Data Availability StatementThe datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request. decreased significantly, while percentage of cued freezing time was significantly increased in POCD+NL1 group and POCD+EV group (P 0.01). The differences in freezing time were not statistically significant among the 4 groups in the tone-related fear test (P 0.05). Then NL1 was overexpressed in mice with POCD, the protein levels of PV, Nrx1 and PSD95 were subsequently increased, and the conversation between NL1 and Nrx1 protein was enhanced, dramatically increasing the excitability of PV interneurons. The overexpression of NL1 can upregulate the expression levels of PV, Nrx1 and PSD95 in mice with POCD, enhance the conversation between NL1 and Nrx1 and further increase the excitability of PV interneurons, thus restoring the hippocampus-dependent memorial and cognitive impairment in POCD. transfection of vacant vector), POCD+EV group (n=20, anesthesia, surgery and vacant vector transfection) and POCD+NL1 group (n=20, anesthesia, surgery and NL1 expression vector transfection). POCD modeling: anesthesia chamber was pre-charged with 1.5% isoflurane + 100% oxygen (2 l/min oxygen flow) for 15 min, and then mice were put into the box to maintain anesthesia for 30 min. After the mouse right reflex disappeared, the right lateral position was taken to avoid aspiration and maintain airway patency. Gas concentration AXIN1 in the anesthesia chamber was constantly monitored by a continuous monitoring multi-parameter anesthetic gas monitor, and the vital signs were checked to maintain the normal anesthetic depth. During the SRPIN340 operation, a 1 cm long incision was made along the midline of the abdomen to perform an abdominal exploration and ensure that the direction of the bowel did not change. After exploration, the muscle fascia and skin were sutured using 5-0 and 4-0 sterile surgical sutures. The sterile conditions were ensured throughout the operation. After operation, the mice were returned to the warm table and kept warm. Mice in normal control group were not treated except the injection of solvent in an equal volume. In vivo transfection A total of 60 POCD mice were divided randomly and equally into the POCD+EV and POCD+NL1 groups. Nucleic acids (12.5 g) were diluted into 1 g/l with an appropriate amount of endotoxin-free pure water, and added with 12.5 l water and 25 l 10% glucose solution (w/v), and the final volume of 50 l was mixed evenly. Twenty-five microliters of Entranster?-reagent was diluted with 25 l of 10% glucose solution to a final volume of 50 l. After that, the diluted transfection reagent was immediately added into the diluted nucleic acid answer and mixed evenly, obtaining the transfection complex. After being placed at room heat for 15 min, the transfection complex was injected into mice in POCD+NL1 group SRPIN340 via the caudal vein. Mice in POCD+EV group were injected with an equal amount of normal saline. Open field test The open field test is a method used to evaluate the autonomous behaviors, exploratory behaviors and tension degree of experimental animals in the new environment, in which the frequency and duration of certain behaviors of experimental animals in the new environment are used to reflect their autonomous behaviors and exploratory behaviors in the unfamiliar environment, and the times of urination is used to present the tension degree. The open field test was performed in a silent environment: Mice were SRPIN340 placed in the center of the box bottom, accompanied by shouting and timing using the image automatic monitoring system (Jiangsu SANS Biological Technology Co., Ltd., Jiangsu, China). After observation for a certain period of time based on experimental requirements (generally 3C5 min), shouting was terminated. The inner wall and bottom of the square box were cleaned to prevent the residual information of animals (such as the urine, feces and odor) in the last test from affecting the results of the next test. The SRPIN340 test was performed again after mice were replaced. Fear conditioning test At day 1 of the test, mice were put into an experimental box with electric metal fences on the bottom. After mice adapted to the environment for 3 min, they were stimulated by the single-frequency sound (3.0 kHz, 65 Db, 30 sec), as well as the inevitable electric foot-shock (0.7 mA, 2 sec) in the last 2 sec at the same time. Sound and electric shock SRPIN340 were terminated simultaneously. After the test, mice were kept in the box for 3.