Regeneration mechanism of a novel high-performance biochar mercury adsorbent directionally modified by multimetal multilayer loading.

Biochar that is directly obtained by pyrolysis exhibits a low adsorption efficiency; furthermore, the process of recycling adsorbents is ineffective. To solve these problems, conventional chemical coprecipitation, sol-gel, multimetal multilayer loading and biomass pyrolysis coking processes have been integrated. After selecting specific components for structural design, a novel high-performance biochar adsorbent was obtained. The effects of the O2 concentration and temperature on the regeneration characteristics were explored. An isothermal regeneration method to repair the deactivated adsorbent in a specific atmosphere was proposed, and the optimal regeneration mode and conditions were determined. The microscopic characteristics of the regenerated samples were revealed along with the mechanism of Hg0 removal and regeneration by using temperature-programmed desorption technology and adsorption kinetics. The results show that doping multiple metals can reduce the pyrolysis reaction barrier of the modified biomass. On the modified surface of the sample, the doped metals formed aggregated oxides, and the resulting synergistic effect enhanced the oxidative activity of the biochar carriers and the threshold effect of Ce oxide. The optimal regeneration conditions (5% O2 and 600 °C) effectively coordinated the competitive relationship between the deep carbonization process and the adsorption/oxidation site repair process; in addition, these conditions provided outstanding structure-effect connections between the physico-chemical properties and Hg0 removal efficiency of the regenerated samples. Hg0 adsorption by the regenerated samples is a multilayer mass transfer process that involves the coupling of physical and chemical effects, and the surface adsorption sites play a leading role.

Relationship of anifrolumab pharmacokinetics with efficacy and safety in patients with systemic lupus erythematosus.

OBJECTIVES: To characterize the relationship of anifrolumab pharmacokinetics with efficacy and safety in patients with moderate to severe SLE despite standard therapy, using pooled data from two phase 3 trials. METHODS: TULIP-1 and TULIP-2 were randomized, placebo-controlled, 52-week trials of intravenous anifrolumab (every 4 weeks for 48 weeks). For the exposure-response analysis, BILAG-based Composite Lupus Assessment (BICLA) or SLE Responder Index [SRI(4)] response rates at week 52 in each quartile/tertile of average anifrolumab serum concentration (Cave) were compared for anifrolumab and placebo in all-comers, patients who completed treatment, and IFN gene signature (IFNGS)-high patients who completed treatment, using average marginal effect logistic regression. Relationships between exposure and key safety events were assessed graphically. RESULTS: Of patients in TULIP-1/TULIP-2 who received anifrolumab (150 mg, n = 91; 300 mg, n = 356) or placebo (n = 366), 574 completed treatment, of whom 470 were IFNGS high. In the exposure-efficacy analyses, BICLA and SRI(4) treatment differences favouring anifrolumab 300 mg vs placebo were observed across Cave subgroups and all analysis populations. Logistic regression identified Cave as a significant covariate for predicted BICLA response, as higher anifrolumab Cave predicted greater efficacy. There was no evidence of exposure-driven incidence of key safety events through week 52 in patients receiving anifrolumab 150 or 300 mg. CONCLUSION: While higher Cave predicted greater efficacy, consistent positive benefit favouring anifrolumab 300 mg vs placebo was observed in BICLA and SRI(4) responses across Cave subgroups in the TULIP trials. There was no evidence of exposure-driven safety events. CLINICALTRIAL.GOV NUMBERS: NCT02446912, NCT02446899.

Ultrasensitive fluorescent detection of telomerase activity based on tetrahedral DNA nanostructures as carriers for DNA-templated silver nanoclusters.

Precise evaluation of telomerase activity is essential for the clinical diagnosis of early tumors. Herein, we have ingeniously designed a tetrahedral DNA nanostructure, with hairpin-shaped DNA probes rich in cytosine bases at four vertices for telomerase detection. The DNA-templated silver nanoclusters can be formed after the addition of Ag. Then the introduction of telomerase adds the single-strand TTAGGG extension, which can "turn on" the fluorescence of silver nanoclusters quickly by the proximity of the resulting guanine-rich sequences to silver nanoclusters and realize accurate detection of telomerase activity. In this study, integration of high stability tetrahedral DNA nanostructure and fluorescence signal amplification of four DNA-templated silver nanoclusters offers the advantage of high sensitivity, with a low detection limit of 1 cell. More than that, this method is low-cost, facile, and feasible for practical clinical applications.

[Research progress on the effects of plateau hypoxia on blood-brain barrier structure and drug permeability].

Drugs for the treatment of central nervous system diseases need to enter the brain tissue through the blood-brain barrier to function. In high altitude hypoxic environment, there are changes in tight junction proteins of blood-brain barrier tissue structure, transporters in astrocytes and endothelial cells and ATP in endothelial cells; at the same time the permeability of the blood-brain barrier is increased. These changes are an important reference for rational drug use in patients with central nervous system disease in the plateau region. This article reviews the research progress on the effects of plateau hypoxia on the structure of the blood-brain barrier and related drug permeability.

Association of Difference in Coronary Sinus Diameter by Computed Tomographic Angiography Between Patients in and Not in Stable Atherosclerotic Plaque(S).

BACKGROUND Pathological finding fail to describe the morphology of coronary arterial plaques. Retrograde cardiac arteriography is a complicated procedure and does not detect all left posterior and marginal veins of the heart. Magnetic resonance angiography has long scan time and low spatial resolution. The objective of the present study was to assess the possible utility of the difference in coronary sinus diameter to quantify stable atherosclerotic plaque(s) using 256-slice coronary computed tomographic angiography. MATERIAL AND METHODS A total of 336 patients were divided into 2 groups with 168 patients each. Patients who had heart failure were included in the study group and those who did not were included in the non-study group. Patients were subjected to cross-sectional study. Cardiovascular images were performed with 256-slice coronary computed tomographic angiography with a prospective electrocardiogram and clinical manifestation. Two-tailed paired t test following Dunnett's multiple comparison tests was performed for the quantitative measurement of coronary computed tomographic angiography and clinical manifestation at 99% confidence level. RESULTS The clinical manifestation did not clearly show cardiac abnormality. The diameters of the superoinferior coronary sinus ostium was than that of the anteroposterior coronary sinus ostium, (p<0.0001, q=26.325). There was the difference in size of the coronary sinus ostium between patients in and not in heart failure (p<0.0001). The study group patients had longer coronary sinuses than patients in the non-study group (p<0.0001). CONCLUSIONS 256-slice computed tomographic angiography is a feasible and is non-invasive bio-tool for evaluation of coronary artery anatomy.

Low-dose IL-2 expands CD4+ regulatory T cells with a suppressive function in vitro via the STAT5-dependent pathway in patients with chronic kidney diseases.

BACKGROUND: Patients with chronic kidney disease (CKD) often have CD4+ regulatory T cells (Tregs) dysfunction and chronic inflammation. We aim to investigate the effect, function, and related mechanism of low-dose IL-2 on CD4+ regulatory T cells expansion in vitro from patients with CKD. METHODS: A total of 148 newly diagnosed patients with CKD at Stage III and 35 healthy volunteer subjects were recruited into our studies. The number of peripheral Tregs in peripheral blood mononuclear cells isolated from CKD patients, which were characterized by FACS as CD4+CD25hi and CD4+CD25+FoxP3+. The effect of low-dose IL-2 on expansion of Tregs, and the suppressive function of expanded Tregs were also analyzed by FACS. The levels of FoxP3 mRNA were detected by qRT-PCR. The activation of IL-2 induced Stat5 and blocking experiments were assessed by Western Blotting and FACS. RESULTS: We found that the frequency of peripheral Tregs from CKD patients was significantly lower than that in healthy volunteer subjects. We also showed that IL-2 selectively expanded CD4+CD25hi and CD4+CD25+FoxP3+ regulatory T cells, and also upregulated the expression of FoxP3 mRNA. Our in vitro studies demonstrated that expanded CD4+ regulatory T cells from CKD patients suppressed proinflammatory Th1 and Th17 cell response. Furthermore, STAT5 activation is required for IL-2-induced expansion of regulatory T cells and expression of FoxP3 mRNA from CKD patients. CONCLUSIONS: Our findings support the clinical Treg defects in CKD patients with glomerular diseases, and the rationale of evaluating low-dose IL-2 treatment for selectively modulating CD4+ Tregs.

Bioactive spirans and other constituents from the leaves of Cannabis sativa f. sativa.

In this paper, 17 compounds (1-17) were isolated from the leaves of Hemp (Cannabis sativa f. sativa). Among the isolates, two were determined to be new spirans: cannabispirketal (1), and α-cannabispiranol 4'-O-ß-D-glucopyranose (2) by 1D and 2D NMR spectroscopy, LC-MS, and HRESIMS. The known compounds 7, 8, 10, 13, 15, and 16 were isolated from Hemp (C. sativa f. sativa) for the first time. Furthermore, compounds 8 and 13 were isolated from the nature for the first time. All isolated compounds were evaluated for cytotoxicity on different tissue-derived passage cancer cell lines through cell viability and apoptosis assay. Among these compounds, compounds 5, 9 and 16 exhibited a broad-spectrum antitumor effect via inhibiting cell proliferation and promoting apoptosis. These results obtained have provided valuable clues to the understanding of the cytotoxic profile for these isolated compounds from Hemp (C. sativa f. sativa).

Serum A08 C1q antibodies are associated with disease activity and prognosis in Chinese patients with lupus nephritis.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by overproduction of numerous autoantibodies. Many studies have sought to identify such biomarkers to distinguish patients with active lupus nephritis from SLE patients without renal involvement. Because antibodies to complement C1q appear to be prevalent in patients with active lupus nephritis, we analyzed the frequency of antigenic epitopes of C1q and their clinical significance in a large multicenter study of Chinese patients. The lupus cohort consisted of 210 patients with active lupus nephritis as a discovery cohort, 130 active patients as a validation cohort along with 130 SLE patients without clinical renal involvement, and 100 healthy controls. Serum antibodies to intact C1q, the collagen-like region, the globular head region, and the new linear A08 epitope to C1q were screened by specific ELISA. The frequency of antibodies to intact C1q, the C1q-collagen-like region, and the A08 antibodies in the discovery cohort were significantly higher than that in patients without renal involvement or healthy controls. Antibodies to the globular head region were not prevalent enough for further study. The results were confirmed in the validation cohort. The area under the curve for anti-A08 antibodies was significantly greater than those for both the intact and collagen-like region antibodies to discriminate between active lupus nephritis and active SLE without clinical renal involvement. The A08 antibodies were all negative at remission. The serum A08 antibody level correlated better with disease relapse than that of antibodies to either the intact or the collagen-like region, significantly predicting renal prognosis. Thus, serum levels of A08 C1q antibodies are closely associated with disease activity and prognosis in lupus nephritis.

The Effects of Indoxyl Sulfate on Human Umbilical Cord-Derived Mesenchymal Stem Cells In Vitro.

BACKGROUND/AIMS: Indoxyl sulfate, an important protein-bound uremic toxin, can damage stem cells, thus hampering stem cell-based regenerative medicine approaches targeting chronic kidney diseases (CKD). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are thought to have promising clinical application because of their high proliferative potential and ease of isolation than MSCs from other sources. In the present study, we aimed to determine the harmful effects of indoxyl sulfate on the phenotype and functional potential of hUC-MSCs in vitro. METHODS: The toxicity and cell viability was examined by Trypan blue exclusion and MTT assay. The cellular surface markers and the percentage of apoptotic cells by Annexin-V/PI staining were analyzed by flow cytometry. Proliferation was evaluated based on cell number counting and Ki-67 immunostaining. Cell senescence was measured using senescence-associated ß-Galactosidase activity. The ability to stimulate the development of CD4+CD25+FoxP3+ regulatory T cells was assessed by incubating hUC-MSCs with peripheral blood mononuclear cells from the healthy volunteers. RESULTS: Our results demonstrated that the immunophenotype of hUC-MSCs was not affected by indoxyl sulfate flow cytometry. However, a significant decrease in cell numbers and fraction of Ki-67 positive proliferating cells, along with a significant increase in cellular senescence were detected in hUC-MSCs after exposure to indoxyl sulfate. Additionally, their ability to stimulate CD4+CD25+FoxP3+ regulatory T cell production was compromised when hUC-MSCs were pretreated with indoxyl sulfate. CONCLUSION: Taken together, our study clearly demonstrated that the molecular alterations and functional incompetence in hUC-MSCs under the challenge of indoxyl sulfate in vitro.

A Sputum Proteomic Signature That Associates with Increased IL-1ß Levels and Bacterial Exacerbations of COPD.

PURPOSE: Activation of the interleukin-1ß (IL-1ß) signaling pathway has been implicated in COPD, but the proportion of COPD subjects whose disease is principally driven by activation of this pathway is poorly understood. In this study, we sought to differentiate an IL-1ß-associated sputum signature from other inflammation-associated COPD phenotypes. METHODS: Luminex-multiplex assays were used to study IL-1ß-mediated signature proteins within airway epithelium, smooth muscle, and vascular endothelial cell cultures. The IL-1ß-mediated signature was tested in a longitudinal study comprising of 35 paired stable-COPD and acute exacerbation (AECOPD) sputum samples. The presence of respiratory pathogens (H. influenzae, M. catarrhalis, S. pneumoniae, and P. aeruginosa) was evaluated by sputum cultures. RESULTS: Five proteins namely TNF-α, GCSF, IL-6, CD-40L, and MIP-1ß were found to be IL-1ß-regulated across all donors and cell types. All five of these IL-1ß-mediated proteins were significantly increased (p < 0.05) in sputum corresponding to AECOPD events showing at least a twofold increase in IL-1ß (IL-1ß(+) events, 18 of 35 total events), relative to preceding stable-COPD state. Sputum IL-1ß levels showed no significant association (p > 0.05, spearman) with known markers of other major COPD inflammation phenotypes. In addition, there was a significant association with bacterial presence in sputum culture with an odds ratio of 9 (95 % CI 1.56, 51.9) in IL-1ß(+) events versus IL-1ß(-) events. CONCLUSION: Our findings provide insights into potential markers of IL-1ß-associated AECOPD, and reaffirm association between IL-1ß pathway activation and airway bacterial infection in COPD. Taken together, our findings could help identify COPD patient subsets who may benefit from therapies targeting IL-1ß pathway.