Mesoporous Zirconium Phenylphosphonates for Selective Enrichment of Phosphopeptides

Mesoporous zirconium phenylphosphonates were synthesized by one-pot co-condensation of ZrCl₄ and phenylphosphonic acid (PPA) under weak acidic medium using sodium dodecyl sulfate (SDS) as a template. The structure and chemical states of the synthesized materials were characterized by N₂ sorption, powder XRD, TEM and FT-IR, ICP, and solid-state NMR, indicating that the hybrids possess mesoporous structure and the frameworks are constructed by the coordination of zirconium­(IV) with phenylphosphonates. These mesoporous materials present a considerable amount of uniformly distributed zirconium­(IV) throughout the frameworks available for the enrichment of phosphopeptides, which causes them to circumvent the complex preloading of metal ions required for traditional immobilized metal affinity chromatographic (IMAC) adsorbents. Thus, the materials are first applied as IMAC adsorbents to enrich phosphopeptides from the tryptic digests of both standard phosphoproteins and a mixture of proteins. MALDI-TOF MS analysis shows that mesoporous zirconium phenylphosphonates exhibit satisfying efficiency and specificity in the enrichment of phosphopeptides from peptides even under strong interference of nonphophopeptides

Synthesis of Calcium Bisphosphonate/Calcium Polyacrylate Spheres for Gene Delivery

Calcium bisphosphonate/calcium polyacrylate spheres were synthesized by a facile method and applied for the first time as gene vectors for transfection. The colloidal spheres of the PAA–Ca²⁺–H₂O complex, formed by sodium polyacrylate and calcium ions in the solution, were used as template to synthesize a spherical PAA–Ca²⁺–BPMP composite (CaBPMP/CaPAA) in the presence of 1,4-bis­(phosphomethyl)­piperazine (BPMP). The CaBPMP/CaPAA composite exhibits uniform and well-dispersed spheres with a particle size of about 200 nm as expected. The cytotoxicity assays confirm that CaBPMP/CaPAA spheres are quite safe for different cells even at a high concentration of 500 μg/mL. In vitro transfection results show that CaBPMP/CaPAA spheres serving as gene vectors are capable of transferring exogenous genes into different cells with about 25% of transfection efficiency and good reproducibility. The transfection capacity of CaBPMP/CaPAA spheres may be attributed to the controllable sphere morphology, low cytotoxicity, moderate DNA loading capacity, and bioresorbable property. The application of calcium phosphonates with adjustable surface properties derived from the different organic groups of phosphonic acid in gene delivery provides a new design idea for gene vectors

Datasets of our collected dopamine receptor multi-subtype ligands.

<p>Four groups of this dataset were used as negative samples for testing subtype selectivity of our developed multi-label machine learning models.</p

The performance of our new method 2SBR-SVM and that of previously used methods Combi-SVM, ML-kNN and RAkEL-DT in predicting dopamine receptor multi-subtype ligands as non-selective ligands.

<p>The performance of our new method 2SBR-SVM and that of previously used methods Combi-SVM, ML-kNN and RAkEL-DT in predicting dopamine receptor multi-subtype ligands as non-selective ligands.</p

Top-ranked molecular descriptors for distinguishing dopamine receptor subtype D1, D2, D3 or D4 selective ligands selected by RFE feature selection method.

<p>Top-ranked molecular descriptors for distinguishing dopamine receptor subtype D1, D2, D3 or D4 selective ligands selected by RFE feature selection method.</p

Datasets of our collected dopamine receptor D1, D2, D3 and D4 selective ligands against another subtype.

<p>The binding affinity ratio is the experimentally measured binding affinity to the second subtype divided by that to the first subtype: (Ki of the second subtype / Ki of the first subtype). This dataset was used as positive samples for testing subtype selectivity of our developed virtual screening models.</p

Datasets of our collected dopamine receptor D1, D2, D3 and D4 ligands, non-ligands and putative non-ligands.

<p>Dopamine receptor D1, D2, D3 and D4 ligands (Ki <1 μM) and non-ligands (ki >10 μM) were collected as described in method section, and putative non-ligands were generated from representative compounds of compound families with no known ligand. These datasets were used for training and testing the multi-label machine learning models.</p

The performance of our new method 2SBR-SVM and that of previously used methods Combi-SVM, ML-kNN and RAkEL-DT in predicting dopamine receptor subtype selective ligands.

<p>The performance of our new method 2SBR-SVM and that of previously used methods Combi-SVM, ML-kNN and RAkEL-DT in predicting dopamine receptor subtype selective ligands.</p

Table_1_Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response to renin-angiotensin system inhibitors in patients with IgA nephropathy.docx

BackgroundRenin-angiotensin system inhibitors (RASi) are the first choice and basic therapy for the treatment of IgA nephropathy (IgAN) with proteinuria. However, approximately 40% of patients have no response to RASi treatment. The aim of this study was to screen potential biomarkers for predicting the treatment response of RASi in patients with IgAN.MethodsWe included IgAN patients who were treatment-naive. They received supportive treatment, including a maximum tolerant dose of RASi for 3 months. According to the degree of decrease in proteinuria after 3 months of follow-up, these patients were divided into a sensitive group and a resistant group. The plasma of the two groups of patients was collected, and the exosomes were extracted for high-throughput sequencing. The screening of hub genes was performed using a weighted gene co-expression network (WGCNA) and filtering differentially expressed genes (DEGs). We randomly selected 20 patients in the sensitive group and 20 patients in the resistant group for hub gene validation by real-time quantitative polymerase chain reaction (qRT−PCR). A receiver operating characteristic (ROC) curve was used to evaluate hub genes that predicted the efficacy of the RASi response among the 40 validation patients.ResultsAfter screening 370 IgAN patients according to the inclusion and exclusion criteria and the RASi treatment response evaluation, there were 38 patients in the sensitive group and 32 patients in the resistant group. IRAK1, ABCD1 and PLXNB3 were identified as hub genes by analyzing the high-throughput sequencing of the plasma exosomes of the two groups through WGCNA and DEGs screening. The sequencing data were consistent with the validation data showing that these three hub genes were upregulated in the resistant group compared with the sensitive group. The ROC curve indicated that IRAK1 was a good biomarker to predict the therapeutic response of RASi in patients with IgAN.ConclusionsPlasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response of RASi in patients with IgAN.</p

Image_1_Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response to renin-angiotensin system inhibitors in patients with IgA nephropathy.jpeg

BackgroundRenin-angiotensin system inhibitors (RASi) are the first choice and basic therapy for the treatment of IgA nephropathy (IgAN) with proteinuria. However, approximately 40% of patients have no response to RASi treatment. The aim of this study was to screen potential biomarkers for predicting the treatment response of RASi in patients with IgAN.MethodsWe included IgAN patients who were treatment-naive. They received supportive treatment, including a maximum tolerant dose of RASi for 3 months. According to the degree of decrease in proteinuria after 3 months of follow-up, these patients were divided into a sensitive group and a resistant group. The plasma of the two groups of patients was collected, and the exosomes were extracted for high-throughput sequencing. The screening of hub genes was performed using a weighted gene co-expression network (WGCNA) and filtering differentially expressed genes (DEGs). We randomly selected 20 patients in the sensitive group and 20 patients in the resistant group for hub gene validation by real-time quantitative polymerase chain reaction (qRT−PCR). A receiver operating characteristic (ROC) curve was used to evaluate hub genes that predicted the efficacy of the RASi response among the 40 validation patients.ResultsAfter screening 370 IgAN patients according to the inclusion and exclusion criteria and the RASi treatment response evaluation, there were 38 patients in the sensitive group and 32 patients in the resistant group. IRAK1, ABCD1 and PLXNB3 were identified as hub genes by analyzing the high-throughput sequencing of the plasma exosomes of the two groups through WGCNA and DEGs screening. The sequencing data were consistent with the validation data showing that these three hub genes were upregulated in the resistant group compared with the sensitive group. The ROC curve indicated that IRAK1 was a good biomarker to predict the therapeutic response of RASi in patients with IgAN.ConclusionsPlasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response of RASi in patients with IgAN.</p