Aldo-keto reductase family 1 member A1 (AKR1A1) exerts a protective function in alcohol-associated liver disease by reducing 4-HNE accumulation and p53 activation.

BACKGROUND: The development of alcohol-associated liver disease (ALD) is influenced by the amount and duration of alcohol consumption. The resulting liver damage can range from reversible stages, such as steatosis, steatohepatitis and alcoholic fibrosis, to the advanced and irreversible stage of cirrhosis. Aldo-keto reductase family 1 member A1 (AKR1A1) is a member of the aldo-keto reductase family that catalyzes the reduction of aldehyde groups to their corresponding alcohols in an NADPH-dependent manner. AKR1A1 was found to be downregulated in patients diagnosed with ALD. This study aims to interpret the protective effects of AKR1A1 on the development of ALD. METHODS: A 5% alcohol-fed (AF) Akr1a1 knockout (Akr1a1-/-) mouse model and an AML12 hepatocyte model were used. The effects of AKR1A1 on liver function, inflammation, oxidative stress, lipid accumulation, and fibrosis were assessed by ELISA, western blotting, RT‒PCR, and a variety of histological staining methods in AF-induced wild-type (WT) and Akr1a1-/- mice compared to control liquid diet-fed (PF) WT and Akr1a1-/- mice. RESULTS: The results demonstrated that AF-WT mice expressed higher levels of AKR1A1 than WT mice fed a control diet, and they did not show any noticeable liver steatosis. However, AF-Akr1a1-/- mice displayed a lower survival rate and more severe liver injury than AF-WT mice, as demonstrated by increased proinflammatory cytokines, oxidative stress, lipid accumulation, fibrosis, and reduced antioxidant enzymes in their livers. Additionally, elevated levels of 4-HNE and p53 phosphorylation were observed in AF-Akr1a1-/- mice, suggesting that the loss of AKR1A1 led to increased 4-HNE accumulation and subsequent activation of p53, which contributed to the progression of ALD. Furthermore, in AML12 hepatocytes, Akr1a1 knockdown aggravated oxidative stress and steatosis induced by palmitic acid/oleic acid (P/O) inflammation induced by lipopolysaccharide (LPS), and fibrosis induced by TGF-ß1. CONCLUSIONS: This loss-of-function study suggests that AKR1A1 plays a liver-protective role during chronic alcohol consumption by reducing the accumulation of 4-HNE and inhibiting 4-HNE-mediated p53 activation.

Factors affecting the occurrence and accumulation of perfluoroalkyl acids in indoor dust in Tainan, Taiwan.

Perfluoroalkyl acids (PFAAs) are environmentally and biologically persistent chemicals. In this study, we investigated the concentrations of six PFAAs in dust samples collected from different indoor environments in a college campus in Tainan, Taiwan, and assessed the health risk of PFAAs exposure to college students. We also analyzed the effects of dust characteristics (total organic carbon, moisture content, and dust content) on PFAAs levels. With regard to the space type, the median of total PFAAs concentrations were in the order of laboratories (528.9 µg kg-1) > offices (304.2 µg kg-1) > dormitories (180.1 µg kg-1) > classrooms (105.1 µg kg-1). With regard to the height from the ground, the median total PFAAs concentrations were in the order of dust near the floors (>2 m; 383.6 µg kg-1) > near the ceiling (0-2 m; 202.5 µg kg-1) > on the ground (0 m; 145.6 µg kg-1). The main species of PFAAs, perfluorooctane sulfonate and short-chain perfluoroalkyl carboxylates, accounted for respectively 30%-60% and ∼20%-37% of total PFAAs pollution in the indoor space types and sampling heights under consideration. The average daily intake (ADI) values of six PFAAs for college students were found to be 0.059-0.126 ng kg-1 BW day-1 (BW: body weight), with dormitories and workplaces (i.e., laboratories and offices) accounting for over 40% and ∼50% of the ADI, respectively. The estimated hazard quotient ranged from 0.0029 to 0.0063, three orders of magnitude lower than 1, suggesting relatively low risks for college students exposed to the six PFAAs monitored in indoor dust. The analysis of dust characteristics revealed that total organic carbon did not have a significant effect on PFAAs levels as we expected. In contrast, dust moisture and cation content dominated PFAAs accumulation.

Trained immunity induced by high-salt diet impedes stroke recovery.

A high-salt diet (HSD) elicits sustained sterile inflammation and worsens tissue injury. However, how this occurs after stroke, a leading cause of morbidity and mortality, remains unknown. Here, we report that HSD impairs long-term brain recovery after intracerebral hemorrhage, a severe form of stroke, despite salt withdrawal prior to the injury. Mechanistically, HSD induces innate immune priming and training in hematopoietic stem and progenitor cells (HSPCs) by downregulation of NR4a family and mitochondrial oxidative phosphorylation. This training compromises alternative activation of monocyte-derived macrophages (MDMs) without altering the initial inflammatory responses of the stroke brain. Healthy mice transplanted with bone marrow from HSD-fed mice retain signatures of reduced MDM reparative functions, further confirming a persistent form of innate immune memory that originates in the bone marrow. Loss of NR4a1 in macrophages recapitulates HSD-induced negative impacts on stroke outcomes while gain of NR4a1 enables stroke recovery in HSD animals. Together, we provide the first evidence that links HSD-induced innate immune memory to the acquisition of persistent dysregulated inflammatory responses and unveils NR4a1 as a potential therapeutic target.

[Expression and Clinical Significance of Cytokines and Lymphocyte Subsets in Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To study the role of cytokines and lymphocyte subsets in the diagnosis, prognosis and efficacy evaluation of DLBCL patients, and the effects of Tislelizumab on immune function and cytokines in DLBCL patients. METHODS: Twenty-three patients with newly diagnosed DLBCL were selected as DLBCL group and 34 patients with megaloblastic anemia as the control group. The levels of peripheral blood cytokines IL-2, IL-4, IL-6, IL-10, TNF- α and IFN-γ by ELISA method. The levels of peripheral blood CD3+, CD4+, CD8+ T lymphocytes, B lymphocytes and NK cells， the ratio of CD4+/CD8+ were detected by flow cytometry. The levels of cytokins and lymphocyto subsets in DLBCL patients with different clinical data and different therapeutic effects were compared. RESULTS: The levels of cytokines IL-2, IL-6 and IL-10 in DLBCL group were significantly higher than those in control group, but there was no significant correlation between cytokine levels and age and gender. The higher IPI score, higher Ann Arbor stage, B symptoms, higher ß 2-MG, LDH and CRP levels, IL-6 and IL-10 levels were significantly higher, and IL-4 was also significantly higher in patients with high LDH levels. Compared with the ineffective group, the levels of IL-6 and IL-10 were significantly lower and the level of CD4+ T cells and the ratio of CD4+/CD8+ was significantly higher in the effective group before therapy. The levels of IL-6, IL-10 and B lymphocytes in the effective group decreased significantly after therapy compared to those before therapy. After 4 cycles of therapy, the level of IL-2 and the ratio of CD4+/CD8+ in the Tislelizumab group were significantly higher than those in the non-Tislelizumab group, and the level of CD8+ T cells was significantly lower than that in the non-Tislelizumab group(P<0.05). The level of B lymphocytes in both the Tislelizumab group and the non-Tislelizumab group after therapy was significantly lower than that before therapy. CONCLUSION: The expression of cytokines and lymphocyte subsets in peripheral blood of patients with DLBCL is abnormal, which is related to the severity, prognosis and therapeutic effect of the disease. Tislelizumab can improve the immune function of patients with DLBCL by affecting cytokines and lymphocyte subsets and strengthen anti-tumor immunity.

Coexistence of diffuse large B-cell lymphoma, acute myeloid leukemia, and untreated lymphoplasmacytic lymphoma/waldenström macroglobulinemia in a same patient: A case report.

BACKGROUND: The Coexistence of myeloid and lymphoid malignancies is rare. Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies. Synchronous diagnoses of diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML), and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in the same patient have not been reported. Here we report one such case. CASE SUMMARY: An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL. The bone marrow and peripheral blood contained two groups of cells. One group of cells fulfilled the criteria of AML, and the other revealed the features of small B lymphocytic proliferative disorder, which we considered LPL/WM. Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells, including ATM deletion, CCND1 amplification, mutations of MYD88 (L265P) and TP53, WT1 overexpression, and fusion gene of BIRC2-ARAP1, as well as complex chromosomal abnormalities. The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis. CONCLUSION: The coexistence of DLBCL, AML, and untreated LPL/WM in the same patient is extremely rare, which probably results from multiple steps of genetic abnormalities. Asymptomatic LPL/WM might have occurred first, then myelodysplastic syndrome-related AML developed, and finally aggressive DLBCL arose. Therefore, medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.

Biosorption and biotransformation behaviours of veterinary antibiotics under aerobic livestock wastewater treatment processes.

To study the fate of veterinary antibiotics released from swine wastewater treatment plants (SWTP), 10 antibiotics were investigated in each unit of a local SWTP periodically. Over a 14-month period of field investigation into target antibiotics, it was confirmed that tetracycline, chlortetracycline, sulfathiazole, and lincomycin were used in this SWTP, with their presence observed in raw manure. Most of these antibiotics could be effectively treated by aerobic activated sludge, except for lincomycin, which was still detected in the effluent, with a maximum concentration of 1506 µg/L. In addition, the potential for removing antibiotics was evaluated using lab-scale aerobic sequencing batch reactors (SBRs) that were dosed with high concentrations of antibiotics. The SBR results, however, showed that both sulfonamides and macrolides, as well as lincomycin, can achieve 100% removal in lab-scale aerobic SBRs within 7 days. This reveals that the potential removal of those antibiotics in field aeration tanks can be facilitated by providing suitable conditions, such as adequate dissolved oxygen, pH, and retention time. Furthermore, the biosorption of target antibiotics was also confirmed in the abiotic sorption batch tests. Biotransformation and hydrolysis were identified as the dominant mechanism for removing negatively charged sulfonamides and positively charged antibiotics (macrolides and lincomycin) in SBRs. This is due to their relatively low sorption affinity (resulting in negligible to 20% removal) onto activated sludge in abiotic sorption tests. On the other hand, tetracyclines exhibited significant sorption behavior both onto activated sludge and onto soluble organic matters in swine wastewater supernatant, accounting for 70%-91% and 21%-94% of removal within 24 h, respectively. S-shape sorption isotherms with saturation were observed when high amounts of tetracyclines were spiked into sludge, with equilibrium concentrations ranging from 0.4 to 65 mg/L. Therefore, the sorption of tetracyclines onto activated sludge was governed by electrostatic interaction rather than hydrophobic partition. This resulted in a saturated sorption capacity (Qmax) of 17,263 mg/g, 1637 mg/g, and 641.7 mg/g for OTC, TC, and CTC, respectively.

Direct Thermal Growth of Gold Nanopearls on 3D Interweaved Hydrophobic Fibers as Ultrasensitive Portable SERS Substrates for Clinical Applications.

Surface-enhanced Raman spectroscopy (SERS)-based biosensors have attracted much attention for their label-free detection, ultrahigh sensitivity, and unique molecular fingerprinting. In this study, a wafer-scale, ultrasensitive, highly uniform, paper-based, portable SERS detection platform featuring abundant and dense gold nanopearls with narrow gap distances, are prepared and deposited directly onto ultralow-surface-energy fluorosilane-modified cellulose fibers through simple thermal evaporation by delicately manipulating the atom diffusion behavior. The as-designed paper-based SERS substrate exhibits an extremely high Raman enhancement factor (3.9 × 1011 ), detectability at sub-femtomolar concentrations (single-molecule level) and great signal reproductivity (relative standard deviation: 3.97%), even when operated with a portable 785-nm Raman spectrometer. This system is used for fingerprinting identification of 12 diverse analytes, including clinical medicines (cefazolin, chloramphenicol, levetiracetam, nicotine), pesticides (thiram, paraquat, carbaryl, chlorpyrifos), environmental carcinogens (benzo[a]pyrene, benzo[g,h,i]perylene), and illegal drugs (methamphetamine, mephedrone). The lowest detection concentrations reach the sub-ppb level, highlighted by a low of 16.2 ppq for nicotine. This system appears suitable for clinical applications in, for example, i) therapeutic drug monitoring for individualized medication adjustment and ii) ultra-early diagnosis for pesticide intoxication. Accordingly, such scalable, portable and ultrasensitive fibrous SERS substrates open up new opportunities for practical on-site detection in biofluid analysis, point-of-care diagnostics and precision medicine.

Visible-Light Driven H2O-to-H2O2 Reaction by Nitrogen-Enriched Resins for Photocatalytic Oxidation of an Organic Pollutant in Wastewater.

A photocatalytic H2O-to-H2O2 reaction for sustainable organic wastewater treatment is environmentally attractive. Phenolic resins, inexpensive metal-free photocatalysts, are capable of harvesting visible light. Herein, novel nitrogen-enriched resin photocatalysts with a desired band-gap energy (1.83-1.98 eV) for harvesting visible light were prepared by copolymerization of resorcinol and melem for simultaneous photocatalytic H2O-to-H2O2 and oxidation of methylene blue. Under visible light irradiation for 5 h, very high yields of H2O2 (870-975 µM of H2O2/g/h) by RFM resin photocatalysts could be achieved. The photocatalytic H2O2 for reactive oxygen species (•OH) and photogenerated h+ could account for high conversion (40% conversion under visible light irradiation within 3 h) in oxidation of methylene blue. Such unique low-cost metal-free resins demonstrate the visible light photocatalytic H2O-to-H2O2 reaction which can synergize with the oxidation of organic pollutants in wastewater.

Robust O2 Supplementation from a Trimetallic Nanozyme-Based Self-Sufficient Complementary System Synergistically Enhances the Starvation/Photothermal Therapy against Hypoxic Tumors.

Much effort has been focused on novel nanomedicine for cancer therapy. However, tumor hypoxia limits the efficacy of various cancer therapeutics. Herein, we constructed a self-sufficient hybrid enzyme-based silk fibroin hydrogel system, consisting of Pt-decorated hollow Ag-Au trimetallic nanocages (HGN@Pt) and glucose oxidase (GOx), to supply O2 continuously and consume glucose concurrently and, thereby, synergistically enhance the anti-cancer efficacy of a combined starvation and photothermal therapy operating in a hypoxic tumor microenvironment. Thanks to the cooperative effects of the active surface atoms (resulting from the island-like features of the Pt coating), the intrinsically hollow structure, and the strain effect induced by the trimetallic composition, HGN@Pt displayed efficient catalase-like activity. The enhancement in the generation of O2 through the decomposition of H2O2 mediated by the as-designed nanozyme was greater than 400% when compared with that of hollow Ag-Pt bimetallic nanospheres or tiny Pt nanoparticles. Moreover, in the presence of HGN@Pt, significant amounts of O2 could be generated within a few minutes, even in an acidic buffer solution (pH 5.8-6.5) containing a low concentration of H2O2 (100-500 µM). Because HGN@Pt exhibited a strong surface plasmon resonance peak in the near-infrared wavelength range, it could be used as a photothermal agent for hyperthermia therapy. Furthermore, GOx was released gradually from the SF hydrogel into the tumor microenvironment to mediate the depletion of glucose, leading to glucose starvation-induced cancer cell death. Finally, the O2 supplied by HGN@Pt overcame the hypoxia of the microenvironment and, thereby, promoted the starvation therapeutic effect of the GOx-mediated glucose consumption. Meanwhile, the GOx-produced H2O2 from the oxidation of glucose could be used to regenerate O2 and, thereby, construct a complementary circulatory system. Accordingly, this study presents a self-sufficient hybrid enzyme-based system that synergistically alleviates tumor hypoxia and induces an anti-cancer effect when combined with irradiation of light from a near-infrared laser.

Inhibition of Retinal Ganglion Cell Loss By a Novel ROCK Inhibitor (E212) in Ischemic Optic Nerve Injury Via Antioxidative and Anti-Inflammatory Actions.

Purpose: This study investigated the neuroprotective effects of administration of ROCK inhibitor E212 on ischemic optic neuropathy. Methods: Rats received an intravitreal injection of either E212 or PBS immediately after optic nerve infarct. The oxidative stress in the retina was detected by performing superoxide dismutase activity and CellROX assays. The integrity of retinal pigment epithelium was determined by staining of zona occludens 1. The visual function, retinal ganglion cell (RGC) density, and RGC apoptosis were determined by using flash visual-evoked potential analysis, retrograde FluoroGold labeling, and TdT-dUTP nick end-labeling assay. Macrophage infiltration was detected by staining for ED1. The protein levels of TNF-α, p-CRMP, p-AKT1, p-STAT3, and CD206 were evaluated using Western blotting. Results: Administration of E212 resulted in a 1.23-fold increase in the superoxide dismutase activity of the retina and 2.28-fold decrease in RGC-produced reactive oxygen species as compared to the levels observed upon treatment with PBS (P < 0.05). Moreover, E212 prevented the disruption of the blood-retinal barrier (BRB) in contrast to PBS. The P1-N2 amplitude and RGC density in the E212-treated group were 1.75- and 2.05-fold higher, respectively, than those in the PBS-treated group (P < 0.05). The numbers of apoptotic RGCs and macrophages were reduced by 2.93- and 2.54-fold, respectively, in the E212-treated group compared with those in the PBS-treated group (P < 0.05). The levels of p-AKT1, p-STAT3, and CD206 were increased, whereas those of p-PTEN, p-CRMP2, and TNF-α were decreased after treatment with E212 (P < 0.05). Conclusions: Treatment with E212 suppresses oxidative stress, BRB disruption, and neuroinflammation to protect the visual function in ischemic optic neuropathy.

A Highly Selective Rho-Kinase Inhibitor (ITRI-E-212) Potentially Treats Glaucoma Upon Topical Administration With Low Incidence of Ocular Hyperemia.

Purpose: The purpose of this study was to investigate the IOP-lowering effects of the ITRI-E-212, a new Rho-associated protein kinase (ROCK) inhibitor. ITRI-E-212 improved fluid outflow through the trabecular meshwork and reduced IOP with transient and mild conjunctival hyperemia. ITRI-E-212 can potentially be developed into new antiglaucoma agents. Methods: ITRI-E-212 was selected from more than 200 amino-isoquinoline structures because of its adequate solubility and drug-loading percentage in eye drops. ITRI-E-212 has less than 50% inhibitory concentration (IC50) against ROCK2. The in vitro kinase inhibition was evaluated using the ADP-Glo kinase assay. A comprehensive analysis of the kinase inhibitor selectivity of ITRI-E-212 was performed using the KINOMEscan methodology. The IOP-lowering effect and tolerability of ITRI-E-212 were investigated in normotensive and ocular hypertensive rabbits. The pharmacokinetics study was performed in vivo in the aqueous humor (AH), and hyperemia was assessed. Results: ITRI-E-212 showed high in vitro inhibitory activity against ROCK2 and high specificity against AGC kinases. The mean IOP-lowering effect of ITRI-E-212 in normotensive and ocular hypertensive models was 24.9% and 28.6%, respectively; 1% ITRI-E-212 produced notable reductions in IOP that were sustained for at least 6 hours after each dose once per day. Only transient, mild hyperemia was observed. The compound extracted from the AH reached 78.4% ROCK2 kinase inhibition at 1 hour after dose administration and was sustained for 4 hours. Conclusions: ITRI-E-212 is a novel and highly specific ROCK2 inhibitor with the ability to lower IOP in animal models. It has favorable pharmacokinetic and ocular tolerability profiles with only minimal conjunctival hyperemia.

Oxidation of cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) with chlorine, permanganate, ozone, hydrogen peroxide and hydroxyl radical.

Beta-N-methylamino-L-alanine (BMAA), a new cyanobacterial neurotoxin produced by more than 20 genera of cyanobacteria, has been associated with amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) or Alzheimer's disease. Although BMAA has been shown to be removed in drinking water treatment plants (DWTPs), studies regarding the reactions between BMAA and the commonly used oxidants in DWTPs are limited to chlorine under specific conditions. In this study, the reaction kinetics between BMAA and five oxidants commonly used in DWTPs, including chlorine, potassium permanganate, ozone, hydrogen peroxide and hydroxyl radical were investigated. The oxidation of BMAA by chlorine, ozone or OH radical followed the second order reaction rate law, and the reaction rate was in the order of OH radicals > ozone >> chlorine. The rate constants increased by 20 times from 2 × 103 M-1s-1 at pH 5.8 to 4.93 × 104 M-1s-1 at pH 7, and kept in a relatively stable level at pH 7-9.5; rate constants of OH radicals were 1.11 × 108 M-1s-1 at pH 6.5 and 5.51 × 109- 1.35 × 1010 M-1s-1 at pH > 6.5. For both permanganate and H2O2 only, the removal of BMAA was negligible. The pH dependency of chlorine and the OH radical may be attributed to the neutral form of BMAA with free lone pair electrons readily to be attacked by oxidants. However, for ozonation of BMAA, the rate constants were 1.88 × 106-3.72 × 1010 M-1s-1, with a linear dependency on pH, implying that the hydroxide concentration governs the reaction. In addition, the rate of BMAA degradation was found to be slower in natural water if compared with that in deionized water.

Voltage adjustment improves rigidity and tremor in Parkinson's disease patients receiving deep brain stimulation.

Deep brain stimulation of the subthalamic nucleus is recognized as the most effective treatment for moderate and advanced Parkinson's disease. Programming of the stimulation parameters is important for maintaining the efficacy of deep brain stimulation. Voltage is considered to be the most effective programming parameter. The present study is a retrospective analysis of six patients with Parkinson's disease (four men and two women, aged 37-65 years), who underwent bilateral deep brain stimulation of the subthalamic nucleus at the First Affiliated Hospital of Sun Yat-sen University, China, and who subsequently adjusted only the stimulation voltage. We evaluated motor symptom severity using the Unified Parkinson's Disease Rating Scale Part III, symptom progression using the Hoehn and Yahr scale, and the levodopa equivalent daily dose, before surgery and 1 and 2 years after surgery. The 2-year follow-up results show that rigidity and tremor improved, and clinical symptoms were reduced, while pulse width was maintained at 60 µs and frequency at 130 Hz. Voltage adjustment alone is particularly suitable for patients who cannot tolerate multiparameter program adjustment. Levodopa equivalent daily dose was markedly reduced 1 and 2 years after surgery compared with baseline. Our results confirm that rigidity, tremor and bradykinesia can be best alleviated by voltage adjustment. The trial was registered at ClinicalTrials.gov (identifier: NCT01934881).

Oxidative transformation kinetics and pathways of albendazole from reactions with manganese dioxide.

Albendazole (ABZ) is a benzimidazole-based veterinary anthelmintic used extensively in the treatment of intestinal parasites. Due to its high hydrophobicity, ABZ tends to accumulate in soils and sediments in the environment. This study aims to investigate ABZ's possible degradation by manganese oxides. Minor effects from ionic strength and metal cations on ABZ degradation were observed. By contrast, decrease of pH greatly enhanced the reaction rate. Surface complexation between ABZ and MnO2 was indicated to be the dominant control in the reaction kinetics. Suppression by the presence of co-solvents was negatively proportional to the solvent polarities (suppression from high to low: diethyl ether ～ n-butanol > ethanol > methanol > acetonitrile). Humic acid was found to cause significant inhibition due to the reductive dissolution of MnO2. Four hydrolysis and six oxidative products were identified. ABZ and its hydrolysis products containing the propylthio side chain underwent the same oxidative transformation to form their corresponding sulfoxide compounds. Dehydrogenative coupling reaction between sulfoxide products and hydrolysis products could occur to generate dimers. All hydrolysis and oxidative products were eluted faster than ABZ in liquid chromatogram, suggesting that the spreading out of ABZ will be significantly enhanced if reacting with MnO2.

Adsorption of sulfamethoxazole and sulfapyridine antibiotics in high organic content soils.

Many antibiotics, including sulfonamides, are being frequently detected in soil and groundwater. Livestock waste is an important source of antibiotic pollution, and sulfonamides may be present along with organic-rich substances. This study aims to investigate the sorption reaction of two sulfonamides, sulfamethoxazole (SMZ) and sulfapyridine (SPY) in two organic-rich sorbents: a commercial peat soil (38.41% carbon content) and a composted manure (24.33% carbon content). Batch reactions were conducted to evaluate the impacts of pH (4.5-9.5) and background ions (0.001 M-0.1 M CaCl2) on their sorption. Both linear partitioning and Freundlich sorption isotherms fit the reaction well. The n values of Freundlich isotherm were close to 1 in most conditions suggesting that the hydrophobic partition is the major adsorption mechanism. In terms of SMZ, Kd declined with increases in the pH. SPY has a pyridine group that is responsible for adsorption at high pH values, and thus, no significant trend between Kd and pH was observed. At high pH ranges, SPY sorption deviated significantly from linear partitioning. The results suggested the sorption mechanism of these two sulfonamide antibiotics tended to be hydrophobic partitioning under most of the experimental conditions, especially at pH values lower than their corresponding pKa2. The fluorescence excitation emission matrix and dissolved organic carbon leaching test suggested composted manure has higher fulvic acid organics and that peat soil has higher humus-like organics. Small organic molecules showed stronger affinity toward sulfonamide antibiotics and cause the composted manure to exhibit higher sorption capacity. Overall, this study suggests that the chemical structure and properties of sulfonamides antibiotics and the type of organic matter in soils will greatly influence the fate and transport of these contaminants into the environment.

Reaction Pathways and Kinetics of a Cyanobacterial Neurotoxin ß-N-Methylamino-L-Alanine (BMAA) during Chlorination.

ß-N-Methylamino-L-alanine (BMAA), a probable cause of the amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC), or Alzheimer's disease, has been identified in more than 20 cyanobacterial genera. However, its removal and fate in drinking water has never been reported before. In this study, the reaction of BMAA with chlorine, a common drinking-water oxidant/disinfectant, was investigated. A liquid chromatograph coupled with a triple quadrupole mass spectrometer was employed to quantify BMAA and its intermediates. Upon chlorination, four chlorinated intermediates, each with one or two chlorines, were identified. The disappearance of BMAA caused by chlorine follows a second-order reaction, with the rate constant k1 is 5.0 × 104 M-1 s-1 at pH ∼7.0. The chlorinated intermediates were found to further react with free chlorine, exhibiting a second-order rate constant k3 = 16.8 M-1 s-1. After all free chlorine was consumed, the chlorinated intermediates autodecomposed slowly with a first order rate constant k2 = 0.003 min-1; when a reductant was added, these chlorinated intermediates were then reduced back to BMAA. The results as described shed a useful light on the reactivity, appearance, and removal of BMAA in the chlorination process of a drinking-water system.

[Establishment of Mouse Model with Humanized Chronic Myeloid Leukemia].

OBJECTIVE: To establish a BALB/c nude mouse model with the huamanized chronic myeloid leukemia (CML) for the study of human CML. METHODS: The BALB/c nude mice aged 4 weeks pretreated by splenectomy, the cyclophosphamide intraperitoneal injection and sublethal irradiation (SLI) were transplanted intravenously with bone marrow mononuclear cells from CML patients. The SLI-pretreated nude mice were divided into 2 groups: group A, in which the nude mice were injected with 0.3 ml PBS; group B, in which the nude mice were infused intravenously with 4.5×107 mononuclear cells from CML patients. Then the changes of body weight and appetite were observed, the hemogram and cell morphology were determined, the expressions of human CD13 and CD45 were detected by flow cytometry, the pathologic analysis of bone, liver and intestine were performed by biopsy, and the BCR/ABL fusion gene was detected by RT-PCR. RESULTS: The mice in group B displayed weakness, auantic, less foodintake and instabiligy of gait as time want on. The average survival time was 46.2±4.2 d (45-57 d). On the third week, the CD13+CD45+ cells accounted for 0.56±0.05% and 2.56±0.36% respectively in group A and B. While on the sixth week, the CD13+CD45+ cells accounted for 0.44±0.07% and 4.97±0.43% in A and B groups respectively, these results showed that cell count in B group was significantly higher than that in A group(P<0.05). Pathological examination showed that the leukemic cells were found in bone marrow of group B. The BCR/ABL fusion gene could be detected in bone marrow. CONCLUSION: BALB/c nude mouse model with huamanized chronic myeloid leukemia(CML) model has been established by pretreating mice with SLI. The survival time of mice in this model has been long, and the cost to establish the model is low.

Roxarsone desorption from the surface of goethite by competitive anions, phosphate and hydroxide ions: Significance of the presence of metal ions.

Aromatic organoarsenical roxarsone (ROX) is a common additive for livestock feed. This arsenic containing pollutant could be discharged into the environment through agricultural application of animal manure, and pose potential threats to both humans and the wider environment. In this study, the influence of pH, competing anions and metal ions on the adsorption and desorption of ROX on goethite were investigated in order to understand their mobility in the environment. Both hydroxide ions and phosphate are common substances in the environment, and both are potential competing anions for ROX. Our results showed the addition of phosphate desorbed more ROX than the addition of hydroxide ions. As pH increased, the effect of phosphate did not show much difference to that of hydroxide ion. The results indicate that the presence of phosphate will greatly increase the mobility of ROX at low pH. Six common metal ions, including Zn(2+), Cu(2+), Fe(3+), Mn(2+), Mg(2+), and Ca(2+), were tested and all spiked metal ions enhanced the stability of ROX adsorption on the surface of goethite, and led to less desorption when phosphate was added. The results demonstrate that metal ions may form complex/surface precipitation with ROX to enhance its adsorption. The effect from Fe(3+), Zn(2+) and Cu(2+) was more pronounced than other metal ions, which might result from the fact that these three metal ions tend to associate with hydroxide ions and decrease the pH. The results of this research may shed light on the environmental fate and transportation of aromatic organoarsenicals in soil.

Mechanism of amitriptyline adsorption on Ca-montmorillonite (SAz-2).

The uptake of amitriptyline (AMI) from aqueous environment by Ca-montmorillonite (SAz-2) was studied in a batch system under different physicochemical conditions. The adsorbent was characterized by X-ray diffraction and Fourier transform infrared (FTIR) analyses. The AMI adsorption on SAz-2 obeyed the Langmuir isotherm with a capacity of 330mg/g (1.05mmol/g) at pH 6-7. The adsorption kinetics was fast, almost reaching equilibrium in 2h, and followed a pseudo-second-order kinetic model. Desorption of exchangeable cations correlated with the AMI adsorption well, indicating that cation exchange was the major mechanism. X-ray diffraction patterns showing significant expansions of the d001 spacing and characteristic FTIR band shifts toward higher frequencies after AMI adsorption onto SAz-2 indicated that the adsorbed AMI molecules were intercalated into the interlayers of the mineral. Thermodynamic parameters based on partitioning coefficients suggested that the AMI adsorption was an endothermic physisorption at high adsorption levels. At low and higher AMI adsorption levels, the intercalated AMI molecules take a horizontal monolayer and bilayer conformation, respectively. The higher adsorption capacity suggested that SAz-2 could be a good candidate to remove AMI from wastewater and would be an important environmental sink for the fate and transport of AMI in soils and groundwater.

Reduction of carbadox mediated by reaction of Mn(III) with oxalic acid.

Manganese(III) geocomponents are commonly found in the soil environment, yet their roles in many biogeochemical processes remain unknown. In this study, we demonstrated that Mn(III) generated from the reaction of MnO(2) and oxalic acid caused rapid and extensive decompositions of a quinoxaline-di-N-oxide antibiotics, viz carbadox. The reaction occurred primarily at the quinoxaline-di-N-oxide moiety resulting in the removal of one -O from N1-oxide and formation of desoxycarbadox. The reaction rate was accelerated by increasing amounts of Mn(III), carbadox and oxalate. The critical step in the overall reaction was the formation of a quinoxaline-di-N-oxide/Mn(III)/oxalate ternary complex in which Mn(III) functioned as the central complexing cation and electron conduit in which the arrangement of ligands facilitated electron transfer from oxalate to carbadox. In the complex, the C-C bond in oxalate was cleaved to create CO(2)(-•) radicals, followed by electron transfer to carbadox through the Mn(III) center. This proposed reaction mechanism is supported by the reaction products formed, reaction kinetics, and quantum mechanical calculations. The results obtained from this study suggest that naturally occurring Mn(III)-oxalic acid complexes could reductively decompose certain organic compounds in the environment such as the antibiotic quinoxaline-di-N-oxide.