Osteonecrosis of the Jaw After Bisphosphonates Treatment in Patients with Multiple Myeloma

Bone lytic lesion in Multiple myeloma are the most commonly presented symptoms which require treatment with bisphosphonates (BPs). BPs are providing supportive care, reducing the rate of skeletal morbidity but evidently not abolishing it, the criteria for stopping their administration have to be different from those used for classic antineoplastic drugs, and they should not be stopped when metastatic bone disease is progressing. Osteonecrosis of the jaw (ONJ) has been associated recently with the use of BPs. The aim of these study is to evaluate the incidence of ONJ in patients with MM treated with mixed biphosphonates. We analyzed total 296 myeloma patients (150 male and 146 female). Mostly effected age group with 58,1% is age more than 60 years up to 88 years, diagnosed in our institution in the period 2005-2015. We used intravenous or oral forms of biphosphonates such as pamidronate, ibandronate, clodronate and zolendronic acid. The patients were evaluated for ONJ. The incidence of ONJ in our group of patients treated with Bps was 4,6% from our group of 260 patients 87,8% received BPs therapy and patients which haven’t received BPs 12,2%. From this group, 95,4% (248) didn’t show ONJ, and 4,6% (12) showed ONJ. The period of this treatment with BPs is an important risk factor for development of ONJ, average duration of BPs therapy in patients which show adverse effects is 26.8±13.7 months, from the total number of 12 patients that developed ONJ adverse effects, we have 8 patients which received treatment with Zolendronic acid and the remaining 4 patients which were treated with other BPs combinations without Zolendronic acid. All patients treated for MM must continue with the therapy with Zolendronic acid and Pamidronate, each patient must be individually treated according to his response of the treatment (dose, frequency and duration of therapy)

Acute kidney injury in China: A neglected truth and perspective

Acute kidney injury in China: A neglected truth and perspectiv

Combustion kinetic model development using surrogate model similarity method

<p>An ideal combustion kinetic model needs to be validated by different experimental targets over a wide range of temperatures and pressures that represent operating conditions in real engines. However, conditions of laboratory experiments for model validation are often limited by the constraint of experimental techniques. In order to improve model predictions under certain conditions (for example, at a relatively higher pressure), it is often needed to use the experimental data obtained under other conditions. In this work, the surrogate model similarity (SMS) method is proposed to find the experimental conditions or targets for model optimisation under certain conditions where the experiments are hard to be conducted. The similarity coefficient is calculated by the cosine similarity between the characteristic coefficients (vectors) of the High Dimensional Model Representation (HDMR) models for different model predictions. A larger similarity coefficient represents a closer relationship between two model predictions. The experimental data with larger similarity coefficients could be more effective to model uncertainty reduction under the concerned conditions. To demonstrate this method, simulations were conducted for two selected combustion systems with hydrogen or methanol as the fuel. In addition to its strength in available experimental data selection for model optimization, this method can be used to screen out experimental targets with strong constraint effect beforehand, thus providing an effective way to maximise utilisation of experimental resources.</p

Single-Step Enrichment of <i>N</i>‑Glycopeptides and Phosphopeptides with Novel Multifunctional Ti⁴⁺-Immobilized Dendritic Polyglycerol Coated Chitosan Nanomaterials

Protein glycosylation and phosphorylation, two of the most important post-translational modifications (PTMs) in the proteome, play a vital role in regulating a number of complex biological processes and involvement in a variety of diseases. Comprehensive characterization of the phosphoproteome and glycoproteome requires highly specific and sensitive enrichment methods of purification of phosphopeptides and glycopeptides because many glycoproteins and phosphoproteins naturally occur at low abundances and substoichiometry. Here, we reported a facile route to fabricate a novel multifunctional Ti⁴⁺-mmobilized dentritic polyglycerol CS@PGMA@IDA (CS, chitosan; PGMA, poly­(glycidyl methacrylate); IDA, iminodiacetic acid) nanomaterials. The polymer surface endows the nanomaterials with biocompatibility, excellent hydrophilic property, and a large amount of Ti ⁴⁺ which have the property of immobilized metal ion affinity chromatography (IMAC)- and hydrophilic interaction liquid chromatography (HILIC)-based functional materials. The CS@PGMA@IDA-Ti⁴⁺ nanomaterials demonstrate an outstanding ability for <i>N</i>-glycopeptides and phosphopeptides enrichment simultaneously, evaluated by the extremely high binding capacity (150 mg g^–1), sensitivity (above 0.1 fmol), and high enrichment recovery (above 75.4%). Its outstanding specificity and efficiency for purification of phosphopeptides is reflected in quantities as low as 1:5000 molar ratios of phosphopeptides which can be detected. Furthermore, we used CS@PGMA@IDA-Ti⁴⁺ to enrich for <i>N</i>-glycopeptides and phosphopeptides followed by PNGase F treatment, fractionated and separated <i>N</i>-glycopeptides and phosphopeptides with different eluents, and then analyzed by MS, a total of 423 (84.4 ID/μg, 3.525 ID/min) <i>N</i>-glycopeptides in 235 different glycoproteins and 422 (84.4 ID/μg, 3.517 ID/min) phosphopeptides in 256 different phosphoproteins which were finally identified in two independent LC–MS/MS runs (with a total time of 120 min) from 50 μg of mouse liver. The results demonstrated that the method based on CS@PGMA@IDA-Ti⁴⁺ to single-step enrichment of <i>N</i>-glycopeptides and phosphopeptides is simple, efficient, specific, and compatible to MS. It can be expected that CS@PGMA@IDA-Ti⁴⁺ would hold great applicability of modification-based proteomics to the precious and low amounts of clinical samples

Quantum Dots Labeling Strategy for “Counting and Visualization” of HepG2 Cells

We report a sensitive, selective, simple, and reliable magnetic immunoassay protocol for detection and imaging of HepG2 cells. After being captured by Cs-doped multicore magnetic nanoparticles (MMNPs), HepG2 cells were labeled by CdSe/ZnS quantum dots (QDs), which could be visualized by fluorescence imaging using the photoluminescence property of QDs, and subsequently, they can be counted by inductively coupled plasma mass spectrometry (ICP-MS) with Cd/Cs as elemental tag. Because of the superior photoluminescence properties and the large quantities of detectable Cd atoms contained in the QDs core, QDs play a dual function role in this assay, making the method easier and more comprehensive than other similar approaches. Under the optimal conditions, the limit of detection of 61 HepG2 cells and the relative standard deviation of 5.4% (800 HepG2 cells, <i>n</i> = 7) were obtained. The linear range was 200–30 000 cells, and the recoveries in human whole blood were in the range of 86–104%. The proposed method enables us not only to count but also to see the cancer cells with the same labeling process, opening a promising avenue for research and clinical application

Alignment of the <i>Tomicus yunnanensis</i> HSP40 amino acid sequence with other insects HSP40 amino acid sequences.

<p>The conserved J domain is underlined. The Gly/Phe-rich domain is double underlined. The cysteine-rich domain is indicated as dotted line. Identical residues are shaded black, conserved substitutions are shaded grey. Dash (–) indicates insertion or deletion. Tca, <i>Tribolium castaneum</i> (EFA11191); Lsa, <i>Liriomyza sativae</i> (ABE57132); Lmi, <i>Locusta migratoria</i> (ABC84495); Bmo, <i>Bombyx mori</i> (BAD90846).</p

Characteristics of homology search of Illumina sequences against the nr database.

<p>(A) E-value distribution of BLAST hits for each unique sequence with a cut-off E-value of 1.0E-5. (B) Species distribution of the BLASTX results. We used the first hit of each sequence for analysis.</p

Alignment of the predicted amino acid sequences of <i>Tomicus yunnanensis</i> sHSPs. The conserved α-crystallin domain is underlined.

<p>Identical residues are shaded black, conserved substitutions are shaded grey. Dash (–) indicates insertion or deletion.</p

Length distribution of unigenes.

<p>The number of y-axis has been transfer into logarithmic scale.</p

Synthesis, Characterization, and Photopolymerization of Polyisobutylene Phenol (Meth)acrylate Macromers

Polyisobutylene (PIB) phenol (meth)­acrylates were produced by reacting di- or triphenol-terminated PIB with (meth)­acryloyl chloride. ¹H NMR, GPC, and MALDI-TOF MS characterization showed that meth­(acrylate) end-functionality was 2 and 3, respectively, and that targeted molecular weights and relatively low polydispersities were achieved. Comparative aliphatic PIB triol triacrylate was prepared by end-quenching living polyisobutylene with 4-phenoxy-1-butyl acrylate. A photopolymerization study of PIB diphenol di­(meth)­acrylates with <i>M</i>_n about 3000 g/mol, PIB triphenol tri­(meth)­acrylates with <i>M</i>_n about 4000 and 10 000 g/mol, and control aliphatic PIB triol triacrylate with <i>M</i>_n about 10 000 g/mol was conducted. Darocur 1173 and Irgacure 819 and 651 photoinitiators were studied, and FTIR reaction monitoring showed that Darocur 1173 afforded the highest rate of photopolymerization and final conversion, apparently due to its higher solubility in PIB. At <i>M</i>_n ≅ 4000 g/mol, the rate of photopolymerization and conversion of PIB triphenol triacrylate was faster than that of PIB triphenol methacrylate under the same conditions; at <i>M</i>_n ≅ 10 000 g/mol, PIB triphenol triacrylate, PIB triphenol trimethacrylate, and aliphatic PIB triacrylate all showed the same high rate of photopolymerization, which was higher than any rate observed at <i>M</i>_n ≅ 4000 g/mol. Similarly, PIB triphenol tri­(meth)­acrylate at <i>M</i>_n ≅ 4000 g/mol displayed a higher rate of photopolymerization and double-bond conversion than PIB diphenol di­(meth)­acrylate at <i>M</i>_n ≅ 3000 g/mol, although they have similar chain end concentrations. This phenomenon was attributed to reduced diffusional mobility at higher <i>M</i>_n, resulting in decreased rate of bimolecular radical termination and autoacceleration. <i>T</i>_g of UV-cured PIB networks decreased as <i>M</i>_n of PIB macromer increased regardless of end-group type, and thermal stability of cured networks remained constant regardless of end-group type. Mechanical properties were characteristic of rubbery networks, but weak, apparently due to low <i>M</i>_n and low PDI of the starting macromers and lack of chain entanglements. Networks from macromers with <i>M</i>_n ≅ 10 000 g/mol gave higher elongations, but lower Young’s moduli, compared to those from macromers with <i>M</i>_n ≅ 4000 g/mol