Activation of aryl hydrocarbon receptor (AhR) alleviates depressive-like behaviors in LPS-induced mice.

The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.

Effects of brief mindfulness meditation training on attention and dispositional mindfulness in young adult males.

This study examined the impact of brief mindfulness meditation (BMM) training on attention function and dispositional mindfulness in young males. 126 male participants aged 18-26 from the security industry were recruited, with 66 participants (M = 22.84, SD = 2.41) undergoing 4-week mindfulness meditation training and 60 participants (M = 23.07, SD = 2.29) in the active control group. The intervention was integrated into the participants' schedules. Measures included Five Facets Mindfulness Questionnaires (FFMQ), concentration and assignment attention tasks, Attention Network Test (ANT), and saliva cortisol concentration. Findings indicate that brief mindfulness meditation training led to significant improvements in participants' FFMQ scores), with marginally significant enhancements in the executive control network. However, it had no discernible effect on alertness and orientation networks. Additionally, brief mindfulness meditation training enhanced attention allocation to light stimulation and prolonged individual attention. Surprisingly, there was no observed decrease in saliva cortisol concentration among meditation training participants. However, this study did not find a decrease in saliva cortisol concentration in the brief mindfulness meditation group. In conclusion, this study highlights the potential of a 4-week brief mindfulness meditation training program to enhance dispositional mindfulness and specific aspects of attention function in young men, offering practical insights into the benefits of mindfulness meditation practices for this demographic.

The changes of intestinal flora and its relevance with memory Tfh and B cells in rheumatoid arthritis patients treated with csDMARDs and csDMARDs + bDMARDs.

BACKGROUND: A growing body of experimental and clinical evidence has implicated gut microbiota in the onset and course of rheumatoid arthritis (RA). The imbalance of intestinal flora in RA patients may lead to abnormal expression of immune cells and related cytokines. PURPOSE: Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and conventional synthetic disease-modifying antirheumatic drugs combined with biological disease-modifying antirheumatic drugs (csDMARDs + bDMARDs) are widely used to treat RA, but the characteristics of gut microbiota before and after treatment and their relationship with memory Tfh/B cells and cytokines remain unclear. METHODS: Stool samples were collected from 50 RA patients and 25 healthy controls (HCs) for 16SrRNA gene sequencing. We examined the proportion of lymphocyte subsets in healthy controls and RA patients. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of related cytokines in serum. The α and ß diversity of intestinal flora, and the correlation between intestinal flora and clinical indicators, lymphocyte subsets, cytokines were analyzed. RESULT: At the genus level, Ruminococcaceae_Ruminococcus was decreased in the csDMARDs and csDMARDs + bDMARDs treatment group, whereas Faecalibacterium was reduced in the csDMARDs treatment group, compared to untreated group. CD4+CD45RO+CCR7+CXCR5+central memory Tfh cells and CD4+CD45RO+CCR7-CXCR5+effector memory Tfh cells were significantly lower in the csDMARDs + bDMARDs treatment group than in untreated group. CD19+CD27+IgD+pre-switched memory B cells were higher in the csDMARDs and csDMARDs + bDMARDs treatment groups, whereas CD19+CD27+IgD-switched memory B cells were significantly lower than in untreated group. Ruminococcaceae_Ruminococcus was negatively correlated with CD19+CD27+IgD+ pre-switched memory B cells but positively correlated with CD4+CD45RO+CCR7-CXCR5+effector memory Tfh and CD19+CD27+IgD-switched memory B cells in patients with RA treated with DMARDs. CONCLUSION: The gut microbiota, memory Tfh cells, memory B cells, and cytokines of patients with RA changed significantly under different treatment regimens and had certain correlations with the clinical indicators of RA.

Cool the Inflamed Brain: A Novel Anti-inflammatory Strategy for the Treatment of Major Depressive Disorder.

BACKGROUND: Abundant evidence suggests that inflammatory cytokines contribute to the symptoms of major depressive disorder (MDD) by altering neurotransmission, neuroplasticity, and neuroendocrine processes. Given the unsatisfactory response and remission of monoaminergic antidepressants, anti-inflammatory therapy is proposed as a feasible way to augment the antidepressant effect. Recently, there have been emerging studies investigating the efficiency and efficacy of anti-inflammatory agents in the treatment of MDD and depressive symptoms comorbid with somatic diseases. METHODS: In this narrative review, prospective clinical trials focusing on anti-inflammatory treatment for depression have been comprehensively searched and screened. Based on the included studies, we summarize the rationale for the anti-inflammatory therapy of depression and discuss the utilities and confusions regarding the anti-inflammatory strategy for MDD. RESULTS: This review included over 45 eligible trials. For ease of discussion, we have grouped them into six categories based on their mechanism of action, and added some other anti-inflammatory modalities, including Chinese herbal medicine and non-drug therapy. Pooled results suggest that anti-inflammatory therapy is effective in improving depressive symptoms, whether used as monotherapy or add-on therapy. However, there remain confusions in the application of anti-inflammatory therapy for MDD. CONCLUSION: Based on current clinical evidence, anti-inflammatory therapy is a promisingly effective treatment for depression. This study proposes a novel strategy for clinical diagnosis, disease classification, personalized treatment, and prognostic prediction of depression. Inflammatory biomarkers are recommended to be assessed at the first admission of MDD patients, and anti-inflammatory therapy are recommended to be included in the clinical practice guidelines for diagnosis and treatment. Those patients with high levels of baseline inflammation (e.g., CRP > 3 mg/L) may benefit from adjunctive anti-inflammatory therapy.

Microsphere-Based Microsensor for Miniature Motors' Vibration Measurement.

We present a microsphere-based microsensor that can measure the vibrations of the miniature motor shaft (MMS) in a small space. The microsensor is composed of a stretched fiber and a microsphere with a diameter of 5 µm. When a light source is incident on the microsphere surface, the microsphere induces the phenomenon of photonic nanojet (PNJ), which causes light to pass through the front. The PNJ's full width at half maximum is narrow, surpassing the diffraction limit, enables precise focusing on the MMS surface, and enhances the scattered or reflected light emitted from the MMS surface. With two of the proposed microsensors, the axial and radial vibration of the MMS are measured simultaneously. The performance of the microsensor has been calibrated with a standard vibration source, demonstrating measurement errors of less than 1.5%. The microsensor is expected to be used in a confined space for the vibration measurement of miniature motors in industry.

Significant Strain Dissipation via Stiff-Tough Solid Electrolyte Interphase Design for Highly Stable Alloying Anodes.

The pulverization of alloying anodes significantly restricts their use in lithium-ion batteries (LIBs). This study presents a dual-phase solid electrolyte interphase (SEI) design that incorporates finely dispersed Al nanoparticles within the LiPON matrix. This distinctive dual-phase structure imparts high stiffness and toughness to the integrated SEI film. In comparison to single-phase LiPON film, the optimized Al/LiPON dual-phase SEI film demonstrates a remarkable increase in fracture toughness by 317.8 %, while maintaining stiffness, achieved through the substantial dissipation of strain energy. Application of the dual-phase SEI film on an Al anode leads to a 450 % enhancement in cycling stability for lithium storage in dual-ion batteries. A similar enhancement in cycling stability for silicon anodes, which face severe volume expansion issues, is also observed, demonstrating the broad applicability of the dual-phase SEI design. Specifically, homogeneous Li-Al alloying has been observed in conventional LIBs, even when paired with a high mass loading LiNi0.5 Co0.3 Mn0.2 O2 cathode (7 mg cm-2 ). The dual-phase SEI film design can also accelerate the diffusion kinetics of Li-ions through interface electronic structure regulation. This dual-phase design can integrate stiffness and toughness into a single SEI film, providing a pathway to enhance both the structural stability and rate capability of alloying anodes.

Study on Mass Erosion and Surface Temperature during High-Speed Penetration of Concrete by Projectile Considering Heat Conduction and Thermal Softening.

The mass erosion of the kinetic energy of projectiles penetrating concrete targets at high speed is an important reason for the reduction in penetration efficiency. The heat generation and heat conduction in the projectile are important parts of the theoretical calculation of mass loss. In this paper, theoretical models are established to calculate the mass erosion and heat conduction of projectile noses, including models of cutting, melting, the heat conduction of flash temperature, and the conversion of plastic work into heat. The friction cutting model is modified considering the heat softening of metal, and a model of non-adiabatic processes for the nose was established based on the heat conduction theory to calculate the surface temperature. The coupling numerical calculation of the erosion and heat conduction of the projectile nose shows that melting erosion is the main factor of mass loss at high-speed penetration, and the mass erosion ratio of melting and cutting is related to the initial velocity. Critical velocity without melting erosion and a constant ratio of melting and cutting erosion exists, and the critical velocities are closely related to the melting temperature. In the process of penetration, the thickness of the heat affected zone (HAZ) gradually increases, and the entire heat conduction zone (EHZ) is about 5~6 times the thickness of the HAZ.

Microglial NLRP3 inflammasome activation mediates diabetes-induced depression-like behavior via triggering neuroinflammation.

BACKGROUND: Abundant evidence suggests that the prevalence and risk of depression in people with diabetes is high. However, the pathogenesis of diabetes-related depression remains unclear. Since neuroinflammation is associated with the pathophysiology of diabetic complications and depression, this study aims to elucidate the neuroimmune mechanism of diabetes-related depression. METHODS: Male C57BL/6 mice were injected with streptozotocin to establish a diabetes model. After screening, diabetic mice were treated with the NLRP3 inhibitor MCC950. Then, metabolic indicators and depression-like behaviors were evaluated in these mice, as well as their central and peripheral inflammation. To explore the mechanism of high glucose-induced microglial NLRP3 inflammasome activation, we performed in vitro studies focusing on its canonical upstream signal I (TLR4/MyD88/NF-κB) and signal II (ROS/PKR/P2X7R/TXNIP). RESULTS: Diabetic mice exhibited depression-like behaviors and activation of NLRP3 inflammasome in hippocampus. In vitro high-glucose (50 mM) environment primed microglial NLRP3 inflammasome by promoting NF-κB phosphorylation in a TLR4/MyD88-independent manner. Subsequently, high glucose activated the NLRP3 inflammasome via enhancing intracellular ROS accumulation, upregulating P2X7R, as well as promoting PKR phosphorylation and TXNIP expression, thereby facilitating the production and secretion of IL-1ß. Inhibition of NLRP3 with MCC950 significantly restored hyperglycemia-induced depression-like behavior and reversed the increase in IL-1ß levels in the hippocampus and serum. CONCLUSION: The activation of NLRP3 inflammasome, probably mainly in hippocampal microglia, mediates the development of depression-like behaviors in STZ-induced diabetic mice. Targeting the microglial inflammasome is a feasible strategy for the treatment of diabetes-related depression.

The involvement of NLRP3 inflammasome in CUMS-induced AD-like pathological changes and related cognitive decline in mice.

BACKGROUND: Numerous studies have found that inhibiting the expression of NLRP3 inflammasome can significantly improve depressive-like behaviors in mice, but the research on its effect on cognitive decline in depression and its mechanism is still lacking. This study aimed to elucidate the role of NLRP3 inflammasome in cognitive decline in depression and explore the common neuro-immunological mechanisms of depression and Alzheimer's disease (AD). METHODS: Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) for 5 weeks, treatment group was administered with the NLRP3 inhibitor MCC950 (10 mg/kg, i.p.), fluoxetine served as positive control. Then, the mice were assessed for cognitive behaviors and depression-like behaviors, and changes of microglia and neurons in hippocampus and levels of Aß metabolic pathway and tau protein were measured. To explore the mechanism of NLRP3 activation on neurons, we performed in vitro studies using BV2 microglia and mouse primary neurons. Furthermore, we focused on the role of NLRP3 inflammasome in the function of neurons and the expression of AD pathological indicators. RESULTS: CUMS induced depressive-like behaviors and cognitive decline in mice, which could be reversed by inhibiting NLRP3 inflammasome. MCC950, a specific NLRP3 inhibitor, alleviated CUMS-induced neuron injury and AD-like pathological changes, including the abnormal expression of Aß metabolic pathway and the hyper-phosphorylation of tau protein. LPS (1 µg/mL) + ATP (1 mM) treatment activated the expression of NLRP3 inflammasome and IL-1ß in vitro. In vitro experiment also proved that inhibiting the expression of NLRP3 inflammasome in microglia can restore the Aß metabolic pathway to normal, decrease neuronal tau protein phosphorylation and protect neurons. CONCLUSIONS: Inhibition of NLRP3 inflammasome effectively alleviated CUMS-induced depressive-like behaviors and cognitive decline in mice, and inhibited the activation of AD physiological indicators.

Completely non-invasive cell manipulation in lens-integrated microfluidic devices by single-fiber optical tweezers.

In a fiber-based optical tweezer system, it is a common practice to insert the fiber probe into the sample solution to perform the tweezer function. Such a configuration of the fiber probe may lead to unwanted contamination and/or damage to the sample system and is thus potentially invasive. Here, we propose a completely non-invasive method for cell manipulation by combining a microcapillary microfluidic device and an optical fiber tweezer. We demonstrate that Chlorella cells inside the microcapillary channel can be successfully trapped and manipulated by an optical fiber probe located outside of the microcapillary, thus making the process completely non-invasive. The fiber does not even invade the sample solution. To our knowledge, this is the first report of such a method. The speed of stable manipulation can reach the 7 µm/s scale. We found that the curved walls of the microcapillaries worked like a lens, which helped to boost the light focusing and trapping efficiency. Numerical simulation of optical forces under medium settings reveals that the optical forces can be enhanced by up to 1.44 times, and the optical forces can change direction under certain conditions.

Simultaneous trapping of high and low refractive index particles using a single-fiber optical trap with coexisting LP01 and LP11 modes.

We propose and demonstrate a fiber optical trap based on the coexistence of LP01 and LP11 modes for the simultaneous trapping of both high refractive index particles and low refractive index particles. Since different mode beams have different propagation constants, they exhibit different focused light fields. We fabricated a tapered fiber probe using thermal fusion to converge the beam, which generates a strong gradient force field near the fiber tip, as well as a dark trap along the axial direction. High refractive index particles are attracted near the fiber tip by a strong gradient force, and low refractive index particles are trapped in the dark cage along the axial direction. The proposed optical trap, which can simultaneously trap particles with different refractive indices, makes it easier to manipulate cells or molecules with different properties and explore multi-molecule interactions, which can facilitate research related to biology and chemistry.

The Effect of Brief Mindfulness Meditation on Suicidal Ideation, Stress and Sleep Quality.

OBJECTIVES: Suicide is the fourth leading cause of death for individuals aged 15-29 years, and early intervention on suicidal ideation and risk factors should be priortized. Brief mindfulness meditation (BMM) is convenient and cost-effective in improving physical and mental well-being, but less is known about its efficacy for suicidal ideation, stress and sleep quality. We investigated the effects of BMM on suicidal ideation, stress, and sleep quality for individuals with suicide risk. METHODS: Sixty-four college students with high suicidal ideation (aged 18-30 years) were randomly allocated to either a BMM (n = 32) or control group (n = 32). The BMM was based on Anapanasati and core mindfulness concepts. Sixty participants completed all scheduled sessions including pretest, one month of intervention or waiting, and posttest. Suicidal ideation was measured with the Beck Scale for Suicidal Ideation. Stress was evaluated using the Perceived Stress Scale and salivary cortisol levels. Sleep was measured using the Pittsburgh Sleep Quality Index and actigraphy accompanied with 7-day sleep diaries. RESULTS: Post-intervention, the BMM group showed significant decrease in suicidal ideation with a large effect size; the decrease showed a medium effect size in the control group. The BMM group, but not the control group, showed significant decrease in morning salivary cortisol and sleep latency, and improved sleep efficiency. CONCLUSIONS: BMM could help reduce suicidal ideation, stress, and sleep disturbance for individuals with high suicidal ideation and it may implicate effective suicide prevention strategy.

Association between Sleep and Suicidal Ideation in Chinese Undergraduate Students.

Suicide is an important global public health issue, which deserves more attention. This study aims to examine the relative independent relationship between suicide ideation and subjective sleep quality, sleep hygiene, and insomnia symptoms in undergraduate students in China. This population-based study included 2379 undergraduate students aged 18-26, randomly recruited from three public universities in Shanghai. The participants completed four questionnaires: the Pittsburgh Sleep Quality Index; Sleep Hygiene Practice Scale; Insomnia Severity Index; and the Symptom Checklist 90 (specifically the depression and anxiety dimensions and Q15-suicide ideation). The results of Spearman's correlation analysis indicate that poor sleep quality, short sleep duration, poor sleep hygiene, and insomnia symptoms were all associated with suicidal ideation in undergraduate students. However, according to the results of the hierarchical linear regression, no experience of sharing a bedroom at home, poor relationship with roommates, short sleep duration, sleep medicine use, and good daytime function were related to suicidal ideation, after controlling for the symptoms of depression and anxiety, which may be important in the identification of suicidal ideation. Sleep problems are highly discoverable and modifiable, and have a low sense of shame, therefore, sleep interventions for individuals with suicidal ideation and poor sleep quality may be an efficient and effective approach to suicide prevention.

Microsphere-assisted Fabry-Perot interferometry: proof of concept.

We propose a microsphere-assisted Fabry-Perot interferometry (MAFPI) for microstructure measurement. We stretch the single-mode fiber and combine it with microspheres of different sizes and refractive indices, which can form super-focused spots with different characteristics, that is, a photonic nanojet phenomenon. As a proof of principle, we performed scanning imaging of optical discs and holographic gratings by MAFPI. The optical disc image obtained by MAFPI is consistent with the result obtained by a scanning electron microscope, and the obtained grating image is consistent with the actual result.

Nanovibration detection based on a microsphere.

We propose a novel, to the best of our knowledge, sensor for nanovibration detection based on a microsphere. The sensor consists of a stretched single-mode fiber and a 2 µm microsphere. The light from the optical fiber passes through the microsphere, forming a photonic nanojet (PNJ) phenomenon at the front of the microsphere. The evanescent field in the PNJ enhances the light reflected from the measured object to the single-mode fiber-microsphere probe (SMFMP). Results showed that the system can detect arbitrary nanovibration waveforms in real time with an SMFMP detection resolution of 1 nm. The voltage signal received and the vibration amplitude showed a good linear relationship within the range of 0-100 nm, with a sensitivity of 0.7 mV/nm and a linearity of more than 99%. The sensor is expected to have potential applications in the field of cell nanovibration detection.

Combined Feature Extraction and Random Forest for Laser Self-Mixing Vibration Measurement without Determining Feedback Intensity.

To measure the vibration of a target by laser self-mixing interference (SMI), we propose a method that combines feature extraction and random forest (RF) without determining the feedback strength (C). First, the temporal, spectral, and statistical features of the SMI signal are extracted to characterize the original SMI signal. Secondly, these interpretable features are fed into the pretrained RF model to directly predict the amplitude and frequency (A and f) of the vibrating target, recovering the periodic vibration of the target. The results show that the combination of RF and feature extraction yields a fit of more than 0.94 for simple and quick measurement of A and f of unsmooth planar vibrations, regardless of the feedback intensity and the misalignment of the retromirror. Without a complex optical stage, this method can quickly recover arbitrary periodic vibrations from SMI signals without C, which provides a novel method for quickly implementing vibration measurements.

Childhood Trauma and Suicide: The Mediating Effect of Stress and Sleep.

This study aimed to investigate the relationship between suicide risk, perceived stress, and sleep quality through a structural equation modeling approach. This study used convenience sampling to survey 780 undergraduate and graduate students aged 18-30 years. Students were invited to participate in the online questionnaires, which included the Beck Scale for Suicide Ideation, the Suicidal Behaviors Questionnaire-Revised, the Perceived Stress Scale, the Childhood Trauma Questionnaire-Short Form, and the Pittsburgh Sleep Quality Index. The results showed that suicide ideation and suicidal behavior were positively correlated with childhood trauma, stress, and sleep. A well-fitted structural equation model (χ2 = 1.52, df = 1, χ2/df = 1.52, RMSEA = 0.03, CFI = 1.00, NFI = 1.00) was constructed in this study. The hierarchical regression test showed significance in all the path coefficients of the model. The total effect of emotional abuse on suicide behaviors was 49.5%. The mediating effects accounted for 73.7% of the total effects of emotional abuse on suicidal behaviors. The results demonstrate efforts targeting stress and poor sleep might mitigate the risk of suicidal behaviors among individuals with early emotional abuse experiences.

Unusual Size Effect in Ion and Charge Transport in Micron-Sized Particulate Aluminum Anodes of Lithium-Ion Batteries.

Aluminum is a promising anode material for lithium-ion batteries owing to its high theoretical capacity, excellent conductivity, and natural abundance. An anomalous size effect was observed for micron-sized aluminum powder electrodes in this work. Experimental and theoretical investigations reveal that the insulating oxide surface layer is the underlying cause, which leads to poor electrical conductivity and limited capacity utilization when the particle is too small. Additionally, poor electrolyte wettability also accounts for the hindered reaction kinetics due to the weak polarity feature of the oxide layer. Surface grafting of polar amino groups was demonstrated to be an effective strategy to improve electrolyte wettability. The present work revealed the critical limitations and underlying mechanisms for the aluminum anode, which is crucial for its practical application. Our results are also valuable for other metallic anodes with similar issues.

Animal Models and Pathogenesis of Ulcerative Colitis.

Background: Ulcerative colitis (UC) is a kind of inflammatory bowel disease which is needed to be predicted. Objective: To analyze various animal models of UC conditions and summarizes the animal selection, model progression, and pathogenic mechanisms of UC animal models. Methods: We surveyed the research papers published in PubMed, Google Scholar, Baidu Scholar, CNKI, SciFinder, and Web of Science in the past 5 years and discussed the experimental animals, modeling methods, and pathogenic mechanisms. Results: In the selection of experimental animals, rats are considered the best experimental animals. The mainstream modeling methods can be categorized into the chemical stimulation method, immune stimulation method, and compound method, among which the compound method is the most successful. In the study of the pathogenesis of UC, the pathogenesis of UC is due to various pathogenic factors, such as nitric oxide (NO), prostaglandins (PG), proinflammatory factors (IL, TNF-α), and intestinal flora. Conclusion: The method of building an animal model of UC is well-established, providing a more targeted selection of animal models for future related experiments.

Pinocembrin ameliorates depressive-like behaviors by regulating P2X7/TRL4 receptors expression in mouse hippocampus.

Mounting evidence indicates that immune dysfunction may contribute to the neurobiology of major depressive disorder (MDD). Toll-like receptor 4 (TLR4) and P2X7 receptor (P2X7R) were recently reckoned pivotally to regulate NOD-like receptor protein 3 (NLRP3) in microglia. Pinocembrin, one of the primary flavonoids from Pinus heartwood and Eucalyptus, has been studied in various animal models of human disease with anti-inflammatory and antioxidant activities. Herein, we investigated the potential antineuroinflammatory effects of pinocembrin on chronic unpredictable mild stress (CUMS)-induced depressive-like behavior. Male C57BL/6J mice were subjected to CUMS for 4 weeks, treatment group was injected with pinocembrin at a dose of 20 mg/kg. After the stress procedure, behavioral tests, including sucrose preference tests (SPTs) and tail suspension tests (TSTs) were performed to evaluate depressive-like phenotype. Subsequently, the expression of cytokines and microglia-related inflammatory biomarkers were assessed. In the study, we found that pinocembrin significantly blocked the declination of SPT percentage and the extension of TST immobility durations in the depression mouse model. Also, we observed that pinocembrin significantly suppressed microglial activation in the hippocampus. Additionally, pinocembrin downregulated hippocampal NLRP3 through P2X7/TLR4 pathway, and also regulated the CUMS-induced imbalance of pro-inflammatory cytokines, including interleukin-1beta, tumor necrosis factor-alpha and interleukin-6. In conclusion, pinocembrin ameliorates CUMS-induced depressive-like behaviors possibly through downregulating P2X7/TLR4 pathway, providing the mechanism of antidepressant treatment.