Lopinavir/ritonavir is associated with pneumonia resolution in COVID-19 patients with influenza coinfection: A retrospective matched-pair cohort study.

During the early stages of the pandemic, some coronavirus disease (COVID-19) patients were misdiagnosed as having influenza, which aroused the concern that some deaths attributed to influenza were actually COVID-19-related. However, little is known about whether coinfection with influenza contributes to severity of COVID-19 pneumonia, and the optimal therapeutic strategy for these patients. We retrospectively studied 128 hospitalized patients with COVID-19 pneumonia. All patients were positive severe acute respiratory syndrome coronavirus 2 positive by nucleic acid detection. Sixty-four cases were coinfected with influenza A/B and the other 64 were influenza negative, matched by age, sex, and days from onset of symptoms. Among the 64 coinfected patients, 54 (84.4%) were coinfected with influenza A, and 10 (15.6%) with influenza B. The median duration of viral shedding time from admission was longer for patients with influenza coinfection (17.0 days) than for those without influenza coinfection (12.0 days) (P < .001). The multivariable Cox proportional hazards model showed that the hazards ratio of resolution in lung involvement was 1.878 (P = .020) for patients administered lopinavir/ritonavir, compared with those not administered lopinavir/ritonavir (95% confidence interval: 1.103-3.196). Among influenza coinfected patients, those treated with lopinavir/ritonavir exhibited faster pneumonia resolution within 2 weeks after symptom onset (37% vs 1%; P = .001). There was no difference in lung involvement between influenza coinfected and noninfected groups. Lopinavir/ritonavir eliminated the difference of lung involvement between influenza coinfected and noninfected groups, indicating that lopinavir/ritonavir is associated with pneumonia resolution in COVID-19.

A novel Schiff base cobalt(III) complex induces a synergistic effect on cervical cancer cells by arresting early apoptosis stage.

A new schiff base cobalt(III) complex [N,N'-bis(2'-hydroxyphenylacetone)-o-ethanediamine] cobalt(III) (M3) has been synthesized and characterized by single X-ray crystallography. The cytotoxicity of complex M3 was evaluated against HeLa, LoVo, A549, A549/cis cancer cell lines, and the normal cell lines LO2 by MTT assays. The IC50 is in the range of 6.27-22.68 µM, which is somewhat lower than cisplatin on the basis of platinum molar concentration. Furthermore, anticancer mechanistic studies showed that the complex M3 inhibited cell proliferation by blocking DNA synthesis and then acted on nuclear division of HeLa cells over time. Moreover, western blot analysis indicated M3 dramatically decreased the target protein c-Myc and KLF5 expression levels, and activated many signaling pathways including ER stress, apoptosis, cell cycle and DNA damage in HeLa. M3 did not affect proteasomal activity.

The clinical characteristic of eight patients of COVID-19 with positive RT-PCR test after discharge.

Corona virus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The phenomenon of positive real time reverse transcription polymerase chain reaction (RT-PCR) result of SARS-CoV-2 in recovered patients had occurred and the research about these patients was rare. In our study, we did a retrospective review of medical records from COVID-19 patients admitted to one ward of Tongji Hospital of Hua Zhong University of Science and Technology from 10 February to 13 April 2020. From 10 February to 13 April 2020, there were 108 patients of COVID-19 admitted in the one ward of Tongji Hospital. Among them, eight cases were readmission patients because the RT-PCR result of SARS-CoV-2 was positive again after discharge. On the second admission, they had no symptoms and their chest computed tomography was almost normal. Data from laboratory tests of the readmission patients showed that all eight patients had normal white blood cell count, lymphocyte count. The inflammatory factors like procalcitonin and interleukin 6 were normal. After treatment, two patients met the standard and were discharged. The other six patients were still in the hospital because their RT-PCR of SARS-CoV-2 did not get three consecutive negative results and the course of two patients had persisted more than 90 days. We still needed to be alert that these patients could infect other people as a source of infection, and we also needed to be alert that these patients become chronic virus carriers. It also aroused our concern about the discharge standard of COVID-19.

Association of plasma macrophage colony-stimulating factor with cardiovascular morbidity and all-cause mortality in chronic hemodialysis patients.

BACKGROUND: Cardiovascular disease (CVD) events are the main cause of death in long-term hemodialysis (HD) patients. Macrophage colony- stimulating factor (M-CSF) is actively involved in the formation of atherosclerosis and causes plaque instability, thrombosis and the development of acute coronary syndromes. However, little information is available on the role of M-CSF in HD patients. We aimed to investigate the association between plasma M-CSF levels and CVD events as well as all-cause mortality in patients undergoing long-term HD. METHODS: Fifty two HD patients and 8 healthy controls were recruited in this study. HD patients were followed up from September 2014 to May 2017. The primary end point was CVD event, the secondary outcome was death from any cause. Patients were divided into two groups with low and high M-CSF levels based on the optimal cut-off value determined by the ROC curve. Cox regression analyses were used to assess the predictive value of plasma M-CSF for CVD events and all-cause mortality in HD patients. We tested the levels of plasma M-CSF and other inflammatory cytokines in surviving HD patients using ELISA or CBA kit. RESULTS: The average plasma level of M-CSF in 52 patients was approximately twice that of healthy controls (992.4 vs. 427.2 pg/mL; p <  0.05). During 32 months of follow-up, 26 patients (50.0%) had at least one CVD event and 8 patients (15.4%) died. The mean plasma M-CSF concentration increased in survivors after follow-up compared to that detected at baseline (1277.8 ± 693.3 vs. 997.2 ± 417.4 pg/mL; p <  0.05). Multivariate Cox regression analysis showed that plasma M-CSF is an independent risk factor for CVD events in HD patients (p <  0.05). In the Cox regression model after adjusting for gender and age, high M-CSF levels were related to an increased risk of all-cause death (p <  0.05). We also found that M-CSF levels were positively correlated with IL-6 and IL-18 levels (both p < 0.05), which are the major pathogentic cytokines that contribute to HD-related CVD events. CONCLUSION: M-CSF is a prognostic factor for CVD events and all-cause mortality in HD patients.

Biliverdin Reductase A (BVRA) Mediates Macrophage Expression of Interleukin-10 in Injured Kidney.

Biliverdin reductase A is an enzyme, with serine/threonine/tyrosine kinase activation, converting biliverdin (BV) to bilirubin (BR) in heme degradation pathway. It has been reported to have anti-inflammatory and antioxidant effect in monocytes and human glioblastoma. However, the function of BVRA in polarized macrophage was unknown. This study aimed to investigate the effect of BVRA on macrophage activation and polarization in injured renal microenvironment. Classically activated macrophages (M1macrophages) and alternative activation of macrophages (M2 macrophages) polarization of murine bone marrow derived macrophage was induced by GM-CSF and M-CSF. M1 polarization was associated with a significant down-regulation of BVRA and Interleukin-10 (IL-10), and increased secretion of TNF-α. We also found IL-10 expression was increased in BVRA over-expressed macrophages, while it decreased in BVRA knockdown macrophages. In contrast, BVRA over-expressed or knockdown macrophages had no effect on TNF-α expression level, indicating BVRA mediated IL-10 expression in macrophages. Furthermore, we observed in macrophages infected with recombinant adenoviruses BVRA gene, which BVRA over-expressed enhanced both INOS and ARG-1 mRNA expression, resulting in a specific macrophage phenotype. Through in vivo study, we found BVRA positive macrophages largely existed in mice renal ischemia perfusion injury. With the treatment of the regular cytokines GM-CSF, M-CSF or LPS, excreted in the injured renal microenvironment, IL-10 secretion was significantly increased in BVRA over-expressed macrophages. In conclusion, the BVRA positive macrophage is a source of anti-inflammatory cytokine IL-10 in injured kidney, which may provide a potential target for treatment of kidney disease.

Heterogeneous Multidomain Recommender System Through Adversarial Learning.

To solve the user data sparsity problem, which is the main issue in generating user preference prediction, cross-domain recommender systems transfer knowledge from one source domain with dense data to assist recommendation tasks in the target domain with sparse data. However, data are usually sparsely scattered in multiple possible source domains, and in each domain (source/target) the data may be heterogeneous, thus it is difficult for existing cross-domain recommender systems to find one source domain with dense data from multiple domains. In this way, they fail to deal with data sparsity problems in the target domain and cannot provide an accurate recommendation. In this article, we propose a novel multidomain recommender system (called HMRec) to deal with two challenging issues: 1) how to exploit valuable information from multiple source domains when no single source domain is sufficient and 2) how to ensure positive transfer from heterogeneous data in source domains with different feature spaces. In HMRec, domain-shared and domain-specific features are extracted to enable the knowledge transfer between multiple heterogeneous source and target domains. To ensure positive transfer, the domain-shared subspaces from multiple domains are maximally matched by a multiclass domain discriminator in an adversarial learning process. The recommendation in the target domain is completed by a matrix factorization module with aligned latent features from both the user and the item side. Extensive experiments on four cross-domain recommendation tasks with real-world datasets demonstrate that HMRec can effectively transfer knowledge from multiple heterogeneous domains collaboratively to increase the rating prediction accuracy in the target domain and significantly outperforms six state-of-the-art non-transfer or cross-domain baselines.

Controllable Preparation of Highly Crystalline Sulfur-Doped Π-Conjugated Polyimide Hollow Nanoshell for Enhanced Photocatalytic Performance.

In this study, a series of highly crystalline π-conjugated polyimide photocatalysts with porous nano hollow shell (HSPI) was prepared for the first time by the hard template method by adjusting the addition ratio of the template precursor. SiO2 nanospheres not only serve as template agents but also as dispersants to make precursors of SPI more uniform, and the degree of polymerization will be better, resulting in significantly enhanced crystallinity of HSPI relative to bulk SPI (BSPI). More strikingly, it is found that HSPI has a larger specific surface area, stronger visible light absorption, and higher separation efficiency of photogenerated electron and hole pairs compared with BSPI by various spectral means characterization analysis. These favorable factors significantly enhanced the photocatalytic degradation of methyl orange (MO) by HSPI. This work provides a promising approach for the preparation of cheap, efficient, environmentally friendly, and sustainable photocatalysts.

Spatial differences and influence mechanisms of construction land development intensity in China, 2002-2020.

Construction land development intensity is a spatial mapping of modern urbanization level, which integrally reflects urban development strategy, land use efficiency, and population carrying intensity. This article analyzed the spatial and temporal evolution of construction land development intensity using panel data of 31 provincial administrative divisions in China from 2002 to 2020, with the application of the Theil index and spatial autocorrelation. To further investigate the relationship between human activities and land development, the article used geographic detectors to analyze the influencing mechanisms. The results showed that: (1) The average intensity of construction land development of Chinese provinces from 2002 to 2020 showed a trend of "steady increase, a short decline, and then a steady increase," and there were significant differences in the characteristics of construction land development intensity changes in different regions. (2) The regional differences in construction land development intensity between provinces showed a decreasing trend. There were uneven differences among regions, with more minor regional differences in Central, South, and North China but more significant differences in Northwest, East, Southwest, and Northeast China. (3) The spatial agglomeration of construction land development intensity in the region increased initially and then decreased during the study period. The overall pattern was "small agglomeration and large dispersion." (4) Economic development factors such as GDP per land, industrial structure, and fixed asset investment completion significantly affect land development intensity. The interaction between the factors was apparent, and the effect of "1 + 1 > 2" was produced. Based on the study's results, it is suggested that scientific regional development planning, guiding inter-provincial factor flow, and rational control of land development efforts are the key to promoting sustainable regional development.

Comparing machine learning methods for predicting land development intensity.

Land development intensity is a comprehensive indicator to measure the degree of saving and intensive land construction and economic production activities. It is also the result of the joint action of natural, social, economic, and ecological elements in land development and utilization. Scientific prediction of land development intensity has particular reference significance for future regional development planning and the formulation of reasonable land use policies. Based on the inter-provincial land development intensity and its influencing factors in China, this study applied four algorithms, XGBoost, random forest model, support vector machine, and decision tree, to simulate and predict the land development intensity, and then compared the prediction accuracy of the four algorithms, and also carried out hyperparameter adjustment and prediction accuracy verification. The results show that the model with the best prediction performance among the four algorithms is XGBoost, and its R2 and MSE between predicted and valid values are 95.66% and 0.16, respectively, which are higher than the other three models. During the training process, the learning curve of the XGBoost model exhibited low fluctuation and fast fitting. Hyperparameter tuning is crucial to exploit the model's potential. The XGBoost model has the best prediction performance with the best hyperparameter combination of max_depth:19, learning_rate: 0.47, and n_estimatiors:84. This study provides some reference significance for the simulation of land development and utilization dynamics.

(8-Hydroxyquinoline) Gallium(III) Complex with High Antineoplastic Efficacy for Treating Colon Cancer via Multiple Mechanisms.

A series of (8-hydroxyquinoline) gallium(III) complexes (CP-1-4) was synthesized and characterized by single X-ray crystallography and density functional theory (DFT) calculation. The cytotoxicity of the four gallium complexes toward a human nonsmall cell lung cancer cell line (A549), human colon cancer cell line (HCT116), and human normal hepatocyte cell line (LO2) was evaluated using MTT assays. CP-4 exhibited excellent cytotoxicity against HCT116 cancer cells (IC50 = 1.2 ± 0.3 µM) and lower toxicity than cisplatin and oxaliplatin. We also evaluated the anticancer mechanism studies in cell uptake, reactive oxygen species analysis, cell cycle, wound-healing, and Western blotting assays. The results showed that CP-4 affected the expression of DNA-related proteins, which led to the apoptosis of cancer cells. Moreover, molecular docking tests of CP-4 were performed to predict other binding sites and to confirm its higher binding force to disulfide isomerase (PDI) proteins. The emissive properties of CP-4 suggest that this complex can be used for colon cancer diagnosis and treatment, as well as in vivo imaging. These results also provide a foundation for the development of gallium complexes as potent anticancer agents.

Gallium Metal-Organic Nanoparticles with Albumin-Stabilized and Loaded Graphene for Enhanced Delivery to HCT116 Cells.

Background: Gallium (III) metal-organic complexes have been shown to have the ability to inhibit tumor growth, but the poor water solubility of many of the complexes precludes further application. The use of materials with high biocompatibility as drug delivery carriers for metal-organic complexes to enhance the bioavailability of the drug is a feasible approach. Methods: Here, we modified the ligands of gallium 8-hydroxyquinolinate complex with good clinical anticancer activity by replacing the 8-hydroxyquinoline ligands with 5-bromo-8-hydroxyquinoline (HBrQ), and the resulting Ga(III) + HBrQ complex had poor water solubility. Two biocompatible materials, bovine serum albumin (BSA) and graphene oxide (GO), were used to synthesize the corresponding Ga(III) + HBrQ complex nanoparticles (NPs) BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs in different ways to enhance the drug delivery of the metal complex. Results: Both of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs can maintain stable existence in different solution states. In vitro cytotoxicity test showed that two nanomedicines had excellent anti-proliferation effect on HCT116 cells, which shown higher level of intracellular ROS and apoptosis ratio than that of cisplatin and oxaliplatin. In addition, the superior emissive properties of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs allow their use for in vivo imaging showing highly effective therapy in HCT116 tumor-bearing mouse models. Conclusion: The use of biocompatible materials for the preparation of NPs against poorly biocompatible metal-organic complexes to construct drug delivery systems is a promising strategy that can further improve drug delivery and therapeutic efficacy.

Ozone control strategies for local formation- and regional transport-dominant scenarios in a manufacturing city in southern China.

Given the leveling off of fine particulate matter (PM2.5), ground-level ozone (O3) pollution has become one of the most significant atmospheric pollution issues in the Pearl River Delta (PRD) region in China, especially in the manufacturing city of Dongguan, which faces more severe O3 pollution. The development of strategies to control O3 precursor emissions, including volatile organic compounds (VOCs) and nitrogen oxide (NOx), depends to a large extent on the source region of the O3 pollution. In this study, by combining the Weather Research and Forecasting model coupled with chemistry (WRF-Chem), the Empirical Kinetic Modeling Approach (EKMA), and the Flexible Particle model (FLEXPART), more effective strategies of controlling O3 precursor emissions were identified under two typical types of O3 pollution episodes: local formation (LF)-dominant (8-12 September 2019) and regional transport (RT)-dominant (23-27 October 2017) episodes, distinguished by the WRF-FLEXPART model. During the LF-dominant episode, the EKMA revealed that the O3 formation in Dongguan was in a transitional regime, and the abatement of solvent use-VOCs emissions in the key area of Dongguan was more effective in reducing O3 levels, with an emission reduction benefit 1.7 times that of total VOCs emission sources throughout Dongguan. With respect to the RT-dominant episode, the reduction in VOCs emissions in the local region did not effectively curb O3 pollution, although the photochemical regime of the O3 formation in Dongguan was VOCs-limited. A 50% reduction in NOx emissions in the upwind regions (parts of Guangzhou and Huizhou) effectively decreased the O3 concentration in Dongguan by 17%. The results of this study emphasize the importance of the source region of O3 pollution in the implementation of effective O3 control strategies and provide valuable insights for region-specific precursor emission policy formulation, not only in Dongguan, but also in other regions facing severe O3 pollution.

Role of Sema4C in TGF-ß1-induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells.

BACKGROUND: The p38 mitogen-activated protein kinase (p38 MAPK) is an important intracellular signal transduction pathway involved in TGF-ß1-induced epithelial-mesenchymal transition (EMT). Sema4C, a member of the semaphorin family, was found to be essential for the activation of p38 MAPK. However, the role of Sema4C in promoting TGF-ß1-induced EMT is unclear. METHODS: Renal fibrosis was induced by 5/6 subtotal nephrectomy rat model. In vitro, Sema4C was induced in human proximal tubular epithelial cells (HKC) by treatment with TGF-ß1, or was inhibited by siRNA or was over-expressed by Sema4C transfection. The selective p38 MAPK inhibitor, SB203580, was administered to inhibit the p38 pathway. The expression of Sema4C, the markers of EMT, p38 phosphorylation and fibronectin secretion were measured by western blotting, immunohistochemistry, immunocytochemistry or enzyme-linked immunosorbent assay. RESULTS: The expression of Sema4C increased in HKC cells that were treated with TGF-ß1. Knockdown of Sema4C potently inhibited phosphorylation of p38 MAPK and reversed TGF-ß1-induced EMT. Over-expression of Sema4C via Sema4C transfection elicited p38 MAPK phosphorylation and promoted EMT. The effects of Sema4C during EMT were blocked by a p38-specific inhibitor. In vivo, the expression of Sema4C increased in the tubular epithelia of 5/6-nephrectomized rats and human fibrotic renal tissue, and similar localization of phosphorylated p38 and Sema4C was demonstrated by immunohistochemistry on serial sections. CONCLUSIONS: Our findings suggest that Sema4C plays an important role in TGF-ß1-induced EMT through activation of p38 MAPK in proximal tubular epithelial cells.

Selecting Classification Methods for Small Samples of Next-Generation Sequencing Data.

Next-generation sequencing has emerged as an essential technology for the quantitative analysis of gene expression. In medical research, RNA sequencing (RNA-seq) data are commonly used to identify which type of disease a patient has. Because of the discrete nature of RNA-seq data, the existing statistical methods that have been developed for microarray data cannot be directly applied to RNA-seq data. Existing statistical methods usually model RNA-seq data by a discrete distribution, such as the Poisson, the negative binomial, or the mixture distribution with a point mass at zero and a Poisson distribution to further allow for data with an excess of zeros. Consequently, analytic tools corresponding to the above three discrete distributions have been developed: Poisson linear discriminant analysis (PLDA), negative binomial linear discriminant analysis (NBLDA), and zero-inflated Poisson logistic discriminant analysis (ZIPLDA). However, it is unclear what the real distributions would be for these classifications when applied to a new and real dataset. Considering that count datasets are frequently characterized by excess zeros and overdispersion, this paper extends the existing distribution to a mixture distribution with a point mass at zero and a negative binomial distribution and proposes a zero-inflated negative binomial logistic discriminant analysis (ZINBLDA) for classification. More importantly, we compare the above four classification methods from the perspective of model parameters, as an understanding of parameters is necessary for selecting the optimal method for RNA-seq data. Furthermore, we determine that the above four methods could transform into each other in some cases. Using simulation studies, we compare and evaluate the performance of these classification methods in a wide range of settings, and we also present a decision tree model created to help us select the optimal classifier for a new RNA-seq dataset. The results of the two real datasets coincide with the theory and simulation analysis results. The methods used in this work are implemented in the open-scource R scripts, with a source code freely available at https://github.com/FocusPaka/ZINBLDA.

Outlier detection and robust variable selection via the penalized weighted LAD-LASSO method.

This paper studies the outlier detection and robust variable selection problem in the linear regression model. The penalized weighted least absolute deviation (PWLAD) regression estimation method and the adaptive least absolute shrinkage and selection operator (LASSO) are combined to simultaneously achieve outlier detection, and robust variable selection. An iterative algorithm is proposed to solve the proposed optimization problem. Monte Carlo studies are evaluated the finite-sample performance of the proposed methods. The results indicate that the finite sample performance of the proposed methods performs better than that of the existing methods when there are leverage points or outliers in the response variable or explanatory variables. Finally, we apply the proposed methodology to analyze two real datasets.

Separated parabiont reveals the fate and lifespan of peripheral-derived immune cells in normal and ischaemia-induced injured kidneys.

Immune cell infiltration plays a key role in acute kidney injury (AKI) to chronic kidney disease (CKD) progression. T lymphocytes, neutrophils, monocytes/macrophages and other immune cells regulate inflammation, tissue remodelling and repair. To determine the kinetics of accumulation of various immune cell populations, we established an animal model combining parabiosis and separation surgery to explore the fate and lifespan of peripheral leucocytes that migrate to the kidney. We found that peripheral T lymphocytes could survive for a long time (more than 14 days), whereas peripheral neutrophils survived for a short time in both healthy and ischaemia-induced damaged kidneys. Nearly half of the peripheral-derived macrophages disappeared after 14 days in normal kidneys, while their existing time in the inflammatory kidneys was prolonged. A fraction of F4/80high macrophages were renewed from the circulating monocyte pool. In addition, we found that after renal ischaemia reperfusion, neutrophils increased significantly in the early phase, and T lymphocytes mainly accumulated in the late stage, whereas macrophages infiltrated throughout AKI-CKD progression and were sustained longer in injured as opposed to normal kidneys. In conclusion, peripheral-derived macrophages, T lymphocytes and neutrophils exhibit different lifespans in the kidney, which may play different roles during AKI-CKD progression.

[Effect of ginkgolide B on the production of NO, IL-6 and RANTES from astrocytes].

This study is to explore the effect of ginkgolide B (BN52021) on the production of nitric oxide (NO), interleukin (IL)-6 and regulated upon activation normal T cell expressed and secreted (RANTES) from astrocytes induced by stimulators. Primary cultured rat astrocytes were stimulated with lipopolysaccharides (LPS), the production of NO was assayed using Griess reaction; U251 cells were stimulated with IL-1 beta, the contents of IL-6 and RANTES in the supernatant were measured using ELISA. The mRNA expressions of IL-6 and RANTES were detected using RT-PCR. LPS (10 ng mL(-1) to 10 microg mL(-1)) could stimulate rat astrocytes to produce NO in a dose-dependent manner. Ginkgolide B at the concentrations of 0.1-10 micromol L(-1) were shown to decrease NO production significantly. IL-1 beta could induce the mRNA expression and protein secretion of IL-6 from U251 cells, as well as RANTES. Ginkgolide B at concentrations of 0.1-10 micromol L(-1) were shown to inhibit RANTES secretion, and to inhibit mRNA expression of IL-6 and RANTES at concentration of 10 micromol L(-1). Ginkgolide B has inhibitory effect on the production of NO, IL-6 and RANTES from astrocytes treated with inflammatory stimulators.

Temporal and spatial patterns of nitrogen wet deposition in different weather types in the Pearl River Delta (PRD), China.

The temporal and spatial patterns of nitrogen wet deposition were investigated in the Pearl River Delta (PRD) under different weather types. The study was carried out in 27 monitoring sites with reliable meteorological data from 2010 to 2017. Large spatial variation data showed that both annual volume weighted mean (VWM) concentrations and fluxes were higher in the central PRD while lower in the outer area. The annual mean concentrations and fluxes were in the range of 0.8-1.3 mg N L-1 and 10.9-20.6 kg N ha-1 yr-1, respectively. The monthly mean concentrations and fluxes ranged from 0.1 to 0.2 mg N L-1 and 0.4 to 2.4 kg N ha-1, respectively. Further the study data revealed that the ratio of NH4+/NO3- was 1.1 which was much lower than the ratio reported in other regions like Northern China, Sichuan Basin, the US and Europe. The flux of NH4+ in urban sites was comparable to rural sites, implying that potential non-agricultural NH3 emissions were likely to be high in the PRD. The top three weather types were E, C and SE, with the total contribution of more than a half to the flux. Multiple linear regression was used to set up an equation to predict the variation of annual fluxes under the changes in weather conditions. The result hints that the variation on annual fluxes in the PRD tends to be stable in the next 30 years. Considering the increasing impact on the ecosystem, more effort should be exerted to reduce nitrogen wet deposition in the future.

CSF-1R inhibition attenuates ischemia-induced renal injury and fibrosis by reducing Ly6C+ M2-like macrophage infiltration.

Acute kidney injury (AKI) to chronic kidney disease (CKD) progression has become a life-threatening disease. However, an effective therapeuticstrategyis still needed. The pathophysiology of AKI-to-CKD progression involves chronic inflammation and renal fibrosis driven by macrophage activation, which is physiologically dependent on colony-stimulating factor-1 receptor (CSF-1R) signaling. In this study, we modulated macrophage infiltration through oral administration of the CSF-1R inhibitor GW2580 in an ischemia-reperfusion (I/R)-induced AKI model to evaluate its therapeutic effects on preventing the progression of AKI to CKD. We found that GW2580 induced a significant reduction in the number of macrophages in I/R-injured kidneys and attenuated I/R-induced renal injury and subsequent interstitial fibrosis. By flow cytometry, we observed that the reduced macrophages were primarily Ly6C+ inflammatory macrophages in the GW2580-treated kidneys, while there was no significant difference in the number and percentage of Ly6C-CX3CR1+ macrophages. We further found that these reduced macrophages also demonstrated some characteristics of M2-like macrophages, which have been generally regarded as profibrotic subtypes in chronic inflammation. These results indicate the existence of phenotypic and functional crossover between Ly6C+ and M2-like macrophages in I/R kidneys, which induces AKI worsening to CKD. In conclusion, therapeutic GW2580 treatment alleviates acute renal injury and subsequent fibrosis by reducing Ly6C+ M2-like macrophage infiltration in ischemia-induced AKI.

Dry deposition of reactive nitrogen to different ecosystems across eastern China: A comparison of three community models.

The assessment of nitrogen ecosystem loads mostly use the method of sampling observation combined with numerical model to estimate the spatial distribution pattern of nitrogen dry deposition flux. The selection of models is important which directly affects the reliability of the deposition flux results. In this study, the performance of three widely used models (WRF-Chem, EMEP, CMAQ) are compared. The dry deposition fluxes of typical active nitrogen components over eastern China showed uncertainties by a factor of 0.5 ~ 2 between the oxidized nitrogen (OXN) results of the three models and the observation network while the reduced nitrogen (RDN) simulation results are underestimated by a quarter of the observation reports. These three models show different results on four typical ecosystems: simulation of EMEP got the highest for OXN dry deposition flux on each ecosystem (urban 14.94 ± 4.92kgN â‹… ha-1 â‹… yr-1, cropland/grassland 5.53 ± 5.11kgN â‹… ha-1 â‹… yr-1, forest 4.75 ± 4.32kgN â‹… ha-1 â‹… yr-1, water bodies 1.48 ± 1.53kgN â‹… ha-1 â‹… yr-1); WRF-Chem has the highest value of RDN on the urban (8.91 ± 6.44kgN â‹… ha-1 â‹… yr-1) and water bodies (1.01 ± 1.44kgN â‹… ha-1 â‹… yr-1) while EMEP is highest in cropland/grassland (3.42 ± 3.43kgN â‹… ha-1 â‹… yr-1) and forest (2.34 ± 1.94kgN â‹… ha-1 â‹… yr-1). CMAQ is in medium range for both OXN and RDN simulations on each ecosystem. Compare with the critical loads, CMAQ generates more exceeded critical load areas than WRF-Chem and EMEP on cropland/grassland and forests ecosystem. For water bodies, WRF-chem and CMAQ showed higher exceeding critical load areas than EMEP. In summary, EMEP generally underestimates while the CMAQ and WRF-Chem model would overestimate the impacts on the ecosystems. So, policy implementation needs special attention accounting the difference of simulation effect with different models.