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Inflammation leads to systemic osteoporosis or local bone destruction, however, the underlying molecular mechanisms are still poorly understood. In this study, we report that PRL2 is a negative regulator of osteoclastogenesis and bone absorption. Mice with PRL2 deficiency exhibit a decrease in bone volume and an increase in osteoclast numbers. PRL2 negatively regulates RANKL-induced reactive oxygen species production through the activation of RAC1, thus PRL2 deficient osteoclast precursors have both increased osteoclast differentiation ability and bone resorptive capacity. During inflammation, oxidized PRL2 is a selected substrate of HSC70 and conditions of oxidative stress trigger rapid degradation of PRL2 by HSC70 mediated endosomal microautophagy and chaperone-mediated autophagy. Ablation of PRL2 in mouse models of inflammatory bone disease leads to an increase in the number of osteoclasts and exacerbation of bone damage. Moreover, reduced PRL2 protein levels in peripheral myeloid cells are highly correlated with bone destruction in a mouse arthritis model and in human rheumatoid arthritis, while the autophagy inhibitor hydroxychloroquine blocked inflammation-induced PRL2 degradation and bone destruction in vivo. Therefore, our findings identify PRL2 as a new regulator in osteoimmunity, providing a link between inflammation and osteoporosis. As such, PRL2 is a potential therapeutic target for inflammatory bone disease and inhibition of HSC70 mediated autophagic degradation of PRL2 may offer new therapeutic tools for the treatment of inflammatory bone disease.

As a nutrients reservoir of surface-flow constructed wetlands (SFCWs), the substrate plays an important role in water purification, and it is significant to investigate the accumulation and release characteristics of nutrients to maximize the efficiency of constructed wetlands (CWs) for wastewater purification. In this study, we analyzed the total nitrogen (TN), total phosphorus (TP) and organic matter (OM) in the bottom sediment and conducted static release experiments on column core samples in order to evaluate the accumulation characteristics of nutrients and the current status of the ecological water environment in the SFCWs of Mata Lake, which has been in operation for 6 years. Results showed that: (1) The average contents of TN, TP and OM were 2.30 ± 0.006 g/kg, 0.26 ± 0.0006 g/kg and 10.49 ± 0.04 g/kg, respectively. There were differences in the spatial distribution of nutrients based on ArcGIS spatial interpolation simulation analysis. (2) The organic index (Org-index) in the sediment was evaluated as lightly polluted and the TP was evaluated as clean, but the organic nitrogen (Org-N) index was evaluated as heavily polluted. (3) The release amount of nutrients in the static release experiment showed a general trend of ascending and then descending, and the maximum release rate was observed between 9 and 12 days.

T follicular helper (Tfh) cells with the phenotype of mainly expressing surface molecules C-X-C motif chemokine receptor type 5 (CXCR5), inducible co-stimulator (ICOS), secreting cytokine interleukin-21 (IL-21) and requiring the transcription factor B cell lymphoma 6 (BCL-6) have been recently defined as a new subset of CD4

This work developed an environmentally-friendly soil remediation method based on BC and g-C

Intestinal stromal cells are known to modulate the propagation and differentiation of intestinal stem cells1,2. However, the precise cellular and molecular mechanisms by which this diverse stromal cell population maintains tissue homeostasis and repair are poorly understood. Here we describe a subset of intestinal stromal cells, named MAP3K2-regulated intestinal stromal cells (MRISCs), and show that they are the primary cellular source of the WNT agonist R-spondin 1 following intestinal injury in mice. MRISCs, which are epigenetically and transcriptomically distinct from subsets of intestinal stromal cells that have previously been reported3–6, are strategically localized at the bases of colon crypts, and function to maintain LGR5+ intestinal stem cells and protect against acute intestinal damage through enhanced R-spondin 1 production. Mechanistically, this MAP3K2 specific function is mediated by a previously unknown reactive oxygen species (ROS)–MAP3K2–ERK5–KLF2 axis to enhance production of R-spondin 1. Our results identify MRISCs as a key component of an intestinal stem cell niche that specifically depends on MAP3K2 to augment WNT signalling for the regeneration of damaged intestine. A subset of intestinal stromal cells that is regulated by the kinase MAP3K2 protects intestinal stem cells against injury by producing the WNT agonist R-spondin 1.

BackgroundThe four major RNA adenosine modifications, i.e., m6A, m1A, alternative polyadenylation, and adenosine-to-inosine RNA editing, are mediated mostly by the “writer” enzymes and constitute critical mechanisms of epigenetic regulation in immune response and tumorigenesis. However, the cross-talk and potential roles of these “writers” in the tumor microenvironment (TME), drug sensitivity, and immunotherapy remain unknown.MethodsWe systematically characterized mRNA expression and genetic alterations of 26 RNA modification “writers” in colorectal cancer (CRC), and evaluated their expression pattern in 1697 CRC samples from 8 datasets. We used an unsupervised clustering method to assign the samples into two patterns of expression of RNA modification “writers”. Subsequently, we constructed the RNA modification “writer” Score (WM_Score) model based on differentially expressed genes (DEGs) responsible for the RNA modification patterns to quantify the RNA modification-related subtypes of individual tumors. Furthermore, we performed association analysis for WM_Score and characteristics of TME, consensus molecular subtypes (CMSs), clinical features, transcriptional and post-transcriptional regulation, drug response, and the efficacy of immunotherapy.ResultsWe demonstrated that multi-layer alterations of RNA modification “writer” are associated with patient survival and TME cell-infiltrating characteristics. We identified two distinct RNA modification patterns, characterized by a high and a low WM_Score. The WM_Score-high group was associated with worse patient overall survival and with the infiltration of inhibitory immune cells, such as M2 macrophages, EMT activation, and metastasis, while the WM_Score-low group was associated with a survival advantage, apoptosis, and cell cycle signaling pathways. WM_Score correlated highly with the regulation of transcription and post-transcriptional events contributing to the development of CRC. In response to anti-cancer drugs, WM_Score highly negatively correlated (drug sensitive) with drugs which targeted oncogenic related pathways, such as MAPK, EGFR, and mTOR signaling pathways, positively correlated (drug resistance) with drugs which targeted in apoptosis and cell cycle. Importantly, the WM_Score was associated with the therapeutic efficacy of PD-L1 blockade, suggesting that the development of potential drugs targeting these “writers” to aid the clinical benefits of immunotherapy.ConclusionsOur study is the first to provide a comprehensive analysis of four RNA modifications in CRC. We revealed the potential function of these writers in TME, transcriptional and post-transcriptional events, and identified their therapeutic liability in targeted therapy and immunotherapy. This work highlights the cross-talk and potential clinical utility of RNA modification “writers” in cancer therapy.

Imbalance of macrophage polarization plays an indispensable role in acute lung injury (ALI), which is considered as a promising target. Matrix metalloproteinase-9 (MMP-9) is expressed in the macrophage, and has a pivotal role in secreting inflammatory cytokines. We reported that saquinavir (SQV), a first-generation human immunodeficiency virus-protease inhibitor, restricted exaggerated inflammatory response. However, whether MMP-9 could regulate macrophage polarization and inhibit by SQV is still unknown. We focused on the important role of macrophage polarization in CLP (cecal ligation puncture)-mediated ALI and determined the ability of SQV to maintain M2 over M1 phenotype partially through the inhibition of MMP-9. We also performed a limited clinical study to determine if MMP-9 is a biomarker of sepsis. Lipopolysaccharide (LPS) increased MMP-9 expression and recombinant MMP-9 (rMMP-9) exacerbated LPS-mediated M1 switching. Small interfering RNA to MMP-9 inhibited LPS-mediated M1 phenotype and SQV inhibition of this switching was reversed with rMMP-9, suggesting an important role for MMP-9 in mediating LPS-induced M1 phenotype. MMP-9 messenger RNA levels in peripheral blood mononuclear cells of these 14 patients correlated with their clinical assessment. There was a significant dose-dependent decrease in mortality and ALI after CLP with SQV. SQV significantly inhibited LPS-mediated M1 phenotype and increased M2 phenotype in cultured RAW 264.7 and primary murine bone marrow-derived macrophages as well as lung macrophages from CLP-treated mice. This study supports an important role for MMP-9 in macrophage phenotypic switching and suggests that SQV-mediated inhibition of MMP-9 may be involved in suppressing ALI during systemic sepsis.

γ-Tocotrienol (GT3), a member of the vitamin E family, is well known for its medicinal value in clinical treatments. However, the role of GT3 in T helper 17 (Th17)/regulatory T cell (Treg) differentiation and function is not fully understood. Here, we demonstrated that GT3 suppressed Th17 differentiation in vitro by inhibiting signal transducer and activator of transcription 3 (STAT3) phosphorylation in the interleukin 6 (IL-6)/Janus kinase (JAK)/STAT3 signaling pathway. GT3 also inhibited HIF1A expression in Th17 metabolism. Additionally, we showed that GT3 treatment inhibited disease aggravation in an imiquimod (IMQ)-induced psoriasis-like mouse model by reducing the percentage of Th17 cells in the spleen in vivo. The findings of this study demonstrated the effects of GT3 on Th17 cells through the STAT3 signaling pathway.

The adsorption mechanism of Cr6+ on biochar prepared from corn stalks (raw carbon) was studied by extracting the organic components (OC) and inorganic components (IC). Scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy were used to characterize the properties of three kinds of carbon. Kinetic and thermodynamic experiments were performed. The results showed that the experimental data were fitted well by the Freundlich model and the pseudo-second-order kinetic model, and the adsorptions on the three kinds of carbon were all spontaneous, endothermic processes. The adsorption of Cr6+ by biochar was in accordance with a chemisorption process. The adsorption contribution rate of the OC was 97%, which was much higher than that of the IC. Electrostatic attraction and redox reaction were the main mechanisms of adsorption, and among them, the contribution rate of the redox reaction accounted for 61.49%. The reduced Cr3+ could both exchange ions with K+ and dissociate into solution by electrostatic repulsion; the amount of Cr3+ released into the solution was approximately 17.07 mg/g, and the amount of Cr3+ ions exchanged with K+ was 0.29 mg/g. These results further elucidate the adsorption mechanism of Cr6+ by biochar.

T cell-mediated immunity in the intestine is stringently controlled to ensure proper immunity against pathogenic microbes and to prevent autoimmunity, a known cause of inflammatory bowel disease. However, precisely how T cells regulate intestine immunity remains to be fully understood. In this study, we found that mitogen-activated protein kinase kinase kinase 2 (MAP3K2) is required for the CD4+ T cell-mediated inflammation in the intestine. Using a T cell transfer colitis model, we found that MAP3K2-deficient naive CD4 T cells had a dramatically reduced ability to induce colitis compared to wild type T cells. In addition, significantly fewer IFN-γ- but more IL-17A-producing CD4+ T cells in the intestines of mice receiving MAP3K2-deficient T cells than in those from mice receiving wild type T cells was observed. Interestingly, under well-defined in vitro differentiation conditions, MAP3K2-deficient naive T cells were not impaired in their ability to differentiate into Th1, Th17 and Treg. Furthermore, the MAP3K2-regulated colitis severity was mediated by Th1 but not Th17 cells in the intestine. At the molecular level, we showed that MAP3K2-mediated Th1 cell differentiation in the intestine was regulated by IL-18 and required specific JNK activation. Together, our study reveals a novel regulatory role of MAP3K2 in intestinal T cell immunity via the IL-18-MAP3K2-JNK axis and may provide a novel target for intervention in T cell-mediated colitis.

Pollution from polycyclic aromatic hydrocarbons (PAHs) spreads and changes worldwide. The pollution evolution in the regional water environment evolves in response to multiple factors, requiring considerable attention. PAH heterogeneity in the sediment core from Chaihe Reservoir was investigated to indicate dynamic changes in PAH pollution levels and sources and propose recommendations for controlling PAHs. Dynamic PAH patterns showed that the overall decline in PAH pollution was in association with local anthropogenic activities, temperature, and precipitation over the period 1863-2018. Nevertheless, coal, oil, and natural gas consumptions still played significant roles in transferring PAHs to the reservoir. Meanwhile, there were dominant local origins, including grass, wood, and coal combustion. The results highlight that the joint action of natural and anthropogenic interventions mitigated PAH pollution in the reservoir. Promoting improved fuels, new energy vehicles, and cleaner energy may further lower PAH pollution.

Lake sediment records the evolution process of the interaction between human and nature. It is important to master the lacustrine sedimentation rate for the ecological environment assessment of catchment. A 60-cm sediment core was collected in the Da River Reservoir during 2019 to analyze radionuclides (

To remove NO3-N from water, coconut shell biochar (CSB) was modified by a solution of FeCl3, a solution of AlCl3 and a mixture solution of FeCl3 and AlCl3 respectively. The obtained modified biochar with the best effect of NO3-N adsorption was screened out to explore the adsorption behavior and mechanism of NO3-N removal by batch experiments and kinetics and thermodynamics and correlated characterization. The results indicated that the mixture solution of FeCl3- and AlCl3- modified CSB (Fe-Al/CSB) showed the best adsorption performance for NO3-N removal. Iron and aluminum elements existed on the surface of Fe-Al/CSB in the form of FeOOH, Fe2O3, Fe2+, and Al2O3 respectively. The adsorption process could reach equilibrium in 20 min. An acidic condition was favorable for NO3-N adsorption. The presence of coexisting anions was not conducive for NO3-N adsorption. The quasi-second-order model and Freundlich model could be well fitted in the adsorption process. The maximum adsorption capacity of Fe-Al/CSB fitted by the Langmuir model could reach 34.20 mg/g. The adsorption of NO3-N by Fe-Al/CSB was an endothermic and spontaneous process. Ligand exchange and chemical redox reaction were the NO3-N adsorption mechanisms which led to NO3-N adsorption by Fe-Al/CSB.

Prostaglandin E2 (PGE2) is a lipid mediator derived from the fatty acid arachidonic acid. As an essential inflammatory factor, PGE2 has a critical impact on immune regulation through the prostanoid E (EP) receptor pathway. T cells, including CD4+ and CD8+ T cell subsets, play crucial roles in the adaptive immune response. Previous studies have shown that PGE2 is involved in regulating CD4+ T cell differentiation and inflammatory cytokine production via the EP receptor pathway, thereby affecting the development of diseases mediated by CD4+ T cells. In this review, we summarize the signaling pathway of PGE2 and describe the relationship between PGE2 and T cell differentiation. Hence, this review may provide important evidence for immune therapies and may even promote the development of biomedicines.

Additional file 1 : Figure S1. Overview of study design. (A) Flowchart of the steps in the performed analyses. Figure S2. Analysis of mutation frequency and CNV in TCGA- COAD/READ. (A) The mutation frequency of RNA modification “writers” among 33 cancer types in the TCGA cohort. The horizontal axis represents cancer types, and the number of samples is given in the parentheses. The vertical axis lists the names of the genes. (B) Comparison of GSEA enrichment analysis between “writers” mutation samples and non-mutation samples. NES, Normalized enrichment score. (C) The distribution of correlation coefficient between “writers” expression and CNV in CRC. |Rs| > 0.3 and p value

In order to further explore the adsorption mechanism of chromium ion by biochar, organic components (OCs) and inorganic components (ICs) of biochar (RC) were prepared, and adsorption experiments of chromium ions by these types of carbon (RC, OC, IC) were performed. The three types of carbon were characterized before and after adsorption of chromium ions, using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Boehm titration, and zero charge (pHpzc). Results showed that the adsorption efficiency of IC on trivalent chromium (Cr3+) was the strongest, ion exchange of Cr3+ with metal cations present on IC being the main adsorption mechanism, accounting for 61% of the total adsorption capacity. Among the metal ions, K+ accounted for about 51%. The REDOX between Cr3+ and carboxyl accounted for 20% of the total adsorption capacity. Other adsorption mechanisms, such as chelation between Cr3+ and carboxyl, and co-precipitation between Cr3+ and carbonate, occupied a small proportion. OC showed the largest adsorption capacity to hexavalent chromium (Cr6+). The adsorption mechanism of OC to Cr6+ was the result of combined actions, such as electrostatic attraction, and REDOX between Cr6+ with the aromatic π-conjugated system and reductive functional groups like hydroxyl. Among them, the REDOX accounted for 53% of the total adsorption of Cr6+ by OC.

The adsorption mechanisms of mercury ion (Hg2+) by different fractions of biochar were studied, providing a theoretical basis and practical value for the use of biochar to remediate mercury contamination in water. Biochar (RC) was prepared using corn straw as the raw material. It was then fractionated, resulting in inorganic carbon (IC), organic carbon (OC), hydroxyl-blocked carbon (BHC), and carboxyl-blocked carbon (BCC). Before and after Hg2+ adsorption, the biochar fractions were characterized by several techniques, such as energy-dispersive X-ray spectroscopy (EDS), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Obtained results indicate that the reaction mechanisms of RC for Hg2+ removal mainly include electrostatic adsorption, ion exchange, reduction, precipitation, and complexation. The equilibrium adsorption capacity of RC for Hg2+ is 75.56 mg/g, and the adsorption contribution rates of IC and OC are approximately 22.4% and 77.6%, respectively. Despite the lower rate, IC shows the largest adsorption capacity, of 92.63 mg/g. This is attributed to all the mechanisms involved in Hg2+ adsorption by IC, with ion exchange being the main reaction mechanism (accounting for 39.8%). The main adsorption mechanism of OC is the complexation of carboxyl and hydroxyl groups with Hg2+, accounting for 71.6% of the total OC contribution. BHC and BCC adsorb mercury mainly via the reduction&ndash, adsorption mechanism, accounting for 54.6% and 54.5%, respectively. Among all the adsorption mechanisms, the complexation reaction of carboxyl and hydroxyl groups with Hg2+ is the dominant effect.

In this study, the concentrations of seven heavy metals (Cr, Ni, Cu, Zn, As, Hg, and Pb) and Pb isotope in a sediment core from the Shuanglong reservoir, Southwestern China, were investigated. Based on the constant rate of supply (CRS) model, the age span of a 60 cm sediment sample was determined to range from the years 1944 to 2015. Combined with chronology and heavy metal content, the evolution of the sources and pollution levels of heavy metals showed a changing trend composed of various stages. The sources of heavy metals transitioned from natural origins in 1944&ndash, 1964 to industrial origins in 1965&ndash, 2004. The subsequent reduction in heavy metal content was mainly due to the vigorous implementation of environmental protection policies from 2005 to 2012. In recent years (2013&ndash, 2015), the heavy metal content has increased due to frequent human activity. Principal component analysis (PCA), correlation analysis, and the coefficient of variation (CV) analysis indicated that Cr, Ni, Cu, Zn, and As were derived from natural processes, Pb mainly came from automobile manufacturing, and Hg was mainly from industrial sources. The values of the geo-accumulation index (Ig), single pollution index (Pi), and single potential ecological risk index (Er) showed that the contamination of Hg and Pb was slight to moderate. Moreover, the values of the potential ecological risk index (RI), pollution load index (PLI), and Nemerow index (PN) indicated that the Shuanglong reservoir is under low ecological risk.

Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are neuroinflammatory autoimmune diseases characterized by the axonal loss, demyelination, and neurodegeneration of the central nervous system. Overactivation of CD4+ T cells, especially the migration of the Th1 and Th17 subsets into the central nervous system (CNS), leads to the secretion of inflammatory mediators and destruction of the contact between neurons and activated macrophages, which can then result in a series of neurocognitive and motor deficits. In this study, we intended to explore the role of miRNA-467b in regulating Th cell development in EAE. We found that the level of miRNA-467b was decreased and eukaryotic initiation factor 4 F (eIF4E) was increased in lymph nodes and the CNS at EAE peak. eIF4E was confirmed as the direct target of miRNA467b. Overexpression of miRNA-467b could suppress a percentage of CD4+ IL-17+ cells in EAE CD4 + T cells in vitro. In addition, we also identified miRNA-467b, which could suppress Th17 cell differentiation by targeting eIF4E in vitro. Furthermore, injecting miRNA-467b mimics into the caudal vein of EAE mice contributed to less inflammation in the peripheral lymphoid organs and CNS and alleviated disease severity. Taken together, our findings imply that miRNA-467b inhibits the differentiation and function of Th17 cells by targeting eIF4E, thereby alleviating EAE.

To remove NO

In the last few decades, the eutrophication of lakes has been a serious issue in the middle and lower reaches of the Yangtze River watershed. To explore the relationship between lake systems and anthropogenic activities, sediments were collected from the Shuanglong reservoir in the Dianchi watershed in Southwest China. Total nitrogen (TN), total phosphorus (TP), total organic carbon (TOC), and the carbon isotopic ratio (δ13C) were analyzed in sediment cores to reconstruct the effects of natural succession and human activities on the past lacustrine environmental conditions. A reliable chronology of the sediment core was established by using the 210Pb dating technique, which indicated that the age span of the 70-cm sediment core is from the years 1871 to 2011. Above – 31 cm depth in the core, TN, TP, TOC, C/N, and δ13C increased significantly, indicating that eutrophication has occurred since the 1980s. By combining the indicators of δ13C and C/N, it was shown that terrestrial and lacustrine components were the main sources of organic matter (OM) in the reservoir, which was mostly controlled by terrestrial C3 plants and algae. Since the 1980s, increased sewage discharge, fish aquaculture, fertilizer application, population, and economic strength have sped up the eutrophication process, and the eutrophication was further intensified in 2001.

BACKGROUND HSP60-related immunological activities are found in normal-pressure glaucoma (NPG) patients, in whom an elevated intraocular pressure (IOP) found in primary open-angle glaucoma (POAG) is not observed. HSP60 was found in POAG and NPG patients, while anti-HSP60 level was mainly found to be higher in NPG patients. The purpose of this study was to compare the percentages of Th cells and levels of related cytokines, attempting to provide evidence to explain this discrepancy. MATERIAL AND METHODS Blood samples from POAG, NPG, and normal control (NC) groups were collected and peripheral blood monocytes were isolated and cultured with or without the stimulation of HSP60. Flow cytometry and enzyme-linked immunosorbent assay were used to assess the percentages of Th1, Th2, Th17, and Treg cells, as well as HSP60 antibody levels and related cytokine levels, before and after culture. RESULTS Significantly higher titers of anti-HSP60 were observed only in NPG patients. Comparable Th1 and Th2 cell frequencies, IL-4 level, and IFN-γ level were found in POAG and NPG patients, while higher Treg cell frequency was only found in POAG patients. After culturing with HSP60, increased Th2 frequencies and decreased Th1 frequencies were observed in the POAG, NPG, and NC groups, while increased Treg frequency was only identified in the POAG and NC groups. CONCLUSIONS Different Th cell patterns were observed among POAG, NPG, and NC groups. Lack of induction of Treg cells and imbalance of the pro-inflammatory and anti-inflammatory response patterns of Th cells exist in some NPG patients.

The innate immune sensor NLRP3 assembles an inflammasome complex with NEK7 and ASC to activate caspase‐1 and drive the maturation of proinflammatory cytokines IL‐1β and IL‐18. NLRP3 inflammasome activity must be tightly controlled, as its over‐activation is involved in the pathogenesis of inflammatory diseases. Here, we show that NLRP3 inflammasome activation is suppressed by a centrosomal protein Spata2. Spata2 deficiency enhances NLRP3 inflammasome activity both in the macrophages and in an animal model of peritonitis. Mechanistically, Spata2 recruits the deubiquitinase CYLD to the centrosome for deubiquitination of polo‐like kinase 4 (PLK4), the master regulator of centrosome duplication. Deubiquitination of PLK4 facilitates its binding to and phosphorylation of NEK7 at Ser204. NEK7 phosphorylation in turn attenuates NEK7 and NLRP3 interaction, which is required for NLRP3 inflammasome activation. Pharmacological or shRNA‐mediated inhibition of PLK4, or mutation of the NEK7 Ser204 phosphorylation site, augments NEK7 interaction with NLRP3 and causes increased NLRP3 inflammasome activation. Our study unravels a novel centrosomal regulatory pathway of inflammasome activation and may provide new therapeutic targets for the treatment of NLRP3‐associated inflammatory diseases.

SummaryIntestinal stem cell propagation and differentiation are essential for rapid repair of tissue damage in the gut. While intestinal stromal cells were recently identified as key mediators of this process, the cellular and molecular mechanisms by which this diverse population induces tissue repair remains poorly understood. Here we show that Map3k2 has a colon stromal cell specific function critically required for maintenance of Lgr5+ intestinal stem cells and protection against acute intestinal damage. This Map3k2-specific function is mediated by enhancing Wnt agonist R-spondin1 production. We further reveal a unique novel cell population, named Map3k2-regulated intestinal stromal cells (MRISC), as the primary cellular source of R-spondin1 following intestinal injury. Together, our data identify a novel intestinal stem cell niche organized by MRISC, which specifically dependent on the Map3k2-signaling pathway to augment the production of Wnt agonist R-spondin1 and promote regeneration of the acutely damaged intestine.HighlightsMap3k2 protects mice from DSS-induced colitis by promoting intestinal stem cell regeneration.Map3k2-MAPK pathway cross-talks with Wnt signaling pathway via upregulation of R-spondin1.Map3k2-Regulated Intestinal Stromal Cells (MRISC) marked by co-expression of CD90, CD34 and CD81 defines a novel colonic stem cell niche.

Black odorous water contains abundant organics and nutrients, such as nitrogen and phosphorus, which would lead to eutrophication of the water body and affect the water environment. In this study, the eutrophic water body in the campus landscape was taken as the research object, and the biological contact oxidation (BCO) method and co-cultivated indigenous microorganisms were adopted to pretreat black odorous water. Inoculating mutant strain M1 through ultraviolet-B radiation formed algae-bacteria symbiosis system in optimal effluent. The results showed that under the conditions of dissolved oxygen (DO) concentration of 5 mg/L, light intensity of 3000 Lx and inoculum size of 125,000 cells/mL, the optimal organic migration effect was achieved by the combined process. In addition, the ability of H. pluvialis to transform from green vegetative cells to red cyst cells under stressful conditions (strong light, nitrogen starvation, etc.) made it as an indicator for monitoring the degradation status of pollutants in black odorous water.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by bone loss. Degree of inflammation has been identified as an important initiator of skeletal damage in RA. Iguratimod (T-614) is an anti-inflammatory agent which has been reported to show the inhibitory effect of bone destruction in RA. However, the role of T-614 in osteoblast differentiation is still not clear. In this study, we intended to find the effect of T-614 on the osteogenesis process. We detected osteogenesis markers and transcription factors associated with osteoblastic lineage and bone formation in the culture of mesenchymal stem cells which differentiate osteoblast. The contents and activity of alkaline phosphatase, levels of collagen type I and bone gla protein, and calcium nodule formation were increased significantly after T-614 treated. Meanwhile, the mRNAs expressions of Osterix and Dlx5 were also found to be increased significantly by real-time PCR. The changes of levels of phosphorylation of p38 and NF-κB were also detected by Western blot. The results showed that T-614 promotes osteoblastic differentiation by increasing the expression of Osterix and Dlx5 and increasing the activation of P38. T-614 could advance the ectopic expression of NF-κB to suppress inflammation, which indirectly inhibits the damage of the osteoblasts.

Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are chronic neuroinflammatory autoimmune diseases characterized by axonal loss, demyelination and neurodegeneration of the central nervous system (CNS). Overactivation of CD4(+)T cells, especially the Th1 and Th17 subsets, is thought to play a causal role in this disease. In this study, we investigated the immunomodulatory effects of IFN-β treatment in EAE. IFN-β significantly inhibits disease severity, and decreases levels of CCR2, CCR4, CCR5, CCR6 and CXCR3 in the CNS. This was associated with fewer Th1/Th17 cells expressing these chemokine receptors. Furthermore, levels of their corresponding ligands CCL2, CCL3, CCL4, CCL5, CCL20, CCL22 and CXCL10 were also reduced, coinciding with reduced CNS inflammation and demyelination. Chemokine expression significantly correlated with disease severity. Furthermore, we demonstrate that IFN-β reduces CCL2/CCL5 induced-T cell migration by inhibiting p38-MAPK and ERK1/2 activation. Our results reveal that IFN-β reduces the expression of chemokines and chemokine receptors expressed by encephalitogenic Th1/Th17 cells, thereby decreasing their migration into the CNS.