Effects of Phasic Activation of Locus Ceruleus on Cortical Neural Activity and Auditory Discrimination Behavior.

Although the locus ceruleus (LC) is recognized as a crucial modulator for attention and perception by releasing norepinephrine into various cortical regions, the impact of LC-noradrenergic (LC-NE) modulation on auditory discrimination behavior remains elusive. In this study, we firstly recorded local field potential and single-unit activity in multiple cortical regions associated with auditory-motor processing, including the auditory cortex, posterior parietal cortex, secondary motor cortex, anterior cingulate cortex, prefrontal cortex, and orbitofrontal cortex (OFC), in response to optogenetic activation (40 Hz and 0.5 s) of the LC-NE neurons in awake mice (male). We found that phasic LC stimulation induced a persistent high gamma oscillation (50-80 Hz) in the OFC. Phasic activation of LC-NE neurons also resulted in a corresponding increase in norepinephrine levels in the OFC, accompanied by a pupillary dilation response. Furthermore, when mice were performing a go/no-go auditory discrimination task, we optogeneticaly activated the neural projections from LC to OFC and revealed a shortened latency in behavioral responses to sound stimuli and an increased false alarm rate. These impulsive behavioral responses may be associated with the gamma neural activity in the OFC. These findings have broadened our understanding of the neural mechanisms involved in the role of LC in auditory-motor processing.

The Thalamocortical Mechanism Underlying the Generation and Regulation of the Auditory Steady-State Responses in Awake Mice.

The auditory steady-state response (ASSR) is a cortical oscillation induced by trains of 40 Hz acoustic stimuli. While the ASSR has been widely used in clinic measurement, the underlying neural mechanism remains poorly understood. In this study, we investigated the contribution of different stages of auditory thalamocortical pathway-medial geniculate body (MGB), thalamic reticular nucleus (TRN), and auditory cortex (AC)-to the generation and regulation of 40 Hz ASSR in C57BL/6 mice of both sexes. We found that the neural response synchronizing to 40 Hz sound stimuli was most prominent in the GABAergic neurons in the granular layer of AC and the ventral division of MGB (MGBv), which were regulated by optogenetic manipulation of TRN neurons. Behavioral experiments confirmed that disrupting TRN activity has a detrimental effect on the ability of mice to discriminate 40 Hz sounds. These findings revealed a thalamocortical mechanism helpful to interpret the results of clinical ASSR examinations.Significance Statement Our study contributes to clarifying the thalamocortical mechanisms underlying the generation and regulation of the auditory steady-state response (ASSR), which is commonly used in both clinical and neuroscience research to assess the integrity of auditory function. Combining a series of electrophysiological and optogenetic experiments, we demonstrate that the generation of cortical ASSR is dependent on the lemniscal thalamocortical projections originating from the ventral division of medial geniculate body to the GABAergic interneurons in the granule layer of the auditory cortex. Furthermore, the thalamocortical process for ASSR is strictly regulated by the activity of thalamic reticular nucleus (TRN) neurons. Behavioral experiments confirmed that dysfunction of TRN would cause a disruption of mice's behavioral performance in the auditory discrimination task.

RPEMHC: improved prediction of MHC-peptide binding affinity by a deep learning approach based on residue-residue pair encoding.

MOTIVATION: Binding of peptides to major histocompatibility complex (MHC) molecules plays a crucial role in triggering T cell recognition mechanisms essential for immune response. Accurate prediction of MHC-peptide binding is vital for the development of cancer therapeutic vaccines. While recent deep learning-based methods have achieved significant performance in predicting MHC-peptide binding affinity, most of them separately encode MHC molecules and peptides as inputs, potentially overlooking critical interaction information between the two. RESULTS: In this work, we propose RPEMHC, a new deep learning approach based on residue-residue pair encoding to predict the binding affinity between peptides and MHC, which encode an MHC molecule and a peptide as a residue-residue pair map. We evaluate the performance of RPEMHC on various MHC-II-related datasets for MHC-peptide binding prediction, demonstrating that RPEMHC achieves better or comparable performance against other state-of-the-art baselines. Moreover, we further construct experiments on MHC-I-related datasets, and experimental results demonstrate that our method can work on both two MHC classes. These extensive validations have manifested that RPEMHC is an effective tool for studying MHC-peptide interactions and can potentially facilitate the vaccine development. AVAILABILITY: The source code of the method along with trained models is freely available at https://github.com/lennylv/RPEMHC.

Triboelectric Spectroscopy for In Situ Chemical Analysis of Liquids.

Chemical analysis of ions and small organic molecules in liquid samples is crucial for applications in chemistry, biology, environmental sciences, and health monitoring. Mainstream electrochemical and chromatographic techniques often suffer from complex and lengthy sample preparation and testing procedures and require either bulky or expensive instrumentation. Here, we combine triboelectrification and charge transfer on the surface of electrical insulators to demonstrate the concept of triboelectric spectroscopy (TES) for chemical analysis. As a drop of the liquid sample slides along an insulating reclined plane, the local triboelectrification of the surface is recorded, and the charge pattern along the sample trajectory is used to build a fingerprinting of the charge transfer spectroscopy. Chemical information extracted from the charge transfer pattern enables a new nondestructive and ultrafast (<1 s) tool for chemical analysis. TES profiles are unique, and through an automated identification, it is possible to match against standard and hence detect over 30 types of common salts, acids, bases and organic molecules. The qualitative and quantitative accuracies of the TES methodology is close to 93%, and the detection limit is as low as ppb levels. Instruments for TES chemical analysis are portable and can be further miniaturized, opening a path to in situ and rapid chemical detection relying on inexpensive, portable low-tech instrumentation.

Biosynthesis of Octacosamicin A: Uncommon Starter/extender Units and Product Releasing via Intermolecular Amidation.

Octacosamicin A is an antifungal metabolite featuring a linear polyene-polyol chain flanked by N-hydroxyguanidine and glycine moieties. We report here that sub-inhibitory concentrations of streptomycin elicited the production of octacosamicin A in Amycolatopsis azurea DSM 43854T . We identified the biosynthetic gene cluster (oca BGC) that encodes a modular polyketide synthase (PKS) system for assembling the polyene-polyol chain of octacosamicin A. Our analysis suggested that the N-hydroxyguanidine unit originates from a 4-guanidinobutyryl-CoA starter unit, while the PKS incorporates an α-hydroxyketone moiety using a (2R)-hydroxymalonyl-CoA extender unit. The modular PKS system contains a non-canonical terminal module that lacks thioesterase (TE) and acyl carrier protein (ACP) domains, indicating the biosynthesis is likely to employ an unconventional and cryptic off-loading mechanism that attaches glycine to the polyene-polyol chain via an intermolecular amidation reaction.

CAPLA: improved prediction of protein-ligand binding affinity by a deep learning approach based on a cross-attention mechanism.

MOTIVATION: Accurate and rapid prediction of protein-ligand binding affinity is a great challenge currently encountered in drug discovery. Recent advances have manifested a promising alternative in applying deep learning-based computational approaches for accurately quantifying binding affinity. The structure complementarity between protein-binding pocket and ligand has a great effect on the binding strength between a protein and a ligand, but most of existing deep learning approaches usually extracted the features of pocket and ligand by these two detached modules. RESULTS: In this work, a new deep learning approach based on the cross-attention mechanism named CAPLA was developed for improved prediction of protein-ligand binding affinity by learning features from sequence-level information of both protein and ligand. Specifically, CAPLA employs the cross-attention mechanism to capture the mutual effect of protein-binding pocket and ligand. We evaluated the performance of our proposed CAPLA on comprehensive benchmarking experiments on binding affinity prediction, demonstrating the superior performance of CAPLA over state-of-the-art baseline approaches. Moreover, we provided the interpretability for CAPLA to uncover critical functional residues that contribute most to the binding affinity through the analysis of the attention scores generated by the cross-attention mechanism. Consequently, these results indicate that CAPLA is an effective approach for binding affinity prediction and may contribute to useful help for further consequent applications. AVAILABILITY AND IMPLEMENTATION: The source code of the method along with trained models is freely available at https://github.com/lennylv/CAPLA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Research on optical performance of Ln2O2S:Er3+/Yb3+ (Ln = La/Gd/Y) phosphors based on different phonon energies.

It is crucial to explore the intrinsic mechanisms that influence thermometric sensitivity. This study investigates the optical performance of materials with the same crystal structure but different phonon energies. Ln2O2S:Er3+/Yb3+ (Ln = La/Gd/Y) phosphors with similar morphology and particle sizes were prepared to systematically study the influence of different phonon energy matrices on optical properties. The intrinsic mechanism was elucidated through the matching degree between the energy gap and phonon energy, Judd-Ofelt (J-O) theory, and quantum dielectric theory. It was ultimately concluded that the combination of high phonon energy with a large Ω2 and a small Ω6 is beneficial for enhancing the sensitivity of temperature sensing materials.

A gene-based score for the risk stratification of stage IA lung adenocarcinoma.

OBJECTIVE: We aim to molecularly stratify stage IA lung adenocarcinoma (LUAD) for precision medicine. METHODS: Twelve multi-institution datasets (837 cases of IA) were used to classify the high- and low-risk types (based on survival status within 5 years), and the biological differences were compared. Then, a gene-based classifying score (IA score) was trained, tested and validated by several machine learning methods. Furthermore, we estimated the significance of the IA score in the prognostic assessment, chemotherapy prediction and risk stratification of stage IA LUAD. We also developed an R package for the clinical application. The SEER database (15708 IA samples) and TCGA Pan-Cancer (1881 stage I samples) database were used to verify clinical significance. RESULTS: Compared with the low-risk group, the high-risk group of stage IA LUAD has obvious enrichment of the malignant pathway and more driver mutations and copy number variations. The effect of the IA score on the classification of high- and low-risk stage IA LUAD was much better than that of classical clinicopathological factors (training set: AUC = 0.9, validation set: AUC = 0.7). The IA score can significantly predict the prognosis of stage IA LUAD and has a prognostic effect for stage I pancancer. The IA score can effectively predict chemotherapy sensitivity and occult metastasis or invasion in stage IA LUAD. The R package IAExpSuv has a good risk probability prediction effect for both groups and single stages of IA LUAD. CONCLUSIONS: The IA score can effectively stratify the risk of stage IA LUAD, offering good assistance in precision medicine.

Repeated postnatal sevoflurane exposure impairs social recognition in mice by disrupting GABAergic neuronal activity and development in hippocampus.

BACKGROUND: Repeated exposure to sevoflurane during early developmental stages is a risk factor for social behavioural disorders, but the underlying neuropathological mechanisms remain unclear. As the hippocampal cornu ammonis area 2 subregion (CA2) is a critical centre for social cognitive functions, we hypothesised that sevoflurane exposure can lead to social behavioural disorders by disrupting neuronal activity in the CA2. METHODS: Neonatal mice were anaesthetised with sevoflurane 3 vol% for 2 h on postnatal day (PND) 6, 8, and 10. Bulk RNA sequencing of CA2 tissue was conducted on PND 12. Social cognitive function was assessed by behavioural experiments, and in vivo CA2 neuronal activity was recorded by multi-channel electrodes on PND 60-65. RESULTS: Repeated postnatal exposure to sevoflurane impaired social novelty recognition in adulthood. It also caused a decrease in the synchronisation of neuronal spiking, gamma oscillation power, and spike phase-locking between GABAergic spiking and gamma oscillations in the CA2 during social interaction. After sevoflurane exposure, we observed a reduction in the density and dendritic complexity of CA2 GABAergic neurones, and decreased expression of transcription factors critical for GABAergic neuronal development after. CONCLUSIONS: Repeated postnatal exposure to sevoflurane disturbed the development of CA2 GABAergic neurones through downregulation of essential transcription factors. This resulted in impaired electrophysiological function in adult GABAergic neurones, leading to social recognition deficits. These findings reveal a potential electrophysiological mechanism underlying the long-term social recognition deficits induced by sevoflurane and highlight the crucial role of CA2 GABAergic neurones in social interactions.

Cortical and thalamic modulation of auditory gating in the posterior parietal cortex of awake mice.

Auditory gating (AG) is an adaptive mechanism for filtering out redundant acoustic stimuli to protect the brain against information overload. AG deficits have been found in many mental illnesses, including schizophrenia (SZ). However, the neural correlates of AG remain poorly understood. Here, we found that the posterior parietal cortex (PPC) shows an intermediate level of AG in auditory thalamocortical circuits, with a laminar profile in which the strongest AG is in the granular layer. Furthermore, AG of the PPC was decreased and increased by optogenetic inactivation of the medial dorsal thalamic nucleus (MD) and auditory cortex (AC), respectively. Optogenetically activating the axons from the MD and AC drove neural activities in the PPC without an obvious AG. These results indicated that AG in the PPC is determined by the integrated signal streams from the MD and AC in a bottom-up manner. We also found that a mouse model of SZ (postnatal administration of noncompetitive N-methyl-d-aspartate receptor antagonist) presented an AG deficit in the PPC, which may be inherited from the dysfunction of MD. Together, our findings reveal a neural circuit underlying the generation of AG in the PPC and its involvement in the AG deficit of SZ.

Melatonin intervention to prevent nanomaterial exposure-induced damages: A systematic review and meta-analysis of in vitro and in vivo studies.

Given its antioxidant, anti-inflammatory, and antiapoptotic properties, melatonin (MEL), a health-caring food to improve sleep disorders, is hypothesized to protect against nanomaterial exposure-induced toxicity. However, the conclusion derived from different studies seemed inconsistent. A meta-analysis of all available preclinical studies was performed to examine the effects of MEL on nanomaterial-induced damages. Eighteen relevant studies were retrieved through searching five electronic databases up to December 2023. The meta-analysis showed that relative to control, MEL treatment significantly increased cell viability (standardized mean difference [SMD = 1.27]) and alleviated liver function (lowered AST [SMD = -3.89] and ALT [SMD = -5.89]), bone formation (enhanced BV/TV [SMD = 4.13] and lessened eroded bone surface [SMD = -5.40]), and brain nerve (inhibition of AChE activity [SMD = -3.60]) damages in animals. The protective mechanisms of MEL against damages caused by nanomaterial exposure were associated with its antiapoptotic (decreased Bax/Bcl-2 ratio [SMD = -4.50] and caspase-3 levels [dose <100 µM: SMD = -3.66]), antioxidant (decreased MDA [in vitro: SMD = -2.84; in vivo: SMD = -4.27]), and anti-inflammatory (downregulated TNF-α [in vitro: SMD = -5.41; in vivo: SMD = -3.21] and IL-6 [in vitro: SMD = -5.90; in vivo: SMD = -2.81]) capabilities. In conclusion, our study suggests that MEL should be supplemented to prevent damages in populations exposed to nanomaterials.

Effect of a Nursing Health Education Model Based on the Rosenthal Effect on Posttraumatic Growth of Patients with a First Accidental Fracture.

Objective: To investigate the effect of a nursing health education model based on the Rosenthal effect on the posttraumatic growth of patients with a first accidental fracture. Methods: We recruited 212 patients with a first accidental fracture from February 2021 to February 2022; the patients were divided into a control group (n = 106) and an Rosenthal Group (n = 106). The control group received daily care during hospitalization, and the Rosenthal Group received treatment based on a Rosenthal effect health education model. We compared the 2 groups before and after treatment using the Chinese Posttraumatic Growth Inventory (C-PTGI), the Connor-Davidson Resilience Scale (CD-RISC), the Pittsburgh Sleep Quality Index (PSQI), a Visual Analog Scale (VAS) to assess pain, the 36-item Short Form Health Survey (SF-36) to assess quality of life, the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD). Results: The psychological resilience of both groups of patients improved after treatment, as assessed by C-PTGI and CD-RISC (all P < .05), and the Rosenthal Group improved more than the control group after treatment (all P < .05). The sleep quality and pain scores, as measured by PSQI and VAS, improved for both groups of patients after treatment, and the Rosenthal group improved more than the control group after treatment (all P < .05). The quality of life, as assessed by SF-36, of both groups of patients was similar before treatment (all P > .05) and improved significantly after treatment (all P < .05). The patients' depression and anxiety, as assessed by HAMA and HAMD, improved in both groups after treatment (all P < .05), and the Rosenthal group improved more than the control group after treatment (all P < .05). Conclusion: The Rosenthal effect nursing health education model promotes the posttraumatic psychological growth of patients with a first accidental fracture and enhances their psychological resilience, showing that the Rosenthal effect has important health benefits and can be promoted for clinical application to adjust a patient's psychological state.

Effect of GnRH agonist trigger with or without low-dose hCG on reproductive outcomes for PCOS women with freeze-all strategy: a propensity score matching study.

PURPOSE: This study aimed to compare the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone versus dual trigger comprising GnRHa and low-dose human chorionic gonadotropin (hCG) on reproductive outcomes in patients with polycystic ovary syndrome (PCOS) who received the freeze-all strategy. METHODS: A total of 615 cycles were included in this retrospective cohort study. Propensity score matching (PSM) was performed to control potential confounding factors between GnRHa-trigger group (0.2 mg GnRHa) and dual-trigger group (0.2 mg GnRHa plus 1000/2000 IU hCG) in a 1:1 ratio. Multivariate logistic regression was applied to estimate the association between trigger methods and reproductive outcomes. RESULTS: After PSM, patients with dual trigger (n = 176) had more oocytes retrieved, mature oocytes, and 2PN embryos compared to that with GnRHa trigger alone. However, the oocytes maturation rate, normal fertilization rate, and frozen embryos between the two groups were not statistically different. The incidence of ovarian hyperstimulation syndrome (OHSS) (14.8% vs. 2.8%, P < 0.001) and moderate/severe OHSS (11.4% vs. 1.7%, P < 0.001) were significantly higher in dual-trigger group than in GnRHa-alone group. Logistic regression analysis showed the adjusted odds ratio of dual trigger was 5.971 (95% confidence interval 2.201-16.198, P < 0.001) for OHSS. The pregnancy and single neonatal outcomes were comparable between the two groups (P > 0.05). CONCLUSION: For PCOS women with freeze-all strategy, GnRHa trigger alone decreased the risk of OHSS without damaging oocyte maturation and achieved satisfactory pregnancy outcomes.

Visible Light Motivated the Photocatalytic Degradation of P-Nitrophenol by Ca2+-Doped AgInS2.

4-Nitrophenol (4-NP) is considered a priority organic pollutant with high toxicity. Many authors have been committed to developing efficient, green, and environmentally friendly technological processes to treat wastewater containing 4-NP. Here, we investigated how the addition of Ca2+ affects the catalytic degradation of 4-NP with AgInS2 when exposed to light. We synthesized AgInS2 (AIS) and Ca2+-doped AgInS2 (Ca-AIS) with varying amounts of Ca2+ using a low-temperature liquid phase method. The SEM, XRD, XPS, HRTEM, BET, PL, and UV-Vis DRS characteristics were employed to analyze the structure, morphology, and optical properties of the materials. The effects of different amounts of Ca2+ on the photocatalytic degradation of 4-NP were investigated. Under visible light illumination for a duration of 120 min, a degradation rate of 63.2% for 4-Nitrophenol (4-NP) was achieved. The results showed that doping with an appropriate amount of Ca2+ could improve the visible light catalytic activity of AIS. This work provides an idea for finding suitable cheap alkaline earth metal doping agents to replace precious metals for the improvement of photocatalytic activities.

Correction: Wang et al. Visible Light Motivated the Photocatalytic Degradation of P-Nitrophenol by Ca2+-Doped AgInS2. Molecules 2024, 29, 361.

In the original publication [...].

Quality and Flavor Difference in Dry-Cured Meat Treated with Low-Sodium Salts: An Emphasis on Magnesium.

The present study aimed to develop low-sodium curing agents for dry-cured meat products. Four low-sodium formulations (SPMA, SPM, SP, and SM) were used for dry-curing meat. The physicochemical properties and flavor of the dry-cured meat were investigated. The presence of Mg2+ ions hindered the penetration of Na+ into the meat. The weight loss, moisture content, and pH of all low-sodium salt groups were lower than those of S. Mg2+ addition increased the water activity (Aw) of SPMA, SPM, and SM. Dry-curing meat with low-sodium salts promoted the production of volatile flavor compounds, with Mg2+ playing a more prominent role. Furthermore, low-sodium salts also promoted protein degradation and increased the content of free amino acids in dry-cured meat, especially in SM. Principal component analysis (PCA) showed that the low-sodium salts containing Mg2+ were conducive to improving the quality of dry-cured meat products. Therefore, low-sodium salts enriched with Mg2+ become a desirable low-sodium curing agent for achieving salt reduction in dry-cured meat products.

Irradiation-Hardening Model of TiZrHfNbMo0.1 Refractory High-Entropy Alloys.

In order to find more excellent structural materials resistant to radiation damage, high-entropy alloys (HEAs) have been developed due to their characteristics of limited point defect diffusion such as lattice distortion and slow diffusion. Specially, refractory high-entropy alloys (RHEAs) that can adapt to a high-temperature environment are badly needed. In this study, TiZrHfNbMo0.1 RHEAs are selected for irradiation and nanoindentation experiments. We combined the mechanistic model for the depth-dependent hardness of ion-irradiated metals and the introduction of the scale factor f to modify the irradiation-hardening model in order to better describe the nanoindentation indentation process in the irradiated layer. Finally, it can be found that, with the increase in irradiation dose, a more serious lattice distortion caused by a higher defect density limits the expansion of the plastic zone.

A Fluorescent Three-Dimensional Covalent Organic Framework Formed by the Entanglement of Two-Dimensional Sheets.

Herein, we report the introduction of steric hindrance in molecular building blocks to prevent π···π stacking, thus allowing two-dimensional (2D) covalent organic sheets to form three-dimensional (3D) covalent organic frameworks (COFs) through entanglement. Starting from the rationally designed precursors containing a bulky anthracene unit in the vertical direction, a highly crystalline COF (3D-An-COF) was successfully synthesized. Very interestingly, 3D-An-COF was determined as an entangled 2D square net (sql) structure, and the high-resolution data (1.1 Å) obtained by the continuous rotation electron diffraction technique allowed us to directly locate all non-hydrogen atoms. Structurally, the presence of an anthracene group outside the C2h symmetry plane strongly reduces the π···π interactions and promotes the formation of square entanglements. In addition, 3D-An-COF is fluorescent and can be used as a sensor to detect the trace amount of antibiotics in water. This study provides a new strategy for the structural diversification of 3D COFs and will certainly motivate us to construct more entangled COFs for interesting applications in the future.

MiR-22-3p suppresses NSCLC cell migration and EMT via targeting RAC1 expression.

Previous studies have demonstrated the tumor-suppressive function of microRNA-22-3p (miR-22-3p) in several cancers, whereas the significance of miR-22-3p in non-small cell lung cancer (NSCLC) remains unclear. In this study, we explored the biological function and molecular mechanism of miR-22-3p in NSCLC cells. First, we assessed the expression of miR-22-3p in NSCLC tissues and cells based on RT-qPCR and TCGA database. Compared with normal lung tissues and cells, miR-22-3p expression was dramatically decreased in lung cancer tissues and cells. miR-22-3p expression was also correlated with lymph node metastasis and tumor size, but not TNM stages. We further explored the in vitro function of miR-22-3p on the migration and epithelial-mesenchymal transition (EMT) of NSCLC cells. The results showed that overexpression of miR-22-3p suppressed the migration and EMT of NSCLC cells, whereas silencing miR-22-3p showed the opposite effect. Luciferase assay demonstrated that RAS-related C3 botulinum toxin substrate 1 (RAC1) was the target gene for miR-22-3p. Mechanistically, we demonstrated that miR-22-3p suppressed the cell migration and EMT via downregulation of RAC1 because the inhibitory effect of miR-22-3p on cell migration and EMT of NSCLC cells was reversed by RAC1 overexpression. Based on these novel data, the miR-22-3p/RAC1 axis may be an alternative target in the therapeutic intervention of NSCLC.

Disturbance of neuron-microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice.

OBJECTIVES: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron-microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron-microglia crosstalk and is involved in the pathogenic process of NPSLE. METHODS: Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. RESULTS: The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. CONCLUSION: GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron-microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE.