The E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated immune tolerance. Using a murine model infected with Schistosoma japonicum, we observed that there were more cercariae developed into adults and more eggs deposited in the livers of the USP21fl/flFOXP3Cre (KO) mice. However, immunohistochemistry showed that the degree of egg granuloma formation and liver fibrosis was reduced. In USP21fl/flFOXP3Cre mice, levels of IFN-gamma, IL-4, anti-soluble egg antigen (SEA) IgG and anti-soluble worm antigen preparation (SWAP) IgG increased in blood, as determined using ELISAs and multiplex fluorescent microsphere immunoassays, while the levels of IL-10, lL-17A, IL-23, IL-9, and anti-SEA IgM decreased. In addition, the levels of the USP21 protein and mRNA in the liver and spleen of KO mice decreased. We further observed increased Th1 responses amplified by Tregs (regulatory T cells) and compromised Th17 responses, which alleviated the liver immunopathology. We speculated that these changes were related to polarization of Th1-like Tregs. Our results revealed the roles of USP21 in Treg-cell-mediated regulation of immune interactions between Schistosoma and its host. USP21 may have potential for regulating hepatic fibrosis in patients with schistosomiasis.

We report characteristics of soybean genetic diversity and structure from the resequencing of 481 diverse soybean accessions, comprising 52 wild (Glycine soja) selections and 429 cultivated (Glycine max) varieties (landraces and elites). This data was used to identify 7.8 million SNPs, to predict SNP effects relative to genic regions, and to identify the genetic structure, relationships, and linkage disequilibrium. We found evidence of distinct, mostly independent selection of lineages by particular geographic location. Among cultivated varieties, we identified numerous highly conserved regions, suggesting selection during domestication. Comparisons of these accessions against the whole U.S. germplasm genotyped with the SoySNP50K iSelect BeadChip revealed that over 95% of the re-sequenced accessions have a high similarity to their SoySNP50K counterparts. Probable errors in seed source or genotype tracking were also identified in approximately 5% of the accessions.

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.

Immune cells have emerged as key regulators in the occurrence and development of multiple tumor types. However, it is unclear whether immune-related genes (IRGs) and the tumor immune microenvironment can predict prognosis for patients with gastric cancer (GC). The mRNA expression data in GC tissues (n = 368) were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs in patients with GC were determined using a computational difference algorithm. A prognostic signature was constructed using COX regression and random survival forest (RSF) analyses. In addition, datasets related to "gemcitabine resistance" and "trastuzumab resistance" (GSE58118 and GSE77346) were obtained for GEO database, and DEGs associated with drug-resistance were screened. Then, we analyzed correlations between gene expression and cancer immune infiltrates via Tumor Immune Estimation Resource (TIMER) site. The cBioportal database was used to analyze drug-resistant gene mutation status and survival. One hundred and fifty-five differentially expressed IRGs were screened between GC and normal tissues, and a prognostic signature consisting of four IRGs (NRP1, PPP3R1, IL17RA, and FGF16) was closely related to the overall survival (OS). According to cutoff value of risk score, patients were divided into high-risk and low-risk group. Patients in the high-risk group had shorter OS compared to the low-risk group in both the training (p < 0.0001) and testing sets (p = 0.0021). In addition, we developed a 5-IRGs (LGR6, DKK1, TNFRSF1B, NRP1, and CXCR4) signature which may participate in drug resistance processes in GC. Survival analysis showed that patients with drug-resistant gene mutations had shorter OS (p = 0.0459) and DFS (p < 0.001). We constructed four survival-related IRGs and five IRGs related to drug resistance which may contribute to predict the prognosis of GC.

The increase of blood pressure is accompanied by the changes in the morphology and function of vascular endothelial cells. Vascular endothelial injury and hypertension actually interact as both cause and effect. A large number of studies have proved that inflammation plays a significant role in the occurrence and development of hypertension, but the potential mechanism between inflammation and hypertensive endothelial injury is still ambiguous. The purpose of this study was to explore the association between the activation of NLRP3 inflammasome and hypertensive endothelial damage, and to demonstrate the protective effect of sinapine thiocyanate (ST) on endothelia in hypertension. The expression of NLRP3 gene was silenced by tail vein injection of adeno-associated virus (AAVs) in spontaneously hypertensive rats (SHRs), indicating that activation of NLRP3 inflammasome accelerated hypertensive endothelial injury. ST not only protected vascular endothelial function in SHRs by inhibiting the activation of NLRP3 inflammasome and the expression of related inflammatory mediators, but also improved AngII-induced huvec injury. In summary, our results show that alleviative NLRP3 inflammasome activation attenuates hypertensive endothelial damage and ST ameliorates vascular endothelial dysfunction in hypertension via inhibiting activation of the NLRP3 inflammasome.

Oral cancer is a very aggressive disease with high rates of recurrence and metastasis. This study aimed at addressing how efficiently tongue cancer is suppressed after carbon ion irradiation. Here, the close relationship between upregulated expression of focal adhesion kinase (FAK) and high metastatic status in tongue squamous cell carcinoma patients was validated using bioinformatics and immunohistochemical analyses. Our data indicated that FAK suppression significantly enhanced the killing effect induced by irradiation in the tongue cancer cell line CAL27, as evidenced by increased apoptotic induction and reduced colony formation. More importantly, in FAK-deficient cells, carbon ion irradiation was shown to remarkably inhibit migration and invasion by delaying wound healing and slowing down motility. Further studies revealed that irradiation exposure caused disorganization of the actin cytoskeleton and reduced cell adhesive energy in FAK-deficient cells. Moreover, carbon ion treatment, in combination with FAK silencing, markedly blocked the phosphorylation levels of FAK, and paxillin, which partly contributed to the reduced motility of tongue squamous cell carcinoma CAL27 cells. Collectively, these results suggest that the prominent obstructing role of carbon ion irradiation in the growth inhibition and metastatic behavior of tumors, including attenuation of cell adhesiveness, motility, and invasiveness, could be distinctly modulated by FAK-mediated downstream pathways.

Magnolia biondii Pamp. (Magnoliaceae, magnoliids) is a phylogenetically, economically, and medicinally important ornamental tree species widely grown and cultivated in the north-temperate regions of China. Determining the genome sequence of M. biondii would help resolve the phylogenetic uncertainty of magnoliids and improve the understanding of individual trait evolution within the Magnolia genus. We assembled a chromosome-level reference genome of M. biondii using ~67, ~175, and ~154 Gb of raw DNA sequences generated via Pacific Biosciences single-molecule real-time sequencing, 10X Genomics Chromium, and Hi-C scaffolding strategies, respectively. The final genome assembly was ~2.22 Gb, with a contig N50 value of 269.11 kb and a BUSCO complete gene percentage of 91.90%. Approximately 89.17% of the genome was organized into 19 chromosomes, resulting in a scaffold N50 of 92.86 Mb. The genome contained 47,547 protein-coding genes, accounting for 23.47% of the genome length, whereas 66.48% of the genome length consisted of repetitive elements. We confirmed a WGD event that occurred very close to the time of the split between the Magnoliales and Laurales. Functional enrichment of the Magnolia-specific and expanded gene families highlighted genes involved in the biosynthesis of secondary metabolites, plant-pathogen interactions, and responses to stimuli, which may improve the ecological fitness and biological adaptability of the lineage. Phylogenomic analyses revealed a sister relationship of magnoliids and Chloranthaceae, which are sister to a clade comprising monocots and eudicots. The genome sequence of M. biondii could lead to trait improvement, germplasm conservation, and evolutionary studies on the rapid radiation of early angiosperms.

Purpose: Metabolic impairment is one key contributor to heart failure (HF) pathogenesis and progression. The major causes of HF, coronary heart disease (CHD), dilated cardiomyopathy (DCM), and valvular heart disease (VHD) remains poorly characterized in patients with HF from the view of metabolic profile. We sought to determine metabolic differences in CHD-, VHD-, and DCM-induced HF patients and identify significantly altered metabolites and their correlations. Procedure: In this study, a total of 96 HF cases and 97 controls were enrolled. The contents of 23 amino acids and 26 carnitines in fasting plasma were measured by a targeted liquid chromatography and mass spectrometry (LC-MS) approach. Results: Nine metabolites (Histidine, Arginine, Citrulline, Glutamine, Valine, hydroxyhexadecenyl-carnitine, acylcarnitine C22, hydroxytetradecanoyl-carnitine, and carnitine) were found to be related with the occurrence of HF. Arginine, Glutamine and hydroxytetradecanoyl-carnitine could effectively distinguish CHD and DCM patients, and hydroxytetradecanoyl-carnitine and aspartic acid were able to classify CHD and VHD cohorts. Conclusion: This study indicated that circulating amino acids and long-chain acylcarnitine levels were closely associated with progression of heart failure. Monitoring these metabolic alterations by LC-MS may help the differentiation of CHD, VHD, and DCM in the early stage, and provide new diagnostics targets or therapeutic interventions.

Platelet activation and the risk of thrombosis are increased in cancer patients, especially after chemotherapy. Our previous studies indicated that chemotherapy-induced platelet activation is largely due to endothelial cell damage. Thus, simple in vitro tests, such as aggregometry, are not desirable tests to predict platelet responsiveness to different chemotherapeutic agents because other contributory factors, such as tumor cells, endothelial cells, and the flow rate of platelets, also contribute to the formation of cancer-associated thrombosis. Therefore, developing a platelet detection system, which includes all possible risk parameters, is necessary. In the present study, we described a microengineered microfluidic system that contained a drug concentration generator, cancer cell culture chip, and three-dimensional (3D) circular microvascular model covered with a confluent endothelial layer and perfused with human platelets at a stable flow rate. Doxorubicin was injected through two injection sites. Endothelial cell injury was evaluated by counting, cell cytoskeleton observation, and the level of IACM1 and ET-1 in endothelial cells or a culture medium. Prestained platelets were perfused into the artificial blood vessel, and platelet-endothelial cell adhesion was measured. We found that (i) MCF7 cell-released factors had a cytotoxicity effect on both endothelial cells and platelets. (ii) We confirmed that doxorubicin-induced platelet activation was endothelial cell-dependent. (iii) A lower dosage of doxorubicin (0-2.0 μM) induced platelet activation, while a higher dosage of doxorubicin (2.0-4.0 μM) led to platelet death. Our findings indicated that platelet-endothelial cell adhesion could be used as a diagnostic marker of platelet activation, providing a simple and rapid detective way to predict platelet responsiveness before or during chemotherapy.

Hepatocellular carcinoma (HCC), one of the main causes of cancer-related deaths globally, is characterized by rapid growth and high invasiveness. Accumulating evidence demonstrates that long noncoding RNAs (lncRNAs) play critical roles in the growth and metastasis of HCC. Recently, lncRNA LINC01123 has been found to contribute to cell proliferation and aerobic glycolysis in lung cancer. However, the function of LINC01123 in HCC, as well as the underlying mechanism of its action, remain unclear. Here, we found that the expression of LINC01123 was clearly upregulated in HCC tissues compared to nontumor tissues. Furthermore, expression of LINC01123 in HCC cells was significantly higher than in LO2 cells. Importantly, the upregulated level of LINC01123 was related to unfavorable clinical features and poor prognosis of HCC. Next, we demonstrated that LINC01123 knockdown suppressed the proliferation, migration and invasion of HCC cells in vitro. Depletion of LINC01123 inhibited HCC xenograft growth in vivo. Conversely, ectopic expression of LINC01123 facilitated HCC cell proliferation and invasion. Mechanistically, LINC01123 acted as a molecular sponge for miR-34a-5p in HCC cells. Tuftelin1 (TUFT1) was identified as the target gene of miR-34a-5p. LINC01123 positively regulated TUFT1 level by targeting of miR-34a-5p in HCC cells. Notably, TUFT1 restoration can abolish miR-34a-5p-induced inhibitory effects on HCC cell proliferation, migration and invasion. In conclusion, LINC01123 was overexpressed in HCC and accelerated cancer cell proliferation and invasion by regulating the miR-34a-5p/TUFT1 axis.

The new outbreak of Coronavirus Disease 2019 (COVID-19) has emerged as a serious global public health concern. A more in-depth study of blood coagulation abnormality is needed. We retrospectively analyzed 147 consecutive patients with COVID-19 who were admitted to three ICUs in Wuhan from February 9th, 2020 to March 20th, 2020. The baseline coagulation and other characteristics were studied. Our results showed that the prolonged PT, FDP, DD were positively correlated with the levels of neutrophils, ferritin, LDH, total bilirubin, multi-inflammation cytokines, and negatively correlated with the lymphocytes level (p < 0.01). The level of ATIII was significantly negatively correlated with the levels of neutrophils, ferritin, LDH, total bilirubin, IL2R, IL6 and IL8 (p < 0.05). The patients in the ARDS group had a more prominent abnormality in PT, FDP, DD and ATIII, while the patients in the AKI group had more prolonged PT, more severe FDP and DD level, more inferior ATIII and Fib level than those in the non-AKI group (p < 0.01). The value of PT, DD and FDP were positively correlated with the classical APACHE II, SOFA and qSOFA scores, while the ATIII was negatively correlated with them (p < 0.001). The high levels of PT, FDP and DD were correlated with in-hospital mortality (p < 0.001). In conclusion, blood coagulation disorder was prominent in ICU patients with COVID-19 and was correlated with multi-inflammation factors. The abnormality of blood coagulation parameters could be an adverse prognostic indicator for ICU patients with COVID-19.

Zika virus (ZIKV) is an infectious disease that has become an important concern worldwide, it associates with neurological disorders and congenital malformations in adults, also leading to fetal intrauterine growth restriction and microcephaly during pregnancy. However, there are currently no approved vaccines or specific antiviral drugs for preventing or treating ZIKV infection. Here, we show that two FDA-approved Na+/K+-ATPase inhibitors, ouabain and digoxin, can block ZIKV infection at the replication stage by targeting Na+/K+-ATPase. Furthermore, ouabain reduced the viral burden of ZIKV in adult mice, penetrated the placental barrier to enter fetal tissues, and protected fetal mice from ZIKV infection-induced microcephaly in a pregnant mouse model. Thus, ouabain has therapeutic potential for ZIKV.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a well-characterized transcription factor that protects cells against oxidative and electrophilic stresses. Emerging evidence has suggested that NRF2 protects cells against DNA damage by mechanisms other than antioxidation, yet the mechanism remains poorly understood. Here, we demonstrate that knockout of NRF2 in cells results in hypersensitivity to ionizing radiation (IR) in the presence or absence of reactive oxygen species (ROS). Under ROS scavenging conditions, induction of DNA double-strand breaks (DSBs) increases the NRF2 protein level and recruits NRF2 to DNA damage sites where it interacts with ATR, resulting in activation of the ATR-CHK1-CDC2 signaling pathway. In turn, this leads to G2 cell cycle arrest and the promotion of homologous recombination repair of DSBs, thereby preserving genome stability. The inhibition of NRF2 by brusatol increased the radiosensitivity of tumor cells in xenografts by perturbing ATR and CHK1 activation. Collectively, our results reveal a novel function of NRF2 as an ATR activator in the regulation of the cellular response to DSBs. This shift in perspective should help furnish a more complete understanding of the function of NRF2 and the DNA damage response.

Tigecycline is one of the last-resort antibiotics to treat severe infections. Recently, tigecycline resistance has sporadically emerged with an increasing trend, and Tet(X) family represents a new resistance mechanism of tigecycline. In this study, a novel chromosome-encoded tigecycline resistance gene, tet(X14), was identified in a tigecycline-resistant and colistin-resistant Empedobacter stercoris strain ES183 recovered from a pig fecal sample in China. Tet(X14) shows 67.14-96.39% sequence identity to the other variants [Tet(X) to Tet(X13)]. Overexpression of Tet(X14) in Escherichia coli confers 16-fold increase in tigecycline MIC (from 0.125 to 2 mg/L), which is lower than that of Tet(X3), Tet(X4) and Tet(X6). Structural modelling predicted that Tet(X14) shared a high homology with the other 12 variants with RMSD value from 0.003 to 0.055, and Tet(X14) can interact with tetracyclines by a similar pattern as the other Tet(X)s. tet(X14) and two copies of tet(X2) were identified on a genome island with abnormal GC content carried by the chromosome of ES183, and no mobile genetic elements were found surrounding, suggesting that tet(X14) might be heterologously obtained by ES183 via recombination. Blasting in Genbank revealed that Tet(X14) was exclusively detected on the chromosome of Riemerella anatipestifer, mainly encoded on antimicrobial resistance islands. E. stercoris and R. anatipestifer belong to the family Flavobacteriaceae, suggesting that the members of Flavobacteriaceae maybe the major reservoir of tet(X14). Our study reports a novel chromosome-encoded tigecycline resistance gene tet(X14). The expanded members of Tet(X) family warrants the potential large-scale dissemination and the necessity of continuous surveillance for tet(X)-mediated tigecycline resistance.

Circular RNAs (circRNAs) are emerging regulators in the development of human cancers. However, the role of circRNAs in melanoma is poorly understood. Microarray analysis and qRT-PCR was applied to screen out circRNAs that were differentially expressed in melanoma cells compared to normal cells. Currently, we first proved that inhibition of CYR61, an angiogenesis factor with controversial functions in melanoma, restrained cell migration, invasion and angiogenesis in melanoma. Thereafter, a novel circRNA hsa_circ_0027247 derived from GLI1 (circ-GLI1) was identified to positively modulate CYR61 expression in melanoma cell lines. Besides, silencing circ-GLI1 hindered melanoma cell metastasis as well. Interestingly, we unveiled that circ-GLI1 enhanced CYR61 transcription by an indirect manner. Meanwhile, circ-GLI1 activated Hedgehog/GLI1 and Wnt/β-catenin pathways by affecting the degradation of GLI1 and β-catenin. Moreover, we found that circ-GLI1 interacted with p70S6K2 to induce GSK3β phosphorylation at Ser9, and therefore blocked the binding of GSK3β with GLI1 and β-catenin so as to elevate their protein expression. Of note, CYR61 was transcriptionally activated by MYC, a well-recognized downstream target of both GLI1 and β-catenin. In conclusion, circ-GLI1 exacerbates the metastasis and angiogenesis of melanoma by upregulating Cyr61 via p70S6K2-dependent activation of Hedgehog/GLI1 and Wnt/β-catenin pathways.

A number of studies have demonstrated the crucial functions of GINS2 within the GINS complex in various types of cancer. However, the molecular mechanisms and prognostic value of GINS2 in breast cancer remain unknown. The present study used; BC-GenExMiner, COSMIC, UCSC Xena, The Human Protein Atlas, GEPIA, cBioPortal, GeneMANIA, TIMER and Oncomine, in order to investigate gene expression, co-expression, clinical parameters and mutations in GINS2 in patients with breast cancer. Furthermore, the present study assessed the prognostic value of GINS2 in patients with breast cancer via the Kaplan-Meier plotter database. The results of the present study demonstrated that the mRNA levels of GINS2 were significantly higher in breast cancer tissue compared with normal tissue. In addition, high mRNA expression levels of GINS2 were associated with high Scarff-Bloom-Richardson status grades, a basal-like status and age (≤51 years); however, it was not associated with lymph node metastasis. The survival analysis revealed that increased GINS2 mRNA levels were associated with a worse prognosis for relapse-free survival in all patients with breast cancer, particularly in those with estrogen receptor-positive and progesterone receptor-positive subtypes. In addition, a positive association between the GINS2, CENPM and MCM4 genes was confirmed. The results of the present study suggest that GINS2 could be used as a potential prognostic biomarker for breast cancer. Nevertheless, further studies are necessary to confirm the effects of GINS2 on the pathogenesis and development of patients with breast cancer.

Chicken coccidiosis is a protozoan parasitic disease that leads to considerable economic losses in the poultry industry. In this study, we used invasive Lactobacillus plantarum (L.P) expressing the FnBPA protein as a novel bacterial carrier for DNA delivery into epithelial cells to develop a live oral DNA vaccine. A fusion DNA vaccine co-expressing EtMIC2 and chicken IL-18 (chIL-18) was constructed and then delivered to the host by invasive L.P. Its efficacy against Eimeria tenella challenge was evaluated in chickens by examining the relative weight gain rate; caecal lesion score; OPG; anti-coccidial index (ACI); levels of EtMIC2 antibody, FnBPA, IL-4, IL-18, IFN-γ and SIgA; and proliferation ability and percentages of CD4+ and CD8+ splenocytes. The experimental results showed that chickens immunized with invasive L.P carrying the eukaryotic expression vector pValac-EtMIC2 (pValac-EtMIC2/pSIP409-FnBPA) had markedly improved immune protection against challenge compared with that of chickens immunized with non-invasive L.P (pValac-EtMIC2/pSIP409). However, invasive L.P co-expressing EtMIC2 with the chIL-18 vector exhibited the highest protection efficiency against E. tenella. These results indicate that invasive Lactobacillus-expressing FnBPA improved humoural and cellular immunity and enhanced resistance to E. tenella. The DNA vaccine delivered by invasive Lactobacillus provides a new concept and method for the prevention of E. tenella.

Pseudomonas aeruginosa is a biofilm-forming opportunistic pathogen which causes chronic infections in immunocompromised patients and leads to high mortality rate. It is identified as a common coinfecting pathogen in COVID-19 patients causing exacerbation of illness. In our hospital, P. aeruginosa is one of the top coinfecting bacteria identified among COVID-19 patients. We collected a strong biofilm-forming P. aeruginosa strain displaying small colony variant morphology from a severe COVID-19 patient. Genomic and transcriptomic sequencing analyses were performed with phenotypic validation to investigate its adaptation in SARS-CoV-2 infected environment. Genomic characterization predicted specific genomic islands highly associated with virulence, transcriptional regulation, and DNA restriction-modification systems. Epigenetic analysis revealed a specific N6-methyl adenine (m6A) methylating pattern including methylation of alginate, flagellar and quorum sensing associated genes. Differential gene expression analysis indicated that this isolate formed excessive biofilm by reducing flagellar formation (7.4 to 1,624.1 folds) and overproducing extracellular matrix components including CdrA (4.4 folds), alginate (5.2 to 29.1 folds) and Pel (4.8-5.5 folds). In summary, we demonstrated that P. aeuginosa clinical isolates with novel epigenetic markers could form excessive biofilm, which might enhance its antibiotic resistance and in vivo colonization in COVID-19 patients.

The potential treatment effects and safety of Yu ping feng san (YPFS) for pediatric allergic rhinitis (PAR) patients have yet to be studied systematically.

Neuroinflammation has been recognized as a major cause for neurocognitive diseases. Although the hippocampus has been considered an important region for cognitive dysfunction, the influence of hippocampal neuroinflammation on brain functional connectivity (FC) has been rarely studied. In this study, lipopolysaccharide (LPS) was used to induce systemic inflammation and neuroinflammation in the aged rat brain, while elamipretide (SS-31) was used for treatment. Systemic and hippocampal inflammation were determined using ELISA, while astrocyte responses during hippocampal neuroinflammation were determined by interleukin 1 beta (IL-1β)/tumor necrosis factor alpha (TNFα) double staining immunofluorescence. Oxidative stress was determined by reactive oxidative species (ROS), electron transport chain (ETC) complex, and superoxide dismutase (SOD). Short- (<7 days) and long-term (>30 days) learning and spatial working memory were tested by the Morris water maze (MWM). Resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyze the brain FC by placing seed voxels on the left and right hippocampus. Compared with the vehicle group, rats with the LPS exposure showed an impaired MWM performance, higher oxidative stress, higher levels of inflammatory cytokines, and astrocyte activation in the hippocampus. The neuroimaging examination showed decreased FC on the right orbital cortex, right olfactory bulb, and left hippocampus on day 3, 7, and 31, respectively, after treatment. In contrast, rats with SS-31 treatment showed lower levels of inflammatory cytokines, less astrocyte activation in the hippocampus, and improved MWM performance. Neuroimaging examination showed increased FC on the left-parietal association cortex (L-PAC), left sensory cortex, and left motor cortex on day 7 with the right flocculonodular lobe on day 31 as compared with those without SS-31 treatment. Our study demonstrated that inhibiting neuroinflammation in the hippocampus not only reduces inflammatory responses in the hippocampus but also improves the brain FC in regions related to the hippocampus. Furthermore, early anti-inflammatory treatment with SS-31 has a long-lasting effect on reducing the impact of LPS-induced neuroinflammation.