash CAR-T) was innovatively developed by shortening the duration of ex vitro culture to reduce CAR-T manufacturing time. We evaluated the anti-tumor efficacy of CD276 CAR-T and further compared the functional assessment of Dash CAR-T and conventional CAR-T in vitro and in vivo by detecting the immunophenotypes, killing ability, expansion capacity and tumor-eradicating effect of CAR-T. Results We found that CD276 was strongly expressed in multiple solid cancer cell lines and that CD276 CAR-T could efficiently kill these solid cancer cells. Moreover, Dash CAR-T was successfully manufactured within 48–72 h and the functional validation was carried out subsequently. In vitro, CD276 Dash CAR-T possessed a less-differentiated phenotype and robust proliferative ability compared to conventional CAR-T. In vivo xenograft mouse model, CD276 Dash CAR-T showed enhanced anti-pancreatic cancer efficacy and T cell expansion. Besides, except for the high-dose group, the body weight of mice was maintained stable, and the state of mice was normal. Conclusions In this study, we proved CD276 CAR-T exhibited powerful activity against pancreatic cancer cells in vitro and in vivo. More importantly, we demonstrated the manufacturing feasibility, acceptable safety and superior anti-tumor efficacy of CD276 Dash CAR-T generated with reduced time. The results of the above studies indicated that CD276 Dash CAR-T immunotherapy might be a novel and promising strategy for pancreatic cancer treatment.

Abstract Background Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. Methods and results A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P

Abstract A pressing challenge in spatially resolved transcriptomics (SRT) is to benchmark the computational methods. A widely-used approach involves utilizing simulated data. However, biases exist in terms of the currently available simulated SRT data, which seriously affects the accuracy of method evaluation and validation. Herein, we present scCube ( https://github.com/ZJUFanLab/scCube ), a Python package for independent, reproducible, and technology-diverse simulation of SRT data. scCube not only enables the preservation of spatial expression patterns of genes in reference-based simulations, but also generates simulated data with different spatial variability (covering the spatial pattern type, the resolution, the spot arrangement, the targeted gene type, and the tissue slice dimension, etc.) in reference-free simulations. We comprehensively benchmark scCube with existing single-cell or SRT simulators, and demonstrate the utility of scCube in benchmarking spot deconvolution, gene imputation, and resolution enhancement methods in detail through three applications.

Sodium-glucose cotransporter 2 inhibitors are a class of glucose-lowering drugs known for robust cardiovascular protective properties. However, the side effects induced by Sodium-glucose cotransporter 2 inhibition limit application in cardiovascular medicine. Our prior research showed that thoughtful structural modifications can dissociate the anti-heart failure activity from glucose-lowering effects. Moreover, we showed that the glyceraldehyde derivative, JX22, developed by scaffold hopping from empagliflozin, exhibits a superior cardiomyocyte protective effect, albeit with increased cytotoxicity compared to empagliflozin. In the current study systematic structural modifications of JX22 were performed to enhance anti-heart failure efficacy and safety, while reducing glucose-lowering activity. Twenty glyceraldehyde-based derivatives were synthesized and compound 12 emerged as an optimal candidate by exhibiting an improved cytoprotective effect compared to JX22. Compound 12 significantly inhibited the activity of NHE1 on the myocardial membrane, thereby maintaining intracellular ion homeostasis. In vivo efficacy results demonstrated that compound 12 at 10 mg/kg significantly ameliorated cardiac dysfunction, myocardial fibrosis, and exercise tolerance in isoproterenol-induced heart failure mice without a glucose-lowering effect. Furthermore, compound 12 exhibited favorable safety profiles in single-dose toxicity and hERG inhibition tests, along with promising pharmacokinetic properties in mice. The current study not only underscores the potential of compound 12 for further investigation but also highlights the effectiveness of the scaffold hopping strategy.

AIM: To evaluate the effect of bone morphogenetic protein-6 (BMP-6) on transforming growth factor (TGF)-β2-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE). METHODS: Adult retinal pigment epithelial cell line (ARPE-19) were randomly divided into control, TGF-β2 (5 µg/L), and BMP-6 small interfering RNA (siRNA) group. The cell morphology was observed by microscopy, and the cell migration ability were detected by Transwell chamber. The EMT-related indexes and BMP-6 protein levels were detected by Western blotting. Furthermore, a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group, TGF-β2+empty plasmid group, BMP-6 overexpression group, and TGF-β2+BMP-6 overexpression group. The EMT-related indexes and extracellular regulated protein kinases (ERK) protein levels were detected. RESULTS: Compared with the control group, the migration of RPE cells in the TGF-β2 group was significantly enhanced. TGF-β2 increased the protein expression levels of α-smooth muscle actin (α-SMA), fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6 (P

Background: A. baumannii is an important and common clinical pathogen, especially in the intensive care unit (ICU). This study aimed to characterize one hypervirulent A. baumannii strain in a patient with community-acquired pneumonia and herpes simplex type 1 virus infection. Methods: Minimum inhibitory concentrations (MICs) were determined using the Kirby-Bauer (K-B) and broth microdilution methods. Galleria mellonella infection model experiment was conducted. Whole-genome sequencing (WGS) was performed using the Illumina and Nanopore platforms. The resistance and virulence determinants were identified using the ABRicate program with ResFinder and the VFDB database. The capsular polysaccharide locus (K locus) and lipooligosaccharide outer core locus (OC locus) were identified using Kleborate with Kaptive. Phylogenetic analyses were conducted using the BacWGSTdb server. Results: A. baumannii XH2146 strain belongs to ST10Pas and ST447Oxf. The strain was resistant to cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole (TMP-SMX). Bautype and Kaptive analyses showed that XH2146 contains OCL2 and KL49. WGS analysis revealed that the strain harbored blaADC-76, blaOXA-68, ant(3′’)-IIa, tet(B), and sul2. Notably, tet(B) and sul2, both were located within a 114,700-bp plasmid (designated pXH2146–1). Virulence assay revealed A. baumannii XH2146 possessed higher virulence than A. baumannii AB5075 at 12 h. Comparative genomic analysis showed that A. baumannii ST447 strains were mainly isolated from the USA and exhibited a relatively close genetic relationship. Importantly, 11 strains were observed to carry blaOXA-58; blaOXA-23 was identified in 11 isolates and three ST447 A. baumannii strains harbored blaNDM-1. Conclusions: Early detection of community-acquired hypervirulent Acinetobacter baumannii strains is recommended to prevent their extensive spread in hospitals.

C23H25NO3, monoclinic, P21 (no. 4), a = 15.2433(7) Å, b = 5.8687(3) Å, c = 22.3558(11) Å, β = 105.461(2)°, V = 1927.54(16) Å3, Z = 4, R gt(F) = 0.0413, wR ref(F 2) = 0.1055, T = 100(2) K.

Abstract Background Small extracellular vesicles (sEVs) mediate intercellular communication that contributes to hepatocellular carcinoma (HCC) progression via multifaceted pathways. The success of cell entry determines the effect of sEV on recipient cells. Here, we aimed to delineate the mechanisms underlying the uptake of sEV in HCC. Methods Macropinocytosis was examined by the ability of cells to internalize dextran and sEV. Macropinocytosis was analyzed in Na(+)/H(+) exchanger 7 (NHE7)‐knockdown and ‐overexpressing cells. The properties of cells were studied using functional assays. pH biosensor was used to evaluate the intracellular and endosomal pH. The expression of NHE7 in patients’ liver tissues was examined by immunofluorescent staining. Inducible silencing of NHE7 in established tumors was performed to reveal the therapeutic potential of targeting NHE7. Results The data revealed that macropinocytosis controlled the internalization of sEVs and their oncogenic effect on recipient cells. It was found that metastatic HCC cells exhibited the highest efficiency of sEV uptake relative to normal liver cells and non‐metastatic HCC cells. Attenuation of macropinocytic activity by 5‐(N‐ethyl‐N‐isopropyl)‐amiloride (EIPA) limited the entry of sEVs and compromised cell aggressiveness. Mechanistically, we delineated that high level of NHE7, a sodium‐hydrogen exchanger, alkalized intracellular pH and acidized endosomal pH, leading to the maturation of macropinosomes. Inducible inhibition of NHE7 in established tumors developed in mice delayed tumor development and suppressed lung metastasis. Clinically, NHE7 expression was upregulated and linked to dismal prognosis of HCC. Conclusions This study advances the understanding that NHE7 enhances sEV uptake by macropinocytosis to promote the malignant properties of HCC cells. Inhibition of sEV uptake via macropinocytosis can be exploited as a treatment alone or in combination with conventional therapeutic approaches for HCC.

The emergence and spread of Acinetobacter baumannii pose a severe threat to public health, highlighting the urgent need for the next generation of therapeutics due to its increasing resistance to existing antibiotics. BfmR, a response regulator modulating virulence and antimicrobial resistance, shows a promising potential as a novel antimicrobial target. Developing BfmR inhibitors may propel a new therapeutic direction for intractable infection of resistant strains. In this study, we conducted a structure-based hierarchical virtual screening pipeline combining molecular docking, molecular dynamic simulation, and MM/GBSA calculation to sift the Specs chemical library and finally discover three novel potential BfmR inhibitors. The three hits can reduce the MIC of meropenem for the carbapenem-resistant Acinetobacter baumannii (CRAB) strain ZJ06. Similar to the BfmR knockout strain, Cmp-98 was demonstrated to downregulate the expression of K locus genes, indicating it as a BfmR inhibitor. Bacteria underwent harmful morphological changes after treatment with these inhibitors. Molecular dynamic simulations found that all the hits tend to dynamically bind to different positions of the phosphorylation site of BfmR. Wherein we identified a potential inhibitory-binding cleft, beside a possible activated binding cleft at the edge of the phosphorylation site. Restraining the ligand binding poses may help exert inhibitory effects. This study reports a group of new scaffold BfmR inhibitors, offering new insights for novel antibiotic therapeutics against CRAB.

With the development of intelligent protective wearable equipment, flexible materials with impact resistance have become a focus of attention. Shear stiffening gel (SSG) is a flexible smart material that can perceive external force loads and generate mechanical responses, boasting exceptional properties like fast response, adaptability, and self-healing. Since the SSG can absorb a large amount of energy during dynamic impact, it shows remarkable advantages for safety protection applications. During the past decade, there has been strong interests in the research community on the SSG composites and their various applications in cutting-edge fields. In this review, we summarize the recent research achievements of SSG composite, by focusing on the improved properties, enhanced functions, and manifold structures. Meanwhile, we also discuss the practical applications of SSG composite in battery protection, vibration control, intelligent sensing, wearable safety protection, and triboelectric nanogenerator (TENG). Finally, we propose the prospects and challenges for the further development and application of SSG composite in the future.

Abstract In histopathology, doctors identify diseases by characterizing abnormal cells and their spatial organization within tissues. Polarization microscopy and supervised learning have been proved as an effective tool for extracting polarization parameters to highlight pathological features. Here, we present an alternative approach based on unsupervised learning to group polarization-pixels into clusters, which correspond to distinct pathological structures. For pathological samples from different patients, it is confirmed that such unsupervised learning technique can decompose the histological structures into a stable basis of characteristic microstructural clusters, some of which correspond to distinctive pathological features for clinical diagnosis. Using hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) samples, we demonstrate how the proposed framework can be utilized for segmentation of histological image, visualization of microstructure composition associated with lesion, and identification of polarization-based microstructure markers that correlates with specific pathology variation. This technique is capable of unraveling invisible microstructures in non-polarization images, and turn them into visible polarization features to pathologists and researchers.

NH2-MIL-125(Ti) is a Ti-MOFs (MOFs: metal-organic frameworks) with high adsorption properties and is therefore widely used for wastewater purification. However, the powdered MOF material suffers from the disadvantages of being difficult to separate and being potentially wasted due to easy agglomeration, which limits its application in practical applications. Here, a mesoporous Ti-MOF/polymer (PEG, PVA, and PAM) monolithic material was prepared by freeze casting in liquid nitrogen (−196 °C) as an adsorbent for wastewater remediation. The composites could be easily picked up with tweezers and used for recovery tests. Characterization results such as XRD, BET, FT-IR, and SEM proved the successful synthesis of Ti-MOF/polymer. Adsorption tests using 100 mg/L methylene blue (MB) simulated wastewater showed that the Ti-MOF/PEG monolithic material had the best adsorption capacity. The order of adsorption was Ti-MOF@PEG10 (747.4 mg/g) > Ti-MOF@PVA10 (687.4 mg/g) > Ti-MOF@PAM10 (633.7 mg/g) > NH2-MIL-125(Ti) (571.4 mg/g). The effects of polymer dosage, different pollutants (methylene blue, methyl orange, indigo, actual textile wastewater), pH, anions, and cations on the adsorption effect of Ti-MOF/polymer were also investigated. It was demonstrated that all the above pollutants were well adsorbed by this Ti-MOF/polymer in the pH range 3–9. The adsorption isotherms and kinetic data are fully consistent with the Langmuir and pseudo-secondary models. This suggests that the adsorption between the pollutant and the adsorbent is a chemical interaction. Thermodynamic studies indicate that the adsorption process is exothermic and spontaneous. This work provides the potential methods to fabricate Ti-MOF/polymer monolith to avoid the pollution from powdery adsorbents that could be practical applications.

This research investigated the impact of Cr content on the properties of (Mo,Cr)Si2 composites. Composites with CrSi2 molar fractions ranging from 0% to 10% were fabricated using spark plasma sintering (SPS). The study undertook a systematic analysis of the surface morphology, phase composition, mechanical properties, and high-temperature oxidation resistance of the sintered samples across different compositions. Notably, the (Mo95,Cr5)Si2 composite sintered at 1400 °C exhibited enhanced properties, including a Vickers hardness of 11.6 GPa, a fracture toughness of 4.6 MPa·m1/2, and a flexural strength of 397 MPa. Upon oxidation at 1500 °C, the (Mo,Cr)Si2 composites formed a protective oxide layer comprised of SiO2 and Cr2O3. It was found that the generation and thickening of the protective oxide layer was promoted by the addition of moderate amounts of Cr to MoSi2.

Motion artifacts are a major challenge in the in vivo application of catheter-based cardiac imaging modalities. Gating is a critical tool for suppressing motion artifacts. Electrocardiogram (ECG) gating requires a trigger device or synchronous ECG recordings for retrospective analysis. Existing retrospective software gating methods extract gating signals through separate steps based on changes in vessel morphology or image features, which require a high computational cost and are prone to error accumulation. In this paper, we report on an end-to-end unsupervised learning framework for retrospective image-based gating (IBG) of catheter-based intracoronary images, named IBG Network. It establishes a direct mapping from a continuously acquired image sequence to a gated subsequence. The network was trained on clinical data sets in an unsupervised manner, addressing the difficulty of obtaining the gold standard in deep learning-based motion suppression techniques. Experimental results of in vivo intravascular ultrasound and optical coherence tomography sequences show that the proposed method has better performance in terms of motion artifact suppression and processing efficiency compared with the state-of-the-art nonlearning signal-based and IBG methods.

Cigarette combustion has the potential to generate over 7000 chemicals, the majority of which are reactive free radicals that are known to trigger pro-inflammatory and carcinogenic responses. Numerous contemporary investigations have proposed that the pathophysiological and cellular mechanisms underlying the release of extracellular vesicles (EVs) in response to cigarette smoke (CS) may serve as potential pathways for CS-induced pathogenesis, while also reflecting the physiological state of the originating cells. This review provides a concise overview of the pathophysiological mechanisms linked to CS-induced EVs in various lung diseases, including chronic obstructive pulmonary disease, lung cancer, pulmonary fibrosis, and pulmonary hypertension. Additionally, it explores the potential and prospects of EVs as diagnostic biomarkers for CS-related lung diseases.

The mechanical properties and microstructure of the cemented paste backfill (CPB) in dry–wet cycle environments are particularly critical in backfill mining. In this study, coal gangue, fly ash, cement, glass fiber, and nano-SiO2 were used to prepare CPB, and dry–wet cycle tests on CPB specimens with different curing ages were conducted. The compressive, tensile, and shear strength of CPB specimens with different curing ages under different dry–wet cycles were analyzed, and the microstructural damage of the specimens was observed by scanning electron microscopy (SEM). The results show that compared with the specimens without dry–wet cycles, the uniaxial compressive strength, tensile strength, and shear strength of the specimens with a curing age of 7 d after seven dry–wet cycles were the smallest, being reduced by 40.22%, 58.25%, and 66.8%, respectively. After seven dry–wet cycles, the compressive, tensile, and shear strength of the specimens with the curing age of 28 d decreased slightly. The SEM results show that with the increasing number of dry–wet cycles, the internal structure of the specimen becomes more and more loose and fragile, and the damage degree of the structural skeleton gradually increases, leading to the poor mechanical properties of CPB specimens. The number of cracks and pores on the specimen surface is relatively limited after a curing age of 28 d, while the occurrence of internal structural damage within the specimen remains insignificant. Therefore, the dry–wet cycle has an important influence on the both mechanical properties and microstructure of CPB. This study provides a reference for the treatment of coal-based solid waste and facilitates the understanding of the mechanical properties of backfill materials under dry–wet cycling conditions.

Objective To investigate the dynamic changes of leukotriene C4 (LTC4), type 2 innate lymphoid cell(ILC2) and related cytokines (IL-4, IL-5 and IL-13) in the lung tissue of mice with bronchopulmonary dysplasia (BPD). Methods C57BL / 6 mice were randomly divided into air group and hyperoxia group.The hyperoxia group was exposed to 85% oxygen for 1, 7 and 14 days to replicate the BPD model.HE staining microscopy was used to observe the pathological changes of the lung tissue of mice. The percentages of ILC2 and CysLT1R+ILC2 were detected by flow cytometry.The contents of LTC4, IL-4, IL-5 and IL-13 were detected by ELISA.Western blot was used to detect the expression of LTC4-C synthase (LTC4S).RT-qPCR was used to detect the mRNA expression of LTC4S and cysteine leukotriene type 1 receptor (CysLT1R). Results Compared with air group, the percentage of ILC2 and CysLT1R+ILC2 in hyperoxia group and the expression of CysLT1R mRNA all increased(P＜0.05);The expression of IL-4, IL-5 and IL-13 in the hyperoxia group increased and were higher than those in the air group at the same time point (P＜0.05);LTC4 content, LTC4S protein and mRNA expression were significantly increased in hyperoxia group (P＜0.05). Conclusions In BPD, LTC4 increases and may induce the increase of ILC2 and related cytokines (IL-4, IL-5 and IL-13) through CysLT1R.

Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system with a low early diagnosis rate. Owing to the side effects, tolerance, and patient contraindications of existing therapies, effective drug treatments for HCC remain a major clinical challenge. However, using approved or investigational drugs not initially intended for cancer therapy is a promising strategy for resolving this problem because their safety have been tested in clinic. Therefore, this study evaluated differentially expressed genes between liver cancer and normal tissues in a cohort of patients with HCC from The Cancer Genome Atlas and applied them to query a connectivity map to identify candidate anti-HCC drugs. As a result, fluphenazine was identified as a candidate for anti-HCC therapy in vitro and in vivo. Fluphenazine suppressed HCC cell proliferation and migration and induced cell cycle arrest and apoptosis, possibly owing to disrupted lysosomal function, blocking autophagy flux. Additionally, in vivo studies demonstrated that fluphenazine suppresses HCC subcutaneous xenografts growth without causing severe side effects. Strikingly, fluphenazine could be used as an analgesic to alleviate oxaliplatin-induced pain as well as pain related anxiety-like behavior. Therefore, fluphenazine could be a novel liver cancer treatment candidate.

Cognitive impairment frequently coexists with diabetes. Trelagliptin is a once-weekly taking selective dipeptidyl peptidase-4 (DPP-4) inhibitor and a long-term effective hypoglycemic medicine; nonetheless, its effects for the treatment of diabetes-related cognitive impairment have only sometimes been explored. In this study, a DM model was built using streptozotocin (STZ) and a high-fat diet (HFD). The morris water maze test on DM rats revealed a considerably reduced capacity for spatial learning and memory, but trelagliptin was able to restore function. Trelagliptin could lower the mRNA expression of inflammatory factors such IL-1β, TNF-α, and IL-6 in DM rats. It could also reduce the ratio of p-IKKα/IKKα, and the immunofluorescence result of NF-κB also demonstrated a drop. Trelagliptin partially restored dendritic spines and prevented the loss or shrinkage of neurons, respectively, according to the results of Nissl's staining and golgi staining. Furthermore, PI3K/Akt/GSK-3β has been activated, and synaptic plasticity has been modified during this process. In conclusion, trelagliptin improved the cognitive lesion in DM rats by suppressing the activation of the inflammatory route and by activating the PI3K/Akt/GSK-3β pathway at the same time, as well as interacting with the pathways that protect neurons, which still need further research.