Analyzing river disruption factors and ecological flow in China's Liu River Basin amid environmental changes.

Water resources variability and availability in a basin affect river flows and sustain river ecosystems. Climate change and human activities disrupt runoff sequences, causing water environmental issues like river channel interruptions. Therefore, determining ecological flow in changing environments is challenging in hydrological research. Based on an analysis of long-term changes in hydrological and meteorological variables and interruption conditions in the semi-arid Liu River Basin (LRB), this study summarizes the controlling factors of river interruption at different temporal and spatial scales and proposes a framework to determine ecological flow under changing environments. Hydrological model and the monthly optimal probability distribution were used to determine the optimal ecological runoff of LRB. The results showed that from 1956 to 2017, precipitation and potential evapotranspiration in the basin showed no significant decreasing trend, but the streamflow significantly decreased, and the downstream interruption worsened, with an average annual interruption duration of 194 days at Xinmin Station from 1988 to 2017. The controlling factors of river interruption are as follows: (1) soil and water conservation measures in the upstream significantly reduce the runoff capacity; (2) the operation mode of the controlling reservoir in the middle reaches changes from "all-year discharge" to "winter storage and spring release" to "combined storage and supply," severing the hydraulic connection between upstream and downstream; and (3) siltation in the downstream river channel coupled with over-extraction of groundwater increases the seepage capacity of the river. The monthly ecological flow of Naodehai Reservoir was determined by considering the monthly seepage losses after reconstructing the natural runoff using the SWAT model and determining the optimal probability distribution function for monthly runoff. The findings are important for downstream LRB ecological restoration and for determining the ecological flow of other river basins in changing environments.

Quantifying the impact of climate variability and human activities on streamflow variation in Taoer River Basin, China.

Climate variability and human activity are the two driving forces that alter the hydrological cycle and spatiotemporal distribution of water resources. Using the Taoer River Basin (TRB) as an example, this study analyzed the impacts of climate variability and human activities on streamflow discharge in various periods and the resulting hydrological alterations. First, historical streamflow data were divided into four periods (baseline period and altered periods 1, 2, and 3). Based on the proposed basic identification framework, four assessment methods (the hydrological sensitivity method, distributed hydrological model, linear regression model, and runoff restoring computation) are used and provided relatively consistent estimates of streamflow attribution. Climate variability is the driving factor for streamflow changes, and the relative contributions in altered periods 1, 2, and 3 are 81% (+ 50.34 mm), 68% (+ 13.37 mm), and 53% (-19.23 mm), respectively. In addition, climate variability and reservoir construction have different impacts on the hydrological regime at different periods, and reservoir regulation's effect on the hydrological regime depends on climatic conditions. Combined with this case study, we further discuss the necessity of breakpoint selection and period subdivision in the attribution of streamflow changes, and analyze the applicability of different methods with current ideas for improvement. This study not only has practical significance for water resource planning and adaptive policy formulation in the TRB but also provides a useful reference for similar studies.

[Distribution Characteristics and Influencing Factors of Nitrate Pollution in Shallow Groundwater of Liujiang Basin].

Taking the nitrate in shallow groundwater of Liujiang basin as the research object, a total of 215 groups of shallow groundwater samples were collected during the wet period in July 2014 and the drought period in April 2015 on the basis of groundwater pollution investigation. The characteristics of spatial and temporal variability and the account of nitrate pollution were analyzed based on the model of semivariogram, the geostatistics of ArcGIS and factor analysis, respectively. The results showed that the study region in the southeast was the main nitrate-polluted area, with concentrations of up to 30-120 mg · L⁻¹, in both wet and drought periods, while the nitrate-contaminated area in drought period was about 1. 4 times higher than that in wet period. The spatial distribution of nitrate was primarily influenced by human activities and the geological conditions, and secondarily by Eh, DO, pH and landform conditions. The nitrate concentration was less than 20 mg · L⁻¹ in north. Pollution in local middle area was rather serious, due to human activities and the loss of nitrogen fertilizer in agricultural cultivation; the area to the south, which was confined by impervious boundary, was seriously contaminated, as indicated by the nitrate accumulation effects.

IL-33 accelerates cutaneous wound healing involved in upregulation of alternatively activated macrophages.

IL-33 is a recently recognized member of the IL-1 family and has been best identified as a potent inducer of Th2-type immune responses. Increasing evidence, however, indicates that IL-33 also represents an important mediator of mucosal healing and epithelial restoration and repair. In this study, we further explore the potential effect of IL-33 in cutaneous wound healing. A full-thickness skin wound was generated on the back of mice and treated with IL-33 or vehicle intraperitoneally. Our results revealed that the levels of IL-33 mRNA and protein were significantly enhanced in incisional wound skin. Meantime, administration of IL-33 obviously accelerated wound healing with wounds gaping narrower and exhibiting enhanced reepithelialization. IL-33 upregulation also promoted the collagen deposition and the expression of extracellular matrix (ECM)-associated genes such as fibronectin and collagen IIIa, which implies a direct effect of IL-33 on matrix synthesis. Furthermore, IL-33 facilitated the development of alternatively activated macrophages (AAM) in incisional wound tissue, which closely related to resolution of inflammation and promotion of wound repair. Taken together, these findings suggest that IL-33 may play a pivotal role in maintenance of cutaneous homeostasis and acceleration of normal wound healing.

IL-33 promotes Staphylococcus aureus-infected wound healing in mice.

Interleukin (IL)-33, a newly identified member of IL-1 family of cytokines, plays a crucial role in polarizing Th2-associated immune responses. Recently growing evidence indicates that IL-33 also represents an important mediator of mucosal healing and epithelial restoration. In this study, we investigated the effect of IL-33 on antimicrobial infection and wound healing using a Staphylococcus aureus-infected incision model in mice. Our findings showed that the expression of IL-33 mRNA and protein was promptly increased in cutaneous wound tissues when challenged by methicillin-resistant S. aureus (MRSA). At the same time, exogenous IL-33 administration profoundly inhibited MRSA colonization and accelerated cutaneous wound repair. IL-33 upregulation promoted the proliferation of neutrophils and CXCR2 expression, which is related to augmented neutrophil trafficking into infectious sites for bactericidal effect. In addition, the beneficial effect of IL-33 is also implicated in enhancement of collagen deposition and the expression of extracellular matrix (ECM)-associated genes such as fibronectin and collagen IIIa, which implies a potential effect of IL-33 on matrix synthesis and reepithelialization during the wound repair process. All together, these findings reveal that IL-33 plays an essential effect in maintenance of cutaneous homeostasis and improvement of infectious wound healing.

Sirolimus ameliorates inflammatory responses by switching the regulatory T/T helper type 17 profile in murine colitis.

Inflammatory bowel disease is characterized by dysregulated immune responses in inflamed intestine, with dominance of interleukin-17 (IL-17)--producing cells and deficiency of regulatory T (Treg) cells. The aim of this study was to investigate the effect and mechanisms of sirolimus, an inhibitor of the mammalian target of rapamycin, on immune responses in a murine model of Crohn's disease. Murine colitis was induced by intrarectal administration of 2,4,6-trinitrobenzene sulphonic acid at day 0. Mice were then treated intraperitoneally with sirolimus daily for 3 days. The gross and histological appearances of the colon and the numbers, phenotype and cytokine production of lymphocytes were compared with these characteristics in a control group. Sirolimus treatment significantly decreased all macroscopic, microscopic and histopathological parameters of colitis that were analysed. The therapeutic effects of sirolimus were associated with a down-regulation of pro-inflammatory cytokines tumour necrosis factor-α, IL-6 and IL-17A. Intriguingly, sirolimus administration resulted in a prominent up-regulation of the regulatory cytokine transforming growth factor-ß. Supporting the hypothesis that sirolimus directly affects the functional activity of CD4+ CD25+ Treg cells, we observed a remarkable enhancement of FoxP3 expression in colon tissues and isolated CD4+ T cells of sirolimus-treated mice. Simultaneously, sirolimus treatment led to a significant reduction in the number of CD4+ IL-17A+ T cells in the mesenteric lymph node cells as well as IL-17A production in mesenteric lymph node cells. Therefore, sirolimus may offer a promising new therapeutic strategy for the treatment of inflammatory bowel disease.

Heme oxygenase-1 ameliorates LPS-induced acute lung injury correlated with downregulation of interleukin-33.

Although studies have shown that heme oxygenase-1 (HO-1) can abrogate leukocyte recruitment and tissue injury after LPS stimulation, the underlying mechanisms remain incompletely understood. Interleukin (IL)-33, a new member of the IL-1 family, is found to play a crucial immunoregulatory effect on the MD2/TLR4 complex expression. Moreover, TLR4 further promotes the activation of NF-κB and the production of proinflammatory mediators, which exacerbate neutrophil infiltration and organ damage. The present study was designed to determine whether the protection of HO-1 against LPS-induced acute lung injury (ALI) is involved in downregulation of IL-33. We observed that the levels of IL-33 mRNA and protein in LPS-stimulated macrophages were strongly suppressed by a potent HO-1 inducer, CoPP, treatment. Meanwhile, CoPP significantly reduced the expression of TLR4 and TNF-α in IL-33-pretreated macrophages followed LPS challenge. In the murine model of LPS-induced ALI, CoPP treatment resulted in a remarkable decrease in LPS-mediated leukocyte exudation, Evans blue dye albumin (EBA) leakage as well as histopathologic disruption. Notably, CoPP treatment markedly inhibited the expression of IL-33 and TLR4 in lung tissues under LPS stimulation. Therefore, these data suggest that the cytoprotection of HO-1 in LPS-induced pulmonary injury is associated with negative regulation of IL-33 and TLR4-mediated inflammatory response.

Association of -27T>C and its haplotype at the putative promoter for IgA-specific receptor gene with IgA nephropathy among the Chinese Han population.

BACKGROUND: One-third to half of IgA nephropathy (IgAN) patients have raised serum IgA levels. Decreased clearance of IgA/IgA complex has been observed in IgAN patients. FCAR codes for IgA-specific receptor and plays an important role in IgA metabolism. Previous small sample-sized studies reported controversial findings in its association with IgAN. METHODS: We re-sequenced the FCAR in 107 IgAN patients and 112 controls. Association of -27T/C and their haplotypes were performed in 606 patients versus 606 controls, its two independent subsets: 293 single patients with family members and 313 cases versus 606 controls. Functional impact of -27T>C and their haplotypes were analyzed by bioinformatics, allelic differential expression and luciferase activity assays. Cell surface FCAR density between -27T/C heterozygous patients and -27T/T homozygous controls was assessed by flow cytometry. RESULTS: -27T>C, on the consensus TATA box of transcription factor-binding motif in the putative promoter of the gene was the only variation identified in all coding, splice-site and known protein-binding sequence in re-sequencing. -27C and its haplotype were associated with IgAN (P = 0.0034/0.0013, 0.0099/0.0054, 0.0129/0.0076 and 0.00039/0.00014 in 606 cases versus 606 controls, family-based study, 313 cases versus 606 controls and meta-analysis, respectively). Bioinformatics predicted 2 bp binding changes by -27C. Allelic differential expression and luciferase activity assays showed a reduced expression/activity by the associated haplotype/allele (P < 0.001). -27T/C heterozygous patients had a lower receptor density on cell surface compared to -27T/T homozygous controls (P < 0.001). CONCLUSIONS: Our results provide evidence for genetic variation at the putative promoter region of FCAR conferring susceptibility to IgAN, suggesting -27C and its haplotype may be causative for the susceptibility among the Chinese Han population.

[Effect of sodium phenylbutyrate on the apoptosis of human tongue squamous cancer cell line and expression of p21 and survivin genes].

OBJECTIVE: To examine the effects of sodium phenylbutyrate on the apoptosis of human tongue squamous cancer cell line and expression of p21 and survivin genes. METHODS: The inhibition effects of sodium phenylbutyrate on Tca8113 and human tongue squamous cell carcinoma (TCSSA) cell lines were detected by methyl thiazoly terazolium (MTT) and the apoptosis of the cancer cells after being induced by sodium phenylbutyrate examined by flow cytometry (FCM). The expression of p21 and survivin genes were observed with Western blotting and RT-PCR. RESULTS: Compared with control group, the level of p21 mRNA and protein of Tca8113 cellline increased to 0.09 ± 0.08 and increased 0.72 ± 0.10, that of TCSSA cellline increased 1.34 ± 0.12 and 1.56 ± 0.09 (P < 0.05). Compared with control group, the level of surrive mRNA and protein of Tca8113 cellline decreased to 1.10 ± 0.05 and 1.14 ± 1.10, that of TCSSA cellline decreased to 0.12 ± 0.08 and 0.94 ± 0.09 (P < 0.05). Sodium phenylbutyrate inhibited the cell proliferation, promoted cell apoptosis and arrested the cells in G1/G0 phase. The amount of p21 mRNA and protein were increased, and the expression of survivin gene was decreased. CONCLUSIONS: Sodium phenylbutyrate exhibited remarkable inhibitory effects on human tongue squamous cancer cell proliferation and induced cancer cell apoptosis. The mechanism may be due to up-regulation of p21 gene and down-regulation of survivin gene. The mRNA level of p21 gene and survivin gene showed a strong correlation.

Heme oxygenase-1 upregulation improves lipopolysaccharide-induced acute lung injury involving suppression of macrophage migration inhibitory factor.

Although studies have demonstrated that heme oxygenase-1 (HO-1) prevents leukocyte infiltration and organ damage following LPS challenge, the mechanisms involved in this protection are incompletely understood. Macrophage migration inhibitory factor (MIF) is thought to play a pivotal role in modulation of inflammatory and immune response through upregulation of TLR4 expression. Activation of TLR4 results in the production of proinflammatory mediators including MIF, which induce neutrophils recruitment and subsequent tissue insults. We hypothesized that HO-1 mediates its salutary effects in lipopolysaccharide (LPS)-induced inflammatory lung injury via downregulation of MIF through modulation of TLR4-induced proinflammatory mediator production. Compared with wild-type cells, MIF-knockdown macrophages in vitro are hyporesponsive to LPS stimulation, as shown by a profound reduction in TLR4 expression and TNF-alpha production. In the murine model of LPS-induced acute lung injury, administration of CoPP, a potent HO-1 inducer, leaded to a significant reduction in LPS-induced pulmonary edema, leucocytes influx, myeloperoxidase activity as well as histopathologic insults. Most strikingly, pretreatment with CoPP markedly decreased the expression of TLR4 and MIF in lung tissues in response to LPS challenge. These findings herein suggest that the cytoprotective functions of HO-1 in LPS-induced lung injury are associated with negative regulation of lung MIF and TLR4-induced inflammatory response.

[Radiosensitivity of nasopharyngeal carcinoma in relation to cell cycle synchronization effect of tumor necrosis factor alpha].

OBJECTIVE: To investigate the effect of tumor necrosis factor alpha (TNFalpha) on radiosensitivity of nasopharyngeal carcinoma (NPC) in relation to TNFalpha-induced cell cycle synchronization. METHODS: The radio-resistance of a NPC cell line subclone CNE-2Z-S1 was verified by in vivo experiments and flow cytometry was performed to evaluate cell cycle synchronization in TNFalpha-treated CNE-2Z-S1 cells. The radiosensitivity of the cell synchronized CNE-2Z-S1 cells was determined by clone formation in vitro and in vivo experiment in nude mice. RESULTS: TNFalpha was capable of inducing cell cycle arrest and synchronization of CNE-2Z-S1 cells. Pretreatment with TNFalpha remarkably enhanced the radiosensitivity of CNE-2Z-S1 in vitro, and in vivo experiments with nude mice also suggested the role of TNFalpha in enhancing the radiosensitivity of NPC. CONCLUSION: TNFalpha can enhance the radiosensitivity of NPC cells by inducing cell cycle synchronization.