Sewage sludge pyrolysis 'kills two birds with one stone': Biochar synergies with persulfate for pollutants removal and energy recovery.

The disposal and resource utilization of sewage sludge (SS) have always been significant challenges for environmental protection. This study employed straightforward pyrolysis to prepare iron-containing sludge biochar (SBC) used as a catalyst and to recover bio-oil used as fuel energy. The results indicated that SBC-700 could effectively activate persulfate (PS) to remove 97.2% of 2,4-dichlorophenol (2,4-DCP) within 60 min. Benefiting from the appropriate iron content, oxygen-containing functional groups and defective structures provide abundant active sites. Meanwhile, SBC-700 exhibits good stability and reusability in cyclic tests and can be easily recovered by magnetic separation. The role of non-radicals is emphasized in the SBC-700/PS system, and in particular, single linear oxygen (1O2) is proposed to be the dominant reactive oxygen. The bio-oil, a byproduct of pyrolysis, exhibits a higher heating value (HHV) of about 30 MJ/kg, with H/C and O/C ratios comparable to those of biodiesel. The energy recovery rate of the SS pyrolysis system was calculated at 80.5% with a lower input cost. In conclusion, this investigation offers a low-energy consumption and sustainable strategy for the resource utilization of SS while simultaneously degrading contaminants.

Effect of ultrasonic degradation on the physicochemical characteristics, GLP-1 secretion, and antioxidant capacity of Polygonatum cyrtonema polysaccharide.

This study aimed to evaluate the influence of ultrasonic degradation on the physicochemical and biological characteristics of Polygonatum cyrtonema polysaccharide (PCP, 8.59 kDa). PCP was subjected to ultrasonic treatment for 8, 16, and 24 h and yielded the degraded fractions PCP-8, PCP-16, and PCP-24 (5.06, 4.13, and 3.69 kDa), respectively. Compared with the intact PCP, PCP-8, PCP-16 and PCP-24 had a reduced particle size (decrements of 28.03 %, 46.15 % and 62.54 %, respectively). Although ultrasonic degradation did not alter the primary structure of PCP, its triple helical and superficial structures were disrupted, with degraded fractions demonstrating reduced thermal stability and apparent viscosities compared with those of the intact PCP. Furthermore, the functional properties of the degraded fractions were different. PCP-16 most favourably affected GLP-1 secretion, while PCP-8 and PCP-24 exhibited the strongest antioxidant and enzyme inhibitory activities, respectively. Hence, controlled ultrasound irradiation is an appealing approach for partially degrading PCP and enhancing its bioactivity as a functional agent.

Study on the Mechanism of the Combination of Methotrexate and Leflunomide in the Treatment of Rheumatoid Arthritis Based on Network Pharmacology, Molecular Docking, and in vitro Experimental Verification.

BACKGROUND: To date, disease-modifying antirheumatic drugs (DMARDs) are widely used as the primary first-line treatment option for patients with rheumatoid arthritis (RA), and the curative effect of methotrexate (MTX) and leflunomide (LEF; MTX + LEF) is greater than that of single-agent MTX therapy, but the synergistic mechanism of MTX + LEF is unclear. METHODS: First, we explored the mechanism of action of MTX + LEF in RA through network pharmacology and molecular docking. Venn diagram analysis revealed 97 overlapping gene targets of MTX + LEF-RA and STRING, along with Cytoscape plug-in MOCDE and cytoHubba; and GO enrichment analysis revealed that the functions of 97 synergistic targets were related to 123 molecular functions (MF), 63 cell components (CC), and 1,068 biological processes (BP). The Cytoscape plug-in ClueGO demonstrated that these targets were enriched in KEGG pathways of 52 terms, whereas 9 pivotal genes were mainly involved in the signaling pathways of estrogen, Ras, Rap1, PI3K-Akt, relaxin, TNF, AMPK, FoxO, prolactin, IL-17, and adherens junction. Finally, CETSA and DARTS validated the direct binding of MTX or LEF to the selected target proteins EGFR, PPARG, MMP9, and SRC in RAW264.7 cells. RESULTS: We identified 292 MTX targets and 247 LEF targets from 7 databases. Furthermore, 2,814 potential targets of RA were identified by merging 1,925 targets from 7 databases and 999 differentially expressed genes (DEGs) between normal controls and patients with RA extracted from 5 GEO databases. Nine pivotal genes, ESR1, ALB, CASP3, EGFR, HSP90AA1, SRC, MMP9, PPARG, and IGF1, were identified. Molecular docking verified that both MTX and LEF strongly bind to most of the 9 pivotal proteins except ESR1 and IGF1. CONCLUSION: These results contribute to our understanding of the enhancement mechanism of MTX combined with LEF and provide a targeted basis for the clinical treatment of RA.

The combination of insulin and linezolid ameliorates Staphylococcus aureus pneumonia in individuals with diabetes via the TLR2/MAPKs/NLRP3 pathway.

Diabetes mellitus (DM) complicated with Staphylococcus aureus (S. aureus) infection lacks effective treatment strategies. In this study, we found that insulin combined with linezolid has potential to deal with the thorny problem. In vitro, our drug sensitivity assay, bacterial growth curve and hemolytic tests showed that a combination of insulin and linezolid exerted good antibacterial and anti-α-hemolysin activity, CCK8 experiment, glucose content and glycogen content determination showed that the combination of insulin and linezolid increased murine macrophage survival rate and reduced the extracellular glucose level of high glucose-treated MH-S cells and intracellular glycogen level, and Western blot showed that the combination inhibited TLR2/MAPKs/NLRP3-related inflammatory pathways in MH-S cells. The results of in vivo experiments showed that the combination therapy stabilized glucose level, remained body weight, ameliorated lung injury including improving pulmonary edema and decreasing lung wet/dry weight ratio, reduced the CFUs and inflammation in the lung tissue in a mouse model of diabetes with S. aureus pneumonia, and inhibited the expression of TLR2, MAPKs and NLRP3 inflammatory pathway. Overall, the combination of insulin and linezolid as autolytic inhibitor exhibited the effects of significant antibacterial and improving glucose level in vitro and in vivo, and also has an anti-inflammation activity via the TLR2/MAPKs/NLRP3 pathway, this paves the way for new treatments for diabetes mellitus complicated with S. aureus infection.

The combination of cloxacillin, thioridazine and tetracycline protects mice against Staphylococcus aureus peritonitis by inhibiting α-Hemolysin-induced MAPK/NF-κB/NLRP3 activation.

Staphylococcus aureus (S. aureus) infection is difficult to fight, previous experimental reports have demonstrated thioridazine (TZ) and tetracycline (TC) is an inhibitor of S. aureus efflux pump NorA and autolysin Atl, respectively, here, by means of molecular docking and molecular dynamics simulation, we observed that thioridazine (TZ) and tetracycline (TC) blocked the binding of substrates to NorA and Atl, respectively, and reduced their activities, and our antibacterial susceptibility test and three-dimensional checkerboard method showed that the three-drug combination of antibiotic cloxacillin (CXN), TZ and TC had a synergistic anti-Staphylococcal activity in vitro, and α-Hemolysin tests and scanning electron microscopy showed that the three-drug combination and the subinhibitory concentration of the combination significantly inhibited the secretion of α-hemolysin relative to the number of membrane-derived vesicles produced by S. aureus. Whereas Western blot and pharmacological inhibition assays showed that the three-drug combination significantly inhibited the expression of MAPK/NF-κB/NLRP3 proteins in macrophages induced with S. aureus α-hemolysin. In vivo, the drug combination significantly reduced bacterial colony-forming unit counts in the viscera of a mouse peritonitis model of S. aureus infection, therapy reduced the primary inflammatory pathology and the bacteria-stimulated release of cytokines such as IL-1ß and TNF-α, and inhibited the expression of MAPK/NF-κB/NLRP3 proteins in peritoneal macrophages. Thus, the combination of efflux pump inhibitor, autolysis inhibitor and antibiotic, is a novel anti-Staphylococcal and anti-inflammatory strategy who owning good antibacterial activity and significant inhibiting staphylococcal α-hemolysin and inflammation.

An Unsupervised Non-rigid Registration Network for Fast Medical Shape Alignment.

Medical shapes alignment can provide doctors with abundant structure information of the organs. As for a pair of the given related medical shapes, the traditional registration methods often depend on geometric transformations required for iterative search to align two shapes. To achieve the accurate and fast alignment of 3D medical shapes, we propose an unsupervised and nonrigid registration network. Different from the existing iterative registration methods, our method estimates the point drift for shape alignment directly by learning the displacement field function, which can omit additional iterative optimization process. In addition, the nonrigid registration network can also adapt to the geometric shape transformations of different complexity. The experiments on two types of 3D medical shapes (liver and heart) at different-level deformations verify the impressive performance of our unsupervised and nonrigid registration network.Clinical Relevance-This paper achieves the real-time medical shape alignment with high accuracy, which can help doctors to understand the pathological conditions of organs better.

An observational study of high- and low-abundance anti-retroviral resistance mutations among treatment-naïve people living with HIV in New Zealand between 2012 and 2017.

HIV resistance genotyping detects drug resistance mutations (DRMs) in ≥20% of circulating virus within an infected individual (high-abundance DRMs). Deep sequencing also detects DRMs in smaller viral subpopulations (low-abundance DRMs), although these are of uncertain importance. In this retrospective analysis of 292 treatment-naïve patients, high-abundance DRMs were present in 30/292 (10%) patients, but only one (0.3%) had resistance to first-line anti-retrovirals. Low-abundance DRMs were present in 36/247 (15%) patients, but none who received anti-retrovirals for which these were present had virologic failure. These findings demonstrate that starting first-line therapy in treatment-naïve patients need not be delayed while awaiting resistance testing.

Compensation of Hysteresis in the Piezoelectric Nanopositioning Stage under Reciprocating Linear Voltage Based on a Mark-Segmented PI Model.

The nanopositioning stage with a piezoelectric driver usually compensates for the nonlinear outer-loop hysteresis characteristic of the piezoelectric effect using the Prandtl-Ishlinskii (PI) model under a single-ring linear voltage, but cannot accurately describe the characteristics of the inner-loop hysteresis under the reciprocating linear voltage. In order to improve the accuracy of the nanopositioning, this study designs a nanopositioning stage with a double-parallel guiding mechanism. On the basis of the classical PI model, the study firstly identifies the hysteresis rate tangent slope mark points, then segments and finally proposes a phenomenological model-the mark-segmented Prandtl-Ishlinskii (MSPI) model. The MSPI model, which is fitted together by each segment, can further improve the fitting accuracy of the outer-loop hysteresis nonlinearity, while describing the inner-loop hysteresis nonlinearity perfectly. The experimental results of the inverse model compensation control show that the MSPI model can achieve 99.6% reciprocating linear voltage inner-loop characteristic accuracy. Compared with the classical PI model, the 81.6% accuracy of the hysteresis loop outer loop is improved.

An observational study of antiretroviral drug resistance in treatment-naïve patients with HIV infection in New Zealand, from 2007 to 2011.

UNLABELLED: Background Genotypic testing for antiretroviral drug resistance is recommended for all patients newly diagnosed with HIV infection. This study sought to quantify the prevalence of antiretroviral drug resistance in treatment-naïve patients with HIV infection in New Zealand. METHODS: All genotypic antiretroviral drug resistance testing in New Zealand is performed at LabPLUS, Auckland City Hospital. The clinicians who requested antiretroviral drug resistance testing during the period 2007-2011 were contacted and were asked to identify which patients with HIV infection were treatment-naïve at the time of testing. Results of the antiretroviral drug resistance tests for treatment-naïve patients with HIV infection were reviewed and the prevalence of resistance determined. RESULTS: Two hundred and 10 treatment-naïve patients with HIV infection who had antiretroviral drug resistance testing performed were included; 20 (10%) were found to have a significant resistance mutation. Nine patients had virus resistant to one or more nucleoside reverse transcriptase inhibitors, 13 to non-nucleoside reverse transcriptase inhibitors and one to protease inhibitors. CONCLUSIONS: The prevalence of antiretroviral drug resistance in treatment-naïve patients with HIV infection identified in this study is comparable to rates identified in studies from North America, the UK and Europe. This prevalence demonstrates the need for antiretroviral drug resistance testing for all treatment-naïve patients with HIV infection in New Zealand.

Energy-efficient key distribution using electrocardiograph biometric set for secure communications in wireless body healthcare networks.

Wireless body sensor network (WBSN) has gained significant interests as an important infrastructure for real-time biomedical healthcare systems, while the security of the sensitive health information becomes one of the main challenges. Due to the constraints of limited power, traditional cryptographic key distribution schemes are not suitable for WBSN. This paper proposes a novel energy-efficient approach, BodyKey, which can distribute the keys using the electrocardiograph biometrics. BodyKey represents the biometric features as ordered set, and deals with the biometric variations using set reconciliation. In this way, only limited necessary information needs to be communicated for key agreement, and the total energy consumption for key distribution can thus be reduced. Experiments on the PhysioBank Database show that BodyKey can perform an energy consumption rate of 0.01 mJ/bit with an equal accuracy rate of 97.28%, allowing the system to be used as an energy-efficient key distribution scheme for secure communications in WBSN.

Beta7 integrins contribute to skin graft rejection.

BACKGROUND: Because integrins alpha4beta7 and alphaEbeta7 contribute to epidermotropism of T-cells during skin inflammation, we sought to study their role in skin allograft rejection. METHODS: Wild-type (WT) (beta7+/+) and beta7 gene knockout (beta7-/-) C57BL/6 (H-2(b)) mice and SJL/J (H-2(s)) mice served as donors and recipients of allogeneic skin grafts. An anti-integrin beta7 subunit mAb (FIB504.64) was used to treat WT beta7+/+ C57BL/6 recipients of skin grafts from SJL/J mice. RESULTS: WT C57BL/6 recipients acutely rejected skin from SJL/J mice in 13 days. In contrast, the survival of SJL/J skin on either beta7-/- gene knockout or WT C57BL/6 recipients treated with anti-beta7 subunit mAb, was prolonged by 6 to 7 additional days (P<0.01). The survival of skin allografts from either beta7-/- or beta7+/+ C57BL/6 mice received by SJL/J recipients was not prolonged (P >0.05). CONCLUSIONS: Beta7 integrins contribute to skin graft rejection, in accord with their role in mediating the epidermotropism of T-cells during skin inflammation.