Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria.

Accumulating evidence suggests that cardiovascular disease (CVD) is associated with an altered gut microbiome. Our understanding of the underlying mechanisms has been hindered by lack of matched multi-omic data with diagnostic biomarkers. To comprehensively profile gut microbiome contributions to CVD, we generated stool metagenomics and metabolomics from 1,429 Framingham Heart Study participants. We identified blood lipids and cardiovascular health measurements associated with microbiome and metabolome composition. Integrated analysis revealed microbial pathways implicated in CVD, including flavonoid, γ-butyrobetaine, and cholesterol metabolism. Species from the Oscillibacter genus were associated with decreased fecal and plasma cholesterol levels. Using functional prediction and in vitro characterization of multiple representative human gut Oscillibacter isolates, we uncovered conserved cholesterol-metabolizing capabilities, including glycosylation and dehydrogenation. These findings suggest that cholesterol metabolism is a broad property of phylogenetically diverse Oscillibacter spp., with potential benefits for lipid homeostasis and cardiovascular health.

Correlation of echocardiographic parameters in prone and supine positions in normal adults using a novel approach.

BACKGROUND: Transthoracic echocardiography (TTE) in prone position is challenging. Innovative use of transesophageal echocardiography (TEE) probe to perform TTE for such patients has been described; but reproducibility and correlation of the TTE measurements by this technique with those obtained by the standard supine TTE study are still unknown. METHODS: We enrolled 30 non-COVID-19 individuals, with a mean (SD) age 35 (10.9) years and 11 females, to study the agreement between the transthoracic measurements of the left ventricular (LV), left atrial (LA), aortic dimensions, and ejection fraction (EF) obtained in prone position using an external TEE probe versus the standard supine position using the conventional TTE probe. RESULTS: There were no significant differences between LV end-diastolic and end-systolic diameters, septal wall thickness, posterior wall thickness, and aortic root dimensions in the prone versus the supine positions, while the mean EF (60.3% vs 63.1%, P = .014) and mean LA dimensions (1.8 vs 1.9 cm/m2 , P < .001) were significantly lower in the prone position. The mean time of scans was significantly longer in the prone as compared to the supine position (12.5 vs 4.5 minutes, P < .001). All supine studies had good quality while in the prone position four studies were of poor quality, and one was nondiagnostic. CONCLUSIONS: Assessment of cardiac dimensions and systolic function in the prone position using transthoracic TEE probe was feasible. LV and aortic dimensions agreed well with the standard TTE in supine position; however, LA dimensions and EF were lower in the prone position.

MERS-CoV in Camels but Not Camel Handlers, Sudan, 2015 and 2017.

We tested samples collected from camels, camel workers, and other animals in Sudan and Qatar in 2015 and 2017 for evidence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. MERS-CoV antibodies were abundant in Sudan camels, but we found no evidence of MERS-CoV infection in camel workers, other livestock, or bats.

The Caenorhabditis elegans Eph receptor activates NCK and N-WASP, and inhibits Ena/VASP to regulate growth cone dynamics during axon guidance.

The Eph receptor tyrosine kinases (RTKs) are regulators of cell migration and axon guidance. However, our understanding of the molecular mechanisms by which Eph RTKs regulate these processes is still incomplete. To understand how Eph receptors regulate axon guidance in Caenorhabditis elegans, we screened for suppressors of axon guidance defects caused by a hyperactive VAB-1/Eph RTK. We identified NCK-1 and WSP-1/N-WASP as downstream effectors of VAB-1. Furthermore, VAB-1, NCK-1, and WSP-1 can form a complex in vitro. We also report that NCK-1 can physically bind UNC-34/Enabled (Ena), and suggest that VAB-1 inhibits the NCK-1/UNC-34 complex and negatively regulates UNC-34. Our results provide a model of the molecular events that allow the VAB-1 RTK to regulate actin dynamics for axon guidance. We suggest that VAB-1/Eph RTK can stop axonal outgrowth by inhibiting filopodia formation at the growth cone by activating Arp2/3 through a VAB-1/NCK-1/WSP-1 complex and by inhibiting UNC-34/Ena activity.

Effect of surgical approach on the early outcome of total hip replacement for femoral neck fractures.

We reviewed the short-term outcome of 171 patients treated with total hip replacement for femoral neck fractures using the lateral (94 patients) or posterior approach (77 patients). The Sernbo score and the Abbreviated Mental Test Score were used to assess patients' pre-injury functional and cognitive status respectively. Patients were uniformly treated with regard to the type of prosthesis, size of femoral head and rehabilitation. They were followed up to a mean of 25 months (range : 13-42 months). The dislocation rate in the lateral group was 2.1% versus 0% in the posterior group. There was no difference with regards to leg length discrepancy and the restoration of medial offset. Our results were attributed the standardised patients' selection and adequate soft tissue repair.

Performance aware shared memory hierarchy model for multicore processors.

Despite the fact that multicore processors have a better instruction execution speed and lower power consumption, they also encounter a set of design challenges. The appearance of multicore and many core architectures has raised the problem of managing shared hierarchical memory systems. The main focus of this paper is to evaluate the behavior of shared hierarchical memory systems by modeling their response time analytically. Since the gap between the memory and processor speed increases rapidly, it gets more crucial to find an analytical model that includes the significant factors that affect the performance of hierarchical memory systems. The proposed model considers the interdependence between different memory layers and differentiates between the memory response time and memory system time. Moreover, the model evaluates the effect of memory hierarchy on the variance of the memory access time. The existence of a large variance can lead to extremely long wait queues which can dramatically affect the performance of multicore processors.

Value of stent boost imaging in decision making after coronary stenting.

BACKGROUND: Several studies reported the comparability of digital stent enhancement techniques (including stent boost imaging) in detecting suboptimal results of coronary stenting with Intra Vascular Ultrasound and optical coherence tomography. AIMS: to assess results of stent deployment and determine the incidence of suboptimal results requiring changing final decision using stent boost imaging. METHODS: This cross-sectional study included 120 patients eligible for PCI were recruited during a period of one year (January 2021 to 2022) using DES. RESULTS: Suboptimal results were found in 38% of the PCI cases with stents (angiography guided). Importantly it was found that improper lesion preparation in our practice could not help improving stent optimization. Also, angiography guided PCI has significant incidence of suboptimal results. Digital stent enhancement techniques like stent boost have significant and important value in better decision making. After adjusting for age and sex, six factors were identified as independent predictors for final decision change (stent length, LAD/RCA affection, proximal segment affection, calcification, and optical coherence tomography. CONCLUSION: This study has confirmed the utility of stent boost for the optimization of PCI in daily practice. Stent Boost is a simple and costless technique that provides an accurate assessment of a deployed stent without extending the procedure time and without more risk. It appears to be useful for the immediate evaluation of stent expansion and optimization of PCI by additional post-dilatation, when appropriate. Future studies are needed to determine whether Stent Boost data will correlate with adverse long-term clinical outcomes in patients undergoing PCI.

Differences in Mechanical and Physicochemical Properties of Several PTFE Membranes Used in Guided Bone Regeneration.

Non-resorbable PTFE membranes are frequently used in dental-guided bone regeneration (GBR). However, there is a lack of detailed comparative studies that define variations among commonly used PTFE membranes in daily dental clinical practice. The aim of this study was to examine differences in physicochemical and mechanical properties of several recent commercial PTFE membranes for dental GBR (CytoplastTM TXT-200, permamem®, NeoGen®, Surgitime, OsseoGuard®-TXT, OsseoGuard®-NTXT). Such differences have been rarely recorded so far, which might be a reason for the varied clinical results. For that reason, we analyzed their surface architecture, chemical composition, tensile strength, Young's modulus, wettability, roughness, density, thickness and porosity. SEM revealed different microarchitectures among the non-textured membranes; the textured ones had hexagonal indentations and XPS indicated an identical spectral portfolio in all membranes. NeoGen® was determined to be the strongest and OsseoGuard®-TXT was the most elastic. Wettability and roughness were highest for Surgitime but lowest for OsseoGuard®-NTXT. Furthermore, permamem® was the thinnest and NeoGen® was identified as the thickest investigated GBR membrane. The defect volumes and defect volume ratio (%) varied significantly, indicating that permamem® had the least imperfect structure, followed by NeoGen® and then Cytoplast TM TXT-200. These differences may potentially affect the clinical outcomes of dental GBR procedures.

Biocatalysis of triglycerides transesterification using fungal biomass: a biorefinery approach.

BACKGROUND: The use of microbial biomasses, such as fungal biomass, to catalyze the transesterification of triglycerides (TG) for biodiesel production provides a sustainable, economical alternative while still having the main advantages of expensive immobilized enzymes. RESULTS: Biomasses of Aspergillus flavus and Rhizopus stolonifera were used to catalyze the transesterification of TG in waste frying oil (WFO). Isopropanol as an acyl-acceptor reduced the catalytic capability of the biomasses, while methanol was the most potent acyl-acceptor with a final fatty acid methyl ester (FAME) concentration of 85.5 and 89.7%, w/w, for R. stolonifer and A. flavus, respectively. Different mixtures of the fungal biomasses were tested, and higher proportions of A. flavus biomass improved the mixture's catalytic capability. C. sorokiniana cultivated in synthetic wastewater was used as feedstock to cultivate A. flavus. The biomass produced had the same catalytic capability as the biomass produced in the control culture medium. Response surface methodology (RSM) was adopted using central composite design (CCD) to optimize the A. flavus biomass catalytic transesterification reaction, where temperature, methanol concentration, and biomass concentration were selected for optimization. The significance of the model was verified, and the suggested optimum reaction conditions were 25.5 °C, 250 RPM agitation with 14%, w/w, biomass, 3 mol/L methanol, and a reaction duration of 24 h. The suggested optimum conditions were tested to validate the model and a final FAME concentration of 95.53%. w/w was detected. CONCLUSION: Biomasses cocktails might be a legitimate possibility to provide a cheaper technical solution for industrial applications than immobilized enzymes. The use of fungal biomass cultivated on the microalgae recovered from wastewater treatment for the catalysis of transesterification reaction provides an additional piece of the puzzle of biorefinery. Optimizing the transesterification reaction led to a valid prediction model with a final FAME concentration of 95.53%, w/w.

Protein Language Models Uncover Carbohydrate-Active Enzyme Function in Metagenomics.

In metagenomics, the pool of uncharacterized microbial enzymes presents a challenge for functional annotation. Among these, carbohydrate-active enzymes (CAZymes) stand out due to their pivotal roles in various biological processes related to host health and nutrition. Here, we present CAZyLingua, the first tool that harnesses protein language model embeddings to build a deep learning framework that facilitates the annotation of CAZymes in metagenomic datasets. Our benchmarking results showed on average a higher F1 score (reflecting an average of precision and recall) on the annotated genomes of Bacteroides thetaiotaomicron, Eggerthella lenta and Ruminococcus gnavus compared to the traditional sequence homology-based method in dbCAN2. We applied our tool to a paired mother/infant longitudinal dataset and revealed unannotated CAZymes linked to microbial development during infancy. When applied to metagenomic datasets derived from patients affected by fibrosis-prone diseases such as Crohn's disease and IgG4-related disease, CAZyLingua uncovered CAZymes associated with disease and healthy states. In each of these metagenomic catalogs, CAZyLingua discovered new annotations that were previously overlooked by traditional sequence homology tools. Overall, the deep learning model CAZyLingua can be applied in combination with existing tools to unravel intricate CAZyme evolutionary profiles and patterns, contributing to a more comprehensive understanding of microbial metabolic dynamics.

The C. elegans nck-1 gene encodes two isoforms and is required for neuronal guidance.

The NCK adaptor proteins are composed entirely of SH3 and SH2 domains and serve as protein interaction bridges for several receptors during signal transduction events. Here we report the molecular and genetic analysis of the Caenorhabditis elegans nck-1 gene. C. elegans nck-1 encodes two isoforms: NCK-1A and a shorter isoform that lacks the first SH3 domain, NCK-1B. C. elegans nck-1 mutants exhibit defects in axon guidance and neuronal cell position, as well as defects in the excretory canal cell, gonad, and male mating. NCK-1 is broadly expressed in neurons and epithelial cells with NCK-1B being the most abundant isoform. NCK-1A and NCK-1B share a similar expression pattern in parts of the nervous system, but also have independent expression patterns in other tissues. Interestingly, NCK-1B is localized to the nuclei of many cells. Genetic rescue experiments show that NCK-1 functions cell autonomously and, in general, either NCK-1A or NCK-1B is sufficient to function in axon guidance. However, there appears to be specific roles for each isoform, for example NCK-1B is required for HSN cell migration while NCK-1A is required for efficient male mating. Genetic epistasis experiments show that NCK-1 functions redundantly with the LAR Receptor Tyrosine Phosphatase, PTP-3, and the Netrin receptor UNC-40.

The relationship between genetic variability and the susceptibility of Biomphalaria alexandrina snails to Schistosoma mansoni infection.

In the present study, Biomphalaria snails collected from five Egyptian governorates (Giza, Fayoum, Kafr El-Sheikh, Ismailia and Damietta), as well as reference control Biomphalaria alexandrina snails from the Schistosome Biological Supply Center (SBSC) (Theodor Bilharz Research Institute, Egypt), were subjected to species-specific polymerase chain reaction (PCR) assays to identify the collected species. All of the collected snails were found to be B. alexandrina and there was no evidence of the presence of Biomphalaria glabrata. Randomly amplified polymorphic DNA (RAPD)-PCR assays showed different fingerprints with varying numbers of bands for the first generation (F1) of B. alexandrina snail populations (SBSC, Giza, Fayoum, Kafr El-Sheikh, Ismailia and Damietta). The primer OPA-1 produced the highest level of polymorphism and amplified the greatest number of specific bands. The estimated similarity coefficients among the B. alexandrina populations based on the RAPD-PCR profiles ranged from 0.56 (between SBSC and Ismailia snails) to 0.72 (between Ismailia and Kafr El-Sheikh snails). Experimental infection of the F1 of progeny from the collected snails with Schistosoma mansoni (SBSC strain) showed variable susceptibility rates ranging from 15% in the Fayoum snail group to 50.3% in SBSC snails. A negative correlation was observed between the infection rates in the different snail groups and the distances separating their corresponding governorates from the parasite source. The infection rates of the snail groups and their similarity coefficients with SBSC B. alexandrina snails were positively correlated. The variations in the rates of infection of different B. alexandrina groups with S. mansoni, as well as the differences in the similarity coefficients among these snails, are dependent not only on the geographical distribution of the snails and the parasite, but also on the genetic variability of the snails. Introduction of this variability into endemic areas may reduce the ability of the parasite to infect local hosts and consequently reduce schistosomiasis epidemiology.

The impact of health status on attitudes toward COVID-19 vaccination.

Background and Aims: The COVID-19 outbreak has had an overwhelming effect on societies' access to essential services. Human-to-human transmission facilitates the spread of the disease, as do other conditions, such as temperature. Individuals with underlying health conditions are at increased risk of acquiring and suffering the devastating effects of COVID-19. Consequently, vaccine manufacturing was envisaged as a milestone toward "normalizing" the world. While scholarly attention has focused on attitudes toward vaccination, the relationship between health status and attitudes toward vaccination is understudied. This study attempted to fill this knowledge gap by assessing the impact of health status on attitudes toward the COVID-19 vaccine. Methods: We developed a 26-item questionnaire titled "Attitudes toward COVID-19 Vaccination Scale" for data collection. A total of 1047 school or university staff members from 22 countries completed the questionnaire. The data were initially validated using exploratory factor analysis to determine its structure and subsequently analyzed using SPSS version 28. Two-way factorial analysis of variance and multiple regression analysis were performed to understand the influence of health status on attitudes toward vaccination. Results: The results showed a direct effect of health status on attitudes toward COVID-19 vaccination, (Step 1; ß = 0.11, p = 0.001; Step 2: ß = 0.10, p = 0.001). In Step 2 also, vaccination status (ß = 0.22, p = 0.001) and place of residence (ß = -0.08, p = 0.04) also influenced attitudes towards vaccination. Health status also moderated the relation between attitude and education level (F[3, 1038] = 3.04) of participants. Conclusion: Results show possible fear and hesitancy toward COVID-19 vaccination among those with underlying health conditions. Therefore, expeditious sensitization programs may be needed to promote the importance of vaccination for developing resistance against COVID-19 and vaccine acceptance. However, such initiatives should target vulnerable groups in society. Policymakers could focus on improving sensitization toward COVID-19 vaccination among those living with underlying health conditions.

FtsK and SpoIIIE, coordinators of chromosome segregation and envelope remodeling in bacteria.

The translocation of DNA during bacterial cytokinesis is mediated by the SpoIIIE/FtsK family of proteins. These proteins ensure efficient chromosome segregation into sister cells by ATP-driven translocation of DNA and they control chromosome dimer resolution. How FtsK/SpoIIIE mediate chromosome translocation during cytokinesis in Gram-positive and Gram-negative organisms has been the subject of debate. Studies on FtsK in Escherichia coli, and recent work on SpoIIIE in Bacillus subtilis, have identified interactions between each translocase and the division machinery, supporting the idea that SpoIIIE and FtsK coordinate the final steps of cytokinesis with completion of chromosome segregation. Here we summarize and discuss the view that SpoIIIE and FtsK play similar roles in coordinating cytokinesis with chromosome segregation, during growth and differentiation.

Genetic Screens Identify Additional Genes Implicated in Envelope Remodeling during the Engulfment Stage of Bacillus subtilis Sporulation.

During bacterial endospore formation, the developing spore is internalized into the mother cell through a phagocytic-like process called engulfment, which involves synthesis and hydrolysis of peptidoglycan. Engulfment peptidoglycan hydrolysis requires the widely conserved and well-characterized DMP complex, composed of SpoIID, SpoIIM, and SpoIIP. In contrast, although peptidoglycan synthesis has been implicated in engulfment, the protein players involved are less well defined. The widely conserved SpoIIIAH-SpoIIQ interaction is also required for engulfment efficiency, functioning like a ratchet to promote membrane migration around the forespore. Here, we screened for additional factors required for engulfment using transposon sequencing in Bacillus subtilis mutants with mild engulfment defects. We discovered that YrvJ, a peptidoglycan hydrolase, and the MurA paralog MurAB, involved in peptidoglycan precursor synthesis, are required for efficient engulfment. Cytological analyses suggest that both factors are important for engulfment when the DMP complex is compromised and that MurAB is additionally required when the SpoIIIAH-SpoIIQ ratchet is abolished. Interestingly, despite the importance of MurAB for sporulation in B. subtilis, phylogenetic analyses of MurA paralogs indicate that there is no correlation between sporulation and the number of MurA paralogs and further reveal the existence of a third MurA paralog, MurAC, within the Firmicutes. Collectively, our studies identify two new factors that are required for efficient envelop remodeling during sporulation and highlight the importance of peptidoglycan precursor synthesis for efficient engulfment in B. subtilis and likely other endospore-forming bacteria. IMPORTANCE In bacteria, cell envelope remodeling is critical for cell growth and division. This is also the case during the development of bacteria into highly resistant endospores (spores), known as sporulation. During sporulation, the developing spore becomes internalized inside the mother cell through a phagocytic-like process called engulfment, which is essential to form the cell envelope of the spore. Engulfment involves both the synthesis and hydrolysis of peptidoglycan and the stabilization of migrating membranes around the developing spore. Importantly, although peptidoglycan synthesis has been implicated during engulfment, the specific genes that contribute to this molecular element of engulfment have remained unclear. Our study identifies two new factors that are required for efficient envelope remodeling during engulfment and emphasizes the importance of peptidoglycan precursor synthesis for efficient engulfment in the model organism Bacillus subtilis and likely other endospore-forming bacteria. Finally, our work highlights the power of synthetic screens to reveal additional genes that contribute to essential processes during sporulation.

Inflammation-associated nitrate facilitates ectopic colonization of oral bacterium Veillonella parvula in the intestine.

Colonization of the intestine by oral microbes has been linked to multiple diseases such as inflammatory bowel disease and colon cancer, yet mechanisms allowing expansion in this niche remain largely unknown. Veillonella parvula, an asaccharolytic, anaerobic, oral microbe that derives energy from organic acids, increases in abundance in the intestine of patients with inflammatory bowel disease. Here we show that nitrate, a signature metabolite of inflammation, allows V. parvula to transition from fermentation to anaerobic respiration. Nitrate respiration, through the narGHJI operon, boosted Veillonella growth on organic acids and also modulated its metabolic repertoire, allowing it to use amino acids and peptides as carbon sources. This metabolic shift was accompanied by changes in carbon metabolism and ATP production pathways. Nitrate respiration was fundamental for ectopic colonization in a mouse model of colitis, because a V. parvula narG deletion mutant colonized significantly less than a wild-type strain during inflammation. These results suggest that V. parvula harness conditions present during inflammation to colonize in the intestine.

Tissue responses exhibited by Biomphalaria alexandrina snails from different Egyptian localities following Schistosoma mansoni exposure.

Snails' susceptibilities to infection with Schistosoma mansoni were determined through observation of infection rates, total cercarial production and tissue responses of the first generation (F1) of Biomphalaria alexandrina snails, originally collected from different Egyptian governorates (Giza, Fayoum, Kafr El-Sheikh, Ismailia and Damietta) and responses were compared between groups. The emergence of cercariae for a 3-month period and the calculation of survival and infection rates, in control (Schistosome Biological Supply Center; SBSC) and infected snails were evaluated. SBSC and Giza snails showed greater susceptibilities to infection and lower mortality rates. In addition, at 6 and 72 h post-exposure to miracidia all the snail groups showed no difference in the anatomical locations of sporocysts. The larvae were found in the head-foot, the mantle collar and the tentacles of the snails. Sporocysts showed normal development with low tissue reactions in SBSC and Giza snail groups infected with S. mansoni miracidia (SBSC). However, in Fayoum, Kafr El-Sheikh, Ismailia and Damietta snail groups, variable tissue responses were observed in which numerous hemocytes made direct contact with S. mansoni larvae forming capsules. The results suggested that, different responses of B. alexandrina snail's hemocytes towards S. mansoni are related to the degree of susceptibility of these snails. So this is important in planning the strategy of schistosomiasis control.

Chromosome Segregation and Peptidoglycan Remodeling Are Coordinated at a Highly Stabilized Septal Pore to Maintain Bacterial Spore Development.

Asymmetric division, a hallmark of endospore development, generates two cells, a larger mother cell and a smaller forespore. Approximately 75% of the forespore chromosome must be translocated across the division septum into the forespore by the DNA translocase SpoIIIE. Asymmetric division also triggers cell-specific transcription, which initiates septal peptidoglycan remodeling involving synthetic and hydrolytic enzymes. How these processes are coordinated has remained a mystery. Using Bacillus subtilis, we identified factors that revealed the link between chromosome translocation and peptidoglycan remodeling. In cells lacking these factors, the asymmetric septum retracts, resulting in forespore cytoplasmic leakage and loss of DNA translocation. Importantly, these phenotypes depend on septal peptidoglycan hydrolysis. Our data support a model in which SpoIIIE is anchored at the edge of a septal pore, stabilized by newly synthesized peptidoglycan and protein-protein interactions across the septum. Together, these factors ensure coordination between chromosome translocation and septal peptidoglycan remodeling to maintain spore development.

Eco-friendly highly efficient BN/rGO/TiO2 nanocomposite visible-light photocatalyst for phenol mineralization.

Boron nitride (BN) and reduced graphene oxide (rGO) of different loadings were composited with commercial P25 TiO2 (Ti) through the hydrothermal method. The as-prepared nanocomposites were characterized using various techniques: X-ray photoelectron spectroscopy, X-ray diffraction, thermal gravimetric analysis, Fourier transform infrared and Raman spectroscopies, and transmission and scanning electron microscopies. It was observed that 10% and 0.1% of BN and rGO, respectively, loaded on TiO2 (10BNr0.1GOTi) resulted in the best nanocomposite in terms of phenol degradation under simulated sunlight. A 93.4% degradation of phenol was obtained within 30 min in the presence of H2O2. Finally, to ensure the safe use of BNrGOTi nanoparticles in the aquatic environment, acute zebrafish toxicity (acutoxicity) assays were studied. The 96-h acute toxicity assays using the zebrafish embryo model revealed that the LC50 for the BNrGOTi nanoparticle was 677.8 mg L-1 and the no observed effect concentration (NOEC) was 150 mg L-1. Therefore, based on the LC50 value and according to the Fish and Wildlife Service Acute Toxicity Rating Scale, BNrGOTi is categorized as a "practically not toxic" photocatalyst for water treatment.

Cognitive effects of the GSK-3 inhibitor "lithium" in LPS/chronic mild stress rat model of depression: Hippocampal and cortical neuroinflammation and tauopathy.

Low-dose repeated lipopolysaccharide pre-challenge followed by chronic mild stress (LPS/CMS) protocol has been introduced as a rodent model of depression combining the roles of immune activation and chronic psychological stress. However, the impact of this paradigm on cognitive functioning has not been investigated hitherto. METHODS: This study evaluated LPS/CMS-induced cognitive effects and the role of glycogen synthase kinase-3ß (GSK-3ß) activation with subsequent neuroinflammation and pathological tau deposition in the pathogenesis of these effects using lithium (Li) as a tool for GSK-3 inhibition. RESULTS: LPS pre-challenge reduced CMS-induced neuroinflammation, depressive-like behavior and cognitive inflexibility. It also improved spatial learning but increased GSK-3ß expression and exaggerated hyperphosphorylated tau accumulation in hippocampus and prefrontal cortex. Li ameliorated CMS and LPS/CMS-induced depressive and cognitive deficits, reduced GSK-3ß over-expression and tau hyperphosphorylation, impeded neuroinflammation and enhanced neuronal survival. CONCLUSION: This study draws attention to LPS/CMS-triggered cognitive changes and highlights how prior low-dose immune challenge could develop an adaptive capacity to buffer inflammatory damage and maintain the cognitive abilities necessary to withstand threats. This work also underscores the favorable effect of Li (as a GSK-3ß inhibitor) in impeding exaggerated tauopathy and neuroinflammation, rescuing neuronal survival and preserving cognitive functions. Yet, further in-depth studies utilizing different low-dose LPS challenge schedules are needed to elucidate the complex interactions between immune activation and chronic stress exposure.