An open GIS based 3D simulation software to predict cooling tower drift diffusion.

This paper developed XJCT-3D, a simulation software for cooling tower wet plume dispersion. By coupling it with the Open GIS component Dotspatial, we have achieved geospatial visual representation of the calculation results, which has solved the problems of low calculation efficiency and insufficient visual representation of the traditional CFD software in the calculation of cooling tower wet plume dispersion. In order to verify the validity of the XJCT-3D software simulation results, we have conducted tracer experimental data from the ChalkPoint power plant. XJCT-3D accurately models wet plume deposition during cooling tower operation. From the XJCT-3D calculation results, we have observed that the maximum value of the cooling tower thermal plume wet deposition occurs near 610 m with a maximum value of 6.9E-07 kg/m2 s. This finding suggests that the cooling tower emissions carry a significant load of particles or droplets that have settled on surfaces at this particular altitude. It provides insights into potential environmental and human health impacts and helps in identifying and assessing areas at relatively higher risk of deposition, such as nearby ecosystems, farmland, or urban areas. This information can contribute to the development of effective mitigation strategies and the implementation of appropriate measures to minimize the impact of cooling tower emissions.

The Development and Application of a Quasi-dynamic Food Chain Model in Chinese Agricultural Conditions.

ABSTRACT: A quasi-dynamic food chain model (Chi-FDMT) was developed to predict the consequences of nuclear accidents on the food chain through the ingestion pathway in Chinese agricultural conditions. The Chi-FDMT structure is based on ECOSYS-87, with some revised calculation processes and the adoption of new parameters; herein, it was applied to two regions in China. The model was used to estimate the spatial and temporal patterns of crop plant activity and ingestion dose in the Chinese agricultural environment at the scale of the Fukushima nuclear disaster. A comparative study between Chi-FDMT and an equilibrium model demonstrated good agreement for depositions occurring during the growth season. The parameter sensitivity analysis of Chi-FDMT indicated that the parameters of food intake and processing factor are sensitive, and the sensitivity of the transfer factors within plant and soil-plant systems are dependent on the deposition scenario.

CD147 Expressed on Memory CD4+ T Cells Limits Th17 Responses in Patients With Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease in which T helper-type 17 (Th17) cells have been critically involved. CD147 is a T cell activation-associated molecule and is involved in T cell development. However, it remains unclear whether CD147 participates in Th17 responses in RA patients. In this study, we demonstrated that in both the RA and healthy controls (HC) groups, CD147 expression on CD4+ T cells was increased in CCR6+ and CD161+ subsets, and was associated with IL-17 production. Ligation of CD147 with its monoclonal antibody (mAb) strongly inhibited Th17 responses, and knock down of CD147 expression on CD4+ Tm cells specifically enhanced Th17 responses, triggered by coculture with in vitro activated monocytes from HC. Further functional studies showed that anti-CD147 mAb decreased the activation of AKT, mTORC1 and STAT3 signaling, which is known to enhance Th17 responses. Ligation of CD147 with its mAb on CD4+ Tm cells specifically reduced Th17 responses induced by in vitro or in vivo activated monocytes from RA patients. In collagen-induced arthritis model, anti-CD147 mAb treatment reduced the Th17 levels and severity of arthritis in vivo. These data suggest that CD147 plays a negative role in regulating human Th17 responses. Anti-CD147 mAb can limit the extraordinary proliferation of Th17 cells and may be a new therapeutic option in RA.

Role and mechanism of LAIR-1 in the development of autoimmune diseases, tumors, and malaria: A review.

The levels of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), a type I transmembrane glycoprotein broadly expressed on the majority of hematopoietic cells, such as T/B cells and natural killer cells, vary significantly during cell differentiation and activation. Previous studies focused mainly on the role of LAIR-1 in physiology and some pathological conditions, including autoimmune diseases. It has been shown that LAIR-1 mediates immune suppression, further resulting in uncontrolled inflammation. Furthermore, recent studies showed that LAIR-1 participates in the development of hematopoietic and non-hematopoietic tumors as well as malaria. This review summarizes the current findings on LAIR-1 in various diseases, its potential roles in pathogenesis, and provides new insight into the treatment of patients through suppression of the function of LAIR-1.

The risk of circulating angiogenic T cells and subsets in patients with systemic sclerosis.

To ascertain the number and percentage of angiogenic T (Tang) cell subsets by flow cytometry in systemic sclerosis (SSc), and their relation with specific clinical features. Thirty SSc patients and 15 healthy controls (HCs) were included. Luminex was performed to analyze the levels of interleukin (IL)-17A, vascular endothelial growth factor (VEGF), tumor necrosis factor-α, and vascular cell adhesion molecule (VCAM). The ratio of circulating CD3 + CD31 + CXCR4 + T (CD3 + Tang) cells and CD8+ CD31 + CXCR4 + T (CD8+ Tang) cells in SSc patients was enlarger than in HCs, while CD4 + CD31 + CXCR4 + T cells (CD4 + Tang) exhibited no difference between SSc patients and HCs. The number and percentage of Tang cells were higher in SSc patients with pulmonary artery hypertension (PAH) than in non-PAH SSc patients and HCs. The ratios of Tang cell subsets in nucleolar pattern-positive SSc patients were markedly raised as compared with their negative ones and HCs. Additionally, the percentage of circulating CD3 + Tang cells was positively associated with VEGF serum levels in SSc patients. Meanwhile, the rate of CD8+ tang cells might have been emphatically corresponded to VEGF and VCAM serum levels in SSc patients. These results imply that the increase in Tang cells in peripheral blood are associated with immunoregulatory disturbances in SSc patients.

CD147 participates in the activation function of circulating angiogenic T cells in patients with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory and angiogenic disease. This study aimed to explore the profiles of circulating angiogenic T cells (Tang cells) and the role of CD147 in Tang cell activation function in RA. METHODS: Samples were obtained from patients with RA and health controls (HC). Then, Tang cells were quantified by flow cytometry (FCM) in the samples from 87 patients with RA and 29 HC. Tang cells were purified by magnetic cell sorting in cell culture-conditioned media, and the phosphorylation signals were determined by FCM. In addition, cytokine levels were assessed by enzyme-linked immunosorbent assay. RESULTS: The percentage of circulating Tang cells increased and positively correlated with the number of endothelial progenitor cells in the RA group. Further, the percentage of Tang cells was closely related to disease activity, autoantibody positivity, and proangiogenic cytokine levels. Meanwhile, the expression of CD147 on Tang cells increased in patients with RA. CD147 participated in the Akt phosphorylation and VEGF level of the activated Tang cells. CONCLUSIONS: CD147 may play a critical role in regulating VEGF production of activated Tang cells by affecting Akt signaling, which in turn may serve an essential function in angiogenesis and RA pathogenesis.

A critical epitope in CD147 facilitates memory CD4+ T-cell hyper-activation in rheumatoid arthritis.

The abnormal activation of CD4+CD45RO+ memory T (Tm) cells plays an important role in the pathogenesis of rheumatoid arthritis (RA). Previous studies have shown that CD147 participates in T-cell activation. However, it remains unclear whether CD147 is involved in abnormal Tm-cell activation in RA patients. In this study, we demonstrated that CD147 was predominantly upregulated in Tm cells derived from RA patients. The anti-CD147 mAb 5A12 specifically inhibited Tm-cell activation and proliferation and further restrained osteoclastogenesis. Using a structural-functional approach, we depicted the interface between 5A12 and CD147. This allowed us to identify two critical residues, Lys63 and Asp65, as potential targets for RA treatment, as the double mutation K63A/D65A inhibited Tm-cell activation, mimicking the neutralization by 5A12. This study provides not only a theoretical basis for a "CD147-Tm/Osteoclast-RA chain" for the potential prevention and treatment of RA or other T-cell-mediated autoimmune diseases but also a new target for related drug design and development.

Circulating Angiogenic T Cells Are Increased in Lupus Nephritis Patients.

BACKGROUND Patients with systemic lupus erythematosus (SLE), especially with lupus nephritis (LN), undergo vascular damage and repair during the course of the disease. Since the recently identified angiogenic T cells (Tang) are involved in endothelial repair coupled with endothelial progenitor cells (EPCs), this study investigated the circulating Tang cells in LN patients and their potential correlations with disease features. MATERIAL AND METHODS Circulating Tang cells and EPCs were assessed by flow cytometry in peripheral blood samples from 67 SLE patients; of these, 32 had LN and 30 were matched healthy controls (HCs). The plasma levels of interleukin IL-17, IL-8, and vascular endothelial growth factor (VEGF) were quantified by immunoassays. RESULTS The percentage of circulating Tang cells in LN patients was significantly increased as compared to the non-LN patients and HCs, and they were positively correlated with the level of EPC and VEGF. Additionally, circulating Tang cell percentages were positively correlated with the extent of proteinuria in LN patients. CONCLUSIONS The increased levels of circulating Tang cells in LN patients might play a role in the balance of endothelium dysfunction in these patients.

The spinal NR2BR/ERK2 pathway as a target for the central sensitization of collagen-induced arthritis pain.

OBJECTIVE: Pain management is a huge challenge in the treatment of rheumatoid arthritis (RA), and central sensitization is reportedly involved in the development of pain. The current study was undertaken to explore the possible role of N-methyl-D-aspartate receptors (NMDARs) in the spinal mechanism of central sensitization in RA using a collagen-induced arthritis (CIA) model. METHODS: Mechanical hypersensitivity was assessed in C57BL/6 mice, before and after the induction of CIA via administration of chick type II collagen. Analgesic drugs, receptor antagonist, and kinase inhibitor were administrated intrathecally in the spinal cord. Protein expression and phosphorylation changes were detected via immunoblotting. RESULTS: CIA mice developed significant mechanical hypersensitivity, and spinal administration of the NMDAR antagonist D-2-amino-5-phosphonovaleric acid (D-APV) effectively attenuated peripheral pain hypersensitivity. There was specific enhancement of synaptic NR2B-containing NMDAR (NR2BR) expression in the spinal dorsal horns of the mice. Both the increased total protein expression of NR2B subunit and the enhanced total phosphorylation level of NR2B subunit at 1472 tyrosine promoted the synaptic expression of NMDAR in the mice. Intrathecal injection of tramadol suppressed synaptic NMDAR expression mainly by changing the synaptic phosphorylation state of NR2B subunit at Tyr1472. Extracellular signal-regulated protein kinases 2 (ERK2) activity synchronized with the synaptic expression of NR2BR, which was downregulated by the action of tramadol. CONCLUSION: Specific enhancement of NR2BR in the spinal dorsal horn may be vital for central sensitization in the CIA model of RA. The NR2BR/ERK2 pathway may be a promising target for pain management in RA patients.

CD147-mediated chemotaxis of CD4+CD161+ T cells may contribute to local inflammation in rheumatoid arthritis.

CD161 is used as a surrogate marker for Th17 cells, which are implicated in the pathogenesis of rheumatoid arthritis (RA). In this study, we evaluated the percentage, clinical significance, and CD98 and CD147 expression of CD4+CD161+ T cells. The potential role of CD147 and CD98 in cyclophilin A-induced chemotaxis of CD4+CD161+ T cells was analyzed. Thirty-seven RA patients, 15 paired synovial fluid (SF) of RA, and 22 healthy controls were recruited. The cell populations and surface expression of CD98 and CD147 were analyzed by flow cytometry. Spearman's rank correlation coefficient and multiple linear regression were applied to calculate the correlations. Chemotaxis assay was used to investigate CD4+CD161+ T cell migration. We found that the percentage of CD4+CD161+ T cells and their expression of CD147 and CD98 in SF were higher than in the peripheral blood of RA patients. Percentage of SF CD4+CD161+ T cells was positively correlated with 28-Joint Disease Activity Score (DAS28). CD147 monoclonal antibody (HAb18) attenuated the chemotactic ability of CD4+CD161+ T cells. An increased CD4+CD161+ T cell percentage and expression of CD147 and CD98 were shown in RA SF. Percentage of SF CD4+CD161+ T cells can be used as a predictive marker of disease activity in RA. CD147 block significantly decreased the chemotactic index of CD4+CD161+ cells induced by cyclophilin A (CypA). These results imply that the accumulation of CD4+CD161+ T cells in SF and their high expression of CD147 may be associated with CypA-mediated chemotaxis and contribute to local inflammation in RA.

Circulating Angiogenic T Cells and Their Subpopulations in Patients with Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerosis and increased cardiovascular risk. Angiogenic T cells (Tang), a specific T cell subset, have been identified and involved in the repair of damaged endothelium. This study aimed to analyze the Tang cell subsets in relation to disease specific features from SLE patients. METHODS: Tang cell subsets were assessed in peripheral blood samples from 41 SLE patients and 22 healthy controls (HC) by flow cytometry on the basis of CD31 and CXCR4 expression on CD3+, CD4+, and CD8+ T cells. RESULTS: The percentage of circulating CD8+CD31+CXCR4+ T cells (CD8+ Tang), but not CD3+CD31+CXCR4+ T cells (Tang) and CD4+CD31+CXCR4+ T cells (CD4+ Tang), in SLE was higher than HC. The percentages of Tang cell subsets in anti-dsDNA-positive SLE patients were significantly increased as compared to their negative counterparts and HC. Additionally, the levels of circulating Tang cell subsets were negatively correlated with age at sampling and at diagnosis, but not disease duration or disease activity. CONCLUSION: Anti-dsDNA-positivity may identify a group of SLE patients with increased Tang cell subsets and circulating CD8+ Tang cells may be viewed as a potentially useful biomarker of endothelial damage and cardiovascular risk in SLE.

Construction, expression, and characterization of a recombinant immunotoxin targeting EpCAM.

Epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein overexpressed in human epithelioma but with relatively low expression in normal epithelial tissues. To exploit this differential expression pattern for targeted cancer therapy, an EpCAM-targeted immunotoxin was developed and its antitumor activity was investigated in vitro. An immunotoxin (scFv2A9-PE or APE) was constructed by genetically fusing a truncated form (PE38KDEL) of Pseudomonas aeruginosa exotoxin with an anti-EpCAM single-chain variable fragment (scFv). ELISA and flow cytometry were performed to verify immunotoxin (scFv2A9-PE or APE) antigen-binding activity with EpCAM. Cytotoxicity was measured by MTT assay. Confocal microscopy was used to observe its cellular localization. The results of ELISA and flow cytometry revealed that the immunotoxin efficiently recognized recombinant and natural EpCAM. Its antigen-binding activity was relatively lower than 2A9. MTT assay confirmed potent reduction in EpCAM-positive HHCC (human hepatocellular carcinoma) cell viability (IC50 50 pM). Immunofluorescence revealed that the immunotoxin localized to endoplasmic reticulum 24 h later. In conclusion, we described the development of an EpCAM-targeted immunotoxin with potent activity against tumor cells, which may lay the foundation for future development of therapeutic antibody for the treatment of EpCAM-positive tumors.

Percentages of CD4+CD161+ and CD4-CD8-CD161+ T cells in the synovial fluid are correlated with disease activity in rheumatoid arthritis.

OBJECTIVE: CD161 has been identified as a marker of human IL-17-producing T cells that are implicated in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the potential link between the percentage of CD161+ T cells and disease activity in RA patients. METHODS: Peripheral blood (PB) from 54 RA patients and 21 healthy controls was evaluated. Paired synovial fluid (SF) (n = 17) was analyzed. CD161 expression levels on CD4+, CD8+, and CD4-CD8- T cells were assessed by flow cytometry. RESULTS: The percentage of CD4+CD161+ T cells in RA SF was higher than RA PB, and it was positively correlated with DAS28, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). CD4-CD8-CD161+ T cell percentage was decreased in RA PB and was further reduced in RA SF, and its level in SF was inversely correlated with DAS28, ESR, and CRP. However, CD8+CD161+ T cell percentage was neither changed in RA PB and SF nor correlated with disease activity indices. CONCLUSION: An increased CD4+CD161+ T cell percentage and a decreased CD4-CD8-CD161+ T cell percentage are present in RA SF and are associated with disease activity, and the accumulation of CD4+CD161+ T cells in SF may contribute to the local inflammation of RA.

CD147 and CD98 complex-mediated homotypic aggregation attenuates the CypA-induced chemotactic effect on Jurkat T cells.

Homotypic cell aggregation plays important roles in physiological and pathological processes, including embryogenesis, immune responses, angiogenesis, tumor cell invasion and metastasis. CD147 has been implicated in most of these phenomena, and it was identified as a T cell activation-associated antigen due to its obvious up-regulation in activated T cells. However, the explicit function and mechanism of CD147 in T cells have not been fully elucidated. In this study, large and compact aggregates were observed in Jurkat T cells after treatment with the specific CD147 monoclonal antibody HAb18 or after the expression of CD147 was silenced by RNA interference, which indicated an inhibitory effect of CD147 in T cell homotypic aggregation. Knocking down CD147 expression resulted in a significant decrease in CD98, along with prominent cell aggregation, similar to that treated by CD98 and CD147 monoclonal antibodies. Furthermore, decreased cell chemotactic activity was observed following CD147- and CD98-mediated cell aggregation, and increased aggregation was correlated with a decrease in the chemotactic ability of the Jurkat T cells, suggesting that CD147- and CD98-mediated homotypic cell aggregation plays a negative role in T cell chemotaxis. Our data also showed that p-ERK, p-ZAP70, p-CD3ζ and p-LCK were significantly decreased in the CD147- and CD98-knocked down Jurkat T cells, which suggested that decreased CD147- and/or CD98-induced homotypic T cell aggregation and aggregation-inhibited chemotaxis might be associated with these signaling pathways. A role for CD147 in cell aggregation and chemotaxis was further indicated in primary CD4(+) T cells. Similarly, low expression of CD147 in primary T cells induced prominent cell aggregation and this aggregation attenuated primary T cell chemotactic ability in response to CypA. Our results have demonstrated the correlation between homotypic cell aggregation and the chemotactic response of T cells to CypA, and these data indicate that CD147 and CD98 might play important roles in cyclophilin-induced cell migration.

[Effect of monocytes activated with lipopolysaccharide on human Th17 cell differentiation].

AIM: To investigate whether monocytes activated with lipopolysaccharide(LPS) have an effect on Th17 cell differentiation in humans, CD4(+) T cell and CD14(+) monocytes activated with LPS were treated in the absence or presence of anti-CD3 mAb with various concentrations at different time points. METHODS: Purification of CD4(+) T cell and CD14(+) monocytes were performed by magnetic cell sorting and cultured together. Cultures were stimulated with LPS alone or anti-CD3 mAb alone or LPS plus anti-CD3 mAb for 3 days. In the anti-CD3 mAb stimulation cells were added different concentrations of LPS. Cells were activated under LPS/anti-CD3 costimulation for 3, 6, or 10 days. The percentage of IL-17(+) T cells and INF-γ(+) T was determined by flow cytometry. RESULTS: LPS or anti-CD3 mAb alone induced only very low levels of IL-17(+) T cells, (1.30 ± 0.19)%, (1.10 ± 0.21)%, respectively. The percentage was substantially higher in the LPS and anti-CD3 mAb costimulationa as much as(2.01 ± 0.46)%. In the presence of 0.1 µg/mL, 1 µg/mL, 10 µg/mL LPS, the proportion of Th17 reached to (1.92 ± 0.21)%, (1.30 ± 0.37)%, (1.01 ± 0.25)%. Low-concentration LPS (0.1 µg/mL) stimulation favored Th17 differentiation. The highest proportion of IL-17(+) T cells was found at day 3(2.13 ± 0.32)%, with levels declining at day 6 and day 10, while, Th1 at day 6(17.45 ± 3.04)%, declining at day 10. CONCLUSION: Low-concentration LPS stimulation plus anti-CD3 mAb in short term support optimal Th17 generation. Nevertheless, this model closely mimics the environment of rheumatoid arthritis in vivo and proposes an effective model for the generation of human Th17 cells.

Conjugation of substituted ferrocenyl to thiadiazine as apoptosis-inducing agents targeting the Bax/Bcl-2 pathway.

Ferrocene compounds are a class of biologically active compounds that has antitumour and antifungal properties. This study investigated the induction of apoptosis in human fibrosarcoma cells (HT1080) after treatment with a series of 6-ferrocenyl-3-subsituted7H-1,2,4-triazolo[3,4-b]- 1,3,4-thiadiazine (FTFs). We found that FTFs could suppress the viability of HT1080 cells. Cell cycle analysis showed that proliferative inhibition of HT1080 cells occurred through apoptosis, as the cells were blocked in G1 phase. Moreover, mitochondrial membrane staining assay demonstrated that FTFs exposure significantly decreased mitochondrial membrane potential. Finally, under the stress of FTFs, Bax/Bcl-2 ratio in HT1080 cells was significantly increased. These results suggested that FTFs-induced apoptosis in HT1080 cells may work dependent on a Bax/Bcl-2 pathway.