15 research outputs found

    Palaeoproterozoic granitic magmatism in the northern segment of the Jiao-Liao-Ji Belt: implications for orogenesis along the Eastern Block of the North China Craton

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    <p>As the northern segment of the Jiao-Liao-Ji Belt (JLJB), the Palaeoproterozoic Liaoji Belt is a key region for deciphering the formation and evolution of the North China Craton (NCC). In this study, we present the geochronology, geochemical, and isotopic studies on the monzogranitic gneiss, which is one of the major lithotectonic elements of the Liaoji Belt. LA-ICP-MS zircon Uā€“Pb dating reveals that the studied monzogranitic gneisses were formed in the period of 2213ā€“2178Ā Ma. They are in tectonic contact with the Palaeoproterozoic volcano-sedimentary rocks in the field. The monzogranitic gneisses belong to the high-K calc-alkaline series, and are metaluminous to peraluminous. They have 10,000Ā Ga/Al ratios of 2.63ā€“3.14 with an average of 2.90, and are thus classified as aluminous A-type granites. Their <i>Īµ</i><sub>Nd</sub>(<i>t</i>) values vary from āˆ’3.4 to +2.5, indicating heterogeneous source region. The monzogranitic gneisses are characterized by enrichment in LREE and LILE (e.g. Rb, Ba, Th, and K) and depletion in HREE and HFSE (such as Nb, Ta, and Ti), and are typical to magmatism in active continental margins formed in a subduction-related tectonic setting. Taking into account their A-type affinity and regional geological data, we suggest that the monzogranitic gneisses were most probably generated in a local extensional back-arc environment during subduction.</p

    Table S1. Geochronological constraint on the Cambrian Chengjiang biota, South China

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    Table S1: Zircon SIMS Uā€“Pb data of 14CJ-2 and 14CJ-3 from Maotianshan Shale, eastern Yunnan Province, South Chin

    Table S2. Geochronological constraint on the Cambrian Chengjiang biota, South China

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    Table S2: CAā€“IDā€“TIMS zircon Uā€“Pb data of sedimentary rocks from Maotianshan Shale in eastern Yunnan Provinc

    Broad-Spectrum Antimicrobial/Antifouling Soft Material Coatings Using Poly(ethylenimine) as a Tailorable Scaffold

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    Microbial colonization and biofilm formation is the leading cause of contact lens-related keratitis. Treatment of the condition remains a challenge because of the need for prolonged therapeutic course and high doses of antimicrobial agents especially for biofilm eradication. The development of strategies to prepare nonfouling contact lens surfaces is a more practical way to ensure usersā€™ safety and relieve the excessive public healthcare burden. In this study, we report a series of polymers that were modified to introduce functionality designed to facilitate coating adhesion, antimicrobial and antifouling properties. Cyclic carbonate monomers having different functional groups including adhesive catechol, antifouling polyĀ­(ethylene glycol) (PEG), and hydrophobic urea/ethyl were conjugated onto branched polyĀ­(ethylenimine) (bPEI, 25 kDa) at various degrees in a facile and well-controlled manner using a simple one step, atom economical approach. Immersion of contact lenses into an aqueous solution of the catechol-functionalized polymers at room temperature resulted in robust and stable coating on the lens surfaces, which survived the harsh condition of autoclaving and remained on the surface for a typical device application lifetime (7 days). The deposition of the polymer was unambiguously confirmed by static contact angle measurement and X-ray photoelectron spectroscopy (XPS). Polymer coating did not change light transmission significantly. Combinatorial optimization demonstrated that lenses coated with bPEI functionalized with catechol, PEG (5 kDa) and urea groups at 1:12:3:23 molar ratio for 18 h provided the highest antifouling effect against four types of keratitis-causing pathogens: Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Fusarium solani, after 7 days of incubation. The polymer coating also inhibited protein adsorption onto the contact lens surfaces after exposure to bovine serum albumin solution for up to 24 h, owing to the flexible and large PEG constituent. Notably, all the polymer coatings used in this study were biocompatible, achieving ā‰„90% cell viability following direct contact with human corneal epithelial cells for 24 h. Hence, these polymer coatings are envisaged to be promising for the prevention of contact lens-related keratitis

    Sub-10 nm Monoclinic Gd<sub>2</sub>O<sub>3</sub>:Eu<sup>3+</sup> Nanoparticles as Dual-Modal Nanoprobes for Magnetic Resonance and Fluorescence Imaging

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    Monoclinic Gd<sub>2</sub>O<sub>3</sub>:Eu<sup>3+</sup> nanoparticles (NPs) possess favorable magnetic and optical properties for biomedical application. However, how to obtain small enough NPs still remains a challenge. Here we combined the standard solid-state reaction with the laser ablation in liquids (LAL) technique to fabricate sub-10 nm monoclinic Gd<sub>2</sub>O<sub>3</sub>:Eu<sup>3+</sup> NPs and explained their formation mechanism. The obtained Gd<sub>2</sub>O<sub>3</sub>:Eu<sup>3+</sup> NPs exhibit bright red fluorescence emission and can be successfully used as fluorescence probe for cells imaging. In vitro and in vivo magnetic resonance imaging (MRI) studies show that the product can also serve as MRI good contrast agent. Then, we systematically investigated the nanotoxicity including cell viability, apoptosis in vitro, as well as the immunotoxicity and pharmacokinetics assays in vivo. This investigation provides a platform for the fabrication of ultrafine monoclinic Gd<sub>2</sub>O<sub>3</sub>:Eu<sup>3+</sup> NPs and evaluation of their efficiency and safety in preclinical application

    Injectable Coacervate Hydrogel for Delivery of Anticancer Drug-Loaded Nanoparticles in vivo

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    In this study, bortezomib (BTZ, a cytotoxic water-insoluble anticancer drug) was encapsulated in micellar nanoparticles having a catechol-functionalized polycarbonate core through a pH-sensitive covalent bond between phenylboronic acid (PBA) in BTZ and catechol, and these drug-loaded micelles were incorporated into hydrogels to form micelle/hydrogel composites. A series of injectable, biodegradable hydrogels with readily tunable mechanical properties were formed and optimized for sustained delivery of the BTZ-loaded micelles through ionic coacervation between PBA-functionalized polycarbonate/polyĀ­(ethylene glycol) (PEG) ā€œABAā€ triblock copolymer and a cationic one having guanidinium- or thiouronium-functionalized polycarbonate as ā€œAā€ block. An in vitro release study showed the pH dependence in BTZ release. At pH 7.4, the BTZ release from the micelle/hydrogel composite remained low at 7%, whereas in an acidic environment, āˆ¼85% of BTZ was released gradually over 9 days. In vivo studies performed in a multiple myeloma MM.1S xenograft mouse model showed that the tumor progression of mice treated with BTZ-loaded micelle solution was similar to that of the control group, whereas those treated with the BTZ-loaded micelle/hydrogel composite resulted in significant delay in the tumor progression. The results demonstrate that this hydrogel has great potential for use in subcutaneous and sustained delivery of drug-loaded micelles with superior therapeutic efficacy

    To What Extent Do Low-Voltage Electrostatic Fields Play a Role in the Physicochemical Properties of Pork during Freezing and Storage?

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    Low-voltage electrostatic fields (LVEF) are recognized as a new technology that can improve the quality of frozen meat. To determine the extent to which LVEF assistance affects the quality of frozen pork for long-term storage, pork was frozen and stored at āˆ’18 and āˆ’38 Ā°C for up to 5 months. Water-holding capacity, muscle microstructure, and protein properties were investigated after up to 5 months of frozen storage with and without LVEF assistance. In comparison to traditional āˆ’18 and āˆ’38 Ā°C frozen storage, LVEF treatment inhibited water migration during frozen storage and thawing. As a result, thawing losses were reduced by 15.97% (āˆ’18 Ā°C) and 3.38% (āˆ’38 Ā°C) in LVEF-assisted compared to conventional freezing methods. LVEF helped to maintain the muscle fiber microstructure and reduce muscle protein denaturation by miniaturizing ice crystal formation by freezing. As a result of this study, LVEF is more suitable for freezing or short-term frozen storage, while a lower temperature plays a more significant role in long-term frozen storage

    Profiling of Cross-Functional Peptidases Regulated Circulating Peptides in BRCA1 Mutant Breast Cancer

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    Women with inherited <i>BRCA1</i> mutations are more likely to develop breast cancer (BC); however, not every carrier will progress to BC. The aim of this study was to identify and characterize circulating peptides that correlate with BC patients carrying <i>BRCA1</i> mutations. Circulating peptides were enriched using our well-designed nanoporous silica thin films (NanoTraps) and profiled by mass spectrometry to identify among four clinical groups. To determine the corresponding proteolytic processes and their sites of activity, purified candidate peptidases and synthesized substrates were assayed to verify the processes predicted by the MERPOS database. Proteolytic processes were validated using patient serum samples. The peptides, KNG1<sub>K438ā€‘R457</sub> and C 3f<sub>S1304ā€‘R1320</sub>, were identified as putative peptide candidates to differentiate <i>BRCA1</i> mutant BC from sporadic BC and cancer-free <i>BRCA1</i> mutant carriers. Kallikrein-2 (KLK2) is the major peptidase that cleaves KNG1<sub>K438ā€‘R457</sub> from kininogen-1, and its expressions and activities were also found to be dependent on <i>BRCA1</i> status. We further determined that KNG1<sub>K438ā€‘R457</sub> is cleaved at its C-terminal arginine by carboxypeptidase N1 (CPN1). Increased KLK2 activity, with decreased CPN1 activity, results in the accumulation of KNG1<sub>K438ā€‘R457</sub> in <i>BRCA1</i>-associated BC. Our work outlined a useful strategy for determining the peptideā€“petidase relationship and thus establishing a biological mechanism for changes in the peptidome in <i>BRCA1</i>-associated BC

    Organocatalytic Anticancer Drug Loading of Degradable Polymeric Mixed Micelles via a Biomimetic Mechanism

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    Although self-assembled polymeric micelles have received significant attention as anticancer drug delivery systems, most of them suffer initial burst release of drugs after injection. Herein, a novel organocatalytic drug loading approach is reported to chemically conjugate anticancer drugs to the micellar core through an acid-labile bond that only breaks in the acidic tumor tissue and endolysosomal environments. Specifically, a degradable polymeric micelle system based on amphiphilic mPEG-<i>b</i>-polycarbonate block copolymers was developed. The mussel-inspired polymer design features catechol side chains to which the anticancer drug doxorubicin (DOX) can be covalently conjugated as pH-sensitive <i>p</i>-quinoneimines via a mechanism that mimics the Raperā€“Mason pathway of mammalian melanogenesis. We demonstrate that a higher drug loading is achieved when <i>N</i>-methylimidazole is cointroduced during self-assembly as an organocatalyst. The DOX-loaded mixed micelles formed from a catechol-functionalized polycarbonate/PEG block copolymer and a sister polymer with imidazole side chains are kinetically stable and display no signs of premature drug release, but possess comparable cytotoxicity in cancer cells to free DOX by a pH-triggered intracellular release. Moreover, we show that the nanoparticles accumulate in tumors through the enhanced permeability and retention (EPR) effect, and that the DOX-loaded mixed micelles suppress tumor growth more effectively than free DOX without causing toxicity in a mouse breast cancer model
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