Imbalance of T follicular helper cell subsets trigger the differentiation of pathogenic B cells in idiopathic membranous nephropathy.

OBJECTIVE: This study aims to elucidate the role of T follicular helper (Tfh) cells and their subsets in idiopathic membranous nephropathy (IMN). METHODS: The frequencies of Tfh cell subsets and B cell subsets in peripheral blood (PB) were detected in both IMN patients and healthy controls (HCs). The involvement of Tfh cells in the disease pathogenesis was examined by coculturing human Tfh cells with B cells. The dynamic changes of Tfh cells in PB or spleen were monitored in passive Heymann nephritis (PHN) rats. RESULTS: The frequencies of circulating Tfh (cTfh) cells, cTfh2 cells, and plasmablasts were enriched in the PB of patients with IMN. cTfh cells expressed higher ICOS, and lower BTLA than healthy counterparts. The frequency of ICOS + cTfh2 was associated with the severity of IMN, including 24h urine protein, IgG4 concentration and the IgG4: IgG ratio. Positive correlations were also observed between the frequency of cTfh2 cells with plasmablasts, serum IL-21 and IL-4 levels. Importantly, cTfh cells isolated from IMN patients were able to induce the differentiation of B cells to memory B cells (MBC) and plasmablasts, this process could be substantially attenuated by blocking the IL-21. Similar increases of ICOS + cTfh cells were also detected in spleen of PHN rats, concomitant with elevated urine protein levels. CONCLUSIONS: Collectively, our results demonstrate that the imbalance of cTfh cell subsets play a crucial pathogenic role in IMN by inducing the differentiation of B cells through IL-21, and cTfh2 cells might serve as useful markers to evaluate the progression of IMN.

Bacterial community assembly and antibiotic resistance genes in soils exposed to antibiotics at environmentally relevant concentrations.

Understanding how bacterial community assembly and antibiotic resistance genes (ARGs) respond to antibiotic exposure is essential to deciphering the ecological risk of anthropogenic antibiotic pollution in soils. In this study, three loam soils with different land management (unmanured golf course, dairy-manured pasture, and swine-manured cornfield) were spiked with a mixture of 11 antibiotics at the initial concentration of 100 and 1000 µg kg-1 for each antibiotic and incubated over 132 days, mimicking a scenario of pulse disturbance and recovery in soils, with unspiked soil samples as the control treatment. The Infer Community Assembly Mechanisms by Phylogenetic-bin-based null model (iCAMP) analysis demonstrated that drift and dispersal limitation contributed to 57%-65% and 16%-25%, and homogeneous selection 12%-16% of soil bacterial community assembly. Interestingly, antibiotic exposure to 1000 µg kg-1 level significantly increased the contribution of drift to community assembly, largely due to the positive response from Acidobacteria-6 in the golf course and pasture soils and from Chthoniobacteraceae in the cornfield soil to the antibiotic exposure. However, ARG abundance and diversity in the three soils exhibited antibiotics-independent temporal fluctuations, but were associated with the changes in soil bacterial communities over time. This study provides the first insight into the relative contributions of different bacterial community assembly processes in soils upon antibiotic exposure at environmentally relevant concentrations.

Influence of organic cosolvents on hexabromobenzene degradation in solution by montmorillonite-templated subnanoscale zero-valent iron.

Organic cosolvents are commonly used to increase the dissolution of poorly water-soluble organic pollutants into aqueous solutions during environmental remediation. In this study, the influences of five organic cosolvents on hexabromobenzene (HBB) degradation catalyzed by one typical reactive material montmorillonite-templated subnanoscale zero-valent iron (CZVI) were investigated. The results demonstrated that all cosolvents promoted HBB degradation but the degree of promotion was different for different cosolvents, which was associated with inconsistent solvent viscosities, dielectric constant properties, and the extent of interactions between cosolvents with CZVI. Meanwhile, HBB degradation was highly dependent on the volume ratio of cosolvent to water, which increased in the range of 10%-25% but persistently decreased in the range of more than 25%. This might be due to the fact that the cosolvents increased HBB dissolution at low concentrations but reduced the protons supplied by water and the contact between HBB with CZVI at high concentrations. In addition, the freshly-prepared CZVI had higher reactivity to HBB than the freeze-dried CZVI in all water-cosolvent solutions, probably because freeze-drying reduced the interlayer space of CZVI and thus the contact probability between HBB and active reaction sites. Finally, the CZVI-catalyzed HBB degradation mechanism was proposed as the electron transfer between zero-valent iron and HBB, which led to the formation of four debromination products. Overall, this study provides helpful information for the practical application of CZVI in the remediation of persistent organic pollutants in the environment.

Biodegradable Microplastics: A Review on the Interaction with Pollutants and Influence to Organisms.

Biodegradable plastics attract public attention as promising substitutes for traditional nondegradable plastics which have caused the serious white pollution problem due to their persistence. However, even for biodegradable plastics, natual conditions for the rapid and complete degradation are rare. Even more serious is that biodegradable plastics might be disintegrated into microplastics more rapidly than tranditional plastics, emerging as another threat to the environment. Similar to traditional microplastics, biodegradable microplastics could adsorb many pollutants by various physicochemical effects and release additives. Biodegradable microplastics have been confirmed to be toxic to the organisms as particle matter and the vector as pollutants. Under some conditions, biodegradable microplastics may pose more severe negative impacts on the organisms. With the fierely increasing trend to replace the nondegradable plastic commodities with biodegradable ones, it is necessary to evaluate whether biodegradable plastics and the generated microplastics would alleviate plastic pollution or induce greater ecological impacts.

Characterization of γδT cells in lung of Plasmodium yoelii-infected C57BL/6 mice.

BACKGROUND: Malaria has high morbidity and mortality rates in some parts of tropical and subtropical countries. Besides respiratory and metabolic function, lung plays a role in immune system. γδT cells have multiple functions in producing cytokines and chemokines, regulating the immune response by interacting with other cells. It remains unclear about the role of γδT cells in the lung of mice infected by malaria parasites. METHODS: Flow cytometry (FCM) was used to evaluate the frequency of γδT cells and the effects of γδT cells on the phenotype and function of B and T cells in Plasmodium yoelii-infected wild-type (WT) or γδTCR knockout (γδT KO) mice. Haematoxylin-eosin (HE) staining was used to observe the pathological changes in the lungs. RESULTS: The percentage and absolute number of γδT cells in the lung increased after Plasmodium infection (p < 0.01). More γδT cells were expressing CD80, CD11b, or PD-1 post-infection (p < 0.05), while less γδT cells were expressing CD34, CD62L, and CD127 post-infection (p < 0.05). The percentages of IL-4+, IL-5+, IL-6+, IL-21+, IL-1α+, and IL-17+ γδT cells were increased (p < 0.05), but the percentage of IFN-γ-expressing γδT cells decreased (p < 0.05) post-infection. The pathological changes in the lungs of the infected γδT KO mice were not obvious compared with the infected WT mice. The proportion of CD3+ cells and absolute numbers of CD3+ cells, CD3+ CD4+ cells, CD3+ CD8+ cells decreased in γδT KO infected mice (p < 0.05). γδT KO infected mice exhibited no significant difference in the surface molecular expression of T cells compared with the WT infected mice (p > 0.05). While, the percentage of IFN-γ-expressing CD3+ and CD3+ CD8+ cells increased in γδT KO infected mice (p < 0.05). There was no significant difference in the absolute numbers of the total, CD69+, ICOS+, and CD80+ B cells between the WT infected and γδT KO infected mice (p > 0.05). CONCLUSIONS: The content, phenotype, and function of γδT cells in the lung of C57BL/6 mice were changed after Plasmodium infection. γδT cells contribute to T cell immune response in the progress of Plasmodium infection.

CD19+CD24hiCD38hi B Cell Dysfunction in Primary Biliary Cholangitis.

CD19+CD24hiCD38hi B cells are immature transitional B cells that, in normal individuals, exert suppressive effects by IL-10 production but are quantitatively altered and/or functionally impaired in individuals with various autoimmune diseases. Primary biliary cholangitis (PBC), an autoimmune disease, clinically presents as chronic cholestasis and nonsuppurative destructive cholangitis. A role for CD19+CD24hiCD38hi B cells in PBC is unknown. This study investigated the frequency and functional variation of circulating CD19+CD24hiCD38hi B cells in PBC patients. Flow cytometry was employed to quantify the percentage of CD19+CD24hiCD38hi B cells in peripheral blood samples. Correlations between CD19+CD24hiCD38hi B cells and routine laboratory parameters were assessed. Levels of IL-10, TNF-α, IL-6 and IL-12, and Tim-1 in CD19+CD24hiCD38hi B cells from PBC patients were analyzed. The effect of CD19+CD24hiCD38hi B cells on CD4+T cell differentiation was evaluated. The percentage of CD19+CD24hiCD38hi B cells in PBC patients was significantly higher than in healthy controls and was positively correlated with liver cholestasis. After activation by anti-B cell receptor and CpG, the production of IL-10 was decreased and the production of IL-6 and IL-12 was increased in CD19+CD24hiCD38hi B cells from PBC patients. Moreover, Tim-1 levels were significantly downregulated in CD19+CD24hiCD38hi B cells from PBC patients. Coculture showed that PBC-derived CD19+CD24hiCD38hi B cells were less capable of CD4+T cell inhibition, but promoted Th1 cell differentiation. In conclusion, PBC patients have expanded percentages, but impaired CD19+CD24hiCD38hi B cells, which correlate with disease damage. In PBC patients, this B cell subset has a skewed proinflammatory cytokine profile and a decreased capacity to suppress immune function, which may contribute to the pathogenesis of PBC.

Transformation and toxicity of environmental contaminants as influenced by Fe containing clay minerals: a review.

Clay minerals are ubiquitous in soil and sediments, and play important roles in environmental processes. Virtually all clay minerals contain some Fe, either in the crystal structure or adsorbed at the surface of the clay minerals, which could promote many reactions on the clay minerals. The interaction between Fe containing clay mineral and its surrounding contaminants would greatly affect the transformation and toxicity of the contaminants. While it is certain that the Fe plays important roles in the fate of the contaminants, relative qualitative and quantitative assessment of these processes is limited. Based on the overall toxicity variation, this paper reviews the active areas of the researches on the interactions between Fe containing clay mineral and contaminants, and provides perspectives for future work.

Interactions of Gaseous 2-Chlorophenol with Fe3+-Saturated Montmorillonite and Their Toxicity to Human Lung Cells.

The interactions of gaseous 2-chlorophenol with Fe3+-saturated montmorillonite particles in a gas-solid system were investigated to simulate the reactions of mineral dusts with volatile organic pollutants in the atmosphere. Results suggested that Fe3+-saturated montmorillonite mediated the dimerization of gaseous 2-chlorophenol to form hydroxylated polychlorinated biphenyl, hydroxylated polychlorinated diphenyl ether, and hydroxylated polychlorinated dibenzofuran. The toxicity of Fe3+-montmorillonite particles to A549 human lung epithelial cells before and after interaction with 2-chlorophenol was examined to explore their adverse impact on human health. Based on cell morphological analysis, cytotoxicity tests, and Fourier-transform infrared imaging spectra, surface-catalyzed reactions of Fe3+-montmorillonite with 2-chlorophenol increased the toxicity of montmorillonite particle on A549 cells. This was supported by increased cellular membrane permeability, the release of extracellular lactate dehydrogenase, and cell damages on cellular DNA, proteins, and lipids. Since mineral dusts are important components of particulate matter, our results help to understand the interactions of volatile organic pollutants with particulate matter in the atmosphere and their adverse impacts on human health.

miR-155 suppresses bacterial clearance in Pseudomonas aeruginosa-induced keratitis by targeting Rheb.

miR-155 (microRNA-155) is an important noncoding RNA in regulating host inflammatory responses. However, its regulatory role in ocular infection remains unclear. Our study first explored the function of miR-155 in Pseudomonas aeruginosa-induced keratitis, one of the most common sight-threatening ocular diseases. We found that miR-155 expression was enhanced in human and mouse corneas after P. aeruginosa infection and was mainly expressed in macrophages but not neutrophils. In vivo studies demonstrated that miR-155 knockout mice displayed more resistance to P. aeruginosa keratitis, with a higher inducible nitric oxide synthase level and a lower bacterial burden. More importantly, in vitro data indicated that miR-155 suppressed the macrophage-mediated bacterial phagocytosis and intracellular killing of P. aeruginosa by targeting Rheb (Ras homolog enriched in brain). To the best of our knowledge, this is the first study to explore the role of miR-155 in bacterial keratitis, which may provide a promising target for clinical treatment of P. aeruginosa keratitis and other infectious diseases.

Effect of CD95 on inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes.

OBJECTIVE: Many CD95-expressing cells don't always undergo apoptosis after stimulation with CD95 ligation. The purpose of this paper is to investigate the role of expression of CD95 (Fas/Apo1) on inflammatory response in fibroblast-like synoviocytes (FLS) obtained from rheumatoid arthritis (RA) and to evaluate the role of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB or Akt) pathways within this process. METHODS: The expression levels of CD95 were monitored by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Apoptotic cells were detected by in situ apoptosis detection (TUNEL) assay. The RA-FLS were treated with agonistic anti-CD95 antibody or CD95 siRNA. Then the proliferation was detected by CCK-8, and mRNA level of inflammatory cytokines was detected by RT-PCR. After the RA-FLS were treated with agonistic anti-CD95 antibody, the total Akt and pAkt protein expression was analyzed by Western blot, and the changes mentioned above were observed while pre-incubated with the PI3K inhibitor LY294002. RESULTS: A significant increase of CD95 antigen was found in RA compared with osteoarthritis (OA) samples, while apoptosis in RA synovial tissue was not obvious. Low concentrations of agonistic anti-CD95 antibody could promote RA-FLS growth and interleukin-6 (IL-6) mRNA expression, while high concentrations could induce apoptosis. And both of these phenomena could be inhibited by CD95 siRNA. Agonistic anti-CD95 antibody could stimulate the expression of pAkt, and PI3K specific inhibitor LY294002 could induce opposite changes. CONCLUSION: Stimulation of CD95 could promote RA-FLS proliferation and inflammation, and activation of the PI3K/Akt signaling pathway might be the possible mechanism.

Characteristics of γδ T cells in Schistosoma japonicum-infected mouse mesenteric lymph nodes.

Gamma delta (γδ) T cells are mainly present in mucosa-associated lymphoid tissues, which play an important role in mucosal immunity. In this study, C57BL/6 mice were infected by Schistosoma japonicum and lymphocytes were isolated from the mesenteric lymph node (MLN) to identify changes in the phenotype and function of γδ T cells using flow cytometry. Our results indicated that the absolute number of γδ T cells from the MLNs of infected mice was significantly higher compared with normal mice (P < 0.05). In addition, the infected γδ T cells expressed a high level of the activated molecule CD69 (P < 0.01) and demonstrated an increasing population of CD4(+) γδ T cells (P < 0.05). MLN γδ T cells secrete interferon-γ (IFN-γ), interleukin (IL)-4, IL-9, and IL-17 in response to propylene glycol monomethyl acetate (PMA) plus ionomycin simulation, and the levels of IL-4, IL-9, and IL-17 increased significantly after S. japonicum infection (P < 0.05). Taken together, these findings indicated that S. japonicum infection could induce γδ T cell activation, proliferation, and differentiation in the MLN. Moreover, our results indicated that the expression of NKG2D (CD314) was not increased in γδ T cells after infection, suggesting that other mechanisms are involved in activating γδ T cells. Furthermore, higher expression of programmed death-1 (CD279) but not IL-10 was detected in the γδ T cells isolated from infected mice (P < 0.05), suggesting that the function of γδ T cells is inhibited gradually over the course of S. japonicum infection.

[Triptolide inhibites Th17 cell differentiation via regulating cyclooxygenase-2/ prostaglandin E2 axis in synovial fibroblasts from rheumatoid arthritis].

Triptolide (TPT), an active compound extracted from Chinese herb Tripterygium wilfordii , has been used in therapy of rheumatoid arthritis (RA). In this study, after synovial fibroblasts from rheumatoid arthritis (RASFs) were treated with TPT, we investigated its effect on the differentiation of Th17 cells. Firstly, the mRNA level of cyclooxygenase (COX) wad detected by qRT-PCR and the protein level of prostaglandin E2 (PGE2) was tested by ELISA in RASFs treated with different concentrations (0, 10, 50, 100 nmol L-1 ) of TPT. Then after TPT pre-treated RASFs and RA CD4 + T cells wer e co-cultured for 3 days in the presence or absence of PGE2, IL-17 and IFN-gamma production in CD4 T cell subsets were detected by flow cytometry. The results showed TPT decreased the mRNA experssion of COX2 and the secretion of PGE2 in RASFs in a dose-dependent manner(P <0. 05). We further found that differentiation of Thl7 cells was downregulated in a dose-dependent manner, and exogenous PGE2 could reverse the inhibition of Th17 cell differentiation(P <0. 05). Taken together, our results demonstrated that TPT inhibited the mRNA level of COX2 and the secretion of PGE2 in RASFs, which partly led to impaired Th17 cell differentiation in vitro.

[Contamination Characteristics，Detection Methods，and Control Methods of Antibiotic Resistance in Pharmaceutical Wastewater].

Pharmaceutical industry wastewater contains a large number of emerging pollutants such as antibiotics， antibiotic resistant bacteria （ARBs）， and antibiotic resistance genes （ARGs）. The present biological water treatment processes cannot effectively remove these pollutants. Eventually， they are discharged into various water bodies or penetrate into soil with the effluent， causing environmental pollution and affecting human health. Therefore， exploring the pollution characteristics of antibiotics， ARBs， and ARGs in pharmaceutical wastewater and knowing the methods to detect and control antibiotic resistance pollution in wastewater are crucial for reducing the contamination of antibiotics and ARGs and assessing the ecological risks of antibiotic resistance. Aiming at the problem of antibiotic resistance pollution in a pharmaceutical wastewater treatment plant （PWWTPs）， the pollution status of antibiotics， ARBs， and ARGs in pharmaceutical wastewater was discussed. Different assessment methods of antibiotic resistance in pharmaceutical wastewater were summarized. Finally， the wastewater treatment technologies commonly used to remove antibiotics and ARGs in PWWTPs were summarized in order to provide a theoretical basis for the ecological risk assessment and scientific control of antibiotics and ARGs in the environment.

Triptolide inhibits the proinflammatory potential of myeloid-derived suppressor cells via reducing Arginase-1 in rheumatoid arthritis.

Triptolide (TPT) is widely used in the treatment of rheumatoid arthritis (RA). However, its regulatory mechanisms are not fully understood. This study demonstrated that Myeloid-derived suppressor cells (MDSCs) were expanded in both RA patients and arthritic mice. The frequency of MDSCs was correlated with RA disease severity and T helper 17 (Th17) responses. MDSCs from RA patients promoted the polarization of Th17 cells in vitro, which could be substantially attenuated by blocking arginase-1 (Arg-1). TPT inhibited the differentiation of MDSCs, particularly the monocytic MDSCs (M-MDSCs) subsets, as well as the expression of Arg-1 in a dose dependent manner. Alongside, TPT treatment reduced the potential of MDSCs to promote the polarization of IL-17+ T cell in vitro. Consistently, TPT immunotherapy alleviated adjuvant-induced arthritis (AIA) in a mice model, and reduced the frequency of MDSCs, M-MDSCs and IL-17+ T cells simultaneously. The presented data suggest a pathogenic role of MDSCs in RA and may function as a novel and effective therapeutic target for TPT in RA.

Elevated circulating CD19+CD24hiCD38hi B cells display pro-inflammatory phenotype in idiopathic membranous nephropathy.

CD19+CD24hiCD38hi regulatory B cells exert immunosuppressive functions by producing IL-10, but their role in idiopathic membranous nephropathy (IMN) remains elusive. Here, we investigated the frequency and functional changes of circulating CD19+CD24hiCD38hi B cells and evaluated the correlation of CD19+CD24hiCD38hi B cells with clinical features and T helper cell subsets in IMN patients. Compared with healthy controls (HCs), IMN patients showed an increased frequency of CD19+CD24hiCD38hi B cells, but a significant reduction in the percentage of CD19+CD24hiCD38hi B cells was observed 4 weeks after cyclophosphamide treatment. The frequency of CD19+CD24hiCD38hi B cells was positively correlated with the levels of 24h urinary protein, but negatively correlated with serum total protein and serum albumin, respectively. CD19+CD24hiCD38hi B cells in IMN patients displayed a skewed pro-inflammatory cytokine profile with a higher level of IL-6 and IL-12, but a lower concentration of IL-10 than their healthy counterparts. Accompanied by upregulation of Th2 and Th17 cells in IMN patients, the percentage of CD19+CD24hiCD38hi B cell subset was positively associated with Th17 cell frequency. In conclusion, CD19+CD24hiCD38hi B cells were expanded but functionally impaired in IMN patients. Their altered pro-inflammatory cytokine profile may contribute to the pathogenesis of IMN.

Halide salts induced the photodegradation of a fat-burning compound 2, 4-dinitrophenol by iron-montmorillonite.

Natural montmorillonite clay and anthropogenic organic pollutants frequently coexist in the estuarine environment where freshwater from rivers mixes with saltwater from the ocean. In this environment, the sharply changed aqueous chemistry especially salt content could significantly alter the photochemical behaviors of pollutants. However, this process was rarely investigated. In this study, the photodegradation of a representative anthropogenic weight-loss compound 2,4-dinitrophenol in the presence of Fe3+-montmorillonite and different halide salts was systematically investigated. Results show that 2,4-dinitrophenol was resistant to photodegradation by Fe3+-montmorillonite alone, but the presence of NaCl, NaBr, and sea salts in the system can evoke significant 2,4-dinitrophenol degradation. The enhancement effect was further elucidated as the replacement reaction between the clay associated Fe3+ and Na + which leads to the release of more interlayer Fe3+ from montmorillonite, resulting in increased production of high active hydroxyl radicals (˙OH) that can substantially damage 2,4-dinitrophenol molecule. In addition, halogen radicals from the reaction of halide ions with ˙OH were also confirmed to participate in 2,4-dinitrophenol degradation. Overall, this study implied that the changed salty condition in the estuarine water could induce the rapid transformation of organic pollutants that move from freshwater and have relatively stable photochemical properties.

NaCl salinity enhances tetracycline bioavailability to Escherichia coli on agar surfaces.

Soil salinity is a worldwide problem and is damaging soil functions. Meanwhile, increasing amounts of anthropogenic antibiotics are discharged to agricultural soils. Little is known about how soil salinity (e.g., NaCl) could influence the bioavailability of antibiotics to bacteria. In this study, a tetracycline-responsive Escherichia coli bioreporter grew on the surfaces of agar microcosms at the same tetracycline concentration (200 µg/L), but various NaCl concentrations (0.5-19.2 g/L) with estimated osmotic potential of -0.18 to -1.80 MPa, and agar content (0.3%-5%) with estimated intrinsic permeability of 38 to 32,928 nm2. These agar microcosms mimicked very fine textured soils with a range of NaCl salinity. Increasing agar content lowered the intrinsic permeability hence decreasing tetracycline bioavailability to E. coli, due likely to the reduced mass transfer of tetracycline via water flow. Intriguingly, tetracycline bioavailability increased with increasing NaCl concentration which caused the increase in osmotic stress. This is contradictory to the notion that osmotic stress reduces bacterial chemical uptake. Further analysis of E. coli membrane integrity demonstrated that the enhanced tetracycline bioavailability to bacteria could result from the compromised cell membranes and enhanced membrane permeability at higher NaCl salinity. Overall, this study suggests that high soil salinity (NaCl) may enhance the selection pressure exerted by antibiotics on bacteria.

Dioxin-like compounds formation mediated by Fe3+-montmorillonite: The substituent effects of halophenols.

Toxic dioxin or/and dioxin-like compounds could be naturally formed from the reaction of halophenols on Fe3+-montmorillonite minerals under ambient conditions. Given that the toxicities and productions of dioxin or/and dioxin-like compounds are largely determined by the number, species, and position of the carried halogen atoms, it is necessary to explore the substituent effects on the reaction of halophenols with Fe3+-montmorillonite. Herein, Fe3+-montmorillonite catalyzed polymerizations of six halophenols were examined in a wide range of relative humidity (10%∼80%) using combinations of mass spectrometry identifications and density functional theory calculations. Results show that both the position and species of the substituents substantially impact the reaction rate, product species, and transformation pathways. In general, regardless of humidity ortho-substituted chlorophenols are more reactive than meta-substituted chlorophenols, which is also supported by the density functional theory calculations indicating that the ortho positions are more likely to be attacked. Regarding substituent species, bromophenols are slightly more reactive and also more easily affected by humidities than chlorophenols, which is due to the weaker electron absorbing ability of the bromine atom than the chlorine atom. Hydroxylated polyhalogenated diphenyl ethers are more frequently detected polymerization products, although hydroxylated polyhalogenated biphenyls are greater quantity of products. Overall, this study provides useful information for understanding the natural formation of dioxin or/and dioxin-like compounds mediated by clay minerals and underlying reaction mechanisms.

Tetracycline photolysis revisited: Overlooked day-night succession of the parent compound and metabolites in natural surface waters and associated ecotoxicity.

Despite the extensive study of tetracycline photolysis in aquatic environments, the phototransformation of tetracycline and its metabolites under natural day-night succession has not been examined. In this study, we investigated tetracycline photolysis and associated ecotoxicity in two natural surface waters and one artificial ultrapure water under simulated day/night cycling over two days. Previously unrecognized and highly pH- and temperature-dependent dark interconversions of tetracycline metabolites were observed. The liquid chromatography-mass spectrometry/mass spectrometry analysis identified a range of isomerized, hydroxylated, demethylated, deaminated, and open-ring photoproducts. The hydrolysis of tetracycline, isotetracycline, and several intermediate products was proposed as the major mechanism for the observed dark transformations. Exposure studies employing Escherichia coli indicated that although the tetracycline degradation products had lower bacterial toxicities than the parent compound, increasing toxicity with irradiation time after the near-complete degradation of the parent compound in natural waters implied that product mixtures retain ecotoxicity. The dark transformations also affected the bacterial toxicity and fluorescence properties of irradiated tetracycline solutions. Overall, this study provides new insights into the photochemical behavior of tetracycline and its associated ecological risk in aquatic environments.

PEG-PEI/siROCK2 inhibits Aß42-induced microglial inflammation via NLRP3/caspase 1 pathway.

OBJECTIVES: There is an urgent need to develop therapeutic strategies to improve the treatment outcome of Alzheimer's disease. The treatment strategy of gene therapy mediated by nanocarrier systems brings new hope for the treatment of Alzheimer's disease. ROCK2 is involved in various pathological processes of Alzheimer's disease and may be a potential target for the treatment of Alzheimer's disease. Our previous study indicated that PEG-PEI/siROCK2 [polyethyleneglycol-polyethyleneimine deliver ROCK2-siRNA, (PPSR)] prevented Aß42-induced neurotoxicity and showed a promising prospect for the treatment of Alzheimer's disease. However, whether PPSR has an effect on the microglial inflammation in Alzheimer's disease is still unclear. MATERIALS AND METHODS: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay was used to detect the cytotoxicity of PEG-PEI and PPSR in primary microglial cells. Real-time PCR and western blotting were used to assess the expression of ROCK2 and nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)/caspase 1 pathway in primary microglial cells. ELISA assay was used to measure the effect of PPSR on attenuating the lipopolysaccharide (LPS) + Aß-induced increase in IL-1ß. RESULTS: PEG-PEI concentration less than 20 µg/ml and the N/P (molar ratio of PEG-PEI amino/siRNA phosphate) ratio of PPSR less than 50 showed no significant cytotoxicity in primary microglia cells. PPSR could effectively inhibit the expression of ROCK2 in primary microglial cells. A further study revealed that PPSR attenuates the LPS+Aß-induced increase in IL-1ß without affecting cell viability. In addition, we found that PPSR suppressed the Aß-induced NLRP3/caspase 1 pathway in primary microglial cells. CONCLUSION: PPSR inhibits Aß42-induced microglial inflammation via NLRP3/caspase 1 pathway.