Selective enrichment of glycopeptides based on copper tetra(N-carbonylacrylic) aminephthalocyanine and iminodiacetic acid functionalized polymer monolith.

Efficient separation and enrichment of low-abundance glycopeptides from complex biological samples is the key to the discovery of disease biomarkers. In this work, a new material was prepared by coating copper tetra(N-carbonylacrylic) aminephthalocyanine and iminodiacetic acid onto poly(glycidyl methacrylate-pentaerythritol triacrylate) monolith. The monolith was applied to polymer monolithic microextraction for specific capture of glycopeptides coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The developed monolith exhibited satisfactory efficiency for glycopeptide enrichment with high selectivity and detection sensitivity. When the tryptic digest of immunoglobulin G was used as the sample, total 24 glycopeptides were identified and the detection limit was determined as 5 fmol. When the approach was applied to the analysis of glycopeptides in the mixture of bovine serum albumin and immunoglobulin G (100:1, m/m) digests, 16 glycopeptides could still be observed. Moreover, the monolith was successfully applied to the selective enrichment of glycopeptides from human serum digests, exhibiting great practicability in identifying low-abundance glycopeptides in complex biological samples.

Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study.

BACKGROUND: Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small-scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first-line treatment in locally advanced or metastatic LSCC. METHODS: Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses. RESULTS: The median duration of follow-up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF-α, IFN-γ, IL-6, and IL-8, demonstrating an overlapping trend. CONCLUSION: The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.

Epidermal growth factor receptor-targeted immunomagnetic liposomes for circulating tumor cell enumeration in non-small cell lung cancer treated with epidermal growth factor receptor-tyrosine kinase inhibitors.

OBJECTIVES: To establish a circulating tumor cell (CTC) enrichment system for non-small cell lung cancer (NSCLC) patients who received first-line treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKI), using EGFR magnetic liposomes (EGFR-ML). MATERIALS AND METHODS: An inverted evaporation method was used to develop antibody modified EGFR-ML. Peripheral blood was collected from NSCLC patients who underwent first-line EGFR-TKI treatment for CTC enumeration. RESULTS: Protein electrophoresis, magnetic saturation curve, and ultraviolet absorption spectrum showed successful incorporation of the EGFR antibody on the surface of the magnetic microspheres, and the development of EGFR-ML was ascertained based on cell morphology and particle size. Using EGFR-ML, CTC were successfully enriched from blood samples and were identified in 77.3% (99/128) of the cohort. When compared to the 21L858R variant, EGFR-19del showed lower CTC counts by EGFR-ML (CTCEGFR). At one month after EGFR-TKI, a lower CTCEGFR was associated with partial response (PR) during treatment (CTCEGFR < 6 vs. ≥ 6/7.5 mL, 75% vs. 49%, P = 0.027). In addition, patients with a lower CTCEGFR at 3 months after EGFR-TKI achieved a longer progression-free survival (PFS) [CTCEGFR < 6 vs. ≥ 6/7.5 mL, 13 months vs. 10.4 months, HR = 2.4, P = 0.042]. CTCEGFR significantly increased at the time of RECIST-progressive disease (RECIST-PD). Representative cases showed that CTCEGFR might increase before and beyond RECIST-PD until no clinical benefit could be acquired from EGFR-TKI. CONCLUSION: We showed that establishing a CTC enrichment system by antibody modified EGFR-ML in NSCLC is feasible. CTC enumeration by EGFR-ML may have the potential to supplement RECIST in dynamically monitoring the response of NSCLC patients' to first-line EGFR-TKI.

Simultaneous determination of sulfonamides and fluoroquinolones from environmental water based on magnetic double-template molecularly imprinting technique.

In this work, a fast and selective method based on magnetic extraction is presented for the simultaneous extraction of sulfonamides (SAs) and fluoroquinolones (FQs), followed by liquid chromatography-tandem mass spectrometry detection. In this method, magnetic surface double-template molecularly imprinted polymers (MSdt-MIPs) with superparamagnetic property and high selectivity toward both SAs and FQs were synthesized and directly applied to the simultaneous extraction of SAs and FQs from environmental water as magnetic adsorbents. The extraction and enrichment procedures could be accomplished in one single step by stirring the mixture of MSdt-MIPs and water sample, and the MSdt-MIPs with adsorbed analytes were easily separated from the water sample by a magnet afterwards. The adsorption mechanism of MSdt-MIPs was investigated by employing the adsorption thermodynamic and kinetic studies, and the selectivity of the MSdt-MIPs toward target analytes was evaluated through the selectivity test. For validation of the proposed method, the matrix effect was evaluated and compared to that of the traditional SPE method. Excellent linearity (R > 0.9990) for both SAs and FQs were obtained in the concentration range of 20-2000 ng L-1, and the limits of detection are in the range of 3.0-4.7 ng L-1 for SAs while 4.1-6.1 ng L-1 for FQs. Finally, the proposed method was successfully applied to the simultaneous determination of SAs and FQs in several environmental water samples.

Magnetic flocculants synthesized by Fe3O4 coated with cationic polyacrylamide for high turbid water flocculation.

A novel magnetic flocculant (CPAMF) was synthesized by using Fe3O4 coated with cationic polyacrylamide (CPAM) for flocculation of high turbid water. The surface morphology and chemical structures of CPAMF were confirmed by Fourier transform infrared spectroscopy (FTIR) and thermo-gravimetric analysis (TGA). X-ray diffraction (XRD) was employed to verify the crystal structure of CPAMF. The magnetic property of CPAMF was compared with Fe3O4 in this study. The flocculation performance by using flocculants CPAMF was evaluated in high turbid water treatment. The maximum transmittance 92.4% of kaolin suspension was achieved at corresponding optimal flocculation conditions. The result indicated that CPAMF was efficient in high turbid water flocculation. Analysis of FTIR, XRD of flocs, and zeta potential (ZP) of supernatant were accomplished for flocculation mechanism investigation. Because of low recovery factor in reflocculation under the effect of shear force on flocs, the bridging effect was found to be dominant in both acidic and alkaline conditions. Sedimentation experiments under the role of permanent magnet indicated that nano-Fe3O4 could effectively improve the settling property of CPAM. Graphical abstract ᅟ.

Selective determination of sulfonamides from environmental water based on magnetic surface molecularly imprinting technology.

In the study, a simple and selective method based on magnetic separation technology is presented for the extraction of sulfonamides (SAs) from environmental water, followed by liquid chromatography-tandem mass spectrometry. In this method, magnetic surface molecularly imprinted polymers (Fe3O4@SiO2@MIPs) with super-paramagnetic property and high selectivity toward SAs were developed as magnetic adsorbents. The Fe3O4@SiO2@MIPs were then applied to the selective extraction of SAs from environmental water. The extraction and enrichment were accomplished simultaneously in a single step by simply stirring the mixture of adsorbents and water samples. The Fe3O4@SiO2@MIPs were characterized by scanning electron microscopy, Fourier-transform infrared spectrometry, and vibrating sample magnetometry. The adsorption thermodynamics and kinetics were employed to study the adsorption mechanism of the Fe3O4@SiO2@MIPs. And the matrix effect of the method was evaluated. Calibration curves obtained by analyzing matrix-matched standards show excellent linear relationship (R = 0.9994-0.9999) in the concentration range of 10-1000 ng L-1, and the limits of detection are in the range of 1.4-2.8 ng L-1. The relative standard deviations of intra- and inter-day obtained are in the range of 2.8 to 7.8 and 3.1 to 7.9%, respectively. The proposed method was successfully applied to determine SAs in six environmental water samples, and SAs were detectable in four of them with the concentration from 10.5 to 120.2 ng L-1.

Safety of polyethylene glycol recombinant human granulocyte colony-stimulating factor in treating non-small cell lung cancer patients at I b stage.

OBJECTIVE: To investigate resistance and safety of HHPG-19K in treating non-small cell lung cancer patients. METHODS: A total of 30 cases were selected and randomly divided into 5 groups: three HHPG-19K groups of different dosage (60 µg/kg/day, 100 µg/kg/day, 200 µg/kg/day), positive control group (Filgrastim, namely G-CSF5 µg/kg/day) and negative control group. Safety indexes of 5 groups were observed and compared. RESULTS: All patients had adverse event (100%) in three HHPG-19K groups, and increased ALP, ALT and AST were main events. The degree was mild to moderate. There was no significant difference in the incidence of adverse event between dosage groups and positive control group no difference. But the incidence of negative control group was 13%, which was significantly lower than dosage groups and positive control group. CONCLUSIONS: non-small cell lung cancer patients have satisfactory tolerance to HHPG-19K, and have no resistance. Besides, dosage at 100 µ g/kg is the most safe.

PEGylated hybrid ytterbia nanoparticles as high-performance diagnostic probes for in vivo magnetic resonance and X-ray computed tomography imaging with low systemic toxicity.

Novel nanoparticulate contrast agents with low systemic toxicity and inexpensive character have exhibited more advantages over routinely used small molecular contrast agents for the diagnosis and prognosis of disease. Herein, we designed and synthesized PEGylated hybrid ytterbia nanoparticles as high-performance nanoprobes for X-ray computed tomography (CT) imaging and magnetic resonance (MR) imaging both in vitro and in vivo. These well-defined nanoparticles were facile to prepare and cost-effective, meeting the criteria as a biomedical material. Compared with routinely used Iobitridol in clinic, our PEG-Yb2O3:Gd nanoparticles could provide much significantly enhanced contrast upon various clinical voltages ranging from 80 kVp to 140 kVp owing to the high atomic number and well-positioned K-edge energy of ytterbium. By the doping of gadolinium, our nanoparticulate contrast agent could perform perfect MR imaging simultaneously, revealing similar organ enrichment and bio-distribution with the CT imaging results. The super improvement in imaging efficiency was mainly attributed to the high content of Yb and Gd in a single nanoparticle, thus making these nanoparticles suitable for dual-modal diagnostic imaging with a low single-injection dose. In addition, detailed toxicological study in vitro and in vivo indicated that uniformly sized PEG-Yb2O3:Gd nanoparticles possessed excellent biocompatibility and revealed overall safety.

Resveratrol and its oligomers from wine grapes are selective (1)O2 quenchers: mechanistic implication by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry and theoretical calculation.

Resveratrol and its oligomers, abundantly present in wine grapes, are believed to be effective phytoalexins for the phenomenon "French paradox" partially by virtue of their powerful antiradical properties. EPR spin-trapping technique was utilized, demonstrating all polyphenols were selective (1)O2 quenchers but not effective (•)OH and O2(•¯) scavengers. On the basis of the HPLC-ESI-MS(2) analysis for the simulated reactions of polyphenols with (1)O2, the molecular weights of the resulting photochemical products were 14 or 28 Da higher than those of their substrates. No fragment C2H2O (42 Da), which was rather distinctive of the resorcinol rings in these cases, had been observed, whereas their MS/MS spectra displayed characteristic neutral fragments including carbon monoxide (CO, 28 Da) and 2-hydroxy[1,4]benzoquinone (C6H4O3, 124 Da). Finally, PM3 semiempirical calculations and HR-FTICR-MS experiments were performed, supporting the assertion that their quenching mechanism involved physical and chemical pathways. Chemical quenching underwent an endoperoxide intermediate form to generate quinones.