OBJECTIVE:To systematically evaluate the diagnostic performance of postmortem computed tomography (PMCT) versus traditional autopsy in the detection of fracture. METHODS:The database of PubMed, Cochrane Library, Embase, and Web of Science were searched to screen the studies comparing PMCT and autopsy in fracture detection from 1 January 1994 to 23 January 2025. Relevant data was extracted for calculating sensitivity and specificity. The QUADAS-2 tool was used for bias assessment and a random effects model was used for meta-analysis. RESULTS:A total of 22 studies were included in the meta-analysis containing 1757 fracture cases, covering 7 anatomical sites. All deceased were scanned on multi-slice scanners with comparable parameters. Images were evaluated by radiologists or pathologists. The meta-analysis found that the pooled sensitivity and specificity were 0.87 (95% CI: 0.85-0.89) and 0.97 (95% CI: 0.97-0.98) for PMCT, respectively. Compared to conventional autopsy, positive likelihood ratio (PLR) was 19.74 (95% CI: 12.66-30.79), negative likelihood ratio (NLR) was 0.15 (95% CI: 0.11-0.20), and the area under the receiver operating characteristic curve (AUC) was 0.97. CONCLUSION:By Demonstrating high diagnostic efficacy for fracture detection, PMCT provides the valuable adjunctive support to traditional autopsy. It can improve the precision and efficiency of forensic examination.

Rapid industrialization worldwide has led to the accumulation of diverse environmental pollutants in water, air, and soil, posing significant threats to the earth’s ecological balance and making environmental remediation an urgent priority. Among the various remediation techniques, ultrasound-assisted advanced oxidation processes (AOPs) have emerged as a promising approach, leveraging the unique effects of acoustic cavitation to enhance pollutant degradation in water. By generating reactive oxygen species (e.g., hydroxyl radicals) through bubble collapse and improving mass transfer, ultrasound amplifies the efficiency of AOPs using catalysts, photo-mediated processes, and chemical reagents. This review synthesizes advancements in ultrasound-assisted AOPs over the past decades, including mechanism of the reactions and novel hybrid systems, offering a global perspective on their potential for large-scale environmental remediation. We systematically explore the mechanisms of ultrasound enhancement, the types of AOPs integrated with ultrasound, and their applications in degrading persistent pollutants. Additionally, we analyze the underlying synergistic effects and discuss current challenges, and future directions for hybrid technologies based on ultrasound for efficient water treatment

Mixed biological stains are commonly encountered biological samples in forensic investigation. They are often challenging particularly when containing contributors of the same tissue type, such as mixed bloodstains. Here, we described a novel genetic marker for the separation of two-individual mixed bloodstain: the human neutrophil antigen (HNA), specifically, the HNA-1 system. HNA-1a and HNA-1b exhibit the high polymorphism across diverse populations. Potential for practical applicability of these markers in mixed blood separation was evaluated through fluorescence-activated cell sorting (FACS) and laser capture microdissection (LCM) techniques. The results found that flow cytometry based on HNA-1a and HNA-1b fluorescent antibody successfully separated minor contributors from mixed samples at ratios as low as 1:16 and 1:32, respectively. Furthermore, LCM enabled complete single-source STR profiling from the fewer cells, indicating promising application in the separation of mixed bloodstains. Collectively, this study provides a new usable genetic marker, which may significantly enhance the effectiveness of antigen-based separation strategies for the identification of mixed blood samples.

Repeated exposure to ketamine leads to mental behavioral disorders and cognitive deficits in mice. As a neurotransmitter receptor, dopamine receptor 1 (DRD1) is involved in mental regulation and memory formation. However, the role of DRD1 in ketamine’s behavioral disorder and neurotoxicity remains unclear. We found that seven-day ketamine exposure induced anxiety-like, depressive-like behavior and cognition dysfunction in mice. DRD1 activation can produce anxiety-like behavior similar to that induced by ketamine. Furthermore, DRD1 activation synergistically exacerbates this effect of ketamine, and DRD1 antagonism partially attenuates the anxiety-like behavior and further aggravated the depressive-like behavior induced by ketamine. Moreover, ketamine induced HT22 cell apoptosis by DRD1 dependent inhibition of Akt/Gsk3β phosphorylation. DRD1 agonist synergistically enhanced the apoptosis induced by ketamine, while DRD1 antagonist or the apoptosis inhibitor partially reversed this apoptosis in vitro. In vivo assay found that ketamine promotes neuronal apoptosis in the hippocampus and prefrontal cortex of mice, and antagonizing DRD1 partially attenuates ketamine-induced apoptosis. In contrast, cell-specific knockdown of DRD1 in neuronal cells exacerbated ketamine-induced neuronal apoptosis and anxiety-like behavior. In summary, ketamine regulates DRD1 to suppress Akt/Gsk3β phosphorylation, inducing neuronal apoptosis, ultimately leading to anxiety-like behaviors in mice. 1. Repeated ketamine exposure induced anxiety-like, depressive-like behavior, and neuronal apoptosis in mice. 2. In cellular level, ketamine induced cell apoptosis by DRD1 dependent inhibition of Akt/Gsk3β phosphorylation. 3. Cell-specific knockdown of DRD1 in neuronal cells exacerbated ketamine-induced neuronal apoptosis and anxiety-like behavior.

Psychotic disorders frequently result from repeated ketamine exposure, yet the underlying mechanisms remain elusive. We propose that repeated exposure to ketamine may induce psychotic-like behaviors via DRD1-mediated nuclear signaling pathways. Our investigation focused on phosphorylated DARPP-32 at Thr34, Thr75, and Ser97, alongside transcriptome profiling in both cell and mouse models. We found that DRD1 antagonist mitigated ketamine-induced psychotic-like behaviors and cognitive deficits, whereas DRD1 agonist partially replicated ketamine-like symptoms. In cellular models, ketamine elevated p-Thr34 DARPP-32 levels and facilitated its nuclear accumulation through PKA, while promoting Ser10 H3 phosphorylation by inhibiting PP1 activity. Phosphorylation at Thr75 and Thr97 inhibited p-Thr34 level, with Thr97 enhancing DARPP-32 and PP1 interaction. In vivo, combined approach of RNA-seq and ATAC-seq in the hippocampus indicated that ketamine suppressed neurogenesis. Immunofluorescence showed reduced neonatal neurons and neural stem cells in the dentate gyrus region, while ketamine increased astrocyte numbers. Single-nucleus transcriptome sequencing revealed enhanced neuron-astrocyte interaction post-ketamine treatment. In summary, we identified the DRD1-DARPP-32-Histone H3 pathway as a key mediator of transcriptional abnormalities and impaired hippocampal neurogenesis in ketamine-induced psychotic-like mouse model.

ObjectiveTo construct a competency evaluation model for forensic practitioners, providing a reference for their training and assessment.MethodsBased on the iceberg and onion models of competency, and with reference to Spencer’s Competency Dictionary, literature research was conducted and focus group interviews were employed to preliminarily construct core indices and measurement items for evaluating the competency of forensic practitioners. The Delphi method was applied for two rounds of expert consultation to further refine the competency evaluation index system. The analytic hierarchy process （AHP） was used to calculate the weights of the indices.ResultsA competency evaluation model for forensic practitioners was constructed, consisting of 7 core indices, encompassing forensic skills, identification service capabilities, and the ability to apply relevant legal knowledge and 49 measurement items. The weights of the core indices and measurement items were determined.ConclusionThe constructed competency evaluation model for forensic practitioners is scientifically sound and innovative, and has unique characteristics of forensic medicine compared with other medical models.

Synucleinopathies and tauopathies are neurodegenerative disorders characterized by the pathological accumulation of α-synuclein (α-syn) and tau proteins, respectively. These disorders are traditionally managed with symptomatic treatments without addressing the underlying pathologies. Recent advancements in passive immunotherapies, notably the FDA approval of the amyloid-beta (Aβ)-targeting antibody lecanemab, have sparked new hope in directly targeting pathological proteins. However, unlike the extracellular Aβ pathology, immunotherapies aimed at α-syn and tau, which predominantly form intracellular inclusions, face substantial challenges. To date, the therapeutic efficacy of five α-syn and 14 tau antibodies has been assessed in patients with synucleinopathies and tauopathies. These immunizations have demonstrated promising preclinical outcomes in alleviating pathological and behavioral deficits, but have not yielded significant clinical improvements in symptoms or measurable biomarkers. Therefore, a clear understanding of potential causes for the discrepancies between preclinical successes and clinical outcomes is critical for the successful translation of immunotherapy in the future. In this review, we examine existing passive immunotherapeutic strategies targeting α-syn and tau, specifically in patients with Alzheimer’s disease and Parkinson’s disease. Lessons learned from initial trial failures are also discussed, including refinement of animal models, inclusion and stratification of participants, improvement of clinical evaluations, and development of biomarkers. Given the overlapping pathologies and clinical manifestations of synucleinopathies and tauopathies, we further explore the potential of combined therapies targeting co-pathologies, offering novel insights for future therapeutic development against these neurodegenerative disorders.

BACKGROUND:Probiotics can colonize both the human and animal bodies and consist of active microorganisms that are beneficial to health. The use of probiotics has been shown to alleviate certain neurological diseases and disturbances in gut microbiota resulting from chronic ethanol exposure. Research indicates that probiotics can influence the nervous system via the microbial-gut-brain axis, wherein extracellular vesicles secreted by the gut microbiota play a significant role in this process. RESULTS:In this study, we first established a 30-day ethanol exposure and probiotic gavage mouse model, both of which influenced behavior and the composition of gut microbiota. We then extracted gut microbiota-derived extracellular vesicles from the feces of these model mice and injected them into new mice via the tail vein to assess the role of each set of extracellular vesicles. The results indicated that the extracellular vesicles derived from the intestinal microbiota in the ethanol group induced anxiety-like behavior and hippocampal neuroinflammation in the recipient mice. In contrast, the extracellular vesicles secreted by the gut microbiota from the probiotic group mitigated the anxiety-like behavior and neuroinflammation induced by ethanol-influenced extracellular vesicles. CONCLUSIONS:Our study demonstrates that extracellular vesicles secreted by the gut microbiota can influence the nervous system via the microbial-gut-brain axis. Furthermore, we found that the extracellular vesicles secreted by the gut microbiota from the probiotic group exert a beneficial therapeutic effect on anxiety and hippocampal neuroinflammation.

Multiple sevoflurane exposures may damage the developing brain. The neuroprotective function of dexmedetomidine has been widely confirmed in animal experiments and human studies. However, the effect of dexmedetomidine on the glymphatic system has not been clearly studied. We hypothesized that dexmedetomidine could alleviate sevoflurane-induced circulatory dysfunction of the glymphatic system in young mice. Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 2 h daily, continuously for 3 days. Intraperitoneal injection of either normal saline or dexmedetomidine was administered before every anaesthesia. Meanwhile the circulatory function of glymphatic system was detected by tracer injection at P8 and P32. On P30-P32, behavior tests including open field test, novel object recognition test, and Y-maze test were conducted. Primary astrocyte cultures were established and treated with the PI3K activator 740Y-P, dexmedetomidine, and small interfering RNA (siRNA) to silence ΔFosB. We propose for the first time that multiple exposure to sevoflurane induces circulatory dysfunction of the glymphatic system in young mice. Dexmedetomidine improves the circulatory capacity of the glymphatic system in young mice following repeated exposure to sevoflurane through the PI3K/AKT/ΔFosB/AQP4 signaling pathway, and enhances their long-term learning and working memory abilities.

Reducing carbon emission intensity is crucial for achieving sustainable development. Carbon emission intensity is expressively affected by the issuance of green bonds. Thus, it is imperative to assess the influence of green bond issuance on carbon emissions and examine their correlation. Such research holds great potential to expedite the overhaul and modernization of businesses and to construct a circular economy system. This paper uses the spatial Durbin model to draw empirical conclusions by using data from 26 provinces in China between 2016 and 2021. Firstly, under different spatial matrices, it has been analyzed that an increase of 1% in the issuance of green bonds leads to a reduction of 0.306% or 0.331% in carbon emission intensity. It shows that green bonds have the potential to substantially reduce carbon intensity. Additionally, the intensity of emissions in the current period is driven by the intensity of emissions in the previous period. Secondly, the analysis of mediated transmission suggests that green bonds can ultimately reduce carbon emission intensity by changing the energy consumption structure or improving the efficiency of green technology innovation. Thirdly, the analysis of heterogeneity shows that the inhibitory effect of green bond issuance on carbon emissions is stronger in less economically developed regions than in economically developed regions. There is a significant inhibitory effect of green bond issuance in neighboring provinces on local carbon emission intensity. This effect is present only in provinces in less economically developed regions and not in economically developed regions.

Background: Ketamine, as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, was originally used in general anesthesia. Epidemiological data show that ketamine has become one of the most commonly abused drugs in China. Ketamine administration might cause cognitive impairment; however, its molecular mechanism remains unclear. The glymphatic system is a lymphoid system that plays a key role in metabolic waste removal and cognitive regulation in the central nervous system. Methods: Focusing on the glymphatic system, this study evaluated the behavioral performance and circulatory function of the glymphatic system by building a short-term ketamine administration model in mice, and detected the expression levels of the 5-HT2c receptor, zFosb, Pten, Akt, and Aqp4 in the hippocampus. Primary astrocytes were cultured to verify the regulatory relationships among related indexes using a 5-HT2c receptor antagonist, a 5-HT2c receptor short interfering RNA (siRNA), and a zFosb siRNA. Results: Ketamine administration induced zFosb accumulation by increasing 5-HT2c receptor expression in mouse hippocampal astrocytes and primary astrocytes. zFosb acted as a transcription factor to recognize the AATGATTAAT bases in the 5 ' regulatory region of the Aqp4 gene (-1096 bp to -1087 bp), which inhibited Aqp4 expression, thus causing the circulatory dysfunction of the glymphatic system, leading to cognitive impairment. Conclusions: Although this regulatory mechanism does not involve the Pten/Akt pathway, this study revealed a new mechanism of ketamine-induced cognitive impairment in non-neuronal systems, and provided a theoretical basis for the safety of clinical treatment and the effectiveness of withdrawal.

The microbiota-gut-brain axis is a bidirectional regulatory pathway between the brain and the gastrointestinal tract, which plays an important role in maintain homeostasis. Gut microbiota could influence the behavior, cognition, stress response and others via the axis. Depression is a complex psychiatric disease, giving rise to heavy social health and economic burden. In recent years, studies have shown that the gut microbiota are closely linked to the pathophysiological processes of depression. In this article, the interaction and its underlying mechanisms between depression and gut microbiota were summarized.

Ketamine as a glutamate receptor antagonist has a rapid, potent, and long-lasting antidepressant effect, but its specific mechanism is still not fully understood. Depression is associated with elevated levels of glutamate and astrocyte loss in the brain; the exploration of the relationships between ketamine’s antidepressant effect and astrocytes has drawn great attention. Astrocytes and aquaporin 4 (AQP4) are essential components of the glymphatic system, which is a brain-wide perivascular pathway to help transport nutrients to the parenchyma and remove metabolic wastes. In this study, we investigated pyroptosis-associated protein Nlrp3/Caspase-1/Gsdmd-N expression in the hippocampus of mice and the toxic effect of high levels of glutamate on primary astrocytes. On this basis, the protective mechanism of ketamine is explored. A single administration of ketamine (10 mg/kg) remarkably relieved anxious and depressive behaviors in the sucrose preference test, elevated plus maze test, and forced swim test. Meanwhile, ketamine reduced the level of hippocampus Nlrp3 and the expression of its downstream molecules in chronic unpredictable mild stress (CUMS) mice model by western blot and reduced the colocalization of Gfap and Gsdmd by nearly 25% via immunofluorescent staining. Ketamine also increased the Gfap-positive cells and AQP4 expression in the hippocampus of the CUMS mice. More important, ketamine increased the distribution of the fluorescent tracer of CUMS mice. Treatment with 128 mM glutamate in cortical and hippocampus astrocytes increased the level of Nlrp3, and Gsdmd-N, and ketamine alleviated high glutamate-induced pyroptosis-associated proteins. In summary, these results suggest that high glutamate-induced astrocyte pyroptosis through the Nlrp3/Caspase-1/Gsdmd-N pathway which was inhibited by ketamine and ketamine can improve the damaged glymphatic function of the CUMS mice. The present study indicates that inhibiting astrocyte pyroptosis and promoting the glymphatic circulation function are a new mechanism of ketamine’s antidepressant effect, and astrocyte pyroptosis may be a new target for other antidepressant medicines.

Ethanol, also known as alcohol, is one of the most common drinks in the world. Chronic ethanol exposure has been reported to induce mental disorders. Ethanol also has a strong effect on the gut microbiota. The gut microbiota has been reported to affect the brain via multiple pathways, including changes in γ-aminobutyric acid (GABA) system, and cause a variety of mental disorders. The GABA system in the cortex is associated with anxiety. However, the role of gut microbiota played in ethanol exposure-induced changes in the GABA system and anxiety is still not clear. We established a 30-day ethanol exposure mouse model and investigated the effects of microbiota using the antibiotic minocycline. Minocycline alleviated ethanol-induced anxiety-like behaviour, dysbiosis of microbiota, intestinal barrier disruption, increased serum endotoxin and interleukin (IL)-6. Minocycline also attenuated ethanol-induced apoptosis and decreased expression of glutamate decarboxylases (GADs) and GABRA1 in the prefrontal cortex. Our results indicated that gut microbiota plays an important role in ethanol-induced anxiety-like behaviour by altering the function of GABA system. In addition, causal mediation analysis showed that endotoxin and IL-6 may mediate the connection between the gut microbiota and the expression of GABAA receptor in the prefrontal cortex.

Psychoactive substances are a class of chemical substances which could cause public health threats. Cognitive disorders are a category of mental health disorders that primarily affect cognitive abilities. Tau protein could maintain neuronal cytoskeleton stabilization. Post-translational modification of tau, especially phosphorylation, is an important way to regulate the structure and function of tau and phosphorylated tau is closely related to cognitive function. Lots of studies have reported the phenomenon that psychoactive substances can cause cognitive function impairment. We reviewed recent related studies and discussed them by drug classification. We mainly focused on cognitive disorders caused by acute or chronic exposure of each drugs, animal experiments and the mechanisms associated with tau phosphorylation, then compared the similarities and differences among them, trying to find out the common rules. The results suggested that tau phosphorylation is involved in psychoactive substance-induced cognitive disorder and different psychoactive substances may act by affecting amount or activity of different kinases and phosphatases in the metabolic pathway of tau. We demonstrated that tau protein is a potential target for psychoactive substances induced cognitive disorder treatments.

BACKGROUND:Ketamine is an intravenous anesthetic. However, whether ketamine can induce neurotoxicity and neurobehavioral deficits remains largely unknown. Delirium is a syndrome of acute brain dysfunction associated with anesthesia and surgery in patients, and tau protein may contribute to postoperative delirium. Finally, ketamine may affect the function of the endosome, the key organelle for tau release from neurons. Therefore, we set out to determine the effects of ketamine on delirium-like behavior in mice and on tau trafficking in cultured cells. METHODS:We used the buried-food test, open-field test, and Y-maze test in adult mice to assess the presence of delirium-like behavior in mice. We quantified tau amounts in the serum of mice. We used cell fraction methods to determine the effects of ketamine on tau intracellular trafficking, extracellular release, and endosome trafficking in cultured cells. RESULTS:Ketamine induced delirium-like behavior in mice and increased tau amounts in serum of mice. The ketamine treatments also led to increased accumulation of endosomes, as evidenced by increased endosomal markers Rab5 and Rab7. Moreover, ketamine inhibited endosome maturation, demonstrated by decreased membrane-bound but increased cytoplasm amounts of Rab5 and Rab7. Consequently, ketamine increased tau in the endosomes of cultured cells and the cell culture medium. CONCLUSIONS:These data suggest that ketamine may interfere with intracellular tau trafficking and induce delirium-like behavior, promoting future research regarding the potential neurotoxicity of anesthetics.

The abnormal expression of the dopamine D1 receptor (DRD1) may be associated with schizophrenia. MicroRNAs (miRNAs) can post-transcriptionally regulate DRD1 expression. Here, we established a ketamine-induced schizophrenia-like behavior mouse model and investigated the changes in miR-15a-3p, miR-15b-3p, miR-16-13p, and DRD1 in response to ketamine. Administration of high-dose ketamine for seven consecutive days to mice simulated the main symptoms of schizophrenia. The mice exhibited increasing excitability and autonomous activity and reduced learning and memory, including spatial memory. Moreover, ketamine decreased miR-15a3p, miR-15b-3p, and miR-16-1-3p expression levels in the prefrontal cortex (PFC) and miR-16-1-3p expression in the hippocampus, whereas DRD1 expression increased in these brain regions. In HT22 mouse hippocampal neuronal cells, ketamine induced a dose-dependent increase of endogenous DRD1, which was partially attenuated by a combination of miR-15b-3p and miR-16-1-3p mimics. Indeed, the miR-15b-3p and miR-16-1-3p mimics could significantly inhibit endogenous DRD1expression. We identified +72 to +78 bp (TGCTGCT) of the DRD1 3'UTR as the core regulatory region recognized by the target miRNAs. In summary, we developed a ketamineinduced schizophrenia-like behavior mouse model and found that ketamine inhibited the levels of miR-15a3p, miR-15b-3p, miR-16-1-3p and increased DRD1 expression in mice.

Chronic ethanol exposure (CEE), which can lead to neuroinflammation, is an increasing risk factor for depression disorder, but the underlying mechanism is not clear. Recent observations have revealed the associations among psychiatric disorders, ethanol exposure and alterations of the gut microbiota. Here, we found that CEE induced depressive-like behavior, which could be alleviated by probiotics and transferred from donor to recipient mice by fecal microbiota transplantation (FMT). Neuroinflammation and the activation of the NLRP3 inflammasome were also observed in recipient mice. The downregulation of NLRP3 in the hippocampus mitigated CEE-induced depressive-like behavior and neuroinflammation but had no significant effect on FMT recipient mice. Moreover, elevated serum inflammatory factors in recipient mice showed a significant mediation effect between the gut microbiota and depressive-like behavior. Together, our study findings indicate that the gut microbiota contributes to both hippocampal NLRP3-mediated neuroinflammation and depressive-like behavior induced by CEE, which may open avenues for potential interventions against CEE-associated psychiatric disorders.

Chronic ethanol exposure (CEE) is associated with greater neurodegenerative effects and an increased risk of depression disorder. The AMPAR is thought to be involved in depression and a reduction in its GluA1 subunit was observed in the mouse hippocampus after CEE. AMPAkines are positive allosteric modulators of the AMPA receptor and have improved depressive-like behavior. However, the role of AMPARs in CEE-induced depressive-like behavior is not clear. It is unclear whether AMPAkines, positive allosteric agonists of AMPARs, protect against ethanol-induced depression. We investigated the effects of CX516 on ethanol-induced depressive-like behavior in a mouse model. CX516 (5 mg/kg) administration alleviated 20% (m/V) ethanol-induced depressive-like behavior in mice. Furthermore, CX516 significantly diminished the inhibition of the ERK1/2-BDNF-TrkB pathway in the hippocampus of ethanol-exposed mice. In addition, CX516 attenuated the levels of pro-inflammatory (IL-6, IL-1β), apoptosis (BAX, BCL-2), and neurodegeneration (FJC) in the mouse hippocampus induced by CEE.

Ketamine is an anesthetic and addictive drug that can cause cognitive dysfunction and neuroinflammation. Studies have shown that carboxy-terminal fragment derived from β-secretase (CTF-β) and amyloid beta (Aβ), the amyloidogenic products of amyloid precursor protein (APP), can also induce neuroinflammation and impair cognitive function. However, it remains unclear whether ketamine regulates the amyloidogenic pathway. In the endosome, APP is cleaved by beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), whose activity is influenced by pH. Endosomal acidification is mainly regulated by sodium hydrogen exchanger 6 (NHE6), which leaks protons out of endosomes, and vacuolar proton translocating ATPases (V-ATPase), which pump protons into endosomes. Therefore, we hypothesized that ketamine lowers the endosomal pH by reducing the endosomal NHE6 protein level, and this hyperacidification promotes the amyloidogenic pathway. We set up C57BL/6 J mouse models using 10, 20, 40, 80, and 100 mg/kg ketamine administration and SH-SY5Y cell models using 1, 10, 100, and 1000 μM ketamine administration to investigate its effects on the amyloidogenic pathway at different doses. Western blotting results showed that 100 mg/kg ketamine treatment in vivo and 1000 μM ketamine treatment in vitro increased endosomal BACE1 and CTF-β protein levels and reduced endosomal NHE6 and APP protein levels. The endosomal accumulation of BACE1 caused by ketamine administration was also observed using confocal imaging. Moreover, flow cytometry indicated that ketamine treatment lowered the endosomal pH value of SH-SY5Y cells. Later, cells were pretreated with monensin to restore the endosomal pH. Monensin did not affect amyloidogenic-related proteins or NHE6 directly; therefore, ketamine-promoted endosomal amyloidogenic processing and BACE1 accumulation were depleted by restoring endosomal acidity through monensin pretreatment. Finally, knockdown of NHE6 promoted the amyloidogenic pathway similarly and prevented further enhancement by ketamine. These results indicated that the effects of ketamine on the amyloidogenic pathway were dependent on the reduction of NHE6 and endosomal pH.