Reactive oxygen/nitrogen species scavenging and inflammatory regulation by renal-targeted bio-inspired rhodium nanozymes for acute kidney injury theranostics.

Acute kidney injury (AKI) results from the rapid deterioration of renal function, which is mainly treated by transplantation and dialysis, and has a high mortality rate. Inflammation induced by excess reactive oxygen/nitrogen species (RONS) plays a crucial role in AKI. Although small molecule antioxidants have been utilized to alleviate AKI, low bioavailability and side-effect of these drugs tremendously limit their clinical use. Hence, we successfully construct ultra-small (2-4 nm) rhodium nanoparticles modified with l-serine (denoted as Rh-Ser). Our results show that Rh-Ser with multiple enzyme-mimicking activities, allows remove various RONS to protect damaged kidney cells. Additionally, the ultrasmall size of Rh-Ser is conducive to enrichment in the renal tubules, and the modification of l-serine enables Rh-Ser to bind to kidney injury molecule-1, which is highly expressed on the surface of damaged renal cells, thereby targeting the damaged kidney and increasing the retention time. Moreover, Rh-Ser allows the production of oxygen at the inflammatory site, thus further improving hypoxia and inhibiting pro-inflammatory macrophages to relieve inflammation, and increasing the survival rate of AKI mice from 0 to 80%, which exhibits a better therapeutic effect than that of small molecule drug. Photoacoustic and fluorescence imaging can effectively monitor and evaluate the enrichment and therapeutic effect of Rh-Ser. Our study provides a promising strategy for the targeted treatment of AKI via RONS scavenging and inflammatory regulation.

rTMS ameliorates depressive-like behaviors and regulates the gut microbiome and medium- and long-chain fatty acids in mice exposed to chronic unpredictable mild stress.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a clinically useful therapy for depression. However, the effects of rTMS on the metabolism of fatty acids (FAs) and the composition of gut microbiota in depression are not well established. METHODS: Mice received rTMS (15 Hz, 1.26 T) for seven consecutive days after exposure to chronic unpredictable mild stress (CUMS). The subsequent depressive-like behaviors, the composition of gut microbiota of stool samples, as well as medium- and long-chain fatty acids (MLCFAs) in the plasma, prefrontal cortex (PFC), and hippocampus (HPC) were evaluated. RESULTS: CUMS induced remarkable changes in gut microbiotas and fatty acids, specifically in community diversity of gut microbiotas and PUFAs in the brain. 15 Hz rTMS treatment alleviates depressive-like behaviors and partially normalized CUMS induced alterations of microbiotas and MLCFAs, especially the abundance of Cyanobacteria, Actinobacteriota, and levels of polyunsaturated fatty acids (PUFAs) in the hippocampus and PFC. CONCLUSION: These findings revealed that the modulation of gut microbiotas and PUFAs metabolism might partly contribute to the antidepressant effect of rTMS.

High-frequency repetitive transcranial magnetic stimulation regulates neural oscillations of the hippocampus and prefrontal cortex in mice by modulating endocannabinoid signalling.

BACKGROUND: Neural oscillations play a role in the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS). However, the effects of high-frequency rTMS on the neural oscillations of the medial prefrontal cortex (mPFC) and hippocampus (HPC) and its molecular mechanism have not been fully clarified. METHODS: The depressive-like behaviours, local field potentials (LFPs) of the ventral HPC (vHPC)-mPFC, and alternations of endocannabinoid system (ECS) in the HPC and mPFC were observed after rTMS treatment. Meanwhile, depressive-like behaviours and LFPs were also observed after cannabinoid type-1 receptor (CB1R) antagonist AM281 or monoacylglycerol lipase inhibitor JZL184 injection. Moreover, the antidepressant effect of rTMS was further assessed in glutamatergic-CB1R and gamma-amino butyric acid (GABA)-ergic -CB1R knockout mice. RESULTS: Alternations of endocannabinoids and energy value and synchronisation of mPFC-vHPC, especially the decrease of theta oscillation induced by CUMS, were alleviated by rTMS. JZL184 has similar effects to rTMS and AM281 blocked the effects of rTMS. GABAergic-CB1R deletion inhibited CUMS-induced depressive-like behaviours whereas Glutaminergic-CB1R deletion dampened the antidepressant effects of rTMS. LIMITATIONS: The immediate effect of rTMS on field-potential regulation was not observed. Moreover, the role of region-specific regulation of the ECS in the antidepressant effect of rTMS was unclear and the effects of cell-specific CB1R knockout on neuronal oscillations of the mPFC and vHPC should be further investigated. CONCLUSION: Endocannabinoid system mediated the antidepressant effects and was involved in the regulation of LFP in the vHPC-mPFC of high-frequency rTMS.

A hypoxia-activated photothermal agent inhibits multiple heat shock proteins for low-temperature photothermal therapy.

A near-infrared (NIR) organic photothermal agent (PTA) to inhibit three types of heat shock proteins (HSPs) was synthesized, which could be activated under hypoxic conditions for low-temperature photothermal therapy (PTT) of cancer.

Multi-stimuli-responsive molecular fluorescent probes for bioapplications.

Stimuli-responsive fluorescent probes have been widely utilized in detecting the physiological and pathological states of living systems. Numerous stimuli-responsive fluorescent probes have been developed due to their advantages of good sensitivity, high resolution, and high contrast fluorescent signals. In this feature article, the progress of multi-stimuli-responsive probes, including organic molecules and metal complexes, for the detection of various biomarkers for bio-applications is summarized. The feature article focuses on the applications of organic-molecule- and metal-complex-based molecular probes in biological systems for detecting different biomarkers of cancer or other diseases. The current challenges and potential future directions of these probes for applications in biological systems are also discussed.

A heat shock protein-inhibiting molecular photothermal agent for mild-temperature photothermal therapy.

A heat shock protein-inhibiting photothermal agent (PTA) with endoplasmic reticulum targeting was synthesized to reduce the thermal resistance and enhance the effect of mild-temperature photothermal therapy (PTT).

Bioimaging agents based on redox-active transition metal complexes.

Detecting the fluctuation and distribution of various bioactive species in biological systems is of great importance in determining diseases at their early stages. Metal complex-based probes have attracted considerable attention in bioimaging applications owing to their unique advantages, such as high luminescence, good photostability, large Stokes shifts, low toxicity, and good biocompatibility. In this review, we summarized the development of redox-active transition metal complex-based probes in recent five years with the metal ions of iron, manganese, and copper, which play essential roles in life and can avoid the introduction of exogenous metals into biological systems. The designing principles that afford these complexes with optical or magnetic resonance (MR) imaging properties are elucidated. The applications of the complexes for bioimaging applications of different bioactive species are demonstrated. The current challenges and potential future directions of these probes for applications in biological systems are also discussed.

Multifunctional Polyurethane Composite Foam with Outstanding Anti-impact Capacity for Soft Body Armors.

Herein, a multifunctional polyurethane (PU) composite foam with a hierarchical structure is fabricated by dip-coating a carbon nanotube/shear-thickening gel (CNT/STG) and spray-coating nano-SiO2/STG on PU foam. The prepared nano-SiO2/CNT/STG@PU (SCS@PU) composite foam is lightweight, highly compressive, electrically conductive, superhydrophobic, and impact-energy absorptive. As a result, it possesses an excellent sensing ability to compression with a stable response up to 80% strain, an outstanding linearity of R2 > 0.99, and a wide response frequency of 0.01 to 1 Hz; it can also be used for effectively detecting impact force and sensing various human motions. Moreover, the superhydrophobicity with a water contact angle up to 154° of SCS@PU composite foam endows it with an excellent resistance to hazardous liquids (strong acid and alkali) to ensure its service reliability under harsh circumstances. In particular, the SCS@PU exhibits an outstanding anti-impact capability with an impact force attenuation rate of SCS@PU as high as 81%. Finally, its applications as soft body armors are demonstrated in protecting a wearer wearing a helmet with the SCS@PU as liner and using the SCS@PU as a smart kneecap against impact. On consideration of its excellent strain-sensing ability, superhydrophobicity, and outstanding anti-impact capability, the multifunctional SCS@PU composite foam developed is promising for personal safety protection.

The Impact of Electroacupuncture Early Intervention on the Brain Lipidome in a Mouse Model of Post-traumatic Stress Disorder.

The neuroprotective effect of electroacupuncture (EA) treatment has been well studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of post-traumatic stress disorder (PTSD) and may be a target for treatment. However, the influence of early EA intervention on brain lipid composition in patients with PTSD has never been investigated. Using a modified single prolonged stress (mSPS) model in mice, we assessed the anti-PTSD-like effects of early intervention using EA and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. mSPS induced changes in lipid composition in the hippocampus, notably in the content of sphingolipids, glycerolipids, and fatty acyls. These lipid changes were more robust than those observed in the PFC. Early intervention with EA after mSPS ameliorated PTSD-like behaviors and partly normalized mSPS-induced lipid changes, notably in the hippocampus. Cumulatively, our data suggest that EA may reverse mSPS-induced PTSD-like behaviors due to region-specific regulation of the brain lipidome, providing new insights into the therapeutic mechanism of EA.

Superstrong, Lightweight, and Exceptional Environmentally Stable SiO2@GO/Bamboo Composites.

Development of lightweight structural materials from fast-growing bamboos is of great significance to building a sustainable society. However, previously developed structural bamboos by delignification combined with densification would easily fail under large external loading after exposure to water due to structure collapse, severely limiting their practical applications. Here, we demonstrate an ultrastrong and exceptional environmentally stable bamboo composite consisting of a graphene oxide (GO)/bamboo core and hierarchical SiO2 protection layer. The GO/bamboo composite exhibits ultrahigh tensile strength (641.6 MPa), superb flexural strength (428.4 MPa), and excellent toughness (17.5 MJ/m3), which are increased by about 480, 250, and 360% compared with natural bamboo, respectively. As a result, the specific tensile strength of the GO/bamboo composite is up to 513.3 MPa·cm3/g due to its low density (1.25 g/cm3), outperforming engineering structural materials such as aluminum alloys, steels, and titanium alloys. These large improvements benefit from the well-preserved bamboo scaffold and the strong hydrogen bonds between bamboo fibers and GO nanosheets. On the other hand, the SiO2@GO/bamboo composite shows superhydrophobicity due to the construction of hierarchical SiO2 layers, which endows it with outstanding water resistance. Moreover, the bamboo composite shows an ultralow coefficient of thermal expansion (≈2.3 × 10-6 K-1), indicating its excellent dimensional stability. Considering the ultrahigh mechanical performance and outstanding environmental stability, the developed lightweight SiO2@GO/bamboo composite is hopeful to be a green and sustainable structural material for practical engineering applications.

Comparative analysis of the quantitative parameter method and elasticity color mode method for real-time shear wave elastography in the diagnosis of benign and malignant solid breast lesions.

OBJECTIVE: To examine the performance of real-time shear wave elastography (RT-SWE) in routine clinical practice. METHODS: This was a prospective study of 500 patients. The elasticity color mode method was judged by a four-mode system. The quantitative parameter method was used to measure the modulus of elasticity of the lesions. Pathologic reports were used as a gold standard to comparatively analyze the diagnostic performance of the two methods. RESULTS: A total of 553 tumors were detected. The average mode value and the modulus of elasticity (Emax) of the benign breast masses was lower than that of malignant masses (p < 0.05). With Emax = 67.4 as the diagnostic threshold value, the sensitivity, specificity, accuracy, negative predictive value, and positive predictive value of the two methods were not statistically significant different (p > 0.05). CONCLUSIONS: The shear wave quantitative parameter method and the elasticity color mode method showed similar performances in the diagnosis of benign and malignant breast masses. The elasticity color mode method is convenient and intuitive, whereas the quantitative parameter method can be used to objectively assess the lesions when it is difficult to score the elasticity of an image, but could not be relied on alone.

One-Step Synthesis of Microdome Patterns for Microstructured Pressure Sensors with Ultra-High Sensing Performance.

Pressure sensors usually suffer from a trade-off between sensitivity and the linear sensing range, which may be improved by manipulating the geometric microstructure of active sensing materials via the molding strategy, standard photolithography technique, and so on. However, these conventional microengineering techniques require specialized equipment, which are extremely complicated, high-cost, and time-consuming to manufacture. Herein, a mold-free, scalable, low-cost, and environment-friendly one-step thermofoaming strategy is proposed to fabricate surface morphology-tunable microdome-patterned composites (MPCs). The microstructured pressure sensor is then prepared by coating the MPCs with highly conductive graphene. Remarkably, the as-prepared pressure sensor presents a better overall sensing performance compared to the previous pressure sensors prepared using complicated microengineering methods. Moreover, an electromechanical response model and finite-element analysis are used to clarify the sensing mechanisms of the present microstructured pressure sensor. Furthermore, several successful application demonstrations are conducted under various pressure levels. Considering the advantages of the one-step fabrication strategy over conventional surface microengineering techniques and the high performance of the microstructured pressure sensor, the present pressure sensor has promising potential applications in health monitoring, tactile sensation, wearable devices, etc.

Stimuli-activated molecular photothermal agents for cancer therapy.

Taking advantage of activatable and imaging-guided properties, stimuli-activated molecular photothermal agents (MPTAs) have drawn great attention in photothermal therapy (PTT) over the past decades. In this review, the recent progress in the study of stimuli-activated MPTAs is summarized from different stimuli, including pH, bioactive small molecules, and enzymes. The features and challenges of stimuli-activated MPTAs are also discussed. This review aims to motivate readers to design and synthesise more efficient MPTAs.

C16, a novel sinomenine derivatives, promoted macrophage reprogramming toward M2-like phenotype and protected mice from endotoxemia.

Macrophage plays a critical part in host defense, tissue repair, and anti-inflammation; Macrophage reprogramming is responsible for disease development or regression. We aimed to clarify the effect of sinomenine-4-hydroxy-palmitate (C16), on macrophage reprogramming and anti-inflammatory in endotoxemia model. According to a structure modification of SIN (Sinomenine), C16 was found. Then, based on the endotoxin model, the mice liver and kidney toxicity was evaluated and serum cytokines level of IL-6 (Interleukin-6), TNF-α (Tumor necrosis factor-α), and IL-1ß (Interleukin-1ß) were measured by ELISA (Enzyme linked immunosorbent assay). Then, we confirmed the effect of C16 on macrophages reprogramming, we used the flow cytometry to test the effect of C16 on macrophages apoptosis in vitro. Then, iNOS (Inducible nitric oxide synthase), M1-type related cytokines, such as IL-1ß, TNF-α, and M2-type related cytokines, such as Arg-1 (Arginase-1), CD206, Fizz1, and Ym1 was detected, which expressed in ANA-1 and primary peritoneal macrophages. To further explore the molecular mechanism of C16 in reprogramming of macrophages from M1 toward M2 phenotype, the expression of STAT1 (signal transducer and activator of Transcription 1), STAT3, ERK1/2 (extracellular signal regulated kinase1/2), AKT, p38, and its corresponding phosphorylation were determined by western blot. Our results demonstrated that C16 improved the survival rate of LPS- (lipopolysaccharide) challenged mice and decreased the inflammatory cytokines expression; After C16 treatment, the expression of M1 phenotype correlation factors decreased significantly, while the expression of M2 phenotype correlation factors increased significantly at different levels compared with normal group. It indicated that C16 reprogram macrophages phenotype from M1 toward M2 following LPS stimulus. Furthermore, the results also showed that C16 showed anti-inflammatory effect by inhibiting LPS-induced p38, AKT and STAT1 phosphorylation and contributing ERK1/2 activation. C16 promoted macrophage reprogramming toward M2-like phenotype via p-p38/p-AKT or STAT1 signals pathway and C16 might be a valid candidate for inflammatory disease.

Ligand Architecture Perturbation Influences the Reactivity of Nonheme Iron(V)-Oxo Tetraamido Macrocyclic Ligand Complexes: A Combined Experimental and Theoretical Study.

Iron(V)-oxo complexes bearing negatively charged tetraamido macrocyclic ligands (TAMLs) have provided excellent opportunities to investigate the chemical properties and the mechanisms of oxidation reactions of mononuclear nonheme iron(V)-oxo intermediates. Herein, we report the differences in chemical properties and reactivities of two iron(V)-oxo TAML complexes differing by modification on the "Head" part of the TAML framework; one has a phenyl group at the "Head" part (1), whereas the other has four methyl groups replacing the phenyl ring (2). The reactivities of 1 and 2 in both C-H bond activation reactions, such as hydrogen atom transfer (HAT) of 1,4-cyclohexadiene, and oxygen atom transfer (OAT) reactions, such as the oxidation of thioanisole and its derivatives, were compared experimentally. Under identical reaction conditions, 1 showed much greater reactivity than 2, such as a 102-fold decrease in HAT and a 105-fold decrease in OAT by replacing the phenyl group (i.e., 1) with four methyl groups (i.e., 2). Then, density functional theory calculations were performed to rationalize the reactivity differences between 1 and 2. Computations reproduced the experimental findings well and revealed that the replacement of the phenyl group in 1 with four methyl groups in 2 not only increased the steric hindrance but also enlarged the energy gap between the electron-donating orbital and the electron-accepting orbital. These two factors, steric hindrance and the orbital energy gap, resulted in differences in the reduction potentials of 1 and 2 and their reactivities in oxidation reactions.

The impact of quetiapine on the brain lipidome in a cuprizone-induced mouse model of schizophrenia.

The antipsychotic effect of Quetiapine (Que) has been extensively studied and growing evidence suggests that Que has a beneficial effect, improving cognitive functions and promoting myelin repair. However, the effects of Que on the brain lipidome and the association between Que-associated cognitive improvement and changes in lipids remain elusive. In the present study, we assessed the cognitive protective effects of Que treatment and used a mass spectrometry-based lipidomic approach to evaluated changes in lipid composition in the hippocampus, prefrontal cortex (PFC), and striatum in a mouse model of cuprizone (CPZ)-induced demyelination. CPZ induces cognitive impairment and remarkable lipid changes in the brain, specifically in lipid species of glycerophospholipids and sphingolipids. Moreover, the changes in lipid classes of the PFC were more extensive than those observed in the hippocampus and striatum. Notably, Que treatment ameliorated cuprizone-induced cognitive impairment and partly normalized CPZ-induced lipid changes. Taken together, our data suggest that Que may rescue cognitive behavioral changes from CPZ-induced demyelination through modulation of the brain lipidome, providing new insights into the pharmacological mechanism of Que for schizophrenia.

Enhanced Redox Reactivity of a Nonheme Iron(V)-Oxo Complex Binding Proton.

Acid effects on the chemical properties of metal-oxygen intermediates have attracted much attention recently, such as the enhanced reactivity of high-valent metal(IV)-oxo species by binding proton(s) or Lewis acidic metal ion(s) in redox reactions. Herein, we report for the first time the proton effects of an iron(V)-oxo complex bearing a negatively charged tetraamido macrocyclic ligand (TAML) in oxygen atom transfer (OAT) and electron-transfer (ET) reactions. First, we synthesized and characterized a mononuclear nonheme Fe(V)-oxo TAML complex (1) and its protonated iron(V)-oxo complexes binding two and three protons, which are denoted as 2 and 3, respectively. The protons were found to bind to the TAML ligand of the Fe(V)-oxo species based on spectroscopic characterization, such as resonance Raman, extended X-ray absorption fine structure (EXAFS), and electron paramagnetic resonance (EPR) measurements, along with density functional theory (DFT) calculations. The two-protons binding constant of 1 to produce 2 and the third protonation constant of 2 to produce 3 were determined to be 8.0(7) × 108 M-2 and 10(1) M-1, respectively. The reactivities of the proton-bound iron(V)-oxo complexes were investigated in OAT and ET reactions, showing a dramatic increase in the rate of sulfoxidation of thioanisole derivatives, such as 107 times increase in reactivity when the oxidation of p-CN-thioanisole by 1 was performed in the presence of HOTf (i.e., 200 mM). The one-electron reduction potential of 2 (Ered vs SCE = 0.97 V) was significantly shifted to the positive direction, compared to that of 1 (Ered vs SCE = 0.33 V). Upon further addition of a proton to a solution of 2, a more positive shift of the Ered value was observed with a slope of 47 mV/log([HOTf]). The sulfoxidation of thioanisole derivatives by 2 was shown to proceed via ET from thioanisoles to 2 or direct OAT from 2 to thioanisoles, depending on the ET driving force.

The impact of repetitive transcranial magnetic stimulation and fluoxetine on the brain lipidome in a rat model of chronic unpredictable stress.

The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) has been extensively studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of depression and may be a targeted mechanism for treatment. However, the influence of rTMS on lipid composition and the differences between these effects compared to antidepressants like fluoxetine (Flx) have never been investigated. Using a chronic unpredictable stress (CUS) model in rats, we assessed the antidepressive effects of rTMS and Flx treatments and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. Both rTMS and Flx treatments ameliorated depressive-like behaviors induced by CUS. Moreover, changes in lipid composition, especially glycerophospholipids, sphingolipids, and glycerolipids induced by CUS in the hippocampus were more robust than those observed in the PFC. CUS led to decreased levels of 20 carbon-containing fatty acyls and polyunsaturated fatty acyls in the PFC, and decreased levels of acyl carnitines (AcCa) in both the hippocampus and PFC. Notably, rTMS treatment had higher impact than Flx on composition of glycerophospholipids and sphingolipids in the hippocampus that were altered by CUS, while Flx attenuated CUS-induced changes in the PFC to a greater extent than rTMS. However, neither was able to restore fatty acyls and AcCa to baseline levels. Altogether, modulation of the brain lipidome may be involved in the antidepressant action of rTMS and Flx, and the degree to which these treatments induce changes in lipid composition within the hippocampus and PFC might explain their differential antidepressant effects.

Suggested amendment of TI-RADS classification of thyroid nodules by shear wave elastography.

BACKGROUND: The application of the ultrasound elastography and Thyroid Imaging Reporting and Data System (TI-RADS) classification further expands the scope of ultrasound differential diagnosis between benign and malignant thyroid nodules. PURPOSE: To investigate the value of the quantitative parameter of ultrasonic shear waves in optimizing the TI-RADS classification of thyroid nodules. MATERIAL AND METHODS: A total of 168 thyroid nodules, initially classified using TI-RADS and scanned by shear wave elastography (SWE), were retrospectively analyzed. All cases were diagnosed by fine needle aspiration and histology following surgery. RESULTS: The benign rate of TI-RADS 3 nodules was 76.5%, while the benign rate of TI-RADS 4a nodules was 71.7%. Furthermore, the malignant rate of TI-RADS 4b nodules was 69.7%, while the malignant rate of TI-RADS 4c nodules was 85.7%. In differentiating benign from malignant nodules, the combination of TI-RADS classification and Emean had the largest area under the receiver operating characteristic curve (AUC). Using an Emean value of 42.25 kpa as the cut-off point, the malignant rate of TI-RADS 4a nodules decreased from 28.3% to 23.5%, while the malignant rate of TI-RADS 4b nodules increased from 69.7% to 79.4%. Compared to conventional ultrasound alone, the sensitivity, negative predictive value, and AUC of conventional ultrasound combined with SWE in the diagnosis of benign and malignant thyroid nodules significantly improved (P=0.012, 0.029, 0.001). CONCLUSION: The SWE technique can be used to further determine the benign and malignant nature of TI-RADS 4 lesions, providing further reference for the choice of clinical treatment. The TI-RADS classification system corrected by SWE is more significant in the diagnosis of benign and malignant thyroid nodules.

Electroacupuncture Pretreatment Ameliorates PTSD-Like Behaviors in Rats by Enhancing Hippocampal Neurogenesis via the Keap1/Nrf2 Antioxidant Signaling Pathway.

Electroacupuncture (EA) pretreatment is a clinically useful therapy for several brain disorders. However, whether and via which exact molecular mechanisms it ameliorates post-traumatic stress disorder (PTSD) remains unclear. In the present study, rats received EA stimulation for seven consecutive days before exposure to enhanced single prolonged stress (ESPS). Anxiety-like and fear learning behaviors; hippocampal neurogenesis; the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (keap1), and heme oxygenase 1 (HO-1); and the activity of AMP-activated kinase (AMPK) were evaluated at 14 days after ESPS. EA pretreatment improved hippocampal neurogenesis and ameliorated anxiety-like behaviors in ESPS-treated rats. EA pretreatment also increased the expression of Nrf2 and HO-1 and the activity of AMPK. Furthermore, Nrf2 knockdown by a short hairpin RNA affected anxiety-like behaviors and expression of neuroprotective markers (BDNF, DCX) in a manner similar to ESPS alone and dampened the neuroprotective effects of EA pretreatment. In contrast, Keap1 knockdown increased the expression of HO-1, improved hippocampal neurogenesis, and alleviated PTSD-like behaviors. Altogether, our results suggest that EA pretreatment ameliorates ESPS-induced anxiety-like behaviors and prevents hippocampal neurogenesis disruption in a rat model of PTSD possibly through regulation of the keap1/Nrf2 antioxidant defense pathway.