Targeting FTO induces colorectal cancer ferroptotic cell death by decreasing SLC7A11/GPX4 expression.

Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m6A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m6A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive. Herein, we find that m6A modification is increased during ferroptotic cell death and correlates with the decreased m6A demethylase fat mass and obesity-associated protein (FTO) expression. Functionally, we demonstrate that suppressing FTO significantly induces CRC ferroptotic cell death, as well as enhancing CRC cell sensitivity to ferroptosis inducer (Erastin and RSL3) treatment. Mechanistically, high FTO expression increased solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions in an m6A-YTHDF2 dependent manner, thereby counteracting ferroptotic cell death stress. In addition, we identify Mupirocin as a novel inhibitor of FTO, and Mupirocin induces CRC ferroptosis and inhibits tumor growth. Clinically, the levels of FTO, SLC7A11, and GPX4, are highly correlated expression in CRC tissues. Our findings reveal that FTO protects CRC from ferroptotic cell death in promoting CRC tumorigenesis through triggering SLC7A11/GPX4 expression.

Dual-mode detection of 2,6-pyridinedicarboxylic acid based on the enhanced peroxidase-like activity and fluorescence property of novel Eu-MOFs.

2,6-Pyridinedicarboxylic acid (DPA) is a significant biomarker of anthrax, which is a deadly infectious disease for human beings. However, the development of a convenient anthrax detection method is still a challenge. Herein, we report a novel europium metal-organic framework (Eu-MOF) with an enhanced peroxidase-like activity and fluorescence property for DPA detection. The Eu-MOF was one-step synthesized using Eu3+ ions and 2-methylimidazole. In the presence of DPA, the intrinsic fluorescence of Eu3+ ions is sensitized, the fluorescence intensity linearly increases with an increase in DPA concentration, and the fluorescence color changes from blue to purple. Simultaneously, the peroxide-like activity of the Eu-MOF is enhanced by DPA, which can promote the oxidation of TMB to oxTMB. The absorbance values increase linearly with DPA concentrations, and the colorimetric images change from colorless to blue. The dual-mode detection of DPA has good sensitivity with a colorimetric detection limit of 0.67 µM and a fluorescent detection limit of 16.67 nM. Moreover, a simple detection method for DPA was developed using a smartphone with the RGB analysis system. A portable kit with standard color cards was developed using paper test strips. The proposed methods have good practicability for DPA detection in real samples. In conclusion, the developed Eu-MOF biosensor offers a valuable and general platform for anthrax diagnosis.

Risk stratification for infection during immunosuppressive therapy in patients with lupus nephritis: A nested case-control study.

BACKGROUND: The current prediction models for the risk of infection during immunosuppressive treatment for lupus nephritis (LN) lack a prediction time window and have poor pertinence. This study aimed to develop a risk stratification to predict infection during immunosuppressive therapy in patients with LN. METHODS: This retrospective nested case-control study collected patients with LN treated with immunosuppressive therapy between 2014 and 2022 in the Nephrology ward in Huashan Hospital affiliated to Fudan University and Huashan Hospital Baoshan Branch. Cases were defined as patients who experienced infection during the follow-up period; patients were eligible as controls if they did not have infection during the follow-up period. RESULTS: There were 53 patients with infection by CTCAE V5.0 grade ≥2. According to the 1:3 nested matching, the 53 patients with infection were matched with 159 controls. In the multivariable logistic regression model, the change rate of fibrinogen (OR = 0.97, 95% CI: 0.94-0.99, p = 0.008), leukopenia (OR = 8.68, 95% CI: 1.16-301.72, p = 0.039), and reduced albumin (OR = 6.25, 95% CI: 1.38-28.24, p = 0.017) were independently associated with infection. The AUC of the ROC curve in the validation set of the multivariable logistic regression model in the internal random sampling was 0.864. The scores range from -2 to 10. The infection risk stratification ranges from 2.8% at score -2 to 97.5% at score 10. CONCLUSION: A risk stratification was built to predict the risk of infection in patients with LN undergoing immunosuppressive therapy.

Spatial reconstructed local attention Res2Net with F0 subband for fake speech detection.

The rhythm of bonafide speech is often difficult to replicate, which causes that the fundamental frequency (F0) of synthetic speech is significantly different from that of real speech. It is expected that the F0 feature contains the discriminative information for the fake speech detection (FSD) task. In this paper, we propose a novel F0 subband for FSD. In addition, to effectively model the F0 subband so as to improve the performance of FSD, the spatial reconstructed local attention Res2Net (SR-LA Res2Net) is proposed. Specifically, Res2Net is used as a backbone network to obtain multiscale information, and enhanced with a spatial reconstruction mechanism to avoid losing important information when the channel group is constantly superimposed. In addition, local attention is designed to make the model focus on the local information of the F0 subband. Experimental results on the ASVspoof 2019 LA dataset show that our proposed method obtains an equal error rate (EER) of 0.47% and a minimum tandem detection cost function (min t-DCF) of 0.0159, achieving the state-of-the-art performance among all of the single systems.

Effectiveness and Safety of Anlotinib Combined with PD-1 Blockades in Patients with Previously Immunotherapy Treated Advanced Non-Small Cell Lung Cancer: A Retrospective Exploratory Study.

Objective: This study aimed to investigate the effectiveness and tolerability of anlotinib plus PD-1 blockades in patients with previously immunotherapy treated advanced non-small-cell lung cancer (NSCLC). Methods: A total of 67 patients with previously immunotherapy treated advanced NSCLC who received anlotinib plus PD-1 blockades in clinical practice were screened retrospectively. All the PD-1 blockades used in this study were approved in China and consisted of sintilimab, camrelizumab, tislelizumab and pembrolizumab. Effectiveness and safety of anlotinib plus PD-1 blockades were assessed, and all patients were followed up regularly. Clinical significance between response status to previous immune-related treatment regimens and therapeutic outcomes of anlotinib plus PD-1 blockades was further explored. Results: The best overall response among the 67 patients suggested that a partial response was observed in 16 patients, stable disease was noted in 41 patients and progressive disease was found in 10 patients, which yielded an objective response rate of 23.9% (95% CI: 14.3-35.9%) and a disease control rate of 85.1% (95% CI: 74.3-92.6%). Prognostic outcomes indicated that the median progression-free survival (PFS) was 6.1 months (95% CI: 2.37-9.83) and the median overall survival (OS) was 16.5 months (95% CI: 10.73-22.27). Exploratory analysis highlighted that patients who were intolerant to previous immune-related regimens (17 patients) might have a superior prognosis (median OS: 22.3 months vs 12.5 months, P=0.024). Additionally, adverse reactions with any grades during anlotinib plus PD-1 blockades administration were observed in 62 patients (92.5%), of which 31 patients (46.3%) had ≥grade 3 adverse reactions. Most common adverse reactions were fatigue, hypertension, diarrhea and hepatotoxicity. Conclusion: Anlotinib plus PD-1 blockades demonstrated promising effectiveness and tolerable safety in patients with previously immunotherapy treated advanced NSCLC. Those who were intolerant to previous immune-related regimens might benefit significantly from treatment with anlotinib plus PD-1 blockades. This conclusion should be confirmed in future studies.

Clinical efficacy and pathological outcomes of transanal endoscopic intersphincteric resection for low rectal cancer.

BACKGROUND: Transanal endoscopic intersphincteric resection (ISR) surgery currently lacks sufficient clinical research and reporting. AIM: To investigate the clinical effectiveness of transanal endoscopic ISR, in order to promote the clinical application and development of this technique. METHODS: This study utilized a retrospective case series design. Clinical and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated Hospital of Xiamen University between May 2018 and May 2023 were included. All patients underwent transanal endoscopic ISR as the surgical approach. We conducted this study to determine the perioperative recovery status, postoperative complications, and pathological specimen characteristics of this group of patients. RESULTS: This study included 45 eligible patients, with no perioperative mortalities. The overall incidence of early complications was 22.22%, with a rate of 4.44% for Clavien-Dindo grade ≥ III events. Two patients (4.4%) developed anastomotic leakage after surgery, including one case of grade A and one case of grade B. Postoperative pathological examination confirmed negative circumferential resection margins and distal resection margins in all patients. The mean distance between the tumor lower margin and distal resection margin was found to be 2.30 ± 0.62 cm. The transanal endoscopic ISR procedure consistently yielded high quality pathological specimens. CONCLUSION: Transanal endoscopic ISR is safe, feasible, and provides a clear anatomical view. It is associated with a low incidence of postoperative complications and favorable pathological outcomes, making it worth further research and application.

A Multiplex Recombinase-Aided qPCR Assay for Highly Sensitive and Rapid Detection of khe, blaKPC -2, and blaNDM -1 Genes in Klebsiella pneumoniae.

OBJECTIVE: This study aimed to establish a highly sensitive and rapid single-tube, two-stage, multiplex recombinase-aided qPCR (mRAP) assay to specifically detect the khe, blaKPC-2, and blaNDM-1 genes in Klebsiella pneumoniae. METHODS: mRAP was carried out in a qPCR instrument within 1 h. The analytical sensitivities of mRAP for khe, blaKPC-2, and blaNDM-1 genes were tested using recombinant plasmids and dilutions of reference strains. A total of 137 clinical isolates and 86 sputum samples were used to validate the clinical performance of mRAP. RESULTS: mRAP achieved the sensitivities of 10, 8, and 14 copies/reaction for khe, blaKPC-2, and blaNDM-1 genes, respectively, superior to qPCR. The Kappa value of qPCR and mRAP for detecting khe, blaKPC-2, and blaNDM-1 genes was 1, 0.855, and 1, respectively (p < 0.05). CONCLUSION: mRAP is a rapid and highly sensitive assay for potential clinical identification of khe, blaKPC-2, and blaNDM-1 genes in K. pneumoniae.

Blocking proteinase-activated receptor 2 signaling relieves pain, suppresses nerve sprouting, improves tissue repair, and enhances analgesic effect of B vitamins in rats with Achilles tendon injury.

ABSTRACT: Tendon injury produces intractable pain and disability in movement, but the medications for analgesia and restoring functional integrity of tendon are still limited. In this study, we report that proteinase-activated receptor 2 (PAR2) activation in dorsal root ganglion (DRG) neurons contributes to chronic pain and tendon histopathological changes produced by Achilles tendon partial transection injury (TTI). Tendon partial transection injury increases the expression of PAR2 protein in both somata of DRG neurons and their peripheral terminals within the injured Achilles tendon. Activation of PAR2 promotes the primary sensory neuron plasticity by activating downstream cAMP-PKA pathway, phosphorylation of PKC, CaMKII, and CREB. Blocking PAR2 signaling by PAR2 small-interference RNA or antagonistic peptide PIP delays the onset of TTI-induced pain, reverses the ongoing pain, as well as inhibits sensory nerve sprouting, and promotes structural remodeling of the injured tendon. Vitamin B complex (VBC), containing thiamine (B1), pyridoxine (B6), and cyanocobalamin (B12), is effective to ameliorate TTI-induced pain, inhibit ectopic nerve sprouting, and accelerate tendon repair, through suppressing PAR2 activation. These findings reveal a critical role of PAR2 signaling in the development of chronic pain and histopathological alterations of injured tendon following Achilles tendon injury. This study suggests that the pharmaceuticals targeting PAR2, such as VBC, may be an effective approach for the treatment of tendon injury-induced pain and promoting tendon repair.

Gut-Derived Trimethylamine N-Oxide Promotes CCR2-Mediated Macrophage Infiltration in acute kidney injury.

BACKGROUND: Inflammation is crucial in the development of AKI and subsequent CKD following renal ischemia-reperfusion (IR) injury. Gut microbiota metabolites trigger inflammation and affect IR-induced renal damage. Yet, the driving factors and mechanisms are unclear. Trimethylamine N-oxide (TMAO), a gut-derived choline metabolite, is a strong pro-inflammatory factor that increases in patients with AKI and CKD. We hypothesized that TMAO can promote renal injury caused by IR. METHODS: Mice subjected to unilateral renal IR to induce AKI and CKD were fed a high-choline diet to observe the effects of TMAO on kidney inflammation, fibrosis, and macrophage dynamics. RESULTS: A choline-rich diet altered the gut microbiota and elevated TMAO levels, which exacerbated IR-induced AKI and subsequent CKD. Single-cell analysis identified a distinct subset of CCR2+ macrophages derived from monocytes as key responders to TMAO, intensifying immune cell interactions and worsening renal injury. TMAO promoted sustained CCR2 expression after IR, increasing macrophage infiltration. CCR2 deletion and antagonist RS-102895 improved TMAO-induced inflammation and fibrosis, alleviated renal injury induced by IR. CONCLUSIONS: Our study provides valuable insights into the link between TMAO and IR-incited renal inflammation and fibrosis, emphasizing the critical role of TMAO-mediated macrophage infiltration via CCR2 as a key therapeutic target in the acute and chronic phase after IR.

Ophiorrhizareflexa (Rubiaceae), a new species from a karst region in Guangxi, China.

Ophiorrhizareflexa, a new species from Guangxi, China, is described and illustrated in this study. It is morphologically similar to O.alatiflora due to the branched inflorescence, distylous flowers and the tubular-funnelform corolla with five longitudinal wings. The new species can be distinguished from O.alatiflora by its erect inflorescence, its smaller and equal-sized calyx lobes 0.5-0.7 mm long, its corolla tubes winged to the middle and the wings straight and its strongly reflexed corolla lobes at anthesis. Ophiorrhizareflexa is assessed as least concern (LC) according to IUCN Categories and Criteria.

α-Glucosidase Inhibitory Phytochemical Components of Chinese Endemic Plant Whitfordiodendron filipes var. tomentosum.

Whitfordiodendron filipes var. tomentosum is an endemic plant in China. There have been no chemical or pharmacological studies of this plant reported before. In the current research, eight triterpenes and two steroids were obtained. Their structures were established by the analysis of NMR data and comparison with those reported in the literature. These ten structurally diverse compounds comprised five distinct carbon frameworks with different functionalities. The chemotaxonomic significance of these secondary metabolites was discussed, disclosing the common components between the variant W. filipes var. tomentosum and the species W. filipe. Evaluation of α-glucosidase inhibitory activities of these isolates disclosed that compounds 1, 2, 4, and 6 exhibited significant α-glucosidase inhibitory activities (IC50 = 16.6-19.2 µM), which were close in value to the positive control acarbose (IC50 = 11.5 µM). Moreover, the binding modes between the biologically active compounds 1, 2, 4, and 6 and the α-glucosidase protein were preliminarily studied using molecular docking. This study not only showed the chemical and biological profile of the plant W. filipes var. tomentosum but also revealed that these components could be developed as hypoglycemic lead compounds.

Curcumin/TGF-ß1 siRNA loaded solid lipid nanoparticles alleviate cerebral injury after intracerebral hemorrhage by transnasal brain targeting.

Intracerebral hemorrhage (ICH) is a prevalent cerebrovascular disorder. The inflammation induced by cerebral hemorrhage plays a crucial role in the secondary injury of ICH and often accompanied by a poor prognosis, leading to disease exacerbation. However, blood-brain barrier (BBB) limiting the penetration of therapeutic drugs to the brain. In this paper, our primary objective is to develop an innovative, non-invasive, safe, and targeted formulation. This novel approach aims to synergistically harness the combined therapeutic effects of drugs to intervene in inflammation via a non-injectable route, thereby significantly mitigating the secondary damage precipitated by inflammation following ICH. Thus, a novel "anti-inflammatory" cationic solid lipid nanoparticles (SLN) with targeting ability were constructed, which can enhance the stability of curcumin(CUR) and siRNA. We successfully developed SLN loaded with TGF-ß1 siRNA and CUR (siRNA/CUR@SLN) that adhere to the requirements of drug delivery system by transnasal brain targeting. Through the characterization of nanoparticle properties, cytotoxicity assessment, in vitro pharmacological evaluation, and brain-targeting evaluation after nasal administration, siRNA/CUR@SLN exhibited a nearly spherical structure with a particle size of 125.0±1.93 nm, low cytotoxicity, high drug loading capacity, good sustained release function and good stability. In vitro anti-inflammatory results showcasing its remarkable anti-inflammatory activity. Moreover, in vivo pharmacological studies revealed that siRNA/CUR@SLN can be successfully delivered to brain tissue. Furthermore, it also elicited an effective anti-inflammatory response, alleviating brain inflammation. These results indicated that favorable brain-targeting ability and anti-inflammatory effects of siRNA/CUR@SLN in ICH model mice. In conclusion, our designed siRNA/CUR@SLN showed good brain targeting and anti-inflammatory effect ability after nasal administration, which lays the foundation for the treatment of inflammation caused by ICH and offers a novel approach for brain-targeted drug delivery and brings new hope.

Gut microbiota and its metabolic products in acute respiratory distress syndrome.

The prevalence rate of acute respiratory distress syndrome (ARDS) is estimated at approximately 10% in critically ill patients worldwide, with the mortality rate ranging from 17% to 39%. Currently, ARDS mortality is usually higher in patients with COVID-19, giving another challenge for ARDS treatment. However, the treatment efficacy for ARDS is far from satisfactory. The relationship between the gut microbiota and ARDS has been substantiated by relevant scientific studies. ARDS not only changes the distribution of gut microbiota, but also influences intestinal mucosal barrier through the alteration of gut microbiota. The modulation of gut microbiota can impact the onset and progression of ARDS by triggering dysfunctions in inflammatory response and immune cells, oxidative stress, cell apoptosis, autophagy, pyroptosis, and ferroptosis mechanisms. Meanwhile, ARDS may also influence the distribution of metabolic products of gut microbiota. In this review, we focus on the impact of ARDS on gut microbiota and how the alteration of gut microbiota further influences the immune function, cellular functions and related signaling pathways during ARDS. The roles of gut microbiota-derived metabolites in the development and occurrence of ARDS are also discussed.

Diabetic Neuropathic Pain: Directions for Exploring Treatments.

Diabetic neuropathic pain (DNP) is one of the common and severe late-stage complications of diabetes mellitus, which could greatly influence the patients' quality of life. Patients with DNP often experience spontaneous pain and evoked pain such as mechanical allodynia and thermal hyperalgesia, meaning that their physical and psychological health are severely impaired. Unfortunately, the mechanisms of DNP remain highly elusive, so substantial breakthrough in effective DNP targeted treatments is still clinically challenging. This article will hence summarise the main mechanisms currently known to underlie DNP pathogenesis, along with describing some of the current and potential treatment methods against diabetic neuropathic pain.

Ameliorative effect of resveratrol on acute ocular hypertension induced retinal injury through the SIRT1/NF-κB pathway.

Glaucoma is a kind of neurodegenerative disorder characterized by irreversible loss of retinal ganglion cells (RGCs) and permanent visual impairment. It is reported that resveratrol (RES) is a promising drug for neurodegenerative diseases. However, the detailed molecular mechanisms underlying its protective potential have not yet been fully elucidated. The present study sought to investigate whether resveratrol could protect RGCs and retinal function triggered by acute ocular hypertension injury through the SIRT1/NF-κB pathway. An experimental glaucoma model was generated in C57BL/6J mice. Resveratrol was intraperitoneally injected for 5 days. Sirtinol was injected intravitreally on the day of retinal AOH injury. RGC survival was determined using immunostaining. TUNEL staining was conducted to evaluate retinal cell apoptosis. ERG was used to evaluate visual function. The proteins Brn3a, SIRT1, NF-κB, IL-6, Bax, Bcl2, and Cleaved Caspase3 were determined using western blot. The expression and localisation of SIRT1 and NF-κB in the retina were detected by immunofluorescence. Our data indicated that resveratrol treatment significantly increased Brn3a-labelled RGCs and reduced RGC apoptosis caused by AOH injury. Resveratrol administration also remarkably decreased NF-κB, IL-6, Bax, and Cleaved Caspase3 proteins and increased SIRT1 and Bcl2 proteins. Furthermore, resveratrol treatment obviously inhibited the reduction in ERG caused by AOH injury. Importantly, simultaneous administration of resveratrol and sirtinol abrogated the protective effect of resveratrol, decreased NF-κB protein expression, and increased SIRT1 protein levels. These results suggest that resveratrol administration significantly mitigates retinal AOH-induced RGCs loss and retinal dysfunction, and that this neuroprotective effect is partially regulated through the SIRT1/NF-κB pathway.

ROCK1 inhibition improves wound healing in diabetes via RIPK4/AMPK pathway.

Refractory wounds are a severe complication of diabetes mellitus that often leads to amputation because of the lack of effective treatments and therapeutic targets. The pathogenesis of refractory wounds is complex, involving many types of cells. Rho-associated protein kinase-1 (ROCK1) phosphorylates a series of substrates that trigger downstream signaling pathways, affecting multiple cellular processes, including cell migration, communication, and proliferation. The present study investigated the role of ROCK1 in diabetic wound healing and molecular mechanisms. Our results showed that ROCK1 expression significantly increased in wound granulation tissues in diabetic patients, streptozotocin (STZ)-induced diabetic mice, and db/db diabetic mice. Wound healing and blood perfusion were dose-dependently improved by the ROCK1 inhibitor fasudil in diabetic mice. In endothelial cells, fasudil and ROCK1 siRNA significantly elevated the phosphorylation of adenosine monophosphate-activated protein kinase at Thr172 (pThr172-AMPKα), the activity of endothelial nitric oxide synthase (eNOS), and suppressed the levels of mitochondrial reactive oxygen species (mtROS) and nitrotyrosine formation. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that ROCK1 inhibited pThr172-AMPKα by binding to receptor-interacting serine/threonine kinase 4 (RIPK4). These results suggest that fasudil accelerated wound repair and improved angiogenesis at least partially through the ROCK1/RIPK4/AMPK pathway. Fasudil may be a potential treatment for refractory wounds in diabetic patients.

Synthesis, structural characterization, analytical profiling, and application to authentic samples of synthesized Phase I metabolites of the synthetic cannabinoid 5F-MDMB-PICA.

5F-MDMB-PICA, an indole-type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F-MDMB-PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F-MDMB-PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16. All the compounds were systematic characterized via nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. Furthermore, two methods were developed for the simultaneous detection of all standards using liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. By comparison with authentic samples, R17 was identified as a suitable urine biomarker for 5F-MDMB-PICA uptake.

A Multistate Thermoresponsive Smart Window Based on a Multifunctional Luminescent Solar Concentrator.

Conventional luminescent solar concentrators (LSCs) usually only have the ability to absorb solar energy and convert it to electricity but are not able to regulate the transmitted light. Herein, a multistate thermoresponsive smart window (SW) based on LSC has been fabricated, in which the stimuli-responsive host layer consists of polydimethylsiloxane (PDMS) and ethylene glycol solution (EGS) microdroplets stacking with LSC layer-based on near-infrared (NIR) CuInSe2-xSx/ZnS core/shell quantum dots (QDs) and PDMS matrix. As-synthesized CISSe/ZnS QDs with broad NIR absorption in LSC exhibit controllable emission spectra over 833-1088 nm and high photoluminescence (PL) quantum yield from 45 to 83%. Coupling with Si solar cells as a reference, optimized LSC-SW devices with dimensions of 5 × 5 × 0.9 cm3 exhibit higher power conversion efficiency (PCE) of 1.19-1.36% with increased temperature from 0 to 50 °C than those of sole LSC and SW devices. The corresponding visible light transmissions are regulated from 75.1 to 48.1% accordingly. The improvement of PCEs in an opaque state is mainly due to enhanced absorption of QDs originating from rescattered photons from the EGS/PDMS layer, leading to more emitted photons reaching photovoltaics. This work is expected to bring up new opportunities for applications in greenhouses, building facades, and energy-efficient smart windows.

Neurobiological basis of emergence from anesthesia.

The suppression of consciousness by anesthetics and the emergence of the brain from anesthesia are complex and elusive processes. Anesthetics may exert their inhibitory effects by binding to specific protein targets or through membrane-mediated targets, disrupting neural activity and the integrity and function of neural circuits responsible for signal transmission and conscious perception/subjective experience. Emergence from anesthesia was generally thought to depend on the elimination of the anesthetic from the body. Recently, studies have suggested that emergence from anesthesia is a dynamic and active process that can be partially controlled and is independent of the specific molecular targets of anesthetics. This article summarizes the fundamentals of anesthetics' actions in the brain and the mechanisms of emergence from anesthesia that have been recently revealed in animal studies.