Synergistic effect of Ag@CN with BiVO4 in a unique Z-type heterojunction for enhancing photoelectrochemical water splitting performance.

In the realm of photoelectrochemical technology, the enhancement of photogenerated charge carrier separation is pivotal for the advancement of energy conversion performance. Carbon nitride (CN) is established as a photocatalytic material with significant potential and exhibits unique advantages in addressing the issue of rapid recombination of photogenerated carriers. This study utilized an efficient in situ doping method that combined Mo,W-doped BiVO4 (Mo,W:BVO) with silver-loaded CN (Ag@CN), yielding an all-solid-state Mo,W:BVO/Ag@CN heterostructure that effectively augments the separation efficiency of electron-hole pairs. Through the annealing process, Ag@CN was uniformly coated within the Mo,W:BVO thin film, significantly enlarging the interface contact area to enhance visible light absorption and photogenerated carrier movement. The results of the photoelectrochemical tests showed that the Mo,W:BVO/Ag@CN heterostructure had the highest photocurrent and charge transfer efficiency, which were 6.4 times and 3.6 times higher respectively than those of the unmodified Mo,W:BVO. Our research elucidates the interactions within all-solid-state Z-scheme heterojunctions, outlining strategic approaches for crafting innovative and superior photocatalytic systems.

Exploring the supply and demand imbalance of carbon and carbon-related ecosystem services for dual­carbon goal ecological management in the Huaihe River Ecological Economic Belt.

The measurement of carbon and carbon-related ecosystem services (CCESs) has garnered considerable global attention, primarily due to dual­carbon goals, which are crucial for the rational allocating of ecosystem service (ES) resources and the enhancement of terrestrial carbon sinks. This study developed a novel research framework on CCESs to quantitatively measure carbon storage (CS), food production (FS), habitat quality (HQ), soil conservation (SC), and water yield (WY), and examined the spatiotemporal patterns of the supply-demand and trade-off/synergy processes related to CCESs in the Huaihe River Ecological Economic Belt (HREEB). The findings are as follows: (1) From 2000 to 2020, the supply-demand of the CCESs generally increased, except for carbon storage and food demand. Overall, the supply level of the CCESs exceeds the demand level, with a median ratio of supply and demand ratio (ESDR) of 1.13. (2) During the study period, the synergy relationship of the CCESs is mainly determined by the supply side of the CS-HQ and CS-SC, while on the demand side, it is determined by the CD- FD. And the ESDR of all C-related ecosystem services showed a significant synergy strengthening with CS in the HREEB. (3) Spatially, "high-low" spatial matching of the ESDR decreased, suggesting a gradual reduction in the spatial mismatch of CCESs. (4) We identified seven ecological functional zones and proposed corresponding strategies for promoting ecological management. Our research emphasized the spatiotemporal patterns of supply and demand imbalance in CCESs and the spatial optimization paths of trade-offs/synergies, providing valuable insights for achieving regional dual­carbon goals.

Finite-time tolerant containment control for IT2 T-S fuzzy network multi-agent systems with actuator faults, packet dropouts and DoS attacks.

This article studies finite-time tolerant containment control issue for uncertain nonlinear networked multi-agent systems (MASs) with actuator faults, denial-of-service (DoS) attacks and packet dropouts, under the framework of interval type-2 (IT2) Takagi-Sugeno (T-S) fuzzy method. Firstly, based on establishing the actuator fault models and introducing Bernoulli random distribution to represent the packet dropouts phenomenon, the IT2 T-S fuzzy network MASs under actuator faults and packet dropouts are constructed as switchable systems according to the attack situations on the communication channels. Secondly, the slack matrix with more information of lower and upper membership functions is introduced in the stability analysis to reduce conservatism. And on basis of Lyapunov stability theory and average dwell-time method, finite-time tolerant containment control protocol is proposed, which makes the follower' states converge to the convex hull controlled by the leaders in finite time. Finally, the effectiveness of the control protocol designed in this article is verified by numerical simulation.

Single-cell sequencing reveals effects of chemotherapy on the immune landscape and TCR/BCR clonal expansion in a relapsed ovarian cancer patient.

Cancer recurrence and chemoresistance are the leading causes of death in high-grade serous ovarian cancer (HGSOC) patients. However, the unique role of the immune environment in tumor progression for relapsed chemo-resistant patients remains elusive. In single-cell resolution, we characterized a comprehensive multi-dimensional cellular and immunological atlas from tumor, ascites, and peripheral blood of a chemo-resistant patient at different stages of treatment. Our results highlight a role in recurrence and chemoresistance of the immunosuppressive microenvironment in ascites, including MDSC-like myeloid and hypo-metabolic γδT cells, and of peripheral CD8+ effector T cells with chemotherapy-induced senescent/exhaustive. Importantly, paired TCR/BCR sequencing demonstrated relative conservation of TCR clonal expansion in hyper-expanded CD8+ T cells and extensive BCR clonal expansion without usage bias of V(D)J genes after chemotherapy. Thus, our study suggests strategies for ameliorating chemotherapy-induced immune impairment to improve the clinical outcome of HGSOC.

Hyphopichia xiaguanensis f.a., sp. nov., an ascomycetous yeast species isolated from plant leaves.

Two strains representing a novel yeast species were isolated from plant leaves collected in the Baotianman Nature Reserve in Henan Province, central China. Phylogenetic analysis based on the concatenated sequences of the internal transcribed spacer (ITS) region (ITS1-5.8S-ITS2) and the D1/D2 domain of the large subunit rRNA gene revealed that the novel species belonged to the genus Hyphopichia, although the formation of ascospores was not observed. The novel species was related most closely to Hyphopichia paragotoi CBS 13913T but they differed by 0.9 % sequence divergence (five substitutions) in the D1/D2 domain and by 3.7 % sequence divergence (seven substitutions and eight gaps) in the ITS region. Furthermore, the novel species can also be differentiated from the closely related species in some biochemical and physiological characteristics. The species name of Hyphopichia xiaguanensis f.a., sp. nov. (Holotype CBS 16668, Mycobank MB 842425) is proposed to accommodate strains NYNU 20899T and NYNU 20914.

Carbon hollow matrix anchored by isolated transition metal atoms serving as a single atom cocatalyst to facilitate the water oxidation kinetics of bismuth vanadate.

Here, nitrogen doped carbon hollow matrix anchored by isolated transition metal atoms (M@NC, M = Fe, Co or Ni) are firstly utilized as new single atom cocatalysts (SACCs) to enhance the PEC performance of Mo, W ions co-doped BiVO4 (Mo, W: BVO) through a simple spin-coating method. It is found that Mo, W: BVO modified with Fe@NC exhibits higher photocurrent density than the one decorated with Co@NC or Ni@NC due to the relatively low redox potential of Fe3+/Fe2+ (0.77 V vs SHE). During the photoelectrochemical (PEC) process, the Fe2+ ions are easier to accept the photogenerated holes of BVO and be oxidized to Fe3+ ions. Then, Fe3+ ions are reduced to Fe2+ again by accepting the electrons of water, and evolve oxygen simultaneously. Hence, Fe@NC could facilitate the water oxidation kinetics through the redox cycle of Fe ions and promote the charge separation efficiency by capturing the photogenerated holes. Theoretical calculations demonstrate that the deposition of Fe atoms make NC negatively charged, which is conducive to receiving the photogenerated holes. As a result, Mo, W: BVO/Fe@NC exhibits higher photocurrent density (3.2 mA/cm2 vs RHE) than other BVO-based samples. This work opens up a new application field of SACCs serving as OER cocatalysts, and may provide a universal strategy to construct the efficient PEC photoelectrodes.

Torulaspora jiuxiensis sp. nov., a novel yeast species isolated from rotting wood.

Two strains of a novel ascomycetous yeast species were isolated from rotting wood samples collected in Jiuxi Mountain Forest Park in Yunnan Province, southwest China. Both strains formed one or two spherical ascospores in persistent asci. Phylogenetic analysis of the concatenated sequences of the internal transcribed spacer (ITS) region (ITS1-5.8S-ITS2) and the D1/D2 domain of the large subunit rRNA gene revealed that the novel strains represented a phylogenetically distinct species belonging to the genus Torulaspora. This novel species differed from the type strains of the closest known species, Torulaspora nypae and Torulaspora maleeae, by 0.9 and 1.2 % nucleotide substitutions in the D1/D2 domain and 5.3 and 6 % nucleotide substitutions in the ITS region, respectively. The novel species can also be distinguished from T. nypae and T. maleeae in terms of the ability to assimilate ribitol, succinate and citrate, and its ability to grow at 37 °C. The species name of Torulaspora jiuxiensis sp. nov. is proposed with holotype CBS 16004T (Mycobank MB 844535).

Change of circulating lymphocyte subsets is related to disease activity and secondary infection in children with primary nephrotic syndrome-a retrospective study.

Background: Primary nephrotic syndrome (PNS) is an immune-mediated glomerular disease that often reoccurs. However, the characteristics of circulating lymphocyte subsets in PNS children remain unclear. Immunosuppressive therapy can lead to temporary or persistent remissions, but also increases the risk of infection, and whether the circulating lymphocyte subsets can be used to predict the secondary infection also remains unclear. Here, we explored the distribution of lymphocyte subpopulations in the different stages of PNS, and its predictive value of secondary infection in pediatric patients. Methods: We included 89 children who were first PNS episodes or diagnosed with PNS admitted to Nanfang Hospital from September 2019 to April 2021, and 19 healthy children were recruited as controls (C). PNS patients were divided into three groups according to their serum biochemical tests: active group (A), partial remission (PR) group, and complete remission (CR) group. PNS patients with infection symptoms were divided into a co-infection group, others were divided into the non-infection group. The peripheral lymphocyte subsets were analyzed by flow cytometry. The relationship between the peripheral lymphocyte subsets and PNS activity or infection was analyzed. Results: Compared to the healthy controls, the PNS patients' CD8+CD28+ T cell (TC) (C: 16.6%, 450.8/µL; A: 29.1%, P=0.000, 886.1/µL, P=0.012; PR: 25.7%, P=0.000, 817.3/µL, P=0.012; CR: 24.9%, P=0.001, 747.9/µL, P=0.020), and CD4+CD45RO+ ("memory" helper) T cells (C: 13.2%, 358.9/µL; A: 15.7%, P=0.036, 578.7/µL, P=0.001; PR: 17.6%, P=0.002, 610.0/µL, P=0.000; CR: 13.7%, P=0.676, 398.1/µL, P=0.525) were elevated. In addition, the regulatory T cells counts (non-infection: 117.9/µL; Co-infection: 73.3/µL, P=0.001) were significantly lower in patients with infection. We found that the predictive value measured by the area under the curve (AUC) showed that the AUC (t) Treg cell counts (61.5-84.5%) were almost always higher than the AUC for the (t) CD4+ T cell counts (55.1-77.1%). Conclusions: In this study, we found that T cell subpopulations had different characteristics in PNS during different disease phases. The CD8+CD28+ T cells, and CD4+CD45RO+ T cells increased at the disease quiescence of PNS. Moreover, CD4+ T cell subsets (regulatory T cell <82.5/µL) had higher predictive value than CD4+ T cell counts for PNS infection.

Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals.

Mucosal-associated invariant T (MAIT) cells have important functions in immune responses against pathogens and in diseases, but mechanisms controlling MAIT cell development and effector lineage differentiation remain unclear. Here, we report that IL-2/IL-15 receptor ß chain and inducible costimulatory (ICOS) not only serve as lineage-specific markers for IFN-γ-producing MAIT1 and IL-17A-producing MAIT17 cells, but are also important for their differentiation, respectively. Both IL-2 and IL-15 induce mTOR activation, T-bet upregulation, and subsequent MAIT cell, especially MAIT1 cell, expansion. By contrast, IL-1ß induces more MAIT17 than MAIT1 cells, while IL-23 alone promotes MAIT17 cell proliferation and survival, but synergizes with IL-1ß to induce strong MAIT17 cell expansion in an mTOR-dependent manner. Moreover, mTOR is dispensable for early MAIT cell development, yet pivotal for MAIT cell effector differentiation. Our results thus show that mTORC2 integrates signals from ICOS and IL-1ßR/IL-23R to exert a crucial role for MAIT17 differentiation, while the IL-2/IL-15R-mTORC1-T-bet axis ensures MAIT1 differentiation.

Dysregulated ICOS+ proinflammatory and suppressive regulatory T cells in patients with rheumatoid arthritis.

Regulatory T cells (Tregs) serve an important role in the pathogenesis of rheumatoid arthritis (RA) by regulating autoimmunity and inflammation. Humans and mice contain inducible T-cell costimulator-positive (ICOS+) Tregs, although their role in RA is unclear. A total of 33 patients with RA and 17 normal control (NC) subjects were examined. The proportion of ICOS+ Tregs in the peripheral blood and intracellular cytokine levels in these cells were assessed using flow cytometry. The percentage of ICOS+ Tregs increased in the cohort of patients with RA compared with the NCs. Such increases were much larger in patients with inactive RA compared with patients with active RA. Additionally, ICOS+ Tregs expressed multiple suppressive cytokines, including interleukin (IL)-10, transforming growth factor-ß and IL-35, but expressed low levels of IL-17. Importantly, the expression of suppressive cytokines in ICOS+ Tregs from patients with active RA decreased, but IL-17 expression noticeably increased compared with patients with inactive RA. The present findings suggested that ICOS+ Tregs may perform inflammatory and inhibitory functions, and abnormal ICOS+ Tregs numbers and functions may contribute to the pathogenesis of RA.

MicroRNA-146a-5p enhances ginsenoside Rh2-induced anti-proliferation and the apoptosis of the human liver cancer cell line HepG2.

Liver cancer is one of the leading causes of malignancy-associated mortality worldwide and its clinical therapy remains very challenging. Ginsenoside Rh2 (Rh2) has been reported to have antitumor effects on some types of cancer, including liver cancer. However, its regulatory mechanism has not been extensively evaluated. In the present study, Rh2 increased the expression of microRNA (miR)-200b-5p, miR-224-3p and miR-146a-5p, and decreased the expression of miR-26b-3p and miR-29a-5p. Of the three upregulated miRs, miR-146a-5p exhibited the highest fold elevation. In accordance with a previous study, Rh2 effectively inhibited the survival of liver cancer cells in vitro and in a mouse model. In addition, it was observed that Rh2 markedly promoted liver cancer apoptosis and inhibited colony formation. Cell apoptosis and the inhibition of cell survival as well as colony formation induced by Rh2 were enhanced and weakened by miR-146a-5p overexpression and inhibition, respectively. The results of the present study provide further evidence of the antitumor effect of Rh2 in liver cancer and also demonstrate that this effect may be mediated via the regulation of miR-146a-5p expression in the liver cancer cell line HepG2. The results indicated that miR-146a-5p may be a promising regulatory factor in Rh2-mediated effects in liver cancer.

NLRP3 in human glioma is correlated with increased WHO grade, and regulates cellular proliferation, apoptosis and metastasis via epithelial-mesenchymal transition and the PTEN/AKT signaling pathway.

Glioma is the most prevalent and fatal primary tumor of the central nervous system in adults, while the development of effective therapeutic strategies in clinical practice remain a challenge. Nucleotide-binding domain leucine-rich family pyrin-containing 3 (NLRP3) has been reported to be associated with tumorigenesis and progression; however, its expression and function in human glioma remain unclear. The present study was designed to explore the biological role and potential mechanism of NLRP3 in human glioma. The results demonstrated that overexpression of NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), caspase­1 and interleukin (IL)­1ß protein in human glioma tissues were significantly correlated with higher World Health Organization grades. The in vitro biological experiments demonstrated that NLRP3 downregulation significantly inhibited the proliferation, migration and invasion, and promoted the apoptosis of SHG44 and A172 glioma cell lines. Furthermore, western blot assays revealed that the downregulation of NLRP3 significantly reduced the expression of ASC, caspase­1 and IL­1ß protein. Furthermore, NLRP3 knockdown caused the inhibition of epithelial-mesenchymal transition (EMT), and inhibited the phosphorylation of AKT serine/threonine kinase (AKT) and phosphorylation of phosphatase and tensin homolog (PTEN). Consistently, the upregulation of NLRP3 significantly increased the expression of ASC, caspase­1, IL­1ß and phosphorylated-PTEN, promoted proliferation, migration, invasion and EMT, inhibited apoptosis, and activated the AKT signaling pathway. The data of the present study indicate that NLRP3 affects human glioma progression and metastasis through multiple pathways, including EMT and PTEN/AKT signaling pathway regulation, enhanced inflammasome activation, and undefined inflammasome-independent mechanisms. Understanding the biological effects of NLRP3 in human glioma and the underlying mechanisms may offer novel insights for the development of glioma clinical therapeutic strategies.

Comprehensive circular RNA profiles in plasma reveals that circular RNAs can be used as novel biomarkers for systemic lupus erythematosus.

Circular RNAs (circRNAs), a novel class of widespread endogenous noncoding RNAs, have been involved in the development of various diseases, including atherosclerosis, Alzheimer's disease and several types of cancers, but there is little knowledge about their associations with systemic lupus erythematosus (SLE). This study is aimed to identify the expression profiles of circRNAs in 6 paired SLE and normal participants plasma samples by using a circRNA microarray. The microarray analysis showed that 207 circRNAs were differentially expressed between these two groups, including 113 upregulated and 94 downregulated circRNAs. Then, we selected 8 circRNAs as candidate biomarkers from the microarray analysis and further verified them in another group of subjects consisting of 24 SLE patients and 24 normal controls using quantitative real-time polymerase chain reaction assays (qRT-PCR). Finally, we confirmed four circRNAs that were consistent with the microarray results. In addition, bioinformatics was employed to predict the interaction between validated circRNAs and potential miRNA targets. Taken together, we firstly illustrate the comprehensive expression profiles of circRNAs in SLE patients plasma and lay the foundations to develop circRNAs as novel non-invasive biomarkers for SLE disease in the future.

Interleukin-17A-Induced Epithelial-Mesenchymal Transition of Human Intrahepatic Biliary Epithelial Cells: Implications for Primary Biliary Cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune chronic liver disease with worldwide increasing morbidity. However, the etiology of PBC is still unclear. Recently, the epithelial-mesenchymal transition (EMT) and interleukin-17A (IL-17A), a pro-inflammatory cytokine, were proposed to be involved in the pathogenesis of PBC. Therefore, in this study, we aimed to clarify the roles of IL-17A and/or EMT in the onset of PBC. The results showed that the median serum IL-17A level was significantly higher in 29 PBC patients (average course of 40.69 months) than that of 11 healthy controls. The intrahepatic biliary epithelial cells (IBECs), the major target of destruction in PBC, underwent EMT in PBC patients. The immunohistochemical analysis revealed that the protein levels of IL-17A receptor were increased in IBECs and the IL-17A protein was accumulated around the IBECs in the PBC patients. These results imply that the IL-17A-mediated signaling and EMT of intrahepatic biliary epithelial cells (IBEC-EMT) are key pathogenic processes of PBC. To study the association between IL-17A and IBECs-EMT, we then examined if IL-17A induced EMT using a human cell line of IBECs (HIBECs). After the treatment with IL-17A for 48 h, HIBECs changed into bipolar cells with a fibroblastic morphology. Additionally, the results of real-time PCR and Western blot analyses demonstrated that IL-17A up-regulated the expression of a mesenchymal marker vimentin and down-regulated the expression of an epithelial marker E-cadherin in HIBECs in the dose- and time-dependent manners. These results suggest that IL-17A may play an important role in the IBECs-EMT.

Long non-coding RNA RP5-833A20.1 inhibits proliferation, metastasis and cell cycle progression by suppressing the expression of NFIA in U251 cells.

Early reports suggest that nuclear factor IA (NFIA) is important in the pathogenesis of glioma. Our previous study demonstrated that the long non­coding RNA (lncRNA), RP5­833A20.1, suppressed the expression of NFIA in THP­1 macrophage-derived foam cells. However, the effect and possible mechanism of RP5­833A20.1 on glioma remains to be fully elucidated, and whether the NFIA-dependent pathway is involved in its progression has not been investigated. In the present study, the mechanisms by which RP5­833A20.1 regulates the expression of NFIA in glioma were investigated. The expression levels of RP5­833A20.1 and NFIA were determined in U251 cells and clinical samples using reverse transcription­quantitative polymerase chain reaction (PCR) analysis. The effects of RP5­833A20.1 on cell proliferation, invasion, cell cycle and apoptosis were evaluated using in vitro assays. The potential changes in protein expression were investigated using western blot analysis. The methylation status of the CpG island in the NFIA promoter was determined using bisulfite PCR (BSP) sequencing. It was found that the expression of RP5­833A20.1 was downregulated, whereas the expression of NFIA was upregulated in glioma tissues, compared with corresponding adjacent nontumor tissues from 20 patients with glioma. The overexpression of RP5­833A20.1 inhibited proliferation and cell cycle progression, and induced apoptosis in the U251 cells. The mRNA and protein levels of NFIA were markedly inhibited by overexpression of RP5­833A20.1 in the U251 cells. The overexpression of RP5­833A20.1 increased the expression of microRNA­382­5p in the U251 cells. The BSP assay revealed that the overexpression of RP5­833A20.1 enhanced the methylation level of the NFIA promoter. These results demonstrated that RP5­833A20.1 inhibited tumor cell proliferation, induced apoptosis and inhibited cell­cycle progression by suppressing the expression of NFIA in U251 cells. Collectively, these results indicated RP5­833A20.1 as a novel therapeutic target for glioma.

Antinociceptive effects of dehydrocorydaline in mouse models of inflammatory pain involve the opioid receptor and inflammatory cytokines.

Dehydrocorydaline (DHC) is an alkaloidal component isolated from Rhizoma corydalis. Previous studies have shown that DHC has anti-inflammatory and anti-tumor effects and that it can protect the cardiovascular system. However, there are few studies of the antinociceptive effects of DHC in vivo. This study explored the antinociceptive effects and possible mechanisms of DHC in mice using two inflammatory pain models: the acetic acid-induced writhing test and the formalin paw test. The intraperitoneal administration of DHC (3.6, 6 or 10 mg/kg) showed a dose-dependent antinociceptive effect in the acetic acid-induced writhing test and significantly attenuated the formalin-induced pain responses in mice. The antinociceptive effects of DHC were not associated with changes in the locomotor activity or motor responses of animals, and no obvious acute or chronic toxic effects were observed in the mice. Furthermore, the use of naloxone confirmed the involvement of the opioid receptor in the central antinociceptive effects of DHC. DHC reduced formalin-induced paw edema, which indicated that DHC may produce an anti-inflammatory effect in the periphery. In the formalin test, DHC decreased the expression of caspase 6 (CASP6), TNF-α, IL-1ß and IL-6 proteins in the spinal cord. These findings confirm that DHC has antinociceptive effects in mice.

mTORC2 in Thymic Epithelial Cells Controls Thymopoiesis and T Cell Development.

Thymic epithelial cells (TECs) play important roles in T cell generation. Mechanisms that control TEC development and function are still not well defined. The mammalian or mechanistic target of rapamycin complex (mTORC)2 signals to regulate cell survival, nutrient uptake, and metabolism. We report in the present study that mice with TEC-specific ablation of Rictor, a critical and unique adaptor molecule in mTORC2, display thymic atrophy, which accompanies decreased TEC numbers in the medulla. Moreover, generation of multiple T cell lineages, including conventional TCRαß T cells, regulatory T cells, invariant NKT cells, and TCRγδ T cells, was reduced in TEC-specific Rictor-deficient mice. Our data demonstrate that mTORC2 in TECs is important for normal thymopoiesis and efficient T cell generation.

[Role of glycogen synthase kinase 3ß in maturation and function of murine myeloid dendritic cells in vitro].

OBJECTIVE: To investigate the role of glycogen synthase kinase 3ß (GSK-3ß) in the maturation and function of murine bone marrow-derived dendritic cells (BMDCs). METHODS: Mature DCs (mDCs) induced by LPS were examined for GSK-3ß phosphorylation level with Western blotting before and after LPS exposure. To explore the role of GSK-3ß in maturation and function of DCs, we added SB216763, a selective inhibitor of GSK-3ß, in the cell culture of immature DCs (iDCs), and examined CD40 and CD86 expressions in the cells by flow cytometry and the expression of IL-6, IL-12 and IL-10 mRNA by real-time PCR; the changes of the immunogenicity of the cells was evaluated by mixed lymphocyte reaction. The expression of GSK-3ß and RelB was examined by Western blotting in DC2.4 cells transfected with a lentiviral vector over-expressing murine GSK-3ß gene. RESULTS: LPS exposure significantly lowered GSK-3ß activity in iDCs as demonstrated by increased Ser9 phosphorylation and reduced Tyr216 phosphorylation. GSK-3ß inhibition induced DC maturation by increasing the expression of surface costimulatory molecules CD40 and CD86, lowered the expressions of IL-6 and IL-12 while enhanced the expression of IL-10 in iDCs, and impaired mixed lymphocyte reaction of the cells. In DC2.4 cells, lentivirus-mediated over-expression of GSK-3ß obviously down-regulated the expression of RelB. CONCLUSIONS: GSK-3ß is a crucial enzyme involved in the differentiation and maintenance of an immature phenotype of DCs. GSK-3ß is constitutively active in iDCs to inhibit their spontaneous maturation. DCs become phenotypically mature after inhibition of GSK-3ß, which also executes a proinflammatory task in DC activation. The reduction of RelB protein levels as a result of GSK-3ß overexpression supports GSK-3ß as a new target for inducing tolerogenic DCs.