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Irreversible aggregation can extremely limit the bioavailability and therapeutic activity of peptide-based drugs. There is therefore an urgent demand of effective strategy to control peptide aggregation. Recently, we found that tyrosine nitration at certain sites of peptide can effectively inhibit its aggregation. This minor modification may be an ideal strategy to the rational design of peptide-based drugs with low aggregation propensity yet without loss of bioactivity. Human calcitonin (hCT) is such a peptide hormone known for its hypocalcaemic effect but has limited pharmaceutical potential due to a high tendency to aggregate. In this study, by using multiple techniques including Fluorescence, TEM, Nu-PAGE and CD, we demonstrated that Y12 nitration of hCT would significantly inhibit its self-assembles, and we also found that this modification would not only reduce the cytotoxicity induced by peptide aggregation, but also had little effect on its potency. This finding may provide a novel strategy for clinically application of hCT instead of sCT. Tyr12 nitration of hCT could be a useful strategy for inhibiting its aggregation but not reducing the hypocalcaemic activity. Image 1 • Tyrosine nitration could effectively inhibit the formation of hCT fibril. • The low aggregation propensity of hCT (3 N) makes it less cytotoxicity than hCT. • hCT (3 N) could still maintain the approximately equally potency compared with hCT. [ABSTRACT FROM AUTHOR]

[Display omitted] Solar-driven interface evaporation is promising to alleviate the fresh water scarcity in an economical and sustainable way. However, most of currently reported photothermal conversion materials (PMs) are time-consuming costly, inefficient, or complex preparation process, which causes low utilization efficiency, and difficult to be practical for large-scale application. To solve this problem, a facile and green strategy for preparing hydrogel evaporator (SiO 2 -PILs/starch) by grafting poly(ionic liquid)s onto silica and doping it with starch is proposed. Benefiting from the broad solar absorption (ca. 91 %), strong hydrophilic, and superb salt tolerance and stain resistance of SiO 2 -PILs/starch. Under 1 sun irradiation, the SiO 2 -PILs/starch achieves a remarkable solar evaporation efficiency of 91.72 % in pure water and 81.45 % in 20 wt% NaCl solution, respectively. In particular, SiO 2 -PILs/starch exhibited outstanding long-term salt stability (8 h) and crystalline salt can be self-cleaned in the dark environment. It is worth noting that the prepared hydrogel also possesses a satisfied evaporation efficiency of 75.84 % in oily wastewater (3 wt% n -hexadecane solution) due to its excellent water retention. These properties of SiO 2 -PILs/starch may provide desperately needed solution for efficient desalination and guaranteed high applicability and durability in practice. [ABSTRACT FROM AUTHOR]

Water-soluble iron porphyrins, such as FeTPPS (5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron (III)), FeTMPyP (5,10,15,20-tetrakis (N-methyl-4′-pyridyl) porphyrinato iron (III) chloride) and FeTBAP (5,10,15,20-tetrakis (4-benzoic acid) porphyrinato iron (III)), are highly active catalysts for peroxynitrite decomposition and thereby have been suggested as therapeutic agent for inflammatory diseases that implicate the involvement of nitrotyrosine formation. Here, we systemically investigated catalytic properties of FeTPPS, FeTMPyP and FeTBAP on protein nitration in the presence of hydrogen peroxide and nitrite. We showed that FeTPPS, FeTBAP and FeTMPyP all exhibited higher peroxidase activity in compared with hemin. As to protein nitration, the catalytic effect of FeTPPS and FeTBAP are effective in the presence of hydrogen peroxide and nitrite, while negligible BSA nitration was observed in the case of FeTMPyP. Moreover, the underlying mechanism of the oxidation of FeTPPS, FeTBAP and FeTMPyP was further studied. Collectively, our results suggest that, compound I and II species are involved in as the key intermediates in FeTMPyP/H 2 O 2 system as similar as those in FeTPPS/H 2 O 2 and FeTBAP/H 2 O 2 system. As compared to weak antioxidants, TPPS and TBAP, however, TMPyP scavenges oxo-Fe (IV) intermediates of FeTMPyP at a faster rate by significant self-degradation; results in the shortest lifetimes of O FeIV-TMPyP and the lowest catalytic activity on oxidizing tyrosine and nitrite; and therefore, attributes to inactivation of FeTMPyP in protein nitration. In addition, association of FeTMPyP to BSA was found weak, while strong binding of FeTPPS and FeTBAP were observed. The weak binding keeps away of target residue of BSA from the center of FeTMPyP where the RNS is generated, which might be attributed as additional factors to the inactivation of FeTMPyP in protein nitration. The modification group of water soluble iron porphyrin plays an important role in determining its catalytic effect on catalyzing protein tyrosine nitration in the presence of H 2 O 2 and NO 2 −. Image 1 • FeTPPS and FeTBAP could effectively catalyze BSA nitration in the presence of H 2 O 2 and NO 2 −, FeTMPyP failed to do so. • TMPyP can rapidly scavenge oxo-Fe (IV) intermediates of FeTMPyP by significant self-degradation. • The finding will be help in the designing of balanced therapies for the intervention of peroxynitrite related" diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] Solar steam generation (SSG) is one of the promising technologies for seawater desalination and contaminated water purification. However, SSG devices are always restricted by poor insulation performance, insufficient solar spectrum absorption and serious salt-fouling. Here, a double-layered novel SSG system was fabricated by using poly(ionicliquid)s gels with hollow SiO 2 microspheres in-situ doping to enhance the thermal insulation of lower layer, and co-modified the top surface by polypyrrole (PPy) and silver particles to strengthen the solar absorption capability. Benefiting from the low thermal conductivity (0.082 W m−1 k−1), strong light absorption (ca. 96%) and adequate water transport capability of poly(ionic liquid)s gels. As SSG device, a superb photothermal conversion efficiency of 90.5% is achieved under 1 sun illumination. Moreover, the poly(ionic liquid)s gels based SSG system also shows good desalination performance in artificial sea water and high concentration brine, and the purified water from artificial seawater can achieve the WHO's standard for drinking water. Therefore, this work combined attractive in-situ doping and co-modified strategies for fabricating high performance and thus shows significant potential for real applications. [ABSTRACT FROM AUTHOR]

A significant proportion of patients with recurrent atrial fibrillation (AF) require repeat radiofrequency (RF) ablation after cryoballoon (CB) ablation. However, little is known about the pulmonary vein (PV) potential reconnection to left atrium and localization of gaps in the initial lesion sets following cryoablation in patients with recurrent AF. The data of 29 consecutive patients with repeat RF ablation for recurrent AF were analyzed. During the second ablation procedures, PV foci of AF were explored in 116 PVs by the CARTO system. All patients had complete PV isolation from initial cryoablation procedure. The fluoroscopy duration, mean cryoablation time and mean cryoablation frequency were lowest for the right superior pulmonary vein (RSPV) (58.69 ± 9.18 s, 185.10 ± 49.25 s and 1.07 ± 0.26; p = 0.024, p = 0.042 and p = 0.032). A significantly higher incidence of conduction gaps per patient was found for the RSPVs compared to the other PVs (p < 0.05 or p < 0.01). For RSPVs, it seemed that gaps were predominantly located at the anterior segment (22 gaps) and inferior segment (22 gaps). RSPV reconnection was independently related to a lower risk of major adverse events after the second ablation during follow up in the study patients (HR 0.275, 95%CI 0.078–0.967, p = 0.044). AF recurrence in patients after cryoablation is significantly associated with conduction gaps in the anterior and inferior segments of RSPVs. Various ablation strategies of close touch of CB on anterior and inferior segments of RSPV ostium, more freezing time and frequency for RSPV may help achieving durable PV isolation during follow up. [ABSTRACT FROM AUTHOR]

Abstract Amyloid formation of human islet amyloid polypeptide (hIAPP) is one of the most common pathological features of type 2 diabetes (T2D). Increasing evidences have shown that the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) play an important role in the development of the T2D. Interestingly, our previous studies indicated that heme could bind to hIAPP, and the complex might induce the nitration of tyrosine residue (Y37) of hIAPP in the presence of hydrogen peroxide and nitrite. However, it remains unclear about effect of the nitration on the implicated function of hIAPP in the development of T2D. In this study, fluorescent assays, transmission electron microscopy (TEM), atomic force microscope (AFM) were used to demonstrate that nitration of hIAPP significantly decreased its fibril formation. But the decreased fibril formation was not through the diminished aggregation of hIAPP monomer as suggested by the results of circular dichroism spectroscopy (CD) and gel electrophoresis assay. Surface-enhanced raman spectroscopy (SERS) indicated that nitration of hIAPP impaired the intermolecular hydrogen bonding. On the basis of these results, we hypothesize that nitration of hIAPP may block the intermolecular hydrogen bonding, leading to the inhibition of its fibril formation. In addition, cytotoxicity study of native and modified hIAPP was also performed on INS-1 cells, which revealed exacerbated toxicity of hIAPP by its nitration. The findings in this study that nitration of hIAPP promotes its oligomer formation and thus exacerbates its cytotoxicity suggests a possible link between the nitrite (or the sum of nitrite and nitrate) levels and T2D, and ameliorated nitration of hIAPP by diminishing nitrative stress might be a promising therapeutic strategy for T2D. Graphical abstract Nitration of hIAPP remarkably decreased its fibril formation by blocking its intermolecular hydrogen bonding and π-π stacking interactions. Image 1 Highlights • The tyrosine (Y37) in hIAPP is prone to nitration in the presence of heme, H 2 O 2 and NO 2 −. • Nitration of hIAPP decreases its aggregation. • Nitration of hIAPP enhances its cytotoxicity toward ISN-1 cells. • Nitration of hIAPP blocks the intermolecular hydrogen bonding. [ABSTRACT FROM AUTHOR]

Cascade reactions catalyzed by natural uricase and mimic peroxidase (MPOD) have been applied for uric acid (UA) detection. However, the optimal catalytic activity of MPOD is mostly in acidic conditions (pH 2–5), mismatching the optimal catalytic alkaline environment of uricase. In this paper, using CuSO 4 and urea as raw materials, a MPOD with high catalytic activity in alkaline environment was synthesized by hydrothermal method. Then, based on coupling reaction of uricase/UA/MPOD/guaiacol (GA) system, a novel spectrophotometric method was established to detect 5–60 μmol/L UA (limit of detection = 3.14 μmol/L (S/N = 3)) and accurately quantified serum UA (275.6 ± 39.9 μmol/L, n = 5) with 95–105% of standard addition recovery. The results were consistent with commercial UA kit (p > 0.05). The MPOD could replace natural POD to reduce the cost of UA detection due to simple preparation and cheap raw materials, and is expected to achieve the specific detection of some substances, like glucose and cholesterol, combined with glucose oxidase and cholesterol oxidase. [Display omitted] • A copper doped mimic peroxidase with optimal activity at pH 8 was synthesized. • Due to the instability of ascorbic acid at pH 8, the interference was eliminated. • The new method was successfully applied to detect serum uric acid (UA). • The method for UA detection (including pretreatments) avoids pH adjustment steps. [ABSTRACT FROM AUTHOR]

GAPDH was speculated to function as a transient trap to reduce the potential toxicity of free heme by a specific and reversible binding with heme. Up to now, there has been lack of studies focused on this effect. In this paper, the efficiency of GAPDH-heme complex on catalyzing protein carbonylation and nitration, the cross-linking of heme to protein formation, and cytotoxicity of GAPDH-heme were studied. It was found that the binding of GAPDH could inhibit H 2 O 2 -mediated degradation of heme. Peroxidase activity of GAPDH-heme complex was higher than that of free heme, but significantly lower than that of HSA-heme. Catalytic activity of heme corresponded complex toward tyrosine oxidation/nitration was decreased in the order of HSA-heme, heme and GAPDH-heme. GAPDH also inhibited heme-H 2 O 2 -NO 2 - induced protein carbonylation. No covalent bond was formed between heme and GAPDH after treated with H 2 O 2 . GAPDH was more effective than HSA on protecting cells against heme-NO 2 - -H 2 O 2 induced cytotoxicity. These results indicate that binding of GAPDH inhibits the activity of heme in catalyzing tyrosine nitration and protects the coexistent protein against oxidative damage, and the mechanism is different from that of HSA. This study may help clarifying the protective role of GAPDH acting as a chaperone in heme transfer to downstream areas. [ABSTRACT FROM AUTHOR]