Lewis Type Research Articles

Weightbearing versus non-weight bearing in geriatric distal femoral fractures: a systematic review and meta-analysis.

Demographics of patients who sustain geriatric distal femoral fractures (DFF) match those of patients with neck-of-femur fractures but have limited evidence with which to support post-operative weightbearing protocols. This systematic review sought to identify any difference in outcomes for elderly patients with DFF who were allowed early versus delayed weightbearing postoperatively. DATA SOURCES: PubMed, Medline, Embase and The Cochrane Library, reference lists of retrieved articles. English language papers published between January 2010 and February 2023 with AO-OTA type 33A, B and C femoral fractures as well as Lewis and Rorabeck Type I and II periprosthetic DFF surgically treated with either a lateral locking plate or retrograde intramedullary nail and an average patient age of ≥ 60years. Studies were assessed for inclusion by two authors and quality was assessed using the MINORS tool. Sixteen studies were included, Meta-analysis of non-union, malunion, infection, delayed union and implant complications was performed using Microsoft Excel and the MetaXL extension. The data on return to mobility were presented in narrative form. The analyses demonstrated no difference between the early and delayed weightbearing groups. There are no significant differences in complication rates between early versus delayed weightbearing after surgery for DFF in an elderly population. The study results are limited by high heterogeneity and low-quality studies. High quality, prospective studies are needed to determine the ideal postoperative weightbearing protocol. Level III, Systematic Review and Meta-analysis of Level III studies. International Prospective Register of Systematic Reviews registration-Prospero CRD42022371460.

N-glycoproteomic analyses of human intestinal enteroids, varying in histo-blood group geno- and phenotypes, reveal a wide repertoire of fucosylated glycoproteins.

Human noroviruses, globally the main cause of viral gastroenteritis, show strain specific affinity for histo-blood group antigens (HBGA) and can successfully be propagated ex vivo in human intestinal enteroids (HIEs). HIEs established from jejunal stem cells of individuals with different ABO, Lewis and secretor geno- and phenotypes, show varying susceptibility to such infections. Using bottom-up glycoproteomic approaches we have defined and compared the N-linked glycans of glycoproteins of seven jejunal HIEs. Membrane proteins were extracted, trypsin digested, and glycopeptides enriched by hydrophilic interaction liquid chromatography and analyzed by nanoLC-MS/MS. The Byonic software was used for glycopeptide identification followed by hands-on verifications and interpretations. Glycan structures and attachment sites were identified from MS2 spectra obtained by higher-energy collision dissociation through analysis of diagnostic saccharide oxonium ions (B-ions), stepwise glycosidic fragmentation of the glycans (Y-ions), and peptide sequence ions (b- and y-ions). Altogether 694 unique glycopeptides from 93 glycoproteins were identified. The N-glycans encompassed pauci- and oligomannose, hybrid- and complex-type structures. Notably, polyfucosylated HBGA-containing glycopeptides of the four glycoproteins tetraspanin-8, carcinoembryonic antigen-related cell adhesion molecule 5, sucrose-isomaltase and aminopeptidase N were especially prominent and were characterized in detail and related to donor ABO, Lewis and secretor types of each HIE. Virtually no sialylated N-glycans were identified for these glycoproteins suggesting that terminal sialylation was infrequent compared to fucosylation and HBGA biosynthesis. This approach gives unique site-specific information on the structural complexity of N-linked glycans of glycoproteins of human HIEs and provides a platform for future studies on the role of host glycoproteins in gastrointestinal infectious diseases.

Synthesis, spectroscopic profiling, biological evaluation, DFT, molecular docking and mathematical studies of 3,5-diethyl-2r,6c-diphenylpiperidin-4-one picrate

The title compound 3,5-diethyl-2r,6c-diphenylpiperidin-4-one picrate (3,5-DEDPPP) have been synthesised and characterised by elemental analysis, FT-IR, Mass, 1D NMR (1H and 13C), UV-Vis., and Fluorescence spectral techniques. The title compound had been optimised utilising DFT method with B3LYP/6-311++G(d,p) level of theory. First order hyperpolarisability calculation was used to determine the non-linear optical behaviour of the title molecule. The calculation of the Lewis (bonding) and Non-Lewis (anti-bonding) structural types was done to explore the intra-molecular charge transfer within the molecule. The ICT and bioactivity of the molecule are significantly influenced by the decrease of the HOMO–LUMO energy gap value. The nucleophilic and electrophilic active sites of the molecule are predicted by the MEP surface analysis. Escherichia coli, Bacillus subtilis, Vibreo cholerae, as well as fungi such Candida albicans, Aspergillus niger, and Trichophyton rubrum, were tested for the 3,5-DEDPPP bacterial activity. To establish information about the molecular interactions between protein and this novel compound theoretically, docking studies were carried out in detail. This study is further extended and confirms our synthesised molecular structure using NMR-spectroscopy by mathematical computation through the concept of graph colouring.

Quantifying Vertical Resonance Energy in Aromatic Systems with Natural Bond Orbitals

AbstractNatural bond orbitals (NBOs) provide the familiar Lewis type (2c–2e−) localized description of a molecule. Interactions between nearly filled (2e− π or σ) orbitals and empty (π* or σ*) anti‐bonding orbitals represent delocalization in the system and creates a framework to study stereoelectronic interactions. Here we show that deleting the interactions (NBODel) between π and π* orbitals in aromatic systems and acquiring the energy with the NBO program provides a highly intuitive and quantitative picture of π‐aromaticity that correlates with the well‐established nucleus‐independent chemical shift (NICS) method. This natural bond orbital resonance energy (NBO‐RE) measures the vertical resonance energy (VRE) of aromatic systems without the use of an external reference structure. The NBO‐RE method is applicable to the study of local aromaticity in polycyclic aromatic hydrocarbons (PAHs) and other non‐planar systems.

A large cohort study of the effects of Lewis, ABO, 13 other blood groups, and secretor status on COVID-19 susceptibility, severity, and long COVID-19.

Previous studies have reported Blood type O to confer a lower risk of SARS-CoV-2 infection, while secretor status and other blood groups have been suspected to have a similar effect as well. To determine whether any other blood groups influence testing positive for SARS-CoV-2, COVID-19 severity, or prolonged COVID-19, we used a large cohort of 650,156 Danish blood donors with varying available data for secretor status and blood groups ABO, Rh, Colton, Duffy, Diego, Dombrock, Kell, Kidd, Knops, Lewis, Lutheran, MNS, P1PK, Vel, and Yt. Of these, 36,068 tested positive for SARS-CoV-2 whereas 614,088 tested negative between 2020-02-17 and 2021-08-04. Associations between infection and blood groups were assessed using logistic regression models with sex and age as covariates. The Lewis blood group antigen Lea displayed strongly reduced SARS-CoV-2 susceptibility OR 0.85 CI[0.79-0.93] p < .001. Compared to blood type O, the blood types B, A, and AB were found more susceptible toward infection with ORs 1.1 CI[1.06-1.14] p < .001, 1.17 CI[1.14-1.2] p < .001, and 1.2 CI[1.14-1.26] p < .001, respectively. No susceptibility associations were found for the other 13 blood groups investigated. There was no association between any blood groups and COVID-19 hospitalization or long COVID-19. No secretor status associations were found. This study uncovers a new association to reduced SARS-CoV-2 susceptibility for Lewis type Lea and confirms the previous link to blood group O. The new association to Lea could be explained by a link between mucosal microbiome and SARS-CoV-2.

Streptococcus oralis Employs Multiple Mechanisms of Salivary Mucin Binding That Differ Between Strains

Streptococcus oralis is an oral commensal and opportunistic pathogen that can enter the bloodstream and cause bacteremia and infective endocarditis. Here, we investigated the mechanisms of S. oralis binding to oral mucins using clinical isolates, isogenic mutants and glycoconjugates. S. oralis bound to both MUC5B and MUC7, with a higher level of binding to MUC7. Mass spectrometry identified 128 glycans on MUC5B, MUC7 and the salivary agglutinin (SAG). MUC7/SAG contained a higher relative abundance of Lewis type structures, including Lewis b/y, sialyl-Lewis a/x and α2,3-linked sialic acid, compared to MUC5B. S. oralis subsp. oralis binding to MUC5B and MUC7/SAG was inhibited by Lewis b and Lacto-N-tetraose glycoconjugates. In addition, S. oralis binding to MUC7/SAG was inhibited by sialyl Lewis x. Binding was not inhibited by Lacto-N-fucopentaose, H type 2 and Lewis x conjugates. These data suggest that three distinct carbohydrate binding specificities are involved in S. oralis subsp. oralis binding to oral mucins and that the mechanisms of binding MUC5B and MUC7 differ. Efficient binding of S. oralis subsp. oralis to MUC5B and MUC7 required the gene encoding sortase A, suggesting that the adhesin(s) are LPXTG-containing surface protein(s). Further investigation demonstrated that one of these adhesins is the sialic acid binding protein AsaA.

Dehydration of methanol and ethanol over ferrierite originated layered zeolites - the role of acidity and porous structure.

Ferrierites and their delaminated (ITQ-6) and silica intercalated (ITQ-36) forms, with the intended molar Si/Al ratios of zeolite layers of 30 and 50, were synthesized and tested as catalysts of methanol to dimethyl ether (DME) as well as ethanol to diethyl ether (DEE) and ethylene dehydration. It was shown that increased content of acid sites, especially of Brønsted type, resulted in more active catalysts of alcohol dehydration. Brønsted acid sites dominate in ferrierites and their delaminated forms (ITQ-6). Contribution of the Lewis type of acid sites increased in silica pillared ferrierites (ITQ-36) possibly by deposition of aluminium species on the surface of amorphous silica. Conversion of methanol to DME was not limited by internal diffusion of reactants in narrow pores of ferrierite. Such limitation was observed for synthesis of larger DEE molecules over ferrierites. The ITQ-6 catalysts with the opened interlayer structure presented better efficiency in ethanol to DEE conversion due to overcoming these diffusional restrictions. Moreover, selectivity to DEE over ITQ-6 was higher than in the presence of three-dimensional ferrierite.

Fucosylation in Urological Cancers.

Fucosylation is an oligosaccharide modification that plays an important role in immune response and malignancy, and specific fucosyltransferases (FUTs) catalyze the three types of fucosylations: core-type, Lewis type, and H type. FUTs regulate cancer proliferation, invasiveness, and resistance to chemotherapy by modifying the glycosylation of signaling receptors. Oligosaccharides on PD-1/PD-L1 proteins are specifically fucosylated, leading to functional modifications. Expression of FUTs is upregulated in renal cell carcinoma, bladder cancer, and prostate cancer. Aberrant fucosylation in prostate-specific antigen (PSA) could be used as a novel biomarker for prostate cancer. Furthermore, elucidation of the biological function of fucosylation could result in the development of novel therapeutic targets. Further studies are needed in the field of fucosylation glycobiology in urological malignancies.

Very Distal Femoral Periprosthetic Fractures: Replacement Versus Fixation: A Systematic Review.

To synthesize all-cause reoperations and complications data as well as secondary clinical and functional outcomes, after the management of very distal femur periprosthetic fractures (vDFPFs) in a geriatric patient population with either a distal femoral locking plate (DFLP) or distal femoral replacement (DFR). MEDLINE, Embase, and Web of Science were searched for English language articles from inception to March 16, 2020, in accordance to the PRISMA guidelines. Studies reporting the management of vDFPFs in adults older than 65 years with either a DFLP or DFR were included. To ensure this review solely focused on very distal femoral periprosthetic fractures, only fractures of the following classifications were included: (1) Lewis and Rorabeck type II or III, (2) Su and Associates' Classification of Supracondylar Fractures of the Distal Femur type III, (3) Backstein et al type F2, and/or (4) Kim et al type II or III. Three reviewers independently extracted data from the included studies. Study validity was assessed using the methodological index for nonrandomized studies (MINORS), a quality assessment tool for nonrandomized controlled studies in surgery. Twenty-five studies with 649 vDFPFs were included for analysis. There were 440 knees in the DFLP group (mean age range: 65.9-88.3 years) and 209 knees in the DFR group (mean age range: 71.0-84.8 years). Because of the literature's heterogeneity, the data were qualitatively synthesized. vDFPFs in the elderly treated with DFR underwent fewer reoperations relative to DFLP (0%-45% vs. 0%-77%, respectively). Time to weight-bearing was observably shorter in DFR studies relative to DFLP studies. Functional outcomes and postoperative range of motion indicated a trend for DFLP knees to outperform DFR knees. Future research should include prospective studies and cost-effectiveness evaluations to better understand the utility of DFR for these fractures. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Equilibrium &amp; kinetic studies of reactive extraction of trans-aconitic acid using sunflower oil with tri-n-octylamine

Abstract In order to design an efficient extraction system for the separation of biochemically produced trans-aconitic acid (TAH) from fermentation broth; equilibrium and kinetics of reactive extraction of TAH from aqueous solutions was investigated using tri-n-octylamine (TOA) as an extractant and sunflower oil as a diluent. Through the equilibrium studies stoichiometry (acid, extractant) of complex formations was determined with the help of loading ratio. Formation of (1, 1), (2, 1), &amp; (3, 1) stoichiometry complexes were observed having complexation constants values 179.73 kmol−1 m3, 9512.58 kmol−2 m6, and 614,407.02 kmol−3 m9, respectively. Kinetics experiments were performed in Lewis type stirred cell and results confirmed that reaction between TAH and TOA in sunflower oil fall in regime 1, i.e. slow reaction occurring in bulk organic phase. The overall order of reaction is pseudo first order with rate constant (K mn ) 1.78 × 10−5 (kmol m−3)−0.71 s−1 and physical mass transfer coefficient (K l ) 4.22 × 10−5 m s−1.

A study of the mechanism of triglyceride hydrodeoxygenation over alumina-supported and phosphatized-alumina-supported Pd catalysts

The mechanism of catalytic hydrodeoxygenation (HDO) of fats, vegetable oils, and fatty acids was studied using alumina-supported Pd catalysts and tricaprylin and valeric acid as model reactants. The chemistry of fatty acid/catalyst interaction was studied by quasi-operando Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS). The Pd/γ–Al2O3 catalyst showed good activity in the hydrogenolysis reaction of the ester bonds to convert tricaprylin to caprylic acid, but they were of poor activity in the consecutive hydrodeoxygenation (HDO) of the acid to paraffin. The surface modification of the support alumina by phosphate groups significantly increased the HDO activity of the Pd catalyst and, consequently, the paraffin yield. The activity change was accounted partly for the partial replacement of the weak base Al–OH groups by weak acid P–OH groups but mainly for the partial elimination of Lewis acid (Al⊕) – Lewis base (O⊝) pair sites on the surface of the support. Both surface Al–OH and P–OH groups were shown to participate in the reaction with carboxylic acid and formed bidentate surface carboxylate species, which further reacted with hydrogen to give paraffin. Carboxylates of less basic surface sites were found to be more prone to HDO reaction than those of strong base sites. Monodentate carboxylates, formed on Al⊕ O⊝ pair sites were of low reactivity. Phosphatizing eliminated most of the Lewis type acid-base pair sites, therefore, reactive bidentate carboxylates represented the most abundant surface intermediate (MASI) during the HDO reaction of triglyceride. The hydroxyl coverage of the carboxylated surface was shown to become somewhat higher under steady-state reaction conditions. The increased hydroxyl coverage implies that C–O bond hydrogenolysis of the surface carboxylate proceeds, regenerating OH groups and forming aldehyde that could be intermediate of paraffin formation.

Nanocrystalline cerium oxide for catalytic degradation of paraoxon methyl: Influence of CeO2 surface properties

Cerium oxide (CeO2) prepared by annealing of carbonate precursor was tested for degradation of paraoxon methyl (PO) and the relationships between its properties (specific surface area, crystallite size, number of hydroxyl groups) and the catalytic activity were investigated. Lewis and Brönsted acidity surface sites were identified by adsorption of specific probe molecules (pyridine, acetonitrile, and acetone) using Fourier-transform infrared spectroscopy (FTIR). The abundance of Lewis type sites was recognized while Brönsted type sites were present to a lesser extent. The highest catalytic activity had the sample annealed at 500 °C that was highly crystalline, but the sample retained high surface area and a suitable number of surface hydroxyl groups established to be in the range 0.165–0.190 mmol g−1. Furthermore, the annealing has a negligible effect on the point of zero charge (PZC) but significantly affected the Brunauer-Emmett-Teller surface area (BET), crystallite size and number of surface hydroxyl groups that significantly affected also the degradation efficiency. Nevertheless, it was found that the amount of residual carbonate species on the CeO2 surface may also have a crucial influence on its catalytic activity.

Glycoproteins Presenting Galactose and N-Acetylgalactosamine in Human Seminal Plasma as Potential Players Involved in Immune Modulation in the Fertilization Process.

In light of recent research, there is increasing evidence showing that extracellular semen components have a significant impact on the immune reaction of the female partner, leading to the tolerogenic response enabling the embryo development and implantation as well as further progress of healthy pregnancy. Seminal plasma glycoproteins are rich in the unique immunomodulatory glycoepitopes that may serve as ligands for endogenous lectins that decorate the surface of immune cells. Such interaction may be involved in modulation of the maternal immune response. Among immunomodulatory glycans, Lewis type antigens have been of interest for at least two decades, while the importance of T/Tn antigens and related structures is still far from understanding. In the current work, we applied two plant lectins capable of distinguishing glycoepitopes with terminal GalNAc and Gal to identify glycoproteins that are their efficient carriers. By means of lectin blotting and lectin affinity chromatography followed by LC-MS, we identified lactotransferrin, prolactin inducible protein as well as fibronectin and semenogelins 1 and 2 as lectin-reactive. Net-O-glycosylation analysis results indicated that the latter three may actually carry T and/or Tn antigens, while in the case of prolactin inducible protein and lactotransferrin LacdiNAc and lactosamine glycoepitopes were more probable. STRING bioinformatics analysis linked the identified glycoproteins in the close network, indicating their involvement in immune (partially innate) processes. Overall, our research revealed potential seminal plasma ligands for endogenous Gal/GalNAc specific lectins with a possible role in modulation of maternal immune response during fertilization.

Automated Glycan Assembly of 19 F-labeled Glycan Probes Enables High-Throughput NMR Studies of Protein-Glycan Interactions.

Protein–glycan interactions mediate important biological processes, including pathogen host invasion and cellular communication. Herein, we showcase an expedite approach that integrates automated glycan assembly (AGA) of 19F‐labeled probes and high‐throughput NMR methods, enabling the study of protein–glycan interactions. Synthetic Lewis type 2 antigens were screened against seven glycan binding proteins (GBPs), including DC‐SIGN and BambL, respectively involved in HIV‐1 and lung infections in immunocompromised patients, confirming the preference for fucosylated glycans (Lex, H type 2, Ley). Previously unknown glycan–lectin weak interactions were detected, and thermodynamic data were obtained. Enzymatic reactions were monitored in real‐time, delivering kinetic parameters. These results demonstrate the utility of AGA combined with 19F NMR for the discovery and characterization of glycan–protein interactions, opening up new perspectives for 19F‐labeled complex glycans.

Molecular Structure Vibrational &amp; Electronic Properties of Some Isatin Derivatives

In this study, Natural Bonding Orbitals (NBOs) were applied to isatin, 5‑fluoroisatin, 5‑chloroisatin, 5‑methylisatin and 5‑methoxyisatin using the Lee-Yang-Parr correlation functional B3LYP with 6‑311++G(2d,2p) basis set. Natural bonding analysis was performed to consider the transfer interactions of intra-molecular charge, pre-hybridization and electron density within the isatin, 5‑fluoroisatin, 5‑chloroisatin, 5‑methylisatin and 5‑methoxyisatin. In natural bonding orbital analysis, the wave functions of the electrons were explicated in sets of occupied Lewis type terms, (bonds or lone pairs) and sets of unoccupied non‑Lewis (anti‑bond and Rydberg) localized natural bonding orbitals. The electron density between these orbitals was correlated to stabilize the interaction of donor-acceptor orbitals. Second-order Perturbation Theory was employed to evaluate the stabilization energies of all possible interactions between donor and acceptor orbitals in natural bonding orbitals. The aim was to study the properties of these series and to produce a molecular geometry description, hyper-conjugative interactions, natural bond orbital (NBO) analysis and the HOMO‑LUMO energy gap-dependent properties that are important for the stability of structures. From the results, it can be noted that for all forms, the HOMO‑LUMO energy gap values decreased by substitution for the 5‑fluoroisatin, 5‑chloroisatin, 5‑methylisatin and 5‑methoxyisatin compounds and, with the exception of the deprotonated form in all the compounds, leading to less stable molecules. The anion form of the 5‑methoxyisatin compound and the cation form of the 5‑fluoroisatin, in which the HOMO‑LUMO energy gap values increased, became more stable. It also appeared that the 5‑CH3- and 5‑Cl groups caused an increase in the linear polarizability and anisotropic polarizability values in all forms; however, the 5‑OCH3 and 5‑F groups caused different effects in different forms. Furthermore, we concluded that the intramolecular hyper-conjugative interactions between bonded atoms changed by groups. These changes caused changes in the electron density values in the atoms, which in turn led to a change in the stabilization energy values of the isatin, 5‑fluoroisatin, 5‑chloroisatin, 5‑methylisatin and 5‑methoxyisatin.

Is Immediate Weight-Bearing Safe After Single Implant Fixation of Elderly Distal Femur Fractures?

To compare early complications in elderly patients with extra-articular distal femur fractures (DFFs) allowed to weight-bear as tolerated (WBAT) immediately versus patients prescribed initial touchdown weight-bearing (TDWB). Retrospective cohort study. Level 1 academic trauma center. One hundred thirty-five patients 60 years or older who underwent surgical fixation of an extra-articular DFF, including the OTA/AO fracture classification of 33-A1-3, and periprosthetic fractures with a stable knee prosthesis (Lewis and Rorabeck type I or II) with at least 6 months follow-up. Immediate WBAT or TDWB after surgical fixation of an extra-articular DFF with either an intramedullary nail or locked plate. The primary outcome was a major adverse event within the first 6 months, defined as (1) early fixation failure or change in alignment leading to reoperation, (2) nonunion, or (3) deep infection. Secondary outcomes included postoperative inpatient length of stay, discharge disposition (secondary facility vs. home), malunion, mortality, and patient-reported outcomes. The rate of early adverse events requiring reoperation was similar between the WBAT group (6, 10.7%) and the TDWB group (15, 19.0%; P = 0.23). There was no difference between groups with respect to length of stay, discharge disposition, malunion, and patient-reported outcomes. This study supports allowing carefully selected elderly patients, based on surgeon preference, to immediately weight-bear after operative fixation of an extra-articular DFF regardless of implant choice. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Polymer-Covalent Organic Frameworks Composites for Glucose and pH Dual-Responsive Insulin Delivery in Mice.

Glucose and pH dual-responsive insulin delivery carriers that have been validated in animal models, remain elusive and much desired. Herein, a new class of covalent organic frameworks (COFs)-based insulin delivery nanocarriers is developed by encapsulating insulin (Ins) and glucose oxidase (GOx) into COFs (COF-1 and COF-5) via both Brønsted and Lewis type (N:→B) complexations. Subsequently, polyethylene glycolated fluorescein isothiocyanate (FITC-PEG) is incorporated into the COFs via the exchange reactions between the disulfide in insulin chains and the thiol in FITC-PEG to afford a robust nano-assembly (FITC-PEG-COF@Ins-GOx).Invitro,the nanocarriers rely on the boroxine-linked COFs' response to pH and glucose dual-stimulation and rendered sustainable insulin delivery. Invivo,the polymer-COFs composite displays excellent long-acting anti-diabetic effects on type 1 diabetic mice within 72 h without side effects after one injection. More intriguingly, the nanocomposites also show great promise for the efficient delivery of native proteins with high generality. To the authors' knowledge, this represents the first study pertaining to a facile methodology to prepare COF-based insulin-delivery nanocarriers for in vitro and in vivo therapeutic applications.

Use of the serum glycan state to predict ovarian cancer patients' clinical response to chemotherapy treatment

Ovarian cancer is the most lethal gynecologic carcinoma; because the tumor often relapses shortly after treatment. Glycosylation plays important roles in cancer drug resistance and could be used as biomarkers to predict the drug response of patients.We used MALDI-QIT-TOF MS to analyze the serum glycomic from patients with different drug responses. Samples were collected before treatment; follow-up visit were performed after 6 months. Forty-eight drug-sensitive patients and 16 drug-resistant patients were enrolled.Compared with drug-sensitive patients, 5 glyco-subclasses and 5 single glycans were significantly altered in drug-resistant patients. Lewis type, α2,3 sialic acid and multibranch glycans were increased, α2,6 sialic acid glycans were decreased. The peak at m/z 2986.44 showed stronger prediction abilities than other single glycans, with an AUC of 0.83. A panel of three increased glycans (m/z 2401.36, H5N4F1S2, a Lewis type biantennary glycan; m/z 2986.44, H6N5S3, a triantennary trisialylated glycan; m/z 3086.39, H6N5F1S3, a Lewis type triantennary glycan) combined with CA125 achieved an AUC value of 0.88, showing a strong discrimination performance.This study provides new insights into N-glycosylation patterns in ovarian cancer patients with different drug response. These altered glycans might serve as biomarkers to reflect patients' drug sensitivity and to guide clinical treatment. SignificanceA large number of ovarian cancer patients experience tumor relapse shortly after initial treatment. Glycosylation plays important roles in cancer drug resistance and could be used as a biomarker to predict the drug response of patients. However, the glycosylation expressed in patients with different drug response have not been elucidated. In the present study, we used MALDI-QIT-TOF MS to analyze the serum glycomic levels of patients with different drug responses. Several glycans were changed significantly between these two groups. A panel of three increased glycans (m/z 2401.36, a Lewis type biantennary glycan, 2986.44, a triantennary trisialylated glycan, and 3086.39, a Lewis type triantennary glycan) combined with CA125 performed better descrimination of these two groups with AUC of 0.88. These altered glycans might serve as biomarkers to reflect patients' drug sensitivity and to guide clinical treatment.

Gold Nanoparticle as a Lewis Catalyst for Water Elimination of Tyrosine-•OH Adducts: A Radiation and Quantum Chemical Study.

The role of gold nanoparticles (AuNPs) in the degradation of tyrosine intermediates formed during the radiation-induced •OH reaction with tyrosine at pH 6.5 is investigated by measuring the radiolytic yields, G, of tyrosine (-Tyr), dityrosine (DT), and 3,4 dihydroxyphenylalanine (DOPA). The G(DT) is doubled, whereas G(-Tyr) calculated is halved in the presence of 6.0 × 10-10 mol dm-3 AuNPs. Pulse radiolysis studies are carried out to elucidate the mechanism and nature of the transient formed in the reaction of •OH and •N3 with tyrosine. The formation of tyrosyl radical in the presence of AuNPs is found to be a major pathway through the decay of tyrosine-•OH adducts via the water elimination reaction, which is found to be 3× faster in the presence of AuNPs. Quantum chemical calculations on the system showed favorable formation of the tyrosine-AuNP complex. A new plausible mechanism of tyrosine-AuNP complex acting as a Lewis type catalyst in the decay of tyrosine-•OH adducts leading to reduced DOPA formation is proposed. The proposed mechanism is also complemented by the electronic spectra and energetics of the reaction of •OH with tyrosine using density functional theory calculations. Significantly, the H-shift reaction of ortho-tyrosine-•OH adducts is also found to be energetically viable. The investigation provides a new physical insight into the effect of AuNPs on the decay of free-radical transient species and demonstrates the potential of radiation chemical techniques and quantum chemical calculations as a tool for understanding the impact of metal nanoparticles in free-radical oxidation of amino acids, which is important in the use of metal nanoparticles for biomedical applications.

Proton transfer vs. oligophosphine formation by P-C/P-H σ-bond metathesis: decoding the competing Brønsted and Lewis type reactivities of imidazolio-phosphines.

Studies of the protonation and alkylation of imidazolio-phosphides and deprotonation of imidazolio-phosphines reveal a complex behaviour that can be traced back to an interplay of Brønsted-type proton transfers and Lewis-type P-P bond formation reactions. As a consequence, the expected (de)protonation and (de)alkylation processes compete with reactions producing cyclic or linear oligophosphines. A careful adjustment of the conditions allows us to selectively address each reaction channel and devise specific synthesis methods for primary, secondary and tertiary imidazolio-phosphines, imidazolio-alkylphosphides, and cyclic oligophosphines, respectively. Mechanistic studies reveal that oligophosphines assemble in sequential P-P bond formation steps involving the condensation of cationic imidazolio-phosphines viaσ-bond metathesis and concomitant elimination of an imidazolium ion. Imidazolio-phosphides catalyse these transformations. Computational model studies suggest that the metathesis proceeds in two stages via an initial nucleophilic substitution under expulsion of a carbene, and a subsequent proton transfer step that generates an imidazolium cation and provides the driving force for the whole transformation. As energy barriers are predicted to be low or even absent, different elementary steps are presumed to form a network of mutually coupled equilibrium processes. Cyclic oligophosphines or their dismutation products are identified as the thermodynamically favoured final products in the reaction network.