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71.
72.
Christopher Grimm Simona Pompei Kristina Egger Michael Fuchs Wolfgang Kroutil 《RSC advances》2023,13(9):5770
Lignin-derived aryl methyl ethers (e.g. coniferyl alcohol, ferulic acid) are expected to be a future carbon source for chemistry. The well-known P450 dependent biocatalytic O-demethylation of these aryl methyl ethers is prone to side product formation especially for the oxidation sensitive catechol products which get easily oxidized in the presence of O2. Alternatively, biocatalytic demethylation using cobalamin dependent enzymes may be used under anaerobic conditions, whereby two proteins, namely a methyltransferase and a carrier protein are required. To make this approach applicable for preparative transformations, fusion proteins were designed connecting the cobalamin-dependent methyltransferase (MT) with the corrinoid-binding protein (CP) from Desulfitobacterium hafniense by variable glycine linkers. From the proteins created, the fusion enzyme MT-L5-CP with the shortest linker performed best of all fusion enzymes investigated showing comparable and, in some aspects, even better performance than the separated proteins. The fusion enzymes provided several advantages like that the cobalamin cofactor loading step required originally for the CP could be skipped enabling a significantly simpler protocol. Consequently, the biocatalytic demethylation was performed using Schlenk conditions allowing the O-demethylation e.g. of the monolignol coniferyl alcohol on a 25 mL scale leading to 75% conversion. The fusion enzyme represents a promising starting point to be evolved for alternative demethylation reactions to diversify natural products and to valorize lignin.Lignin-derived aryl methyl ethers (e.g. coniferyl alcohol, ferulic acid) are demethylated under anaerobic conditions using a cobalamin dependent fusion enzyme, which combines the cobalamin carrier protein and the methyltransferase. 相似文献
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Bratu Ovidiu Dragos R. Marcu Dan L. D. Mischianu Catalina Poiana Camelia C. Diaconu Simona G. Bungau Delia M. Tit Alin Cumpanas Roxana Bohiltea 《Archives of Medical Science》2022,18(4):881
Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic syndrome that occurs as result of an androgen receptor mutation; it affects the normal masculinization process in chromosomal male patients. More than 900 androgen receptor mutations that can lead to AIS have been identified. The complete androgen insensitivity is characterized by a total lack of response to androgens, usually in patients with 46XY karyotype but with feminine phenotype. Primary amenorrhoea and inguinal swellings in female patients are the main signs that could raise suspicion for this syndrome. Patients with partial androgen insensitivity have ambiguous genitalia at birth and gynecomastia during puberty, whereas those with mild androgen insensitivity present a normal male phenotype but altered spermatogenesis during adulthood and pubertal gynecomastia. The diagnosis of AIS often proves to be a challenge; its management is complex and requires a multidisciplinary approach to meet decision-making challenges in sex assignment, fertility and timing of gonadectomy, psychological outcomes and genetic counselling. 相似文献
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Emmanuel de Billy Marsha Pellegrino Domenico Orlando Giulia Pericoli Roberta Ferretti Pietro Businaro Maria Antonietta Ajmone-Cat Sabrina Rossi Lucia Lisa Petrilli Nicola Maestro Francesca Diomedi-Camassei Marco Pezzullo Cristiano De Stefanis Paola Bencivenga Alessia Palma Rossella Rota Francesca Del Bufalo Luca Massimi Gerrit Weber Chris Jones Andrea Carai Simona Caruso Biagio De Angelis Ignazio Caruana Concetta Quintarelli Angela Mastronuzzi Franco Locatelli Maria Vinci 《Neuro-oncology》2022,24(7):1150
BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG. 相似文献
77.
Silvia Ferri Bernardo Stefanini Lorenzo Mulazzani Margherita Alvisi Francesco Tovoli Simona Leoni Luca Muratori Tommaso Lotti Alessandro Granito Luigi Bolondi Fabio Piscaglia 《Nutrients》2022,14(12)
The role of moderate alcohol consumption in the evolution of NAFLD is still debated. The aim of this study is to evaluate the impact of current and lifelong alcohol consumption in patients with NAFLD. From 2015 to 2020, we enrolled 276 consecutive patients fulfilling criteria of NAFLD (alcohol consumption up to 140 g/week for women and 210 g/week for men). According to their current alcohol intake per week, patients were divided in: abstainers, very low consumers (C1: <70 g/week) and moderate consumers (C2). We created a new tool, called LACU (Lifetime Alcohol Consuming Unit) to estimate the alcohol exposure across lifetime: 1 LACU was defined as 7 alcohol units per week for 1 drinking year. Patients were divided into lifelong abstainers and consumers and the latter furtherly divided into quartiles: Q1-Q4. Stratification according to alcohol intake, both current and cumulative as estimated by LACU, showed that very low consumers (C1 and Q1-Q3) displayed lower frequency of cirrhosis and hepatocellular carcinoma compared to abstainers and moderate consumers (C2 and Q4). We can speculate that up to one glass of wine daily in the context of a Mediterranean diet may be a long-term useful approach in selected NAFLD patients. 相似文献
78.
Rosanna Palmeri Francesco Corallo Lilla Bonanno Simona Curr Paola Merlino Giuseppe Di Lorenzo Placido Bramanti Silvia Marino Viviana Lo Buono 《Medicine》2022,101(26)
Apathy and impulsiveness are 2 common non-motor symptoms in Parkinson disease that could occur in different periods or simultaneously. Apathy and impulsiveness could be interpreted as opposite extremes of a spectrum of motivated behavior dependent on dopaminergic dysfunction, in which, impulsivity, is a result of a hyperdopaminergic state, whereas apathy is viewed as a hypodopaminergic. The study aimed to investigate the presence of impulsiveness and other neuropsychiatric symptoms in Parkinson disease patients with apathy symptoms.Eighty-one patients with Parkinson disease were enrolled in this retrospective study. All subjects were evaluated by the Italian version of the Dimensional Apathy Scale and the Barratt Impulsiveness Scale-version 11, to assess, respectively, apathy and impulsiveness; they were divided into 2 groups (apathy and no apathy). All patients were administered also with questionnaires assessing depressive and anxious symptoms.Statistical analyses showed relevant results. In no-apathy group, education was a significant predictor on impulsiveness (attentional and motor) and apathy (executive and emotional); depression was a significant predictor on planning impulsivity and apathy.This study aimed to consider the importance of apathy and impulsivity in Parkinson disease. Although these are considered as opposite extremes of a spectrum of motivated behavior dependent on dopaminergic dysfunction, these can also occur separately. Moreover, several variables could represent important predictors of apathy and impulsiveness, such as depression. Future investigations should deepen the role of other demographics and psychological variables. 相似文献
79.
Maria Antonia De Francesco Claudio Poiesi Franco Gargiulo Carlo Bonfanti Patrizia Pollara Simona Fiorentini Francesca Caccuri Valentina Carta Lucia Mangeri Simone Pellizzeri Damiano Rizzoni Paolo Malerba Massimo Salvetti Maria Lorenza Muiesan Federico Alberici Francesco Scolari Andrea Pilotto Alessandro Padovani Arnaldo Caruso 《The Journal of infection》2021,82(4):e4-e7
80.
Danut Vai
iukynien Aras Kantautas Simona Tu
kut Fallon Manhanga Eugenijus Janavi
ius Ernestas Ivanauskas
ymantas Rudionis Aloyzas Gaudutis 《Materials》2021,14(10)
Concrete plants accumulate large amounts of concrete wash water. This water, which pH is highly alkaline, has a negative impact on the environment. Its reuse in fresh concrete slightly reduces its mechanical properties. The combination of concrete wash water and zeolitic by-product led to an increase of 4.6% in the compressive strength at 7 days hydration and up to 30% at 28 days hydration. The same combination led to the denser microstructure compared to the samples made with concrete wash water. This could be explained by the pozzolanic reaction of the zeolitic by-product. The complex chemical reactions of cement, zeolitic by-product, and fines presented in the concrete wash water occurred. Therefore, it was suggested the reusing method of concrete wash water together with zeolitic by-product in the fresh concrete mixtures by substituting some amount of tap water with concrete wash water. In this way, the consumption of tap water is possible to reduce in cement systems. 相似文献