Risk Factors Analysis of Severe Liver Injury Induced by Statins.

The aim of this study is to report the risk factors of severe statin induced liver injury (SILI). From the database of Shandong ADR Monitoring Center and Outpatients and inpatients in our hospital, SILI cases reported from 2013 to 2021 were extracted and screened. The diagnostic criteria of SILI, the inclusion and exclusion criteria of severe and general SILI were established separately. After the SILI cases were selected and confirmed, the socio-demographic and clinical characteristics were collected. Single factor chi-square test and multi-factor unconditional logistic regression analysis were used to analyze the influencing factors of severe SILI. From 1391 reported cases, 1211 met SILI diagnostic criteria, of which 157 were severe SILI and 964 were general SILI. Univariate analysis showed that age, drug combination, statin category were the influencing factors of severe SILI (p<0.1). Multivariate logistic analysis showed that drug combination and statin category were the influencing factors of severe SILI (p<0.05). Atorvastatin caused the most serious SILI, and its risk is 1.77 times higher than rosuvastatin. The serious SILI risk of drug combination was 2.08 times higher than statin alone. The patient with these factors should be monitored intensively during clinical treatment, to ensure their medication safety.

Unraveling the link between childhood maltreatment and depression: Insights from the role of ventral striatum and middle cingulate cortex in hedonic experience and emotion regulation.

Childhood maltreatment is an established risk factor for psychopathology. However, it remains unclear how childhood traumatic events relate to mental health problems and how the brain is involved. This study examined the serial mediation effect of brain morphological alterations and emotion-/reward-related functions on linking the relationship from maltreatment to depression. We recruited 156 healthy adolescents and young adults and an additional sample of 31 adolescents with major depressive disorder for assessment of childhood maltreatment, depressive symptoms, cognitive reappraisal and anticipatory/consummatory pleasure. Structural MRI data were acquired to identify maltreatment-related cortical and subcortical morphological differences. The mediation models suggested that emotional maltreatment of abuse and neglect, was respectively associated with increased gray matter volume in the ventral striatum and greater thickness in the middle cingulate cortex. These structural alterations were further related to reduced anticipatory pleasure and disrupted cognitive reappraisal, which contributed to more severe depressive symptoms among healthy individuals. The above mediating effects were not replicated in our clinical group partly due to the small sample size. Preventative interventions can target emotional and reward systems to foster resilience and reduce the likelihood of future psychiatric disorders among individuals with a history of maltreatment.

Insights into the electrochemical properties of Li2FeS2 after FeS2 discharging.

All-solid-state lithium-sulfur batteries (ASSLSBs) have high reversible characteristics owing to the high redox potential, high theoretical capacity, high electronic conductivity, and low Li+ diffusion energy barrier in the cathode. Monte Carlo simulations with cluster expansion, based on the first-principles high-throughput calculations, predicted a phase structure change from Li2FeS2 (P3̄M1) to FeS2 (PA3̄) during the charging process. LiFeS2 is the most stable phase structure. The structure of Li2FeS2 after charging was FeS2 (P3̄M1). By applying the first-principles calculations, we explored the electrochemical properties of Li2FeS2 after charging. The redox reaction potential of Li2FeS2 was 1.64 to 2.90 V, implying a high output voltage of ASSLSBs. Flatter voltage step plateaus are important for improving the electrochemical performance of the cathode. The charge voltage plateau was the highest from Li0.25FeS2 to FeS2 and followed from Li0.375FeS2 to Li0.25FeS2. The electrical properties of LixFeS2 remained metallic during the Li2FeS2 charging process. The intrinsic Li Frenkel defect of Li2FeS2 was more conducive to Li+ diffusion than that of the Li2S Schottky defect and had the largest Li+ diffusion coefficient. The good electronic conductivity and Li+ diffusion coefficient of the cathode implied a better charging/discharging rate performance of ASSLSBs. This work theoretically verified the FeS2 structure after Li2FeS2 charging and explored the electrochemical properties of Li2FeS2.

Neonatal outcomes after gamma-aminobutyric acid analog use during pregnancy: a meta-analysis of cohort studies.

BACKGROUND: Gamma-aminobutyric acid (GABA) analogs are being used by an increasing number of reproductive-age women. However, there is concern regarding the teratogenic potential of GABA analogs. METHODS: We performed this systematic review and meta-analysis to assess the relationship between GABA analog exposure and risk of adverse neonatal outcomes. RESULTS: Eight cohort studies were included in the meta-analysis. Exposure to a GABA analog during pregnancy was not associated with an increased risk of congenital malformation (odds ratio [OR] 1.19, 95% confidence interval [CI] 0.96-1.46, P = 0.106) or a small for gestational age (SGA) infant (OR 1.99, 95% CI 0.78-5.1, P = 0.152) compared to no exposure. However, exposure to a GABA analog was associated with an increased risk of preterm birth (PB) (OR 1.56, 95% CI 1.04-2.35, P = 0.033), spontaneous abortion (SA) (OR 1.64, 95% CI 1.14-2.38, P = 0.008), or termination of pregnancy (TOP) (OR 3.02, 95% CI 2-4.56, P < 0.001). CONCLUSION: Exposure to GABA analogs during pregnancy does not appear to be associated with congenital malformation, although there was some evidence of a higher risk of several other negative neonatal outcomes. Given the few studies included, larger prospective studies controlling for important confounders are needed to verify our findings.

MiR-21-3p triggers cardiac fibroblasts pyroptosis in diabetic cardiac fibrosis via inhibiting androgen receptor.

AIMS/HYPOTHESIS: MicroRNA-21 has been implicated in diabetic complication, including diabetic cardiomyopathy. However, there is limited information regarding the biological role of the miR-21 passenger strand (miR-21-3p) in diabetic cardiac fibrosis. The aim of this study was to investigate the role of miR-21-3p and its target androgen receptor in STZ-induced diabetic cardiac fibrosis. METHODS: The pathological changes and collagen depositions was analyzed by HE, Sirius Red staining and Masson's Trichrome Staining. MiR-21-3p, AR, NLRP3, caspase1 and collagen I expression were analyzed by western blotting, immunohistochemistry, immunofluorescence, qRT-PCR, miR one step qRT-PCR, respectively. A luciferase reporter assay was used to verify the interaction between miR-21 and the 3' untranslated region (3'UTR) of AR. RESULTS: Our results indicated that miR-21-3p level was up-regulated, while AR was decreased in STZ-induced diabetic cardiac fibrosis tissues and cardiac fibroblast. High glucose triggers cardiac fibroblasts pyroptosis and collagen deposition. Gain-of-function and loss-of-function assays demonstrated that miR-21-3p mediated the crucial role in diabetic cardiac fibrosis. Our results show that miR-21-3p bound to the 3'UTR of AR post-transcriptionally repressed its expression. We also found AR, which regulates cardiac fibroblasts pyroptosis and collagen deposition through caspase1 signaling. CONCLUSIONS: /interpretation: Taken together, our study showed that miR-21-3p aggravates STZ-induced diabetic cardiac fibrosis through the caspase1 pathways by suppressing AR expression.

Valeridoids G - Q, Eleven seco-Iridoids from Valeriana jatamansi and Their Bioactivites.

Eleven new seco-iridoids, valeridoids G-Q (1-6 and 8-12), along with four known products, 9-epi-valtral C (7), desacylbaldrinal (13), 11-methoxyviburtinal (14) and baldrinal (15), were obtained from Valeriana jatamansi. Among them, the new compounds were identified by their NMR, HR-ESI-MS spectroscopic data and ECD calculation. Moreover, valeridoid N and O were a pair of C3 epimers, whose ether bonds between C-1 and C-3 opened, and new ether bonds formed between C-3 and C-6. Valeridoid Q belonged to the C-1 degradation of seco-iridoids. As a result, 9-epi-valtral C displayed significant inhibition on Streptococcus agalactiae, Staphylococcus aureus, Staphylococcus argenteus, Shigella flexneri and Klebsiella pneumoniae, and valeridoid Q exhibited the most significant inhibition against Salmonella enteritidis. 9-Epi-valtral C and baldrinal selectively inhibited the growth of human glioma stem cells. Valeridoid Q exhibited significant anti-influenza activity, while valeridoid O inhibited nitric oxide production.

DNMT1 deregulation of SOCS3 axis drives cardiac fibroblast activation in diabetic cardiac fibrosis.

Cardiac fibrosis is one of the main pathological manifestations of diabetic cardiomyopathy (DCM). Cardiac fibroblast activation is a key effector of cells resulting in diabetic cardiac fibrosis. However, the underlying mechanism of cardiac fibroblast activation and diabetic cardiac fibrosis remains unclear. Accumulating evidence suggests that DNA methylation alterations play a central role in cardiac fibroblast activation. In this study, we demonstrated that DNA methyltransferase 1 (DNMT1)-mediated suppression of cytokine signaling 3 (SOCS3) promoter hypermethylation leads to downregulation of SOCS3 expression in diabetic cardiac fibrosis. High glucose-induced expression of DNMT1 was increased in cardiac fibroblasts, while the expression of SOCS3 was decreased. Downregulation of SOCS3 facilitated activation of STAT3 to promote cardiac fibroblast activation and collagen deposition. Genetic or pharmacological inactivation of DNMT1 reversed the activated phenotype of cardiac fibroblasts. Clinically, we observed a significant inverse correlation between DNMT1 and SOCS3 expression levels, and loss of SOCS3 expression or increased expression of DNMT1. Taken together, these findings identify DNMT1 silencing of SOCS3 axis as a driver of cardiac fibroblast activation in diabetic cardiac fibrosis. These results provide a scientific and new explanation of the underlying mechanism of diabetic cardiac fibrosis.

New role of sertraline against Toxoplasma gondii-induced depression-like behaviours in mice.

Toxoplasma gondii (T. gondii) is a neurotropic protozoan parasite, which can cause mental and behavioural disorders. The present study aimed to elucidate the effects and underlying molecular mechanisms of sertraline (SERT) on T. gondii-induced depression-like behaviours. In the present study, a mouse model and a microglial cell line (BV2 cells) model were established by infecting with the T. gondii RH strain. In in vivo and in vitro experiments, the underlying molecular mechanisms of SERT in inhibiting depression-like behaviours and cellular perturbations caused by T. gondii infection were investigated in the mouse brain and BV2 cells. The administration of SERT significantly ameliorated depression-like behaviours in T. gondii-infected mice. Furthermore, SERT inhibited T. gondii proliferation. Treatment with SERT significantly inhibited the activation of microglia and decreased levels of pro-inflammatory cytokines such as tumour necrosis factor-alpha, and interferon-gamma, by down-regulating tumour necrosis factor receptor 1/nuclear factor-kappa B signalling pathway, thereby ameliorating the depression-like behaviours induced by T. gondii infection. Our study provides insight into the underlying molecular mechanisms of the newly discovered role of SERT against T. gondii-induced depression-like behaviours.

Correlation between sleep characteristics and cognitive decline in the elderly people: A cross-sectional study in China.

STUDY OBJECTIVES: In this study, we conducted a cross-sectional analysis of the sleep characteristics in the elderly Chinese people to comprehensively investigate the association between sleep and cognitive function in the elderly people. We aimed to evaluate the most important demographic factors, conventional physiological indices and living habits that may influence sleep. METHODS: We surveyed 2901 elderly people (age ≥60 years old) face-to-face from 1 July to 31 December 2017, who were recruited from 17 communities of the Pudong New Area (Shanghai, China) by probability proportional to size. The Pittsburgh sleep quality index (PSQI) scale was used to describe the sleep features of each participant. Cognitive assessment was performed using the mini-mental state examination (MMSE) scale, Montreal cognitive assessment (MoCA) and the clinical dementia rating (CDR) scale. Those factors which potentially influence sleep and consequentially may impact cognition in the elderly people were evaluated, and the correlations of sleep characteristics and cognitive function were explored by the linear regression analysis. RESULTS: Altogether, there were 1287 (44.4%) people taking part in the investigation. Sleep quality was significantly correlated with MMSE and MoCA total scores. Healthy sleep (especially enough sleep) was correlated with better cognitive functions. Besides recognised relative factors (such as age, sex and living alone), the number of children was found to be a strong risk factor of poor sleep. Anxiety before sleep and light/noise interference significantly damaged sleep while an exercise routine was associated with better sleep. Moderate levels of reading, watching TV and household work were correlated with superior sleep quality. CONCLUSION: In conclusion, sleep characteristics correlate with cognitive decline in the elderly people, and they can be influenced by multiple demographic factors and living habits. To improve sleep quality, it may be important to change sleep environment, to be relax, to increase physical exercise and recreational activities moderately.

Risk and protective factors for burnout among physicians from standardized residency training programs in Shanghai: a cross-sectional study.

BACKGROUND: High burnout has been reported in physician populations. Although the standardized residency training (SRT) in China includes components that might put residents at a higher risk for burnout, the burnout of Chinese medical residents is unknown. This study aimed to evaluate the prevalence of burnout and the associated risk and protective factors for medical residents in the SRT program in Shanghai, China. METHODS: This study was a prospective cross-sectional design. A random sampling strategy was used to recruit 330 resident physicians from four SRT sites in Shanghai, and 318 completed questionnaires were returned. Respondents completed a self-made questionnaire including demographic and work characteristics, four burnout and wellness-specific surveys. Bivariate analyses and hierarchical multiple regression models were used to analyze factors associated with three sub-scales of burn out separately. RESULTS: The overall burnout rate was 71.4%. Low level rate of personal accomplishment (PA) was extremely high at 69.5%. Night shift experience, high occupational stress, and low social support were significant predictors, which explained 49.1% variance of emotional exhaustion (EE) (F = 26.528, P < 0.01). Factors that significantly predicted depersonalization (DP) included male gender, senior residents, night shift experience, high occupational stress, and low psychological empathy, which explained 51.5% variance totally (F = 29.004, P < 0.01). Senior residents, high income, low occupational stress, and high empathy were also significant predictors of decreased personal achievement (PA), which explained 18.4% variance totally (F = 12.897, P < 0.01). CONCLUSIONS: There was a high burnout rate among SRT residents in Shanghai. Occupational stress and several work-related factors were significant and strong risk factors for burnout, while empathy and social support were mild protective factors. Decreased work-related demands and increased access to resources could assist residents in reducing their work stress and improving their well-being.

Highly effective removal of antibiotics from aqueous solution by magnetic ZnFe2O4/activated carbon composite.

Water pollution from antibiotics has attracted a lot of attention for its serious threat to human health. In this study, a magnetic adsorbent (zinc ferrite/activated carbon (ZnFe2O4/AC) was synthesized via microwave method to effectively remove gemifioxacin mesylate (GEM) and moxifloxacin hydrochloride (MOX). Based on the porosity of AC and the magnetism of ZnFe2O4, the resulting ZnFe2O4/AC has high adsorption capacities and can be easily separated from the solid-liquid system via a magnetic field. The largest adsorption capacities for GEM and MOX can reach up to 433.4 mg g-1 and 388.8 mg g-1, respectively, higher than those of reported adsorbents such as MIL-101 and MOF-808. Fastest adsorptions of GEM and MOX were found at 5 min, and solution pH and coexisting salts do not have a significant influence on the adsorption process. The adsorption mechanism analysis indicates that electrostatic interaction and H-bond interaction contribute to the effective adsorption.

Bioactive 3,8-Epoxy Iridoids from Valeriana jatamansi.

Twelve 3,8-epoxy iridoids, including four new compounds, jatamanins R-U (1-4), and eight known compounds (5-12), were obtained from the roots and rhizomes of Valeriana jatamansi. The structures were elucidated from analysis of spectroscopic data. The absolute configurations of 1-4 were determined by comparison of experimental and literature ECD spectra. Moreover, the compounds were evaluated for cytotoxic effects against glioma stem cells, inhibition of NO production, activity against influenza A virus and reversal of multidrug resistance of HepG2/ADR cells. Compounds 9 and 12 showed significant cytotoxic potency against GSC-18# (IC50 =1.351 and 4.439 µg ml-1 , respectively) and GSC-3# (IC50 =10.88 and 6.348 µg ml-1 , respectively) glioma stem cells, while compound 12 was also slightly less potent against GSC-12# (IC50 =13.45 µg ml-1 ) glioma stem cell growth. In addition, compounds 9 and 12 displayed obvious inhibition of NO production (IC50 =4.6 and 15.8 µm, respectively).

Cellular immunopathogenesis in primary Toxoplasma gondii infection during pregnancy.

Congenital toxoplasmosis is caused by the vertical transmission of infection from mother to foetus through the placenta when a pregnant woman is infected with Toxoplasma gondii (T. gondii). Congenital infection can have serious consequences, such as intrauterine abortion, foetal death and severe neurological, ocular or other organ damage in the foetus. In this review, we focus on recent publications investigating vertical transmission of T. gondii infection, cellular immunopathogenesis and protective immunity in primary toxoplasmosis during pregnancy.

DNMT3A controls miR-200b in cardiac fibroblast autophagy and cardiac fibrosis.

AIM AND OBJECTIVE: Regulation of microRNA gene expression by DNA methylation may represent a key mechanism to drive cardiac fibrosis progression. Cardiac fibroblast autophagy is the primary source of cardiac fibrosis, but the mechanisms underlying this process are incompletely understood. Here we found that DNMT3A suppression of the microRNA-200b (miR-200b) through pathway leads to cardiac fibroblast autophagy in cardiac fibrosis. METHODS: To understand the impact of DNMT3A on miR-200b at cardiac fibrosis, the rat cardiac fibrosis model was established via the abdominal aortic coarctation. Cardiac fibroblasts (CFs) were harvested from SD neonate rats and cultured. The expression of DNMT3A, miR-200b, collagen I was measured by western blotting, immunohistochemistry and qRT-PCR. Gain- or loss-of-function approaches were used to manipulate DNMT3A and miR-200b. RESULTS: DNMT3A level was upregulated and negatively correlated with miR-200b expression in fibrosis tissues and cardiac fibroblast. We found that autophagy was activated by miR-200b inhibitor and inactivated by miR-200b mimic in the rat cardiac fibroblast. Knockdown of DNMT3A notably increased the expression of miR-200b. CONCLUSIONS: Taken together, these findings indicate that DNMT3A regulation of miR-200b controls cardiac fibroblast autophagy during cardiac fibrosis and provide a basis for the development of therapies for cardiac fibrosis.

Unprecedented sugar bridged bisindoles selective inhibiting glioma stem cells.

Unlike reported bisindoles linked by single bond directly, alstoniasidines A (1) and B (2), from Alstonia scholaris featuring unprecedented skeleton with two indole moieties bridged by a sugar, represented a novel bisindole type having strictosamide-glucopyranose-picraline scaffold. Both compounds exhibited selective cytotoxicity against human glioma stem cells (GSCs) and induced caspase-3 dependent extrinsic apoptosis by increasing the expression of interleukin 1 (IL-1), tumor necrosis factor (TNF-α), and the cleaved caspase-3, while damaged the unlimited proliferation and self-renewal capacity of GSCs. This finding might provide new type of leads for the selective killing of human glioma stem cells.

Isocostunolide inhibited glioma stem cell by suppression proliferation and inducing caspase dependent apoptosis.

Glioblastoma multiform (GBM) is a highly aggressive brain tumor with poor life expectancy, and glioma stem cells (GSCs) are a small population of tumor cells existed in GBM, in which GSCs response to drive GBM recurrence, invasion and contribute to the anti-cancer resistance. GSCs have been identified and developed as a therapeutic target for GBM and can be used in drugs screening. Isocostunolide is a natural sesquiterpenoid and contained abundant resource in medicinal plants, but the anti-cancer efficacies of it against GSCs are still unexplored. In this investigation, the anti-tumor activity of isocostunolide against GSCs was investigated and the result demonstrated that it inhibited the growth of GSCs (GSC-3#, GSC-12#, GSC-18#) significantly with an IC50 value of 2.80µg/ml, 2.61µg/ml, 1.07µg/ml, respectively. In further mechanism study, isocostunolide inhibited GSCs cell proliferation, induced GSCs apoptosis significantly, as well as increased the proportion of the cleavage of caspase-3. The result suggested that isocostunolide induced GSCs apoptosis via the caspase dependent apoptotic pathway. Moreover, isocostunolide damaged GSCs colony formation capacity significantly and exhibited the anti-cancer efficacy against GSCs in vitro.

[Diagnosis and treatment for three imported Plasmodium malariae malaria cases in Henan Province].

Giemsa-stained blood film microscopy, CareStart rapid detection and PCR were used to detect the three cases who returned from Angola and Equatorial Guinea to Henan Province. Onset of malaria symptoms for two patients occurred 15 d and 27 d after their return from Angola, respectively. Two months after returning home, another case relapsed who had suffered from malaria in Equatorial Guinea. All three patients had the symptoms such as irregular fever, headache, chills and so on. Two cases had elevated total bilirubin and splenomegaly. The cases were confirmed as P. malariae infection by microscopic morphological examination. Amplified bands were produced by 18S rRNA nested PCR, which was the same with P. malariae in size, whereas the results of CareStart repaid detection test were all negative. They were cured by using artemisinin-based combination therapy (ACT).

Event-Triggered Adaptive Finite-Time Control Using a Fuzzy State Observer for Nonlinear Cyber-Physical Systems Under Deception Attacks.

This article presents a new event-triggered adaptive finite-time control strategy using a fuzzy state observer for a class of nonlinear cyber-physical systems (CPSs) under malicious deception attacks with a more general form. Compared with the traditional assumptions on the deception attacks in the existing results, a more general assumption on deception attacks is given in this article. During the design process, real system states are initially estimated by developing an improved state observer, which effectively addresses the problem of state unavailability. Then, a coordinate transformation technology, in which the estimated states of observer are considered, is presented to stabilize the studied system. By constructing the singularity-free finite time virtual controls, the singularity problem in the traditional finite time design algorithms is cleverly avoided. Furthermore, to minimize communication overhead, a final finite-time controller is established by using a relative threshold event-triggered scheme. The developed event-triggered adaptive finite-time control strategy guarantees that all signals in the closed-loop system are semi-globally bounded in finite time without Zeno behavior. Finally, the correctness of the proposed control strategy is validated through two simulation results.

Leonurus japonicus Houtt. modulates neuronal apoptosis in intracerebral hemorrhage: Insights from network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

Contactin -Associated protein1 Regulates Autophagy by Modulating the PI3K/AKT/mTOR Signaling Pathway and ATG4B Levels in Vitro and in Vivo.

Contactin-associated protein1 (Caspr1) plays an important role in the formation and stability of myelinated axons. In Caspr1 mutant mice, autophagy-related structures accumulate in neurons, causing axonal degeneration; however, the mechanism by which Caspr1 regulates autophagy remains unknown. To illustrate the mechanism of Caspr1 in autophagy process, we demonstrated that Caspr1 knockout in primary neurons from mice along with human cell lines, HEK-293 and HeLa, induced autophagy by downregulating the PI3K/AKT/mTOR signaling pathway to promote the conversion of microtubule-associated protein light chain 3 I (LC3-I) to LC3-II. In contrast, Caspr1 overexpression in cells contributed to the upregulation of this signaling pathway. We also demonstrated that Caspr1 knockout led to increased LC3-I protein expression in mice. In addition, Caspr1 could inhibit the expression of autophagy-related 4B cysteine peptidase (ATG4B) protein by directly binding to ATG4B in overexpressed Caspr1 cells. Intriguingly, we found an accumulation of ATG4B in the Golgi apparatuses of cells overexpressing Caspr1; therefore, we speculate that Caspr1 may restrict ATG4 secretion from the Golgi apparatus to the cytoplasm. Collectively, our results indicate that Caspr1 may regulate autophagy by modulating the PI3K/AKT/mTOR signaling pathway and the levels of ATG4 protein, both in vitro and in vivo. Thus, Caspr1 can be a potential therapeutic target in axonal damage and demyelinating diseases.