The Exploitation of Sodium Deoxycholate-Stabilized Nano-Vesicular Gel for Ameliorating the Antipsychotic Efficiency of Sulpiride.

The present study explored the effectiveness of bile-salt-based nano-vesicular carriers (bilosomes) for delivering anti-psychotic medication, Sulpiride (Su), via the skin. A response surface methodology (RSM), using a 33 Box-Behnken design (BBD) in particular, was employed to develop and optimize drug-loaded bilosomal vesicles. The optimized bilosomes were assessed based on their vesicle size, entrapment efficiency (% EE), and the amount of Sulpiride released. The Sulpiride-loaded bilosomal gel was generated by incorporating the optimized Su-BLs into a hydroxypropyl methylcellulose polymer. The obtained gel was examined for its physical properties, ex vivo permeability, and in vivo pharmacokinetic performance. The optimum Su-BLs exhibited a vesicle size of 211.26 ± 10.84 nm, an encapsulation efficiency of 80.08 ± 1.88% and a drug loading capacity of 26.69 ± 0.63%. Furthermore, the use of bilosomal vesicles effectively prolonged the release of Su over a period of twelve hours. In addition, the bilosomal gel loaded with Su exhibited a three-fold increase in the rate at which Su transferred through the skin, in comparison to oral-free Sulpiride. The relative bioavailability of Su-BL gel was almost four times as high as that of the plain Su suspension and approximately two times as high as that of the Su gel. Overall, bilosomes could potentially serve as an effective technique for delivering drugs through the skin, specifically enhancing the anti-psychotic effects of Sulpiride by increasing its ability to penetrate the skin and its systemic bioavailability, with few adverse effects.

A general and robust Ni-based nanocatalyst for selective hydrogenation reactions at low temperature and pressure.

Catalytic hydrogenations are important and widely applied processes for the reduction of organic compounds both in academic laboratories and in industry. To perform these reactions in sustainable and practical manner, the development and applicability of non-noble metal-based heterogeneous catalysts is crucial. Here, we report highly active and air-stable nickel nanoparticles supported on mesoporous silica (MCM-41) as a general and selective hydrogenation catalyst. This catalytic system allows for the hydrogenation of carbonyl compounds, nitroarenes, N-heterocycles, and unsaturated carbon─carbon bonds in good to excellent selectivity under very mild conditions (room temperature to 80°C, 2 to 10 bar H2). Furthermore, the optimal nickel/meso-silicon dioxide catalyst is reusable (4 cycles) without loss of its catalytic activity.

Streamlining the synthesis of amides using Nickel-based nanocatalysts.

The synthesis of amides is a key technology for the preparation of fine and bulk chemicals in industry, as well as the manufacture of a plethora of daily life products. Furthermore, it constitutes a central bond-forming methodology for organic synthesis and provides the basis for the preparation of numerous biomolecules. Here, we present a robust methodology for amide synthesis compared to traditional amidation reactions: the reductive amidation of esters with nitro compounds under additives-free conditions. In the presence of a specific heterogeneous nickel-based catalyst a wide range of amides bearing different functional groups can be selectively prepared in a more step-economy way compared to previous syntheses. The potential value of this protocol is highlighted by the synthesis of drugs, as well as late-stage modifications of bioactive compounds. Based on control experiments, material characterizations, and DFT computations, we suggest metallic nickel and low-valent Ti-species to be crucial factors that makes this direct amide synthesis possible.

Thoracic Aortic Aneurysm Presenting as a Subacute Cough.

The suprasternal aortic notch cardiac point of care ultrasound (POCUS) window is a useful view for evaluating thoracic aortic pathologies. However, it is not routinely included in the standard cardiac POCUS exam despite its ability to capture emergent pathologies such as aortic dissection and thoracic aortic aneurysm (TAA). Ruptured aortic aneurysms can present with sudden, severe chest or back pain, as well as hemodynamic instability, resulting in a high mortality. We present an atypical case of a patient with hemoptysis who was found to have a contained aortic rupture. In this case, POCUS, specifically the suprasternal aortic notch view, was used to expedite definitive care.

Comparative Study of Commercial Silica and Sol-Gel-Derived Porous Silica from Cornhusk for Low-Temperature Catalytic Methane Combustion.

The synthesis and characterization of sol-gel-derived cornhusk support for low-temperature catalytic methane combustion (LTCMC) were investigated in this study. The prepared cornhusk support was impregnated with palladium and cerium oxide (Pd/CeO2) via the classical incipient wetness method. The resulting catalyst was characterized using various techniques, including X-ray diffraction (XRD), N2 physisorption (BET), transmission electron microscopy (TEM), and hydrogen temperature-programmed reduction (H2-TPR). The catalytic performance of the Pd/CeO2/CHSiO2 catalyst was evaluated for methane combustion in the temperature range of 150-600 °C using a temperature-controlled catalytic flow reactor, and its performance was compared with a commercial catalyst. The results showed that the Pd/CeO2 dispersed on SiO2 from the cornhusk ash support (Pd/CeO2/CHSiO2) catalyst exhibited excellent catalytic activity for methane combustion, with a conversion of 50% at 394 °C compared with 593 °C for the commercial silica catalyst (Pd/CeO2/commercial). Moreover, the Pd/CeO2/CHSiO2 catalyst displayed better catalytic stability after 10 h on stream, with a 7% marginal loss in catalytic activity compared with 11% recorded for the Pd/CeO2/commercial catalyst. The N2 physisorption and H2-TPR results indicated that the cornhusk SiO2 support possessed a higher surface area and strong reducibility than the synthesized commercial catalyst, contributing to the enhanced catalytic activity of the Pd/CeO2/SiO2 catalyst. Overall, the SiO2 generated from cornhusk ash exhibited promising potential as a low-cost and environmentally friendly support for LTCMC catalysts.

A practical concept for catalytic carbonylations using carbon dioxide.

The rise of CO2 in atmosphere is considered as the major reason for global warming. Therefore, CO2 utilization has attracted more and more attention. Among those, using CO2 as C1-feedstock for the chemical industry provides a solution. Here we show a two-step cascade process to perform catalytic carbonylations of olefins, alkynes, and aryl halides utilizing CO2 and H2. For the first step, a novel heterogeneous copper 10Cu@SiO2-PHM catalyst exhibits high selectivity (≥98%) and decent conversion (27%) in generating CO from reducing CO2 with H2. The generated CO is directly utilized without further purification in industrially important carbonylation reactions: hydroformylation, alkoxycarbonylation, and aminocarbonylation. Notably, various aldehydes, (unsaturated) esters and amides are obtained in high yields and chemo-/regio-selectivities at low temperature under ambient pressure. Our approach is of interest for continuous syntheses in drug discovery and organic synthesis to produce building blocks on reasonable scale utilizing CO2.

Oxygen vacancies in Ru/TiO2 - drivers of low-temperature CO2 methanation assessed by multimodal operando spectroscopy.

Hydrogenation of CO2 is very attractive for transforming this greenhouse gas into valuable high energy density compounds. In this work, we developed a highly active and stable Ru/TiO2 catalyst for CO2 methanation prepared by a solgel method that revealed much higher activity in methanation of CO2 (ca. 4-14 times higher turnover frequencies at 140-210°C) than state-of-the-art Ru/TiO2 catalysts and a control sample prepared by wetness impregnation. This is attributed to a high concentration of O-vacancies, inherent to the solgel methodology, which play a dual role for 1) activation of CO2 and 2) transfer of electrons to interfacial Ru sites as evident from operando DRIFTS and in situ EPR investigations. These results suggest that charge transfer from O-vacancies to interfacial Ru sites and subsequent electron donation from filled metal d-orbitals to antibonding orbitals of adsorbed CO are decisive factors in boosting the CO2 methanation activity.

Quaternary diagnostics scheme for mucolipidosis II and detection of novel mutation in GNPTAB gene.

BACKGROUND: Mucolipidosis II (ML II α/ß) is an inherited lysosomal storage disorder caused by deficiency of GlcNAc-phosphotransferase enzyme and results in mis-targeting of multiple lysosomal enzymes. Affected patients are characterized by skeletal deformities and developmental delay. Homozygous or compound heterozygous mutations in GNPTAB gene are associated with the clinical presentation. This is the first study to characterize the underlying genetics of ML among a cohort of Egyptian patients. ML II diagnosis established by clinical assessment, biochemical evaluation of enzymes, electron microscopy examination of gingival inclusion bodies, and molecular study of GNPTAB gene using targeted next-generation sequencing panel in 8 patients form 8 unrelated Egyptian families. RESULTS: Sequencing revealed 3 mutations in GNPTAB gene; 1 novel frame-shift mutation in exon 19 (c.3488_3488delC) and 2 previously reported mutations (c.1759C>T in exon 13 and c.3503_3504delTC in exon 19). All patients were homozygous for their corresponding mutations and the parents were consanguineous. CONCLUSIONS: According to the established quaternary diagnostic scheme, ML II was the final diagnosis in eight patients. The most common mutation was the frame shift c.3503_3504delTC mutation, found in 5 patients and associated with a severe phenotype.

Epigenetic effects toward new insights as potential therapeutic target in B-thalassemia.

BACKGROUND: Fetal hemoglobin (HbF) induction has shown promise for the treatment of ß-hemoglobinopathies. HbF induction in ß-thalassemia could overcome ineffective hematopoiesis and thus terminate transfusion dependency for formerly transfusion dependant patients. Several miRNAs have been found to reactivate γ-globin expression and increase HbF. In this study, we aimed to investigate the expression of 4 miRNAs (miR-15a, miR-16-1, miR-96, and miR-486-3p) in high HbF thalassemia patients and correlate their levels with the patients' HbF levels then, in order to predict the exact role of the studied miRNAs in hematopoiesis, a bioinformatic analysis was carried out. We went through this bioinformatic analysis to determine the network of genes regulated by miRNAs and further investigate the interaction between all of them through their involvement in hematopoiesis. In this study, the differential expression was measured by qRT-PCR for 40 patients with high HbF and compared to 20 healthy controls. Bioinformatics was conducted involving functional annotation and pathway enrichment analyses. RESULTS: The studied microRNAs were significantly deregulated in thalassemia patients in correlation with HbF. Functional annotation and pathway enrichment analyses revealed a major role of miR-486-3p and miR-15a in HbF induction. CONCLUSION: MiR-486-3p and miR-15a are crucial for HbF induction. Further validating studies are needed.

Effect of Formaldehyde in Selective Catalytic Reduction of NOx by Ammonia (NH3-SCR) on a Commercial V2O5-WO3/TiO2 Catalyst under Model Conditions.

The impact of formaldehyde (HCHO, formed in vehicle exhaust gases by incomplete combustion of fuel) on the performance of a commercial V2O5-WO3/TiO2 catalyst in NH3-SCR of NOx under dry conditions has been analyzed in detail by catalytic tests, in situ FTIR and transient studies using temporal analysis of products (TAP). HCHO reacts preferentially with NH3 to a formamide (HCONH2) surface intermediate. This deprives NH3 partly from its desired role as a reducing agent in the SCR and diminishes NO conversion and N2 selectivity. Between 250 and 400 °C, HCONH2 decomposes by dehydration (major pathway) and decarbonylation (minor pathway) to liberate toxic HCN and CO, respectively. HCN was proven to be oxidized by lattice oxygen of the catalyst to CO2 and NO, which enters the NH3-SCR reaction.

A State-of-the-Art Heterogeneous Catalyst for Efficient and General Nitrile Hydrogenation.

Cobalt-doped hybrid materials consisting of metal oxides and carbon derived from chitin were prepared, characterized and tested for industrially relevant nitrile hydrogenations. The optimal catalyst supported onto MgO showed, after pyrolysis at 700 °C, magnesium oxide nanocubes decorated with carbon-enveloped Co nanoparticles. This special structure allows for the selective hydrogenation of diverse and demanding nitriles to the corresponding primary amines under mild conditions (e.g. 70 °C, 20 bar H2 ). The advantage of this novel catalytic material is showcased for industrially important substrates, including adipodinitrile, picolinonitrile, and fatty acid nitriles. Notably, the developed system outperformed all other tested commercial catalysts, for example, Raney Nickel and even noble-metal-based systems in these transformations.

Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the common lethal types of tumor all over the world. The lethality of HCC accounts for many reasons. One of them, the lack of reliable diagnostic markers at the early stage, in this context, serum miRNAs became promising diagnostic biomarkers. Herein, we aimed to identify the predictive value of two miRNAs (miR-122 and miR-224) in plasma of patients with HCC preceded by chronic HCV infection. Taqman miRNA assays specific for hsa-miR-122 and hsa-miR-224 were used to assess the expression levels of the chosen miRNAs in plasma samples collected from three groups; 40 patients with HCC related to HCV, 40 with CHC patients and 20 healthy volunteers. This study revealed that the mean plasma values of miRNA-122 were significantly lower among HCC group when compared to CHC and control groups (P < 0.001). Whereas, miR-224 mean plasma values were significantly higher among HCC group when compared to both CHC group and control group. Moreover, it was found that miR-122 can predict development of HCC at cut-off value <0.67 (RQ) and (AUC = 0.98, P < 0.001). As regards miR-224, it can predict development of HCC at cut-off value >1.2 (RQ) and (AUC = 0.93, P < 0.001), while the accuracy of AFP to diagnose HCC was (AUC: 0.619; P = 0.06). In conclusion, the expression plasma of miR-122 and miR-224 could be used as noninvasive biomarkers for the early prediction of developing HCC at the early stage.