Preliminary Studies Research Articles

Direct Access to Thio- and Seleno-acetamides Bearing (Benzo)thiazoles by a Base-Promoted One-Pot Two-Step Three-Component Reaction of 2-Amino(benzo)thiazoles with Aryl Acetyl Chlorides and Dichalcogenides.

Highly efficient and practical carbon-chalcogen (S, Se) and amide bonds formation methodologies for the synthesis of thio- and seleno-acetamides were developed, via the base-promoted one-pot two-step reactions of 2-amino(benzo)thiazoles and aryl acetyl chlorides with dichalcogenides. This cross-coupling reaction afforded the goal products that had been chalcogenated regioselectively in moderate to good yields. Further transformations of the new synthesized compounds, DFT calculations and preliminary mechanism studies are discussed as well.

Bioactivity of Raphanus Species against Agricultural Phytopathogens and its Role in Soil Remediation: A Review.

Phytopathogens and weeds represent around 20-40% of global agricultural productivity losses. Synthetic pesticide products are the most used to combat these pests, but it reiterates that their use has caused tremendous pressure on ecosystems' self-cleansing capacity and resistance development by pathogens to synthetic fungicides. In the last decades, researchers have demonstrated the vast biological properties of plants against pathogens and diseases. Raphanus species (Brassicaceae) possesses antimicrobial, antioxidant, anti-inflammatory, anticancer, hepatoprotective, antidiabetic, insecticidal, nematicidal, allelopathic, and phytoremediators properties. These are due to the presence of structurally diverse bioactive compounds, such as flavonoids and glucosinolates. In this review, we have provided an update on the biological properties of two Raphanus species (R. sativus and R. raphanistrum), detailing the type of natural product (extract or isolated compound), the bioassays displayed, and the results obtained for the main bioactivities of this genus cited in the literature during the last 30 years. Moreover, preliminary studies on phytopathogenic activities performed in our laboratory have also been depicted. We conclude that Raphanus species could be a source of natural bioactive molecules to treat phytopathogens and weeds that affect crops and remediate contaminated soils.

Berberine: Pharmacological Features in Health, Disease and Aging.

Berberine is the main active compound of different herbs and is defined as an isoquinoline quaternary botanical alkaloid found in barks and roots of numerous plants. It exhibits a wide range of pharmacological effects, such as anti-obesity and antidiabetic effects. Berberine has antibacterial activity against a variety of microbiota, including many bacterial species, protozoa, plasmodia, fungi, and trypanosomes. This review describes the role of berberine and its metabolic effects. It also discusses how it plays a role in glucose metabolism, fat metabolism, weight loss, how it modulates the gut microbiota, and what are its antimicrobial properties along with its potential side effects with maximal tolerable dosage. Representative studies were considered and analyzed from different scientific databases, including PubMed and Web of Science, for the years 1982-2022. Literature analysis shows that berberine affects many biochemical and pharmacological pathways that theoretically yield a positive effect on health and disease. Berberine exhibits neuroprotective properties in various neurodegenerative and neuropsychological ailments. Despite its low bioavailability after oral administration, berberine is a promising tool for several disorders. A possible hypothesis would be the modulation of the gut microbiome. While the evidence concerning the aging process in humans is more limited, preliminary studies have shown positive effects in several models. Berberine could serve as a potential candidate for the treatment of several diseases. Previous literature has provided a basis for scientists to establish clinical trials in humans. However, for obesity, the evidence appears to be sufficient for hands-on use.

Structure and Validation of a Kinematic Surface Simulation Model for the Direct Laser Writing Process

The article introduces the structure and validation of a kinematic surface simulation model for the replication of laser‐structured surfaces and their impressions after hot embossing. The surface replication is accomplished by the stepwise Boolean intersection of a structured and digitized point ablation with the workpiece. The resulting surface is characterized according to ISO 25178. Resulting from the kinematic simulation principle, the model can be applied to a wide range of material–machine combinations in the field of laser structuring and enables a time–efficient, nanometer‐resolved replication of representative surfaces with a size up to several square millimeters. Within the validation process it was proven that the main surface characteristics can be predicted by the model. Compared to AI approaches and numerical or multiphysical simulations, preliminary studies are only needed to a very small extent. Furthermore, complex influences such as material and temperature‐related properties do not need separate consideration as they are taken into account by the digitized point ablation.

Identification of Novel PPAR-β/δ Agonists from Kaempferol, Quercetin, and Resveratrol Derivatives by Targeting Cancer: An Integrative Molecular Docking and Dynamics Simulation Approach

Background: Drug resistance in cancer is a serious threat to human well-being. There is a dire need to develop novel and efficient lead molecules to treat the disease. In lieu of anti-cancer activities, Peroxisome proliferator–activated receptors (PPARs)-β/δ proven to be potential therapeutic targets against cancer. However, there are yet no PPAR-β/δ agonists reported for clinical use. Objective: The present study features in silico screening and identification of 8708 derivatives based on backbone of natural compounds like Kaempferol, Quercetin and Resveratrol against PPAR-β/δ using molecular docking, and molecular dynamics (MD) simulations. Methods: Initial screening of 8708 derivatives was done by recruiting Lipinski’s rule of five. Docking calculations were assessed through FlexX software tool. GROMACS was used to analyze dynamic perturbations and binding free energy (MM/GBSA) analysis of the top compounds. SwissADME was used to analyze pharmacokinetic properties. Results: The results of molecular docking indicated that 2-[2-(2,4-Dihydroxyphenyl)-2- oxoethoxy]benzoate (DOB), (E)-1-(3,4,5-Trihydroxyphenyl)-3-(3,4-dihydroxyphenyl) propene (TDP) and 2-Hydroxy-3-(2,6,7-trihydroxy-3-oxo-3H-xanthen-9-YL) benzoic acid (HTOB); respective derivatives of Kaempferol, Resveratrol and Quercetin strongly binds to the active site residues of PPAR-β/δ. Furthermore, ADME (absorption, distribution, metabolism & excretion) profile conferred their high druglikeness properties. On monitoring their dynamic perturbations, HTOB acquired the most favorable interaction and stability within the vicinity of PPAR-β/δ protein. Conclusion: These outcomes constitute preliminary studies and the obtained lead derivatives could be great options to treat various types of cancer and formulate as oral drug candidates.

A novel n-UV convertible colour-tunable emitting oxynitride phosphor: Realization based on Ce3+ -Tb3+ energy transfer.

In the present work, a novel n-UV convertible colour-tunable emitting phosphor was obtained based on the efficient Ce3+ -Tb3+ energy transfer in the Y10 Al2 Si3 O18 N4 host. By properly controlling the ratio of Ce3+ /Tb3+ , the colour hue of the obtained powder covered the blue and green regions, under excitation of 365 nm. The steady-state and dynamic-state luminescence measurement was performed to shed light on the related mechanism, which was justified by the electronic dipole-quadrupole dominating the related energy transfer process. Preliminary studies showed that Y10 Al2 Si3 O18 N4 :Ce3+ ,Tb3+ can be promising as an inorganic phosphor for white LED applications.

Mathematical modeling of dynamic processes of agricultural mobile energy vehicles on an electric drive

The article considers the issues of modeling the processes of agricultural mobile energy vehicles (MEV) with electric drive (ED). A review of modern literature on the problem under study as well as questions on modeling the functional properties of mobile machines and improving the quality indicators of MEV work are presented. A mathematical model of the motion of the MEV with an electric motor is presented, as well as a description of the method used and a sequence of actions for conducting research. Preliminary theoretical studies of motion in different modes of operation have been carried out. The proposed model is convenient for implementation and calculation in any of the applied software products that support the modeling of dynamic systems with an electromechanical drive. The proposed model, the solution of which is based on the methods of numerical integration of systems in the Matlab Simulink software environment, made it possible to simulate the dynamic processes of electromechanical power transmission of MEV during various agricultural operations. With the help of this model, the analysis of electromechanical processes in transient and steady-state operating modes, as well as dynamic processes in the power transmission were carried out. Graphs of changes in the studied parameters of the MEV power transmission are obtained and elastic moments in the joints of the 5-mass design scheme are determined. The use of the model allows you to track the change in statistical characteristics when the conditions of the experiment change. The model has shown its operability when performing simulation of agricultural operations: fertilization, cultivation and sowing, and it can be used at the design stage to study the characteristics of dynamic processes of small-class traction MEV power transmissions with an electromechanical drive. With different parameters of the model, there is a change in the mathematical expectation of the angular velocity of the ED from 147.89 to 156.87 rad/s, a change in the mathematical expectation of the speed of the MES from 4.51 to 4.79 m/s.

Removal of dyes from aqueous media using environmentally friendly aerogels based on chitosan

According to the World Health Organization, between 17% and 20% of water pollution is caused by dye treatments in the textile industry, which makes the development of efficient technologies for its removal essential. Environmentally friendly adsorbent materials, such as aerogels, can be effectively used in adsorption processes involving water remediation because of their high specific surface area and the possibility of an easy separation from the contaminated solutions. In this work, aerogels were obtained by a simple procedure that includes the cross-linking of chitosan with glutaraldehyde, followed by a freeze-drying step to eliminate water by water sublimation. The obtained aerogels presented low density (0.049–0.083 g/cm3), a three-dimensional skeletal structure that provides them with high porosity, acceptable swelling capacity and good dimensional stability. FTIR and X-Ray analysis were used to identify aerogels’ chemical structure and dynamic-mechanical analysis to complement the characterization of these materials. Selected formulations were also tested as adsorbents of Congo Red in aqueous media. The adsorption results demonstrated that the aerogels adsorption capacity strongly depended not only on the crosslinking agent content but also on the amount of chitosan in the initial solution used in their synthesis. Moreover, preliminary thermodynamic studies of the adsorption process indicate that both adsorption rate and aerogel sorption capacity increase with increasing temperature.

Development of a test bench for biomechanical simulation-a preliminary study of mandibular forces.

Purpose: The aim of this study is to develop a test bench, which integrates different complexity levels and enables in that way a flexible and dynamic testing for mid and long term intervals as well as testing of maximum loads till implant failure of different osteosynthesis systems on the mandible. Material and Methods: For this purpose, an analysis of the state of the art regarding existing test benches was combined with interviews of clinical experts to acquire a list of requirements. Based on these requirements a design for a modular test bench was developed. During the implementation of the test stand, functional tests were continuously carried out and improvements made. Depending on the level of complexity, the test bench can be used either as an incorporated variant or as a standalone solution. In order to verify the performance and the degree of fulfilment of the requirements of these two variants of the test bench, preliminary studies were carried out for all levels of complexity. In these preliminary studies, commercially available osteosynthesis and reconstruction plates were investigated for their biomechanical behaviour and compared with data from the literature. Results: In total, fourteen test runs were performed for the different levels of complexity. Firstly, five test runs were executed to test the simplified load scenario in the incorporated variant of the test bench. High forces could be transmitted without failure of the miniplates. Secondly a quasi-static test scenario was examined using the incorporated variant with simplified load insertion. Five experiments with a number of cycles between 40,896 and 100,000 cycles were carried out. In one case the quasi-static testing resulted in a fracture of the tested reconstruction plate with a failure mode similar to the clinical observations of failure. The last four test runs were carried out using the standalone variant of the test bench simulating complex load patterns via the insertion of forces through imitated muscles. During the test runs joint forces were measured and the amplitude and vector of the resulting joint forces were calculated for both temporomandibular joints. Differences in the force transmission depending on the implant system in comparison to the zero sample could be observed. Conclusion: The presented modular test bench showed to be applicable for examination of the biomechanical behavior of the mandible. It is characterized by the adjustability of the complexity regarding the load patterns and enables the subsequent integration of further sensor technologies. Follow-up studies are necessary to further qualify and optimize the test bench.

Free radical-promoted direct C–H silylation of pyrrolo[2,3-d]pyrimidine derivatives with hydrosilanes

A transition metal-free direct C–H silylation of pharmaceutically relevant pyrrolo[2,3-d]pyrimidine (7-DAPs) derivatives with hydrosilanes has been developed via a radical reaction. This protocol provides the divergent silylated 7-DAPs in moderate to good yields with good regioselectivity. The protocol features operational simplicity, broad substrate scope and the use of safe and readily available LPO (Lauroyl peroxide) as the radical initiators. Preliminary mechanistic studies suggest that the induced silyl radical is involved in this transformation.

Genome scale metabolic network modelling for metabolic profile predictions.

Metabolic profiling (metabolomics) aims at measuring small molecules (metabolites) in complex samples like blood or urine for human health studies. While biomarker-based assessment often relies on a single molecule, metabolic profiling combines several metabolites to create a more complex and more specific fingerprint of the disease. However, in contrast to genomics, there is no unique metabolomics setup able to measure the entire metabolome. This challenge leads to tedious and resource consuming preliminary studies to be able to design the right metabolomics experiment. In that context, computer assisted metabolic profiling can be of strong added value to design metabolomics studies more quickly and efficiently. We propose a constraint-based modelling approach which predicts in silico profiles of metabolites that are more likely to be differentially abundant under a given metabolic perturbation (e.g. due to a genetic disease), using flux simulation. In genome-scale metabolic networks, the fluxes of exchange reactions, also known as the flow of metabolites through their external transport reactions, can be simulated and compared between control and disease conditions in order to calculate changes in metabolite import and export. These import/export flux differences would be expected to induce changes in circulating biofluid levels of those metabolites, which can then be interpreted as potential biomarkers or metabolites of interest. In this study, we present SAMBA (SAMpling Biomarker Analysis), an approach which simulates fluxes in exchange reactions following a metabolic perturbation using random sampling, compares the simulated flux distributions between the baseline and modulated conditions, and ranks predicted differentially exchanged metabolites as potential biomarkers for the perturbation. We show that there is a good fit between simulated metabolic exchange profiles and experimental differential metabolites detected in plasma, such as patient data from the disease database OMIM, and metabolic trait-SNP associations found in mGWAS studies. These biomarker recommendations can provide insight into the underlying mechanism or metabolic pathway perturbation lying behind observed metabolite differential abundances, and suggest new metabolites as potential avenues for further experimental analyses.

Antisocial personality disorder and therapeutic pessimism - how can mentalization-based treatment contribute to an increased therapeutic optimism among health professionals?

Antisocial personality disorder (ASPD) is associated with therapeutic pessimism among health professionals. Several variables are associated with obstacles in therapist's willingness to treat ASPD. Variables that are relevant are (i) confusion associated with the term ASPD, (ii) characteristics of the disorder, (iii) attitudes, experiences, and knowledge clinicians possess, and (iv) insufficient management of countertransference. We assume that therapeutic pessimism is related to the lack of evidence-based, effective treatment for individuals with ASPD. This is problematic because ASPD is associated with large socio-economic costs and considerable suffering for the individual and the society. Mentalization-based treatment (MBT) was developed in treating borderline personality disorder (BPD) and is now considered an effective treatment for this group. Mentalization is defined as the process by which individuals make sense of themselves and others in terms of subjective states and mental processes. This ability affects an individual's psychological functioning, mental health, self-organization, and interpersonal relationships. The overall goal of MBT is to strengthen the individual's mentalizing abilities and facilitate more adaptive handling of problematic, internal states. Recently, a version of MBT tailored for individuals with ASPD (MBT-ASPD) has been developed. The purpose of this review is to investigate how MBT-ASPD relates to the major obstacles that contribute to the therapeutic pessimism toward this group. Despite a limited evidence base, preliminary studies indicate promising results for MBT-ASPD. More research is still required, this review suggests MBT-ASPD can contribute to increased therapeutic optimism and demonstrate specific characteristics of MBT-ASPD that contribute to management of therapeutic pessimism.

Developing Biarylhemiboronic Esters for Biaryl Atropisomer Synthesis via Dynamic Kinetic Atroposelective Suzuki-Miyaura Cross-Coupling.

We herein introduce biarylhemiboronic esters as a new type of bridged biaryl reagent for asymmetric synthesis of axially chiral biaryl structures, and the palladium-catalyzed asymmetric Suzuki-Miyaura cross-coupling of biarylhemiboronic esters is developed. This dynamic kinetic atroposelective coupling reaction exhibits high enantioselectivity, good functional group tolerance, and a broad substrate scope. The synthetic application of the current method was demonstrated by transformations of the product and a programmed synthesis of chiral polyarene. Preliminary mechanistic studies suggested that the reaction proceeded via an enantio-determining dynamic kinetic atroposelective transmetalation step.

Radiation protection aspects in the design of a Boron Neutron Capture Therapy irradiation room

Boron Neutron Capture Therapy (BNCT) is a radiotherapy whose effect is due to the combination of low-energy neutron irradiation prior chemical targeting of tumour tissues with boron-10. The context of this work is the design of a clinical BNCT facility based on a Radio-Frequency Quadrupole proton accelerator, manufactured by the Italian National Institute of Nuclear Physics (INFN). Such a machine can provide a neutron beam suitable for the treatment of deep-seated tumours when coupled to a beryllium target and a Beam Shaping Assembly whose main constituent is densified lithiated aluminium fluoride. This paper refines the design of the facility, already addressed in preliminary studies, from the point of view of dosimetric quantities in the room and in the patient. The presented calculations have been performed with different Monte Carlo codes, and assess the time evolution of the dose due to the neutron activation of the irradiated materials. A comprehensive evaluation of the dose absorbed in the healthy organs of the patient is provided, with focus on the residual radioactivity of the patient urine, for three different treatment positions. Borated concrete is confirmed to be the best material for constructing the walls of the treatment room. A lead shielding at the beam-port is proposed to reduce the gamma dose at the irradiation position due to the activation of the Beam Shaping Assembly.

The Effect of Religious-Spiritual Education and Care on the Quality of Life of Iranian Women: A Systematic Review and Meta-Analysis.

So far, several preliminary studies have been conducted on the effect of religious-spiritual education and care on the quality of life of women in different parts of Iran. Therefore, the current study aims to explore the effect of religious-spiritual education and care on the quality of life of Iranian women through systematic review and meta-analysis. Databases searched for studies related to the research objective include SID, MagIran, Embase, PubMed, Scopus, WoS, and Google Scholar. The search was performed using keywords linked to and validated with MeSH/Emtree with no time limit until April 2022. The I2 index was used to calculate the heterogeneity of the studies and the random effects model was used to combine the data and perform the meta-analysis. Finally, 14 articles with a sample size of 295 intervention group and 288 control group were included in the meta-analysis. The mean score of the quality of life after the intervention showed a significant increase of 1.87 ± 0.29 (95% confidence interval) per unit (P < 0.001). Meta-regression results showed that with the increasing year of study and age, the standardized mean difference decreased and with increasing the number of intervention sessions, this difference increased (P < 0.05). The results of this study show that religious-spiritual education and care significantly increase the quality of life of Iranian women. Therefore, it seems that the use of religious-spiritual education and care can be part of the program to increase the quality of life of women.

Regioselective Alkynylation and Alkenylation at the More Hindered C-B Bond of 1,2-Bis(Boronic) Esters.

Selective transformations at the more sterically hindered sites of organic molecules represent a frontier in the ability to precisely modify molecules. The lack of effective synthetic methods stands in stark contrast to the large number of encumbered sites encountered in molecules of interest. Here, we demonstrate that 1,2-bis(boronates) undergo selective alkynylation and alkenylation at the more sterically hindered C-B bond. Our preliminary mechanistic studies disclosed that this reaction can proceed through two convergent pathways involving direct coupling of sterically encumbered site versus 1,2-boron migratory coupling. Notably, this method facilitated convenient access to alkenyl and alkynyl boron products, which can be diversified by an array of transformations.

Potential of an Isolated Bacteriophage to Inactivate Klebsiella pneumoniae: Preliminary Studies to Control Urinary Tract Infections.

Urinary tract infections (UTIs) caused by resistant Klebsiella pneumoniae can lead to severe clinical complications and even death. An alternative treatment option for infected patients is using bacteriophages. In the present study, we isolated phage VB_KPM_KP1LMA (KP1LMA) from sewage water using a K. pneumoniae strain as a host. Whole-genome analysis indicated that the genome was a double-stranded linear 176,096-bp long DNA molecule with 41.8% GC content and did not contain virulence or antibiotic resistance genes. The inactivation potential of phage KP1LMA was assessed in broth at an MOI of 1 and 10, and a maximum inactivation of 4.9 and 5.4 log CFU/mL, respectively, was observed after 9 h. The efficacy at an MOI of 10 was also assessed in urine to evaluate the phage's performance in an acidic environment. A maximum inactivation of 3.8 log CFU/mL was observed after 9 h. The results suggest that phage KP1LMA could potentially control a UTI caused by this strain of K. pneumoniae, indicating that the same procedure can be used to control UTIs caused by other strains if new specific phages are isolated. Although phage KP1LMA has a narrow host range, in the future, efforts can be made to expand its spectrum of activity and also to combine this phage with others, potentially enabling its use against other K. pneumoniae strains involved in UTIs.

Alendronate-Grafted Nanoemulsions for Bone-Targeted Vincristine Delivery: Preliminary Studies on Cell and Animal Models.

Bone is a site of distant metastases, which are a common cause of morbidity and mortality with a high socio-economic impact, for many malignant tumours. In order to engineer pharmacological therapies that are suitable for this debilitating disease, this experimental work presents injectable lipid nanoemulsions, which are endowed with a long history of safe clinical usage in parenteral nutrition, their loading with vincristine and their grafting with alendronate, with a dual purpose: merging the anticancer activity of bisphosphonates and vincristine, and enhancing bone-targeted delivery. In cell studies, alendronate synergised with the anti-migration activity of vincristine, which is important as migration plays a key role in the metastatisation process. In preliminary animal studies, carried out thanks to IVIS technology, alendronate conjugation enhanced the bone targeting of fluorescently labelled nanoemulsions. These encouraging results will drive further studies on suitable animal models of the disease.

Palladium-Catalyzed α-Arylation of Meyers’s Chiral Bicyclic Lactams and a Deprotonative Ring-Opening Sideline

AbstractDescribed is a deprotonative α-arylation reaction of Meyers’s chiral bicyclic lactams (MCBLs) under palladium catalysis, and a substrate-dependent post-transformation. When the bridgehead carbon of the MCBLs is substituted with a methyl or an ethyl group, the initial arylation product undergoes a further rearrangement reaction to give a conjugated framework. On the other hand, substrates bearing a bridgehead isopropyl or aryl group are converted into the corresponding exo-arylation products. Preliminary studies indicated that the rearrangement pathway was promoted by deprotonation and was independent of palladium catalysis. In addition to mechanistic interests, this study demonstrates a modular and divergent synthesis of functionalized lactams.

Probing hydrogen content in steel using the thermoelectric effect

The issue of hydrogenation of steel is a serious technological problem. Due to its small atomic radius, hydrogen is difficult to analyze quantitatively and qualitatively. Non-destructive estimation of hydrogen content would significantly improve the quality control process. In this work, we attempt to develop a new methodology for the determination of hydrogen content in 4340 steel using the thermoelectric effect. For this purpose, we investigated the mechanisms of hydrogenation, structural and microstructural changes caused by hydrogenation, and performed theoretical calculations of the influence of hydrogen on the electronic structure of steel. Measurements of the Seebeck coefficient were performed using the specially developed μm-resolution scanning thermoelectric microscope (SThM). The KKR-CPA calculations show that hydrogen located at T-voids strongly modifies electronic properties and influences the Seebeck coefficient of the material. Ultraviolet photoelectron spectroscopy (UPS) proves that hydrogenated samples exhibit the valence band onset shift towards higher binding energies concerning the non-hydrogenated materials. Theoretical and experimental studies of the Seebeck coefficient dependence on the total hydrogen content confirm a measurable decrease in the Seebeck coefficient (18.5 µV/K for 0.136 ppm and 13.5 µV/K for 1.03 ppm). Plotted calibration curves for 4340 steel were used for preliminary kinetic studies of the spontaneous dehydrogenation in this material. This work demonstrates that the thermoelectric effect can be used as the basis of a new fast and non-destructive analytical method for the determination of the hydrogen content in 4340 steel.