Etomidate Combined with Propofol versus Remimazolam for Sedation in Elderly Patients During Gastrointestinal Endoscopy: A Randomized Prospective Clinical Trial.

Purpose: Remimazolam is a novel short-acting benzodiazepine used for sedation and general anesthesia. This study aimed to evaluate the efficacy and safety of remimazolam besylate in elderly patients who underwent diagnostic gastrointestinal endoscopy. Patients and Methods: A total of 120 patients aged 60-75 years were randomly allocated to one of two groups. Remifentanil 0.3µg/kg was used for analgesia. Patients were administered remimazolam besylate 7 mg (R group) or etomidate 0.1 mg/kg combined with 1% propofol 0.5 mg/kg (EP group) for induction, supplemental repeated doses were given as needed. Some time metrics, vital signs, adverse events were evaluated. Patients' Mini-cog score and recovery questionnaires were compared. Results: Compared to the EP group, the induction time was slightly longer in the R group (1.50 VS 1.15 minutes) (P<0.05), the time spent in the post-anesthesia care unit (PACU) was shorter (15.17 VS 17.40 minutes) (P<0.05). Compare with EP group, SBP was lower in R group at T15 and T25 time point, but heart rate was higher in T2, T3, T5 (P< 0.05). The Mini-Cog score was higher after the procedure (2.83 VS 2.58) (P<0.05). The incidence of respiratory adverse events was higher in the EP group than R group (18.3% VS 5.0%, P < 0.05). The most common adverse event in R group was hiccups. The sedation satisfaction rate and degree of amnesia were higher in the R group (66.7% VS 11.7%) (P < 0.05), and the effect on patient's life within 24 hours was lower (12.0% VS 30.5%) (P < 0.05). Conclusion: The safety and efficacy of remimazolam besylate are not inferior to those of etomidate combined with propofol, rendering it a safe option for sedation during gastrointestinal endoscopy in ASA I-II elderly patients, but care should be taken to monitor the occurrence of hiccups.

Enhancement of cadmium uptake in Sedum alfredii through interactions between salicylic acid/jasmonic acid and rhizosphere microbial communities.

The focus on phytoremediation in soil cadmium (Cd) remediation is driven by its cost-effectiveness and eco-friendliness. Selecting suitable hyperaccumulators and optimizing their growth conditions are key to enhance the efficiency of heavy metal absorption and accumulation. Our research has concentrated on the role of salicylic acid (SA) and jasmonic acid (JA) in facilitating Cd phytoextraction by "Sedum alfredii (S. alfredii)" through improved soil-microbe interactions. Results showed that SA or JA significantly boosted the growth, stress resistance, and Cd extraction efficiency in S. alfredii. Moreover, these phytohormones enhanced the chemical and biochemical attributes of the rhizosphere soil, such as pH and enzyme activity, affecting soil-root interactions. High-throughput sequencing analysis has shown that Patescibacteria and Umbelopsis enhanced S. alfredii's growth and Cd extraction by modifying the bioavailability and the chemical conditions of Cd in soil. Structural Equation Model analysis further verified that phytohormones significantly enhanced the interaction between S. alfredii, soil, and microbes, leading to a marked increase in Cd accumulation in the plant. These discoveries emphasized the pivotal role of phytohormones in modulating the hyperaccumulators' response to environmental stress and offered significant scientific support for further enhancing the potential of hyperaccumulators in ecological restoration technologies using phytohormones.

Plunge-Freezing Cryopreservation of Tendons.

Allograft transplantation is an important method for tendon reconstruction after injury, and its clinical success highly relies on the storage and transportation of the grafts. Cryopreservation is a promising strategy for tendon storage. In this study, we report a novel cryopreservation agent (CPA) formulation with a high biocompatibility for tendon cryopreservation. Mainly composed of natural zwitterionic betaine and the biocompatible polymer poly(vinylpyrrolidone) (PVP), it exhibited ideal abilities to depress the freezing point and inhibit ice growth and recrystallization. Notably, after cryopreservation via plunge-freezing for 1 month, Young's modulus (144 MPa, 98% of fresh tendons) and ultimate stress (46.7 MPa, 99% of fresh tendons) remained stable, and the cross-linking of collagen microfibers, protein structures, and glycosaminoglycan (GAG) contents changed slightly. These results indicate that the formulation (5 wt % betaine and 5 wt % PVP in phosphate-buffered saline, PBS solution) effectively maintains the biomechanical properties and tissue structure. This work offers a novel cryopreservation method for tendons and may also provide insights into the long-term preservation of various other tissues.

IGFBP2/ITGA5 promotes gefitinib resistance via activating STAT3/CXCL1 axis in non-small cell lung cancer.

There is a paucity of comprehensive knowledge pertaining to the underlying mechanisms leading to gefitinib resistance in individuals diagnosed NSCLC harboring EGFR-sensitive mutations who inevitably develop resistance to gefitinib treatment within six months to one year. In our preceding investigations, we have noted a marked upregulation of IGFBP2 in the neoplastic tissues of NSCLC, predominantly in the periphery of the tissue, implying its plausible significance in NSCLC. Consequently, in the current research, we delved into the matter and ascertained the molecular mechanisms that underlie the participation of IGFBP2 in the emergence of gefitinib resistance in NSCLC cells. Firstly, the expression of IGFBP2 in the bronchoalveolar lavage fluid and lung cancer tissues of 20 NSCLC patients with gefitinib tolerance was found to be significantly higher than that of non-tolerant patients. Furthermore, in vitro and in vivo experiments demonstrated that IGFBP2 plays a significant role in the acquisition of gefitinib resistance. Mechanistically, IGFBP2 can activate STAT3 to enhance the transcriptional activity of CXCL1, thereby increasing the intracellular expression level of CXCL1, which contributes to the survival of lung cancer cells in the gefitinib environment. Additionally, we identified ITGA5 as a key player in IGFBP2-mediated gefitinib resistance, but it does not function as a membrane receptor in the process of linking IGFBP2 to intracellular signaling transduction. In conclusion, this study demonstrates the promoting role and mechanism of IGFBP2 in acquired gefitinib resistance caused by non-EGFR secondary mutations, suggesting the potential of IGFBP2 as a biomarker for gefitinib resistance and a potential intervention target.

Gold-Catalyzed Homo/Heterodimerization of Terminal Alkynes Facilitated by Metal-Ligand Cooperation.

Gold-catalyzed dimerization of terminal alkynes is achieved under mild reaction conditions and in excellent yields. In addition to homodimerizations, heterodimerizations between TBS acetylene and a range of terminal alkynes were realized using the syringe pump technique. The reaction tolerates various functional groups. The rate acceleration experienced in the reactions is enabled by metal-ligand cooperation. A binaphthyl-2-ylphosphine ligand featuring a 3'-diisopropylphosphoryl group plays a pivotal role in facilitating alkyne attack by accommodating and/or deprotonating its terminal proton.

Association of physical performance with cognitive impairment in middle-aged to older haemodialysis patients: a multicentre cross-sectional observational study.

OBJECTIVE: To determine the prevalence of cognitive impairment (CI) among middle-aged to older patients receiving maintenance haemodialysis (MHD) and to investigate the potential association between CI and physical performance. METHODS: This cross-sectional observational study enrolled participants aged 55-85 years who received MHD. Cognitive status was assessed using the Mini Mental State Examination (MMSE). Physical performance was measured by hand grip strength, the Timed Up and Go Test (TUGT) and the 4-m walking speed. Sociodemographic, clinical and laboratory parameters were recorded for each patient. RESULTS: The study included 592 patients (363 males); and of these, 126 (21.3%) were diagnosed with CI. Compared with patients with normal cognitive function, those with CI were significantly older and had significantly longer dialysis duration, lower educational level, higher Malnutrition Inflammation Score, higher depression and higher Charlson Comorbidity Index score. After adjustment for covariates, multiple regression analysis suggested that grip strength (odds ratio [OR] = 0.959, 95% confidence interval [CI] = 0.924, 0.996) and 4-m walking speed (OR = 0.161, 95% CI = 0.070, 0.368) were protective factors. TUGT (OR = 1.037, 95%CI = 1.003, 1.071) was a risk factor. CONCLUSION: Physical performance was correlated with CI and might be a significant indicator for the early identification of CI in middle-aged to older MHD patients.

A Mendelian randomization study of the entire phenome to explore the causal links between epilepsy.

OBJECTIVE: The causes and triggering factors of epilepsy are still unknown. The results of genome-wide association studies can be utilized for a phenome-wide association study using Mendelian randomization (MR) to identify potential risk factors for epilepsy. METHODS: This study utilizes two-sample MR analysis to investigate whether 316 phenotypes, including lifestyle, environmental factors, blood biomarker, and more, are causally associated with the occurrence of epilepsy. The primary analysis employed the inverse variance weighted (IVW) model, while complementary MR analysis methods (MR Egger, Wald ratio) were also employed. Sensitivity analyses were also conducted to evaluate heterogeneity and pleiotropy. RESULTS: There was no evidence of a statistically significant causal association between the examined phenotypes and epilepsy following Bonferroni correction (p < 1.58 × 10-4) or false discovery rate correction. The results of the MR analysis indicate that the frequency of tiredness or lethargy in the last 2 weeks (p = 0.042), blood uridine (p = 0.003), blood propionylcarnitine (p = 0.041), and free cholesterol (p = 0.044) are suggestive causal risks for epilepsy. Lifestyle choices, such as sleep duration and alcohol consumption, as well as biomarkers including steroid hormone levels, hippocampal volume, and amygdala volume were not identified as causal factors for developing epilepsy (p > 0.05). CONCLUSIONS: Our study provides additional insights into the underlying causes of epilepsy, which will serve as evidence for the prevention and control of epilepsy. The associations observed in epidemiological studies may be partially attributed to shared biological factors or lifestyle confounders.

Novel radiopaque ethanol injection: physicochemical properties, animal experiments, and clinical application in vascular malformations.

BACKGROUND: Despite the efficacy of absolute ethanol (EtOH), its radiolucency introduces several risks in interventional therapy for treating vascular malformations. This study aims to develop a novel radiopaque ethanol injection (REI) to address this issue. METHODS: Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution. Overall, 82 male New Zealand white rabbits are selected for in vivo radiopacity testing, peripheral vein sclerosis [animals were divided into the following 5 groups (n = 6): negative control (NC, saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), low-dose REI (L-D REI, 0.125 ml/kg), moderate-dose REI (M-D REI, 0.250 ml/kg), and high-dose REI (H-D REI 0.375 ml/kg)], pharmacokinetic analyses (the blood sample was harvested before injection, 5 min, 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, and 8 h after injection in peripheral vein sclerosis experiment), peripheral artery embolization [animals were divided into the following 5 groups (n = 3): NC (saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)], kidney transcatheter arterial embolization [animals were divided into the following 4 groups (n = 3): positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg); each healthy kidney was injected with saline as negative control], and biosafety evaluations [animals were divided into the following 5 groups (n = 3): NC (0.250 ml/kg), high-dose EtOH (0.375 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)]. Then, a prospective cohort study involving 6 patients with peripheral venous malformations (VMs) is performed to explore the clinical safety and effectiveness of REI. From Jun 1, 2023 to August 31, 2023, 6 patients [age: (33.3 ± 17.2) years] with lingual VMs received sclerotherapy of REI and 2-month follow-up. Adverse events and serious adverse events were evaluated, whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection. RESULTS: The REI contains 81.4% ethanol (v/v) and 111.3 mg/ml iodine, which can be traced throughout the injection in the animals and patients. The REI also exerts a similar effect as EtOH on peripheral venous sclerosis, peripheral arterial embolization, and renal embolization. Furthermore, the REI can be metabolized at a similar rate compared to EtOH and Ultravist® and did not cause injury to the animals' heart, liver, spleen, lungs, kidneys and brain. No REI-related adverse effects have occurred during sclerotherapy of VMs, and 4/6 patients (66.7%) have achieved complete response at follow-up. CONCLUSION: In conclusion, REI is safe, exerts therapeutic effects, and compensates for the radiolucency of EtOH in treating VMs. TRIAL REGISTRATION: The clinical trial was registered as No. ChiCTR2300071751 on May 24 2023.

Remote sensing estimation of sugar beet SPAD based on un-manned aerial vehicle multispectral imagery.

Accurate, non-destructive and cost-effective estimation of crop canopy Soil Plant Analysis De-velopment(SPAD) is crucial for precision agriculture and cultivation management. Unmanned aerial vehicle (UAV) platforms have shown tremendous potential in predicting crop canopy SPAD. This was because they can rapidly and accurately acquire remote sensing spectral data of the crop canopy in real-time. In this study, a UAV equipped with a five-channel multispectral camera (Blue, Green, Red, Red_edge, Nir) was used to acquire multispectral images of sugar beets. These images were then combined with five machine learning models, namely K-Nearest Neighbor, Lasso, Random Forest, RidgeCV and Support Vector Machine (SVM), as well as ground measurement data to predict the canopy SPAD of sugar beets. The results showed that under both normal irrigation and drought stress conditions, the SPAD values in the normal ir-rigation treatment were higher than those in the water-limited treatment. Multiple vegetation indices showed a significant correlation with SPAD, with the highest correlation coefficient reaching 0.60. Among the SPAD prediction models, different models showed high estimation accuracy under both normal irrigation and water-limited conditions. The SVM model demon-strated a good performance with a correlation coefficient (R2) of 0.635, root mean square error (Rmse) of 2.13, and relative error (Re) of 0.80% for the prediction and testing values under normal irrigation. Similarly, for the prediction and testing values under drought stress, the SVM model exhibited a correlation coefficient (R2) of 0.609, root mean square error (Rmse) of 2.71, and rela-tive error (Re) of 0.10%. Overall, the SVM model showed good accuracy and stability in the pre-diction model, greatly facilitating high-throughput phenotyping research of sugar beet canopy SPAD.

Butyrate inhibits the malignant biological behaviors of breast cancer cells by facilitating cuproptosis-associated gene expression.

BACKGROUND: Butyrate is a common short-chain fatty acids (SCFA), and it has been demonstrated to regulate the development of breast cancer (BC), while the underlying mechanism is still unreported. METHODS: Gas chromatography was used to measure the amounts of SCFA (acetate, propionate, and butyrate) in the feces. Cell viability was measured by the CCK-8 assay. The wound healing assay demonstrated cell migration, and the transwell assay demonstrated cell invasion. The levels of protein and gene were determined by western blot assay and RT-qPCR assay, respectively. RESULTS: The levels of SCFA were lower in the faecal samples from BC patients compared to control samples. In cellular experiments, butyrate significantly suppressed the cell viability, migration and invasion of T47D in a dose-dependent manner. In animal experiments, butyrate effectively impeded the growth of BC tumors. Toll like receptor 4 (TLR4) was highly expressed in the tumors from BC patients. Butyrate inhibited the expression of TLR4. In addition, butyrate promoted the expression of cuproptosis-related genes including PDXK (pyridoxal kinase) and SLC25A28 (solute carrier family 25 member 28), which was lowly expressed in BC tumors. Importantly, overexpression of TLR4 can reverses the promotion of butyrate to PDXK and SLC25A28 expression and the prevention of butyrate to the malignant biological behaviors of T47D cells. CONCLUSION: In summary, butyrate inhibits the development of BC by facilitating the expression of PDXK and SLC25A28 through inhibition of TLR4. Our investigation first identified a connection among butyrate, TLR4 and cuproptosis-related genes in BC progression. These findings may provide novel target for the treatment of BC.

A Small Auxin-Up RNA Gene, IbSAUR36, Regulates Adventitious Root Development in Transgenic Sweet Potato.

Small auxin-upregulated RNAs (SAURs), as the largest family of early auxin-responsive genes, play important roles in plant growth and development processes, such as auxin signaling and transport, hypocotyl development, and tolerance to environmental stresses. However, the functions of few SAUR genes are known in the root development of sweet potatoes. In this study, an IbSAUR36 gene was cloned and functionally analyzed. The IbSAUR36 protein was localized to the nucleus and plasma membrane. The transcriptional level of this gene was significantly higher in the pencil root and leaf.This gene was strongly induced by indole-3-acetic acid (IAA), but it was downregulated under methyl-jasmonate(MeJA) treatment. The promoter of IbSAUR36 contained the core cis-elements for phytohormone responsiveness. Promoter ß-glucuronidase (GUS) analysis in Arabidopsis showed that IbSAUR36 is highly expressed in the young tissues of plants, such as young leaves, roots, and buds. IbSAUR36-overexpressing sweet potato roots were obtained by an efficient Agrobacterium rhizogenes-mediated root transgenic system. We demonstrated that overexpression of IbSAUR36 promoted the accumulation of IAA, upregulated the genes encoding IAA synthesis and its signaling pathways, and downregulated the genes encoding lignin synthesis and JA signaling pathways. Taken together, these results show that IbSAUR36 plays an important role in adventitious root (AR) development by regulating IAA signaling, lignin synthesis, and JA signaling pathways in transgenic sweet potatoes.

Impact of sarcopenic obesity on heart failure in people with type 2 diabetes and the role of metabolism and inflammation: A prospective cohort study.

AIMS: We aimed to prospectively evaluate the association of sarcopenic obesity (SO) with the incidence risk of heart failure (HF), and the mediating role of metabolomics and inflammation in people with type 2 diabetes (T2D). METHODS: 22,496 participants with T2D from the UK Biobank were included. SO was defined as the combination of obesity (body mass index ≥30 kg/m2) and sarcopenia (grip strength <27 kg in male or <16 kg in female). The incident HF was identified through linked hospital records. Cox proportional hazard regression models were used to estimate the associations. Mediation analysis was conducted to evaluate the mediating effect of the "metabolomic risk score" of HF, which was derived from 168 plasma metabolites through LASSO regression, and five inflammatory markers (e.g., C-reactive protein [CRP] level) on the aforementioned associations. RESULTS: 1946 (8.7 %) participants developed HF during a median follow-up of 12.0 years. Compared to participants with neither obesity nor sarcopenia, those with obesity & non-sarcopenia (hazard ratio [HR]: 1.80, 95 % confidence interval [CI]: 1.62, 2.00), sarcopenia & non-obesity (HR: 1.90, 95 % CI: 1.56, 2.31) and SO (HR: 2.29, 95 % CI: 1.92, 2.73) showed a higher risk of HF. The metabolomic risk score (20.0 %) and CRP (20.4 %) meditated this association. CONCLUSIONS: SO was associated with an increased risk of HF in people with T2D and metabolomics and inflammation partially mediated this association. Our findings suggest the importance of managing obesity and muscle strength simultaneously in preventing HF among people with T2D and shed light on the underlying mechanisms.

Research Progress of Natural Active Substances with Immunosuppressive Activity.

The increasing prevalence of autoimmune diseases globally has prompted extensive research and the development of immunosuppressants. Currently, immunosuppressive drugs such as cyclosporine, rapamycin, and tacrolimus have been utilized in clinical practice. However, long-term use of these drugs may lead to a series of adverse effects. Therefore, there is an urgent need to explore novel drug candidates for treating autoimmune diseases. This review aims to find potential candidate molecules for natural immunosuppressive compounds derived from plants, animals, and fungi over the past decade. These compounds include terpenoids, alkaloids, phenolic compounds, flavonoids, and others. Among them, compounds 49, 151, 173, 200, 204, and 247 have excellent activity; their IC50 were less than 1 µM. A total of 109 compounds have good immunosuppressive activity, with IC50 ranging from 1 to 10 µM. These active compounds have high medicinal potential. The names, sources, structures, immunosuppressive activity, and the structure-activity relationship were summarized and analyzed.

Salicylic Acid's impact on Sedum alfredii growth and cadmium tolerance: Comparative physiological, transcriptomic, and metabolomic study.

With the acceleration of industrialization, Cd pollution has emerged as a major threat to soil ecosystem health and food safety. Hyperaccumulating plants like Sedum alfredii Hance are considered to be used as part of an effective strategy for the ecological remediation of Cd polluted soils. This study delved deeply into the physiological, transcriptomic, and metabolomic responses of S. alfredii under cadmium (Cd) stress when treated with exogenous salicylic acid (SA). We found that SA notably enhanced the growth of S. alfredii and thereby increased absorption and accumulation of Cd, effectively alleviating the oxidative stress caused by Cd through upregulation of the antioxidant system. Transcriptomic and metabolomic data further unveiled the influence of SA on photosynthesis, antioxidant defensive mechanisms, and metal absorption enrichment pathways. Notably, the interactions between SA and other plant hormones, especially IAA and JA, played a central role in these processes. These findings offer us a comprehensive perspective on understanding how to enhance the growth and heavy metal absorption capabilities of hyperaccumulator plants by regulating plant hormones, providing invaluable strategies for future environmental remediation efforts.

Physiology and transcriptomic analysis revealed the mechanism of silicon promoting cadmium accumulation in Sedum alfredii Hance.

Silicon (Si) effectively promote the yield of many crops, mainly due to its ability to enhance plants resistance to stress. However, how Si helps hyperaccumulators to extract Cadmium (Cd) from soil has remained unclear. In this study, Sedum alfredii Hance (S. alfredii) was used as material to study how exogenous Si affected biomass, Cd accumulation, antioxidation, cell ultrastructure, subcellular distribution and changes in gene expression after Cd exposure. The study has shown that as Si concentration increases (1, 2 mM), the shoot biomass of plants increased by 33.1%-63.6%, the Cd accumulation increased by 31.9%-96.6%, and the chlorophyll, carotenoid content, photosynthetic gas exchange parameters significantly increased. Si reduced Pro and MDA, promoted the concentrations of SOD, CAT and POD to reduce antioxidant stress damage. In addition, Si promoted GSH and PC to chelate Cd in vacuoles, repaired damaged cell ultrastructure, improved the fixation of Cd and cell wall (especially in pectin), and reduced the toxic effects of Cd. Transcriptome analysis found that genes encoding Cd detoxification, Cd absorption and transport were up-regulated by Si supplying, including photosynthetic pathways (PSB, LHCB, PSA), antioxidant defense systems (CAT, APX, CSD, RBOH), cell wall biosynthesis such as pectinesterase (PME), chelation (GST, MT, NAS, GR), Cd absorption (Nramp3, Nramp5, ZNT) and Cd transport (HMA, PCR). Our result revealed the tentative mechanism of Si promotes Cd accumulation and enhances Cd tolerance in S. alfredii, and thereby provides a solid theoretical support for the practical use of Si fertilizer in phytoextraction.

Prognostic value and immunological function of cuproptosis-related genes in lung adenocarcinoma.

Background: Lung cancer is one of the malignant tumors with the highest morbidity and fatality rates worldwide. The overall survival (OS) of lung adenocarcinoma (LUAD) is poor. Cuproptosis is a copper-triggered modality of mitochondrial cell death, however, its contribution to the emergence of lung cancer is unknown. The clinical implication and immunological function of cuproptosis-related genes (CRGs) in LUAD has yet to be established. Methods: TCGA, HPA, GEPIA, Kaplan-Meier, TIMER and CancerSEA database were used to explore the prognostic value and biological function of CRGs in LUAD. Results: CRGs are primarily involved in copper ion transport, the citrate cycle (TCA cycle) and central carbon metabolism in LUAD. The mRNA expression of COA6, UBE2D1, DLAT, SLC25A3, and DBH was significantly increased. The expression of COA6, DLAT, SLC25A3, DBH, and LOXL2 were all strongly associated with the clinicopathological stages in LUAD. Moreover, high expression of COA6, UBE2D1, DLAT, SLC25A3 and LOXL2 was related to poor OS. The expression of SLC25A3 and LOXL2 showed different association with immune cell infiltration. The single cell sequencing demonstrated that CRGs play important roles in the regulation of DNA damage response, inflammation and metastasis in LUAD. Conclusions: In summary, this study comprehensively uncovered that CRGs could be identified as potential prognostic and immunological biomarkers in LUAD. Our current research could provide a solid theoretical basis for LUAD survival research and clinical decision-making.

Psilocybin promotes neuroplasticity and induces rapid and sustained antidepressant-like effects in mice.

BACKGROUND: Psilocybin offers new hope for treating mood disorders due to its rapid and sustained antidepressant effects, as standard medications require weeks or months to exert their effects. However, the mechanisms underlying this action of psilocybin have not been identified. AIMS: To investigate whether psilocybin has rapid and sustained antidepressant-like effects in mice and investigate whether its potential mechanisms of action are related to promoted neuroplasticity. METHODS: We first examined the antidepressant-like effects of psilocybin in normal mice by the forced swimming test and in chronic corticosterone (CORT)-exposed mice by the sucrose preference test and novelty-suppressed feeding test. Furthermore, to explore the role of neuroplasticity in mediating the antidepressant-like effects of psilocybin, we measured structural neuroplasticity and neuroplasticity-associated protein levels in the prefrontal cortex (PFC) and hippocampus. RESULTS: We observed that a single dose of psilocybin had rapid and sustained antidepressant-like effects in both healthy mice and chronic CORT-exposed mice. Moreover, psilocybin ameliorated chronic CORT exposure-induced inhibition of neuroplasticity in the PFC and hippocampus, including by increasing neuroplasticity (total number of dendritic branches and dendritic spine density), synaptic protein (p-GluA1, PSD95 and synapsin-1) levels, BDNF-mTOR signalling pathway activation (BDNF, TrkB and mTOR levels), and promoting neurogenesis (number of DCX-positive cells). CONCLUSIONS: Our results demonstrate that psilocybin elicits robust, rapid and sustained antidepressant-like effects which is accompanied by the promotion of neuroplasticity in the PFC and hippocampus.