Blocking DCIR mitigates colitis and prevents colorectal tumors by enhancing the GM-CSF-STAT5 pathway.

Dendritic cell immunoreceptor (DCIR; Clec4a2), a member of the C-type lectin receptor family, plays important roles in homeostasis of the immune and bone systems. However, the intestinal role of this molecule is unclear. Here, we show that dextran sodium sulfate (DSS)-induced colitis and azoxymethane-DSS-induced intestinal tumors are reduced in Clec4a2-/- mice independently of intestinal microbiota. STAT5 phosphorylation and expression of Csf2 and tight junction genes are enhanced, while Il17a and Cxcl2 are suppressed in the Clec4a2-/- mouse colon, which exhibits reduced infiltration of neutrophils and myeloid-derived suppressor cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) administration ameliorates DSS colitis associated with reduced Il17a and enhanced tight junction gene expression, whereas anti-GM-CSF exacerbates symptoms. Furthermore, anti-NA2, a ligand for DCIR, ameliorates colitis and prevents colorectal tumors. These observations indicate that blocking DCIR signaling ameliorates colitis and suppresses colonic tumors, suggesting DCIR as a possible target for the treatment of these diseases.

The hospitalization burden of inflammatory bowel disease in China: a nationwide study from 2013 to 2018.

Background: The past decade has witnessed a dramatic increase in the number of patients with inflammatory bowel disease (IBD) in China. The nationwide burden of hospitalization remains unclear, however. We aimed to address this gap by conducting analysis using a nationwide database. Methods: Population-based hospitalization rates from 2013 to 2018 were calculated by extrapolating the number of patients in the database to the national level. Surgical rates, annual hospital charges, and length of stay were also used for quantification of hospitalization burden. The Poisson regression analysis and the Cochran-Armitage trend test were conducted to analyze temporal trends as expressed as annual percentage of change (APC) with 95% confidential intervals (CIs). Results: From 2013 to 2018, the hospitalization rates for Crohn's disease (CD) and ulcerative colitis (UC) in China increased from 2.20 (95% CI = 2.17-2.22) to 3.62 (3.59-3.65) per 100,000 inhabitants (p < 0.0001) with an APC of 10.68% (6.00-15.36%) and from 6.24 (6.20-6.28) to 8.29 (8.23-8.33) per 100,000 inhabitants (p < 0.0001) with an APC of 5.73% (2.32-9.15%), respectively. Surgical rates decreased from 7.96% (7.29-8.63%) to 5.56% (5.11-6.00%) for CD patients (p < 0.0001) with APC of -6.30% (-11.33 to -1.27%) and from 3.54% (3.26-3.82%) to 2.52% (2.32-2.72%) for UC patients (p < 0.0001) with APC of -6.35% (-16.21 to 3.51). In 2018, there were estimated 166,000 IBD patients hospitalized costing a total of $426.37 million ($149.91 + $276.46 million) across the entire China. Conclusion: The population-based hospitalization rate of IBD increased, whereas the surgical rate decreased from 2013 to 2018 in China.

The C-type lectin receptor Clec1A plays an important role in the development of experimental autoimmune encephalomyelitis by enhancing antigen presenting ability of dendritic cells and inducing inflammatory cytokine IL-17.

Clec1A, a member of C-type lectin receptor family, has a carbohydrate recognition domain in its extracellular region, but no known signaling motif in the cytoplasmic domain. Clec1a is highly expressed in endothelial cells and weakly in dendritic cells. Although this molecule was reported to play an important role in the host defense against Aspergillus fumigatus by recognizing 1,8-dihydroxynaphthalene-melanin on the fungal surface, the roles of this molecule in un-infected animals remain to be elucidated. In this study, we found that Clec1a-/- mice develop milder symptoms upon induction of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. The maximum disease score was significantly lower, and demyelination and inflammation of the spinal cord were much milder in Clec1a-/- mice compared to wild-type mice. No abnormality was detected in the immune cell composition in the draining lymph nodes and spleen on day 10 and 16 after EAE induction. Recall memory T cell proliferation after restimulation with myelin oligodendrocyte glycoprotein peptide (MOG35-55) in vitro was decreased in Clec1a-/- mice, and antigen presenting ability of Clec1a-/- dendritic cells was impaired. Interestingly, RNA-Seq and RT-qPCR analyses clearly showed that the expression of inflammatory cytokines including Il17a, Il6 and Il1b was greatly decreased in Clec1a-/- mice after induction of EAE, suggesting that this reduced cytokine production is responsible for the amelioration of EAE in Clec1a-/- mice. These observations suggest a novel function of Clec1A in the immune system.

Interleukin-17 family members in health and disease.

The interleukin-17 (IL-17) family consists of six family members (IL-17A-IL-17F) and all the corresponding receptors have been identified recently. This family is mainly involved in the host defense mechanisms against bacteria, fungi and helminth infection by inducing cytokines and chemokines, recruiting neutrophils, inducing anti-microbial proteins and modifying T-helper cell differentiation. IL-17A and some other family cytokines are also involved in the development of psoriasis, psoriatic arthritis and ankylosing spondylitis by inducing inflammatory cytokines and chemokines, and antibodies against IL-17A as well as the receptor IL-17RA are being successfully used for the treatment of these diseases. Involvement in the development of inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis and tumors has also been suggested in animal disease models. In this review, we will briefly review the mechanisms by which IL-17 cytokines are involved in the development of these diseases and discuss possible treatment of inflammatory diseases by targeting IL-17 family members.

Nomogram to predict primary non-response to infliximab in patients with Crohn's disease: a multicenter study.

BACKGROUND: Infliximab (IFX) is effective at inducing and maintaining clinical remission and mucosal healing in patients with Crohn's disease (CD); however, 9%-40% of patients do not respond to primary IFX treatment. This study aimed to construct and validate nomograms to predict IFX response in CD patients. METHODS: A total of 343 patients diagnosed with CD who had received IFX induction from four tertiary centers between September 2008 and September 2019 were enrolled in this study and randomly classified into a training cohort (n = 240) and a validation cohort (n = 103). The primary outcome was primary non-response (PNR) and the secondary outcome was mucosal healing (MH). Nomograms were constructed from the training cohort using multivariate logistic regression. Performance of nomograms was evaluated by area under the receiver-operating characteristic curve (AUC) and calibration curve. The clinical usefulness of nomograms was evaluated by decision-curve analysis. RESULTS: The nomogram for PNR was developed based on four independent predictors: age, C-reactive protein (CRP) at week 2, body mass index, and non-stricturing, non-penetrating behavior (B1). AUC was 0.77 in the training cohort and 0.76 in the validation cohort. The nomogram for MH included four independent factors: baseline Crohn's Disease Endoscopic Index of Severity, CRP at week 2, B1, and disease duration. AUC was 0.79 and 0.72 in the training and validation cohorts, respectively. The two nomograms showed good calibration in both cohorts and were superior to single factors and an existing matrix model. The decision curve indicated the clinical usefulness of the PNR nomogram. CONCLUSIONS: We established and validated nomograms for the prediction of PNR to IFX and MH in CD patients. This graphical tool is easy to use and will assist physicians in therapeutic decision-making.

[Early treatment of suspension moxibustion for Bell's palsy in acute stage].

OBJECTIVE: To observe the efficacy of early treatment of suspension moxibustion for Bell's palsy and its influence on the prognosis, and to explore whether the early treatment of suspension moxibustion has non-inferiority effect to hormone treatment and whether suspension moxibustion combined with hormone treatment has the synergistic effect. METHODS: A total of 132 patients with acute-stage Bell's palsy were divided into a hormone group (94 cases) and a moxibustion group (38 cases) by non-random method, and the hormone group was further randomly divided into a hormone with moxibustion group (48 cases) and a hormone without moxibustion group (46 cases). The acupuncture and oral administration of mecobalamin capsule were used as basic treatment. Acupuncture was applied at Yangbai (GB 14), Sibai (ST 2), Quanliao (SI 18), Dicang (ST 4), Jiache (ST 6), Yifeng (TE 17), etc., with the needles retained for 30 min, once a day, 5 consecutive days per week; there was an interval of 2 days between two weeks, and a total of 4-week treatment was given. The oral administration of mecobalamin capsule was given 0.5 mg each time, 3 times a day for 4 weeks. The patients in the moxibustion group, on the basis of basic treatment, were treated with the suspension moxibustion at Yangbai (GB 14), Sibai (ST 2), Dicang (ST 4), Jiache (ST 6), Wangu (GB 12), Yifeng (TE 17) of affected side, 5 min per acupoint, once a day, 5 consecutive days per week; there was an interval of 2 days between two weeks, and a total of 4-week treatment was given. The patients in the hormone without moxibustion group, on the basis of basic treatment, were treated with prednisone acetate tablets. The patients in the hormone with moxibustion group, on the basis of basic treatment, were treated with suspension moxibustion and prednisone acetate tablets. All the treatment was given for 4 weeks. The House-Brcackmann facial nerve grading (H-B) global score and facial disability index (FDI) scale were used to evaluate the curative effect in the three groups before treatment, 2 weeks and 4 weeks into treatment and 4 weeks after treatment; the efficacy was compared among the three groups. RESULTS: Compared before treatment, the H-B grading and FDI scores were significantly improved 2 weeks and 4 weeks into treatment and 4 weeks after treatment (P<0.05). The various indexs of each group 2 weeks into treatment were not statistically significant in the three groups (P>0.05); the H-B grading and FDI scores in the hormone with moxibustion group were superior to those in the moxibustion group and the hormone without moxibustion group 4 weeks into treatment and 4 weeks after treatment (P<0.05), while there was no significant difference between the moxibustion group and the hormone without moxibustion group (P>0.05). At the end of follow-up, the cured rate in the hormone with moxibustion group was 81.3% (39/48), which was superior to 68.4% (26/38) in the moxibustion group and 60.9% (28/46) in the hormone without moxibustion group (P<0.05). However, there was no significant difference between the moxibustion group and the hormone without moxibustion group (P>0.05). CONCLUSION: The three treatment methods are all safe and effective for acute-stage Bell's palsy. The suspension moxibustion combined with hormone therapy are superior to suspension moxibustion or hormone therapy alone. Early treatment of suspension moxibustion is safe and effective for Bell's palsy, and has obvious synergistic effect with hormone. For the patients who cannot use hormone, suspension moxibustion could replace hormone, which is non-inferior to hormone.

High Capacity of Nutrient Accumulation by Invasive Solidago canadensis in a Coastal Grassland.

BACKGROUND: Solidago canadensis is a notorious invasive species from North America that is spreading across East China. It is invading some coastal grasslands and replacing native grass species. The effects of the S. canadensis invasion on soil nutrient cycling in the grasslands remain unclear. This study examined the effects of the invasion of S. canadensis on macronutrient accumulation in species aboveground part and soil. METHODS: Aboveground biomass, macronutrient (N, P, and K) pools in biomass, litter mass and decomposition rates, soil macronutrient availability and soil microbial biomass and enzyme activity that were related to nutrient transformation were compared between plots invaded by S. canadensis and uninvaded plots dominated by three different native grass species: Phacelurus latifolius, Phragmites australis, and Imperata cylindrica. RESULTS: S. canadensis had higher aboveground biomass, higher leaf N, P, and K concentrations, and consequently, a larger macronutrient pool size in the standing biomass. S. canadensis also produced more litter with higher N, P, and K concentrations and faster decomposition rates. The S. canadensis invasion did not change the total N, P, and K concentration in the topsoil (0-10 cm), but the invasion did increase their availability. The S. canadensis invasion did not increase the total soil organic matter (TSOM) content but did increase the soil microbial biomass and the activities of urease, alkaline phosphatase, invertase, amylase, and glucosidase in the topsoil. CONCLUSION: The invasion of S. canadensis accelerates the macronutrient cycling rate via increases in aboveground productivity and nutrient accumulation in standing biomass, faster nutrient release from litter and higher soil microbial activity. An enhanced nutrient cycling rate may further enhance its invasiveness through a positive feedback on soil processes.

The effects of Solidago canadensis water extracts on maize seedling growth in association with the biomass allocation pattern.

BACKGROUND: Solidago canadensis L. is an aggressive exotic plant species in China that has potential allelopathic effects on competing plant species. Effects of hormesis are frequently observed in studies of allelopathy; however, the mechanisms of such effects need to be elucidated. Allelopathic compounds may affect the growth of recipient plants via alteration of biomass allocation patterns or photosynthetic capacity. The aim of this study was to determine how water extracts from S. canadensis affected the shoot and root growth of recipient plants and whether the underlying mechanism was related to the biomass allocation pattern or photosynthetic gas exchange capacity. METHODS: The water extracts from S. canadensis shoots at 12 different concentrations in the range of 0-0.25 g/ml were applied thrice in 9 days to maize seedlings cultivated in silica sand. The growth (shoot height, leaf length and area and root length) and biomass accumulation and allocation (specific leaf area (SLA), leaf area ratio (LAR) and leaf mass ratio (LMR)) were compared among maize seedlings exposed to different treatment concentrations. Gas exchange (photosynthetic light response curve) was measured and compared among maize seedlings exposed to three concentrations of water extract (0, 0.0125 and 0.2 g/ml) before and after the first application, and seedling growth was measured after the third and final application. RESULTS: The growth of seedlings (shoot height, leaf length and area and root length) was promoted at concentrations below 0.125 g/ml and inhibited at concentrations above this level (P < 0.05). The pattern of change in biomass accumulation and allocation was similar to that of shoot growth, but biomass accumulation and allocation was not significantly affected by the water extract treatments (P > 0.05). The water extract treatments did not significantly affect the photosynthetic capacity (P > 0.05), but the dark respiration rate was higher in the low-dose treatment than that in the high-dose treatment. Shoot height was positively correlated with the biomass allocation indicators SLA and LAR (P < 0.05) but not with LMR (P > 0.05). CONCLUSIONS: The results suggested that the effects of the water extracts from S. canadensis were highly dependent on the concentration, with the growth of maize seedlings promoted at low concentrations of water extracts. The effects of the water extracts on the growth of maize seedlings were mainly due to the effects on the LAR, the allocation to leaf area growth, whereas the effects of the water extracts on leaf gas exchange capacity cannot explain variation of seedling growth. Thus, the stimulation of plant growth was very likely due to increased biomass allocation towards the shoot.

Improved flooding tolerance and carbohydrate status of flood-tolerant plant Arundinella anomala at lower water temperature.

BACKGROUND: Operation of the Three Gorges Reservoir (TGR, China) imposes a new water fluctuation regime, including a prolonged winter submergence in contrast to the natural short summer flooding of the rivers. The contrasting water temperature regimes may remarkably affect the survival of submerged plants in the TGR. Plant survival in such prolonged flooding might depend on the carbohydrate status of the plants. Therefore, we investigated the effects of water temperature on survival and carbohydrate status in a flood-tolerant plant species and predicted that both survival and carbohydrate status would be improved by lower water temperatures. METHODOLOGY: A growth chamber experiment with controlled water temperature were performed with the flood-tolerant species Arundinella anomala from the TGR region. The plants were submerged (80 cm deep water above soil surface) with a constant water temperature at 30°C, 20°C or 10°C. The water temperature effects on survival, plant biomass and carbohydrate content (glucose, fructose and sucrose and starch) in the viable and dead tissues were investigated. PRINCIPAL FINDINGS: The results showed that the survival percentage of A.anomala plants was greatly dependent on water temperature. The two-month submergence survival percentage was 100% at 10°C, 40% at 20°C and 0% at 30°C. Decreasing the water temperature led to both later leaf death and slower biomass loss. Temperature decrease also induced less reduction in glucose, fructose and sucrose in the roots and leaves (before decay, p < 0.05), but only marginally significant in the stems (p < 0.05). However, the starch content level did not differ significantly between the water temperature treatments (p > 0.05). Different water temperatures did not alter the carbon pool size in the stems, leaves and whole plants (p > 0.05), but a clear difference was found in the roots (p < 0.05), with a larger pool size at a lower temperature. CONCLUSIONS/SIGNIFICANCE: We concluded that (1) A. anomala is characterized by high flooding tolerance and sustained capability to mobilize carbohydrate pool. (2) The survival percentage and carbohydrate status of submerged A. anomala plants were remarkably improved by lower water temperatures. The survival of submergence seemed to be closely associated with the sugar content and carbohydrate pool size of the roots, which contained the lowest amount of carbohydrates. Three Gorges reservoir impoundment in winter is beneficial to the survival of submerged A. anomala in riparian area of the reservoir due to the low water temperature.

Responses in shoot elongation, carbohydrate utilization and growth recovery of an invasive species to submergence at different water temperatures.

Widely distributed amphibious exotic plant species may respond plastically to water temperatures when submerged. Alternanthera philoxeroides, a highly flood-tolerant species, originates from tropical regions and has successfully invaded temperate regions. The wide distribution of this species suggests it can respond to flooding at different water temperatures. In this study, the plastic responses of A. philoxeroides plants to submergence at water temperatures of 10 °C, 20 °C and 30 °C were investigated. The A. philoxeroides plants had large pools of non-structural carbohydrates, which were readily mobilized upon submergence. Submergence hindered biomass accumulation and decreased the carbohydrate content level and respiration rate (P < 0.05). Water temperature had remarkable effects on shoot elongation, carbohydrate utilization and recovery growth. With decreasing water temperature, the respiration rate was lower and carbohydrate content decreased more slowly, but the post-submergence biomass accumulation was faster (P < 0.05), indicating a beneficial effect of low water temperature for recovery. However, high water temperatures accelerated shoot elongation (P < 0.05), which benefitted the submerged plants more if contact with air was restored. These results suggest that the species can respond to different water temperatures plastically, which may provide hints for its invasion success in regions with diverse climates.

Submergence Causes Similar Carbohydrate Starvation but Faster Post-Stress Recovery than Darkness in Alternanthera philoxeroides Plants.

Carbon assimilation by submerged plants is greatly reduced due to low light levels. It is hypothesized that submergence reduces carbohydrate contents and that plants recover from submergence in the same way as darkness-treated plants. To test this hypothesis, the responses of plants to submergence and darkness were studied and compared. Plants of a submergence-tolerant species, Alternanthera philoxeroides, were exposed to well drained and illuminated conditions, complete submergence conditions or darkness conditions followed by a recovery growth period in a controlled experiment. The biomass maintenance and accumulation, carbohydrate content dynamics and respiration rate in the plants were assessed to quantify the carbohydrate utilization rate and regrowth. The submerged plants maintained higher chlorophyll contents, more green leaf tissue and more biomass; recovered more quickly; and accumulated more carbohydrates and biomass than darkness-treated plants. The respiration rate was continuously reduced in the same pattern under both stress conditions but was maintained at a significantly lower level in the submerged plants; the total soluble sugar and total fructan contents were decreased at approximately the same rate of decrease, reaching similar low levels, in the two stress treatments. The A. philoxeroides plants were more tolerant of submergence than darkness. The faster recovery of desubmerged plants could not be explained by the similar carbohydrate contents at the start of recovery. Other types of carbon reserves besides carbohydrates or other mechanisms such as higher post-stress photosynthetic performance might be involved.

[Decomposition and phosphorus dynamics of the litters in standing and litterbag of the Hangzhou Bay coastal wetland ].

Wetlands litter decomposition affects wetlands nutrient cycling. The decomposition progress of standing litter was monitored and the litterbag simulation experiment was carried out in order to analyze dynamics of litter decomposition and phosphorus release in Phragmites australis (PA), Spartina alterniflora (SA) and Scirpus mariqueter (SM) marshes of Hangzhou Bay coastal wetland. Results show that the dry mass of standing litter and P concentration decrease gradually and the litter drops to the sediment surface after 180 d. There are distinctive stages of the plant litter decomposition in litterbag simulation experiments. The loss rate is faster during 0- 15 d than that of later days. The loss rate in root decomposition of three plants are SM > PA > SA, while the trend is opposite for that of aboveground tissues. The time needed for 95% of dry mass decomposition in the plant tissues is between 1. 2- 8. 3 a. The P concentration in litters decreases rapidly in the initial stage and then increases slowly while the net P pools decreases all the time. Pearson's correlation coefficient shows that there is no significant correlation between the litter decomposition rate and C/N ratio. However, the litter C/P ratio affects greatly on plant decomposition rate. Environmental factors in the atmospheric temperature also have an impact on the decomposition rate of leaves. The different decomposition progresses between standing litter and litterbag are caused by environmental factors.

[Dynamics of carbon, nitrogen and phosphorus storage of three dominant marsh plants in Hangzhou Bay coastal wetland].

Salt marshes perform important ecosystem functions in carbon, nitrogen and phosphorus recycling. The plant biomass, content and pools of C, N and P were measured seasonally in three marsh species Phragmites australis, Spartina alterniflora and Scirpus mariquezer in Hangzhou Bay coastal wetland for the dynamics of C, N and P storage. The results showed that seasonal variation of aboveground biomass displayed a unimodal curve. The seasonal variability of plant OC content in the aboveground part of the plants was not significant, while the TN and TP content decreased significantly from spring to winter. The seasonal variability of plant C, N and P pools was significant. And there was a significant relationship between plant C/N/P pools and biomass. The pools among plant species were significantly different. S. mariqueter had the lowest C/N/P pools. TN pool in the aboveground part of P. australis was higher than that of S. aterniflora, but its TP pool was lower than that of S. alterniflora, and there was no significant difference for OC pools between P. australis and S. alterniflora. C fixation of the three marsh species was 380%, 376% and 55.5% of the average C fixation of terrestrial vegetations in China, and 463%, 458% and 67.7% of the average C fixation of terrestrial vegetations of the world. Considering the purification capacity of N and P, July would be the best harvest time of the study area for three plants. And the harvest of S. alterniflora could remove the biggest amount of P, since P was a limiting nutrient for phytoplankton growth. In conclusion, the marsh plants had strong C fixation and N/P purification ability.