bluuebunny/crossref_metadata_2025 huggingface dataset:
NF-kB in Signaling Patterns and Its Temporal Dynamics Encode/Decode Human Diseases
Authors: Almowallad Sanaa , Alqahtani Leena S. , Mobashir Mohammad
Published: December 2022

Defects in signaling pathways are the root cause of many disorders. These malformations come in a wide variety of types, and their causes are also very diverse. Some of these flaws can be brought on by pathogenic organisms and viruses, many of which can obstruct signaling processes. Other illnesses are linked to malfunctions in the way that cell signaling pathways work. When thinking about how errors in signaling pathways might cause disease, the idea of signalosome remodeling is helpful. The signalosome may be conveniently divided into two types of defects: phenotypic remodeling and genotypic remodeling. The majority of significant illnesses that affect people, including high blood pressure, heart disease, diabetes, and many types of mental illness, appear to be caused by minute phenotypic changes in signaling pathways. Such phenotypic remodeling modifies cell behavior and subverts normal cellular processes, resulting in illness. There has not been much progress in creating efficient therapies since it has been challenging to definitively confirm this connection between signalosome remodeling and illness. The considerable redundancy included into cell signaling systems presents several potential for developing novel treatments for various disease conditions. One of the most important pathways, NF-κB, controls several aspects of innate and adaptive immune responses, is a key modulator of inflammatory reactions, and has been widely studied both from experimental and theoretical perspectives. NF-κB contributes to the control of inflammasomes and stimulates the expression of a number of pro-inflammatory genes, including those that produce cytokines and chemokines. Additionally, NF-κB is essential for controlling innate immune cells and inflammatory T cells’ survival, activation, and differentiation. As a result, aberrant NF-κB activation plays a role in the pathogenesis of several inflammatory illnesses. The activation and function of NF-κB in relation to inflammatory illnesses was covered here, and the advancement of treatment approaches based on NF-κB inhibition will be highlighted. This review presents the temporal behavior of NF-κB and its potential relevance in different human diseases which will be helpful not only for theoretical but also for experimental perspectives.
Tribological Properties of Polydopamine-Modified Ag as Lubricant Oil Additives
Authors: Zhang Yanxin , Cheng Jun , Lu Changfeng , Chen Hao , Xie Guoxin , Zhang Lin , Luo Jianbin
Published: December 2022

Nanoparticles agglomerate easily because of their high surface energy, which seriously reduces their tribological properties as lubricant additives. In this work, the core-shell nanoparticles Ag@polydopamine (PDA) were successfully prepared by the self-oxidation of dopamine hydrochloride on the surface of Ag nanoparticles and the dispersion of Ag nanoparticles in PAO6 was improved to promote anti-wear behaviors. The tribological properties of Ag@PDA nanocomposites as additives in poly alpha olefin (PAO) oil were studied under different concentrations, pressure and speed conditions by UMT-5 tribometer. It was demonstrated that the strong electrostatic repulsion of the PDA structure made the Ag nanoparticles better dispersed in PAO oil, thus playing a better lubricating role. When the concentration of the modified nanoparticles was 0.25 wt%, the friction coefficient of the lubricating oil decreased by 18.67% and no obvious wear was observed on the friction pair surface. When the Ag@PDA content was higher than 0.25 wt%, the tribological performance of the lubricating oil was weakened, which may be due to excessive Ag@PDA acting as an abrasive on the friction surface, thereby increasing friction and wear. The friction coefficient of the lubricating oil containing Ag@PDA decreased with the increase in load, but hardly changed with the increase in frequency.
N,N′-4,5-Dimethoxy-1,2-phenylenebis(salicylideneiminato)nickel(II)
Authors: Smirnova Evgenia , Baichurin Ruslan , Viktorov Nikolai , Spiridonova Dar’ya , Timonov Alexander , Karushev Mikhail
Published: December 2022

The title compound, which is potentially interesting as a building block for electrochemically active metallopolymers, was synthesized and characterized by single-crystal X-ray diffraction, IR and NMR spectroscopies.
Stability, Hopf Bifurcation and Optimal Control of Multilingual Rumor-Spreading Model with Isolation Mechanism
Authors: Yu Shuzhen , Yu Zhiyong , Jiang Haijun
Published: December 2022

The propagation of rumors on online social networks (OSNs) brings an awful lot of trouble to people’s life and society. Aiming at combating rumors spreading on OSNs, two novel rumor-propagation models without and with time delays are proposed, which combine with the influence of the immune mechanism, isolation mechanism and network structure. Firstly, we analyze the existence of rumor equilibria and obtain some existence conditions of backward bifurcation. Secondly, the local stabilities of rumor-free and rumor equilibria are proved by using the Jacobian matrix method, and some critical conditions for the existence of Hopf bifurcation are acquired by selecting critical parameters and delays as bifurcation parameters. Furthermore, an optimal control method is proposed, which can prevent the spread of rumors within an expected time period and minimize the cost of control. Finally, some numerical simulations are provided to verify the effectiveness of the proposed theoretical results.
Three-Stage-Impulse Control of Memristor-Based Chen Hyper-Chaotic System
Authors: Xie Xianyang , Wen Shiping , Feng Yuming , Onasanya Babatunde Oluwaseun
Published: December 2022

In this paper, on the basis of the three-dimensional Chen system, a smooth continuous nonlinear flux-controlled memristor model is used as the positive feedback term of this system, a hyper-chaotic circuit system is successfully constructed, and a simulated equivalent circuit is built for simulation using Multisim software, which agrees with the numerical simulation results by comparison. Meanwhile, a new impulsive control mode called the three-stage-impulse is put forward. It is a cyclic system with three components: continuous inputs are exerted in the first and third parts of the cycle while giving no input in the second part of the cycle, an impulse is exerted at the end of each continuous subsystem, the controller is simple in structure and effective in stabilizing most existing nonlinear systems. The Chen hyper-chaotic system will be controlled based on the three-stage-impulse control method combined with the Lyapunov stability principle. At the end of this paper, we have employed and simulated a numerical example; the experimental results show that the controller is effective for controlling and stabilizing the newly designed hyper-chaotic system.
A Bibliometric Study on Trends in Proton Exchange Membrane Fuel Cell Research during 1990–2022
Authors: Deng Zhijun , Li Baozhu , Gong Jinqiu , Zhao Chen
Published: December 2022

Proton exchange membrane fuel cell (PEMFC) with high density and safe reliability has been extensively studied in the world. With the circumstance of extensive PEMFC research, in this study we carried out a bibliometric analysis to understand the technological development. The information of 17,769 related publications from 1990 to 2022 was retrieved from the Web of Science Core Collection for bibliometric analysis based on the VOSviewer tool. The results show that the International Journal of Hydrogen Energy dominates among all of the source journals. The closest collaboration is between China and the USA, and publications from both of those account for 53.9% of the total. In terms of institutions, the Chinese Academy of Sciences has prolific publications, in which representative groups, such as Shao Zhigang’s, have achieved many outputs in this field. The theme of PEMFC research can be divided into three aspects: “materials”, “design” and “mechanisms”. This study demonstrated overall mapping knowledge domain and systematic analysis, and contributed to making a guide for researchers on the progress and trends of PEMFC.
Gender Disparity in the Wake of the Pandemic: Examining the Increased Mental Health Risks of Substance Use Disorder and Interpersonal Violence for Women
Authors: Perham-Lippman Karen
Published: December 2022

The global COVID-19 pandemic has profoundly impacted women compared to men in the workplace, creating gender disparity associated with mental health. In occupational fields where women comprise nearly three quarters of the workforce, outcomes of increased depression and psychological distress have resulted, creating even greater gender disparity in terms of mental health risks. These include an exponential increase in substance use associated with mental health issues for which continued stigma and negative perceptions of mental health conditions and substance use have prevented the pursuit of treatment. Further, the increased occurrence of interpersonal violence experienced by women during COVID-19 also presents considerable comorbidity with mental health issues. Research also shows a significant relationship for women between severe intimate partner violence and substance use. It is imperative that gender disparity associated with mental health risks be addressed within the current crisis and that we better prepare for the future to ensure inclusive and accessible resources within workplaces and improved behavioral health outcomes.
Metal Crystal/Polycrystal Plasticity and Strengths
Authors: Armstrong Ronald W.
Published: December 2022

A brief historical sketch is given of Taylor’s dislocation density-based model description, leading to the prediction of a parabolic, tensile, stress–strain curve for the plastic deformation of aluminum. The present focus is on additional results or analyses obtained on the subject for crystal/polycrystal strain hardening. Our current understanding of such material behavior is attributed to post-Taylor descriptions of sequential deformation stages in stress–strain measurements that are closely tied to specific dislocation interaction and reaction mechanisms. A schematic comparison is given for individual face-centered cubic (fcc), body-centered cubic (bcc), and hexagonal close-packed (hcp) crystal curves and to related strength properties determined for individual crystals and polycrystalline material. For the fcc case, an example sessile dislocation reaction is described based on a stereographic projection. Then, quantitative constitutive-relation-based assessments are presented for the tensile strain hardening leading to the plastic instability behaviors of copper and tantalum materials.
Highly Efficient Biotransformation and Production of Selenium Nanoparticles and Polysaccharides Using Potential Probiotic Bacillus subtilis T5
Authors: Duan Yuhua , Li Mengjun , Zhang Sishang , Wang Yidan , Deng Jieya , Wang Qin , Yi Tian , Dong Xingxing , Cheng Shuiyuan , He Yi , Gao Chao , Wang Zhangqian
Published: December 2022

Selenium is an essential microelement required for human health. The biotransformation of selenium nanoparticles has attracted increasing attention in recent years. However, little of the literature has investigated the comprehensive evaluation of the strains for practical application and the effect on the functional properties in the existence of Se. The present study showed the selenite reduction strain Bacillus subtilis T5 (up to 200 mM), which could produce high yields of selenium polysaccharides and selenium nanoparticles in an economical and feasible manner. Biosynthesized selenium nanoparticles by B. subtilis T5 were characterized systematically using UV-vis spectroscopy, FTIR, Zeta Potential, DLS, and SEM techniques. The biosynthesized SeNPs exhibited high stability with small particle sizes. B. subtilis T5 also possessed a tolerance to acidic pH and bile salts, high aggregation, negative hemolytic, and superior antioxidant activity, which showed excellent probiotic potential and can be recommended as a potential candidate for the selenium biopharmaceuticals industry. Remarkably, B. subtilis T5 showed that the activity of α-amylase was enhanced with selenite treatment to 8.12 U/mL, 2.72-fold more than the control. The genus Bacillus was first reported to produce both selenium polysaccharides with extremely high Se-content (2.302 g/kg) and significantly enhance the activity to promote α-amylase with selenium treatment. Overall, B. subtilis T5 showed potential as a bio-factory for the biosynthesized SeNPs and organ selenium (selenium polysaccharide), providing an appealing perspective for the biopharmaceutical industry.
Synthesis of Novel Cavitand Host Molecules via Palladium-Catalyzed Aryloxy- and Azidocarbonylation
Authors: Akash Akash , Kollár László , Kégl Tímea R.
Published: December 2022

Novel, elongated, resorcine[4]arene-based cavitands were synthesized via various consecutive reaction steps, including homogeneous catalytic aryloxy- and azidocarbonylation processes. The effects of carbon monoxide pressure and temperature on the conversion were examined in aryloxycarbonylation. It was revealed that a reaction temperature of 100 °C is required to achieve complete conversion both with monodentate (PPh3) and bidentate (Xantphos) phosphines at different carbon monoxide pressures (1–40 bar). Using ten different phenols as O-nucleophiles, partial hydrolysis of the esters to the corresponding carboxylic acids took place—i.e., 58–90% chemoselectivities toward esters were obtained. Moreover, the influences of temperature, reaction time and the catalyst ratio on the selectivity and conversion were described in the case of azidocarbonylation reaction. The formation of the acyl azide with high chemoselevtivity can be achieved at room temperature only. The higher reaction temperatures (50 °C) and higher catalyst loadings favor the formation of the primary amide. The characterization of the target compounds (esters and acyl azides) was carried out by IR and 1H and 13C NMR. The discussion of the influences of various parameters is based on in situ NMR investigations.
Hydrophilic Silica Nanoparticles in O/W Emulsion: Insights from Molecular Dynamics Simulation
Authors: Liu Shasha , Zhang Hengming , Yuan Shiling
Published: December 2022

Previous studies have been carried out on the effect of silica nanoparticles (SNPs) on the stability of oil–water emulsions. However, the combining configuration of SNPs and oil droplets at the molecular level and the effect of SNP content on the coalescence behavior of oil droplets cannot be obtained through experiments. In this paper, molecular dynamics (MD) simulation was performed to investigate the adsorption configuration of hydrophilic SNPs in an O/W emulsion system, and the effect of adsorption of SNPs on coalescence of oil droplets. The simulation results showed: (i) SNPs adsorbed on the surface of oil droplets, and excessive SNPs self-aggregated and connected by hydrogen bonds. (ii) Partially hydrophilic asphaltene and resin molecules formed adsorption configurations with SNPs, which changed the distribution of oil droplet components. Furthermore, compared with hydrophobic asphaltene, the hydrophilic asphaltene was easier to combine with SNPs. (iii) SNPs would extend the oil droplet coalescence time, and the π–π stacking structures were formed between asphaltene and asphaltene or resin molecules to enhance the connection between oil droplets during the oil droplet contact process. (iv) Enough SNPs tightly wrapped around the oil droplet, similar to the formation of a rigid film on the surface of an oil droplet, which hindered the contact and coalescence of components between oil droplets.
Metabolites Identification and Mechanism Prediction of Neobavaisoflavone In Vitro and In Vivo of Rats through UHPLC-Q-Exactive Plus Orbitrap MS Integrated Network Pharmacology
Authors: Li Linlin , Dong Fan , Wang Bianli , Song Jian , Zhang Huimin , Wang Ping , Wang Feiran , Yan Yingying , Zhang Xiao
Published: December 2022

Neobavaisoflavone is an important isoflavone component isolated from Psoraleae Fructus. It is used extensively worldwide because of its antibacterial, antioxidant, anti-inflammatory, anticancer, and anti-osteoporotic activities. However, there is no systematic and comprehensive research on the metabolism of neobavaisoflavone in vivo and in vitro. The study aimed to analyze the metabolic characteristics and mechanism of neobavaisoflavone for the first time. Firstly, biological samples were pretreated by the solid-phase extraction (SPE) method, methanol precipitation, and acetonitrile precipitation. Secondly, the samples were analyzed on UHPLC-Q-Exactive Plus Orbitrap MS. Thirdly, metabolites were tentatively identified based on retention time, parallel reaction monitoring strategy, diagnostic product ions, and neutral loss fragments. A total of 72 metabolites of neobavaisoflavone were tentatively identified, including 28 in plasma, 43 in urine, 18 in feces, six in the liver, and four in the liver microsome. The results suggested that neobavaisoflavone mainly underwent glucuronidation, sulfation, hydroxylation, methylation, cyclization, hydration, and their composite reactions in vivo and in vitro. In addition, nine active components with high bioavailability and 191 corresponding targets were predicted by the Swiss Drug Design database. The 1806 items of GO and 183 KEGG signaling pathways were enriched. These results showed that metabolites expanded the potential effects of neobavaisoflavone. The present study would provide the scientific basis for the further exploitation and application of neobavaisoflavone.
New TEMPO–Appended 2,2′-Bipyridine-Based Eu(III), Tb(III), Gd(III) and Sm(III) Complexes: Synthesis, Photophysical Studies and Testing Photoluminescence-Based Bioimaging Abilities
Authors: Slovesnova Nataliya V. , Minin Artem S. , Belousova Anna V. , Ustyugov Aleksey A. , Chaprov Kirill D. , Krinochkin Alexey P. , Valieva Maria I. , Shtaitz Yaroslav K. , Starnovskaya Ekaterina S. , Nikonov Igor L. , Tsmokalyuk Anton N. , Kim Grigory A. , Santra Sougata , Kopchuk Dmitry S. , Nosova Emiliya V. , Zyryanov Grigory V.
Published: December 2022

Linked to Alzheimer’s disease (AD), amyloids and tau-protein are known to contain a large number of cysteine (Cys) residues. In addition, certain levels of some common biogenic thiols (cysteine (Cys), homocysteine (Hcy), glutathione (GSH), etc.) in biological fluids are closely related to AD as well as other diseases. Therefore, probes with a selective interaction with the above-mentioned thiols can be used for the monitoring and visualizing changes of (bio)thiols in the biological fluids as well as in the brain of animal models of Alzheimer’s disease. In this study, new Eu(III), Tb(III), Gd(III) and Sm(III) complexes of 2,2′-bipyridine ligands containing TEMPO fragments as receptor units for (bio)thiols are reported. The presence of free radical fragments of the ligand in the complexes was proved by using the electronic paramagnetic resonance (EPR) method. Among all the complexes, the Eu(III) complex turned out to be the most promising one as luminescence- and spin-probe for the detection of biogenic thiols. The EPR and fluorescent titration methods showed the interaction of the resulting complex with free Cys and GSH in solution. To study the practical applicability of the probes for the monitoring of AD in-vivo, by using the above-mentioned Eu(III)-based probe, the staining of the brain of mice with amyloidosis and Vero cell cultures supplemented with the cysteine-enriched medium was studied as well as the fluorescence titration of Bovine Serum Albumin, BSA (as the model for the thiol moieties containing protein), was carried out. Based on the results of fluorescence titration, the formation of a non-covalent inclusion complex between the above-mentioned Eu(III) complex and BSA was suggested.
Discovery and Mechanistic Investigation of Piperazinone Phenylalanine Derivatives with Terminal Indole or Benzene Ring as Novel HIV-1 Capsid Modulators
Authors: Xu Shujing , Sun Lin , Zalloum Waleed , Huang Tianguang , Zhang Xujie , Ding Dang , Shao Xiaoyu , Jiang Xiangyi , Zhao Fabao , Cocklin Simon , De Clercq Erik , Pannecouque Christophe , Dick Alexej , Liu Xinyong , Zhan Peng
Published: December 2022

HIV-1 capsid (CA) performs multiple roles in the viral life cycle and is a promising target for antiviral development. In this work, we describe the design, synthesis, assessment of antiviral activity, and mechanistic investigation of 20 piperazinone phenylalanine derivatives with a terminal indole or benzene ring. Among them, F2-7f exhibited moderate anti-HIV-1 activity with an EC50 value of 5.89 μM, which was slightly weaker than the lead compound PF74 (EC50 = 0.75 μM). Interestingly, several compounds showed a preference for HIV-2 inhibitory activity, represented by 7f with an HIV-2 EC50 value of 4.52 μM and nearly 5-fold increased potency over anti-HIV-1 (EC50 = 21.81 μM), equivalent to PF74 (EC50 = 4.16 μM). Furthermore, F2-7f preferred to bind to the CA hexamer rather than to the monomer, similar to PF74, according to surface plasmon resonance results. Molecular dynamics simulation indicated that F2-7f and PF74 bound at the same site. Additionally, we computationally analyzed the ADMET properties for 7f and F2-7f. Based on this analysis, 7f and F2-7f were predicted to have improved drug-like properties and metabolic stability over PF74, and no toxicities were predicted based on the chemotype of 7f and F2-7f. Finally, the experimental metabolic stability results of F2-7f in human liver microsomes and human plasma moderately correlated with our computational prediction. Our findings show that F2-7f is a promising small molecule targeting the HIV-1 CA protein with considerable development potential.
Structural Investigation of DHICA Eumelanin Using Density Functional Theory and Classical Molecular Dynamics Simulations
Authors: Soltani Sepideh , Sowlati-Hashjin Shahin , Tetsassi Feugmo Conrard Giresse , Karttunen Mikko
Published: December 2022

Eumelanin is an important pigment, for example, in skin, hair, eyes, and the inner ear. It is a highly heterogeneous polymer with 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI) building blocks, of which DHICA is reported as the more abundant in natural eumelanin. The DHICA-eumelanin protomolecule consists of three building blocks, indole-2-carboxylic acid-5,6-quinone (ICAQ), DHICA and pyrrole-2,3,5-tricarboxylic acid (PTCA). Here, we focus on the self-assembly of DHICA-eumelanin using multi-microsecond molecular dynamics (MD) simulations at various concentrations in aqueous solutions. The molecule was first parameterized using density functional theory (DFT) calculations. Three types of systems were studied: (1) uncharged DHICA-eumelanin, (2) charged DHICA-eumelanin corresponding to physiological pH, and (3) a binary mixture of both of the above protomolecules. In the case of uncharged DHICA-eumelanin, spontaneous aggregation occurred and water molecules were present inside the aggregates. In the systems corresponding to physiological pH, all the carboxyl groups are negatively charged and the DHICA-eumelanin model has a net charge of −4. The effect of K+ ions as counterions was investigated. The results show high probability of binding to the deprotonated oxygens of the carboxylate anions in the PTCA moiety. Furthermore, the K+ counterions increased the solubility of DHICA-eumelanin in its charged form. A possible explanation is that the charged protomolecules favor binding to the K+ ions rather than aggregating and binding to other protomolecules. The binary mixtures show aggregation of uncharged DHICA-eumelanins; unlike the charged systems with no aggregation, a few charged DHICA-eumelanins are present on the surface of the uncharged aggregation, binding to the K+ ions.
Fluorescent Organic Small Molecule Probes for Bioimaging and Detection Applications
Authors: Yang Yufei , Gao Fucheng , Wang Yandong , Li Hui , Zhang Jie , Sun Zhiwei , Jiang Yanyan
Published: December 2022

The activity levels of key substances (metal ions, reactive oxygen species, reactive nitrogen, biological small molecules, etc.) in organisms are closely related to intracellular redox reactions, disease occurrence and treatment, as well as drug absorption and distribution. Fluorescence imaging technology provides a visual tool for medicine, showing great potential in the fields of molecular biology, cellular immunology and oncology. In recent years, organic fluorescent probes have attracted much attention in the bioanalytical field. Among various organic fluorescent probes, fluorescent organic small molecule probes (FOSMPs) have become a research hotspot due to their excellent physicochemical properties, such as good photostability, high spatial and temporal resolution, as well as excellent biocompatibility. FOSMPs have proved to be suitable for in vivo bioimaging and detection. On the basis of the introduction of several primary fluorescence mechanisms, the latest progress of FOSMPs in the applications of bioimaging and detection is comprehensively reviewed. Following this, the preparation and application of fluorescent organic nanoparticles (FONPs) that are designed with FOSMPs as fluorophores are overviewed. Additionally, the prospects of FOSMPs in bioimaging and detection are discussed.
Toward High-Performance Electrochromic Conjugated Polymers: Influence of Local Chemical Environment and Side-Chain Engineering
Authors: Lin Kaiwen , Wu Changjun , Zhang Guangyao , Wu Zhixin , Tang Shiting , Lin Yingxin , Li Xinye , Jiang Yuying , Lin Hengjia , Wang Yuehui , Ming Shouli , Lu Baoyang
Published: December 2022

Three homologous electrochromic conjugated polymers, each containing an asymmetric building block but decorated with distinct alkyl chains, were designed and synthesized using electrochemical polymerization in this study. The corresponding monomers, namely T610FBTT810, DT6FBT, and DT48FBT, comprise the same backbone structure, i.e., an asymmetric 5-fluorobenzo[c][1,2,5]thiadiazole unit substituted by two thiophene terminals, but were decorated with different types of alkyl chain (hexyl, 2-butyloctyl, 2-hexyldecyl, or 2-octyldecyl). The effects of the side-chain structure and asymmetric repeating unit on the optical absorption, electrochemistry, morphology, and electrochromic properties were investigated comparatively. It was found that the electrochromism conjugated polymer, originating from DT6FBT with the shortest and linear alkyl chain, exhibits the best electrochromic performance with a 25% optical contrast ratio and a 0.3 s response time. The flexible electrochromic device of PDT6FBT achieved reversible colors of navy and cyan between the neutral and oxidized states, consistent with the non-device phenomenon. These results demonstrate that subtle modification of the side chain is able to change the electrochromic properties of conjugated polymers.
X-ray Structures and Computational Studies of Two Bioactive 2-(Adamantane-1-carbonyl)-N-substituted Hydrazine-1-carbothioamides
Authors: Al-Wahaibi Lamya H. , Alagappan Kowsalya , Blacque Olivier , Mohamed Ahmed A. B. , Hassan Hanan M. , Percino María Judith , El-Emam Ali A. , Thamotharan Subbiah
Published: December 2022

Two biologically active adamantane-linked hydrazine-1-carbothioamide derivatives, namely 2-(adamantane-1-carbonyl)-N-(tert-butyl)hydrazine-1-carbothioamide) 1 and 2-(adamantane-1-carbonyl)-N-cyclohexylhydrazine-1-carbothioamide 2, have been synthesized. X-ray analysis was conducted to study the effect of the t-butyl and cyclohexyl moieties on the intermolecular interactions and conformation of the molecules in the solid state. X-ray analysis reveals that compound 1 exhibits folded conformation, whereas compound 2 adopts extended conformation. The Hirshfeld surface analysis indicates that the contributions of the major intercontacts involved in the stabilization of the crystal structures do not change much as a result of the t-butyl and cyclohexyl moieties. However, the presence and absence of these contacts is revealed by the 2D-fingerprint plots. The CLP–Pixel method was used to identify the energetically significant molecular dimers. These dimers are stabilized by different types of intermolecular interactions such as N–H···S, N–H···O, C–H···S, C–H···O, H–H bonding and C–H···π interactions. The strength of these interactions was quantified by using the QTAIM approach. The results suggest that N–H···O interaction is found to be stronger among other interactions. The in vitro assay suggests that both compounds 1 and 2 exhibit urease inhibition potential, and these compounds also display moderate antiproliferative activities. Molecular docking analysis shows the key interaction between urease enzyme and title compounds.
Synthesis of 2-Cyanobenzothiazoles via Pd-Catalyzed/Cu-Assisted C-H Functionalization/Intramolecular C-S Bond Formation from N-Arylcyanothioformamides
Authors: Broudic Nathan , Pacheco-Benichou Alexandra , Fruit Corinne , Besson Thierry
Published: December 2022

We report herein on a catalytic system involving palladium and copper to achieve the cyclization of N-arylcyanothioformamides and the synthesis of 2-cyanobenzothiazoles. The C-H functionalization/intramolecular C-S bond formation reaction was achieved in the presence of air, using 2.0 equiv of an inorganic additive (KI). In many cases, the reaction led to a sole product regioselectively obtained in good yields, allowing the synthesis of a wide range of substituted 2-cyanobenzothiazole derivatives, providing valuable building blocks for the design of more complex heterocyclic or molecular labeling systems.
Formation of miRNA Nanoprobes—Conjugation Approaches Leading to the Functionalization
Authors: Vilímová Iveta , Hervé-Aubert Katel , Chourpa Igor
Published: December 2022

Recently, microRNAs (miRNA) captured the interest as novel diagnostic and prognostic biomarkers, with their potential for early indication of numerous pathologies. Since miRNA is a short, non-coding RNA sequence, the sensitivity and selectivity of their detection remain a cornerstone of scientific research. As such, methods based on nanomaterials have emerged in hopes of developing fast and facile approaches. At the core of the detection method based on nanotechnology lie nanoprobes and other functionalized nanomaterials. Since miRNA sensing and detection are generally rooted in the capture of target miRNA with the complementary sequence of oligonucleotides, the sequence needs to be attached to the nanomaterial with a specific conjugation strategy. As each nanomaterial has its unique properties, and each conjugation approach presents its drawbacks and advantages, this review offers a condensed overview of the conjugation approaches in nanomaterial-based miRNA sensing. Starting with a brief recapitulation of specific properties and characteristics of nanomaterials that can be used as a substrate, the focus is then centered on covalent and non-covalent bonding chemistry, leading to the functionalization of the nanomaterials, which are the most commonly used in miRNA sensing methods.
Catechin Reduces Blood Pressure in Spontaneously Hypertensive Rats through Modulation of Arachidonic Acid Metabolism
Authors: Elbarbry Fawzy , Jones Gabriel , Ung Aimy
Published: December 2022

(1) Background: hypertension affects approximately half of the adults in the United States (roughly 116 million). The cytochrome P450 (CYP)-mediated metabolism of arachidonic acid (AA) in the kidney has been found to play a major role in the pathogenesis of hypertension. This study examines the anti-hypertensive effect of the natural polyphenolic compound catechin (CAT) and investigates if it impacts the metabolism of AA in the kidney in comparison to captopril (CAP): a commonly used antihypertensive drug. (2) Methods: spontaneously hypertensive rats (SHR) were randomly divided into five groups. The treatment groups were administered CAT in drinking water at doses of 10 and 50 mg/kg. A positive control group received CAP at a dose of 10 mg/kg in the drinking water, and one group received both CAP and CAT at doses of 10 mg/kg and 50 mg/kg, respectively. Blood pressure was monitored weekly for five weeks. The activity of the two major enzymes involved in AA metabolism in the kidney, namely CYP4A and soluble epoxide hydrolase (sEH), were analyzed. (3) Results: CAP monotherapy was found to reduce blood pressure compared to the control untreated rats but did not demonstrate any effect on AA metabolism. Low- and high-dose CAT resisted the rise in blood pressure observed in the untreated SHR and significantly lowered blood pressure compared to the control group, respectively. Only rats treated with high CAT doses demonstrated significant inhibition of CYP4A and sEH enzyme activities. The coadministration of CAP and a high dose of CAT resulted in more pronounced blood pressure-lowering effects, but no more significant effects on AA metabolism were found compared to a high dose of CAT alone. (4) Conclusion: the modulation of AA metabolism in the kidney contributes, at least partially, to the blood pressure-lowering effect of CAT in SHR rats.
Risk Assessment of Coffee Cherry (Cascara) Fruit Products for Flour Replacement and Other Alternative Food Uses
Authors: Eckhardt Sara , Franke Heike , Schwarz Steffen , Lachenmeier Dirk W.
Published: December 2022

Coffee bean harvesting incurs various by-products known for their long traditional use. However, they often still end up being a waste instead of being used to their full potential. On the European market, coffee cherry (cascara) products are not yet common, and a novel food approval for beverages made from coffee cherry pulp was issued only recently. In this article, exposure and risk assessment of various products such as juice, jam, jelly, puree, and flour made from coffee cherry pulp and husk are reviewed. Since caffeine in particular, as a bioactive ingredient, is considered a limiting factor, safe intake will be derived for different age groups, showing that even adolescents could consume limited quantities without adverse health effects. Moreover, the composition can be influenced by harvesting methods and processing steps. Most interestingly, dried and powdered coffee cherry can substitute the flour in bakery products by up to 15% without losing baking properties and sensory qualities. In particular, this use as a partial flour substitute is a possible approach to counteract rising grain prices, transport costs, and disrupted supply chains, which are caused by the Russia–Ukraine war and changing climatic conditions. Thus, the supply of affordable staple foods could be partially ensured for the inhabitants of countries that depend on imported wheat and cultivate coffee locally by harvesting both beans and by-products.
Red Flags and Adversities on the Way to the Robust CE-ICP-MS/MS Quantitative Monitoring of Self-Synthesized Magnetic Iron Oxide(II, III)-Based Nanoparticle Interactions with Human Serum Proteins
Authors: Sikorski Jacek , Drozd Marcin , Matczuk Magdalena
Published: December 2022

The growing interest in superparamagnetic iron oxide nanoparticles (SPIONs) as potential theranostic agents is related to their unique properties and the broad range of possibilities for their surface functionalization. However, despite the rapidly expanding list of novel SPIONs with potential biomedical applications, there is still a lack of methodologies that would allow in-depth investigation of the interactions of those nanoparticles with biological compounds in human serum. Herein, we present attempts to employ capillary electrophoresis-inductively coupled plasma tandem mass spectrometry (CE-ICP-MS/MS) for this purpose and various obstacles and limitations noticed during the research. The CE and ICP-MS/MS parameters were optimized, and the developed method was used to study the interactions of two different proteins (albumin and transferrin) with various synthesized SPIONs. While the satisfactory resolution between proteins was obtained and the method was applied to examine individual reagents, it was revealed that the conjugates formed during the incubation of the proteins with SPIONs were not stable under the conditions of electrophoretic separation.
Cognitive Impairment Mediates the Association between Dietary Inflammation and Depressive Symptoms in the Elderly
Authors: Sun Mengzi , Wang Ling , Hu Yueyang , Wang Xuhan , Yan Shoumeng , Guo Yinpei , Li Jing , Xie Zechun , Li Bo
Published: December 2022

The underlying mechanism in both cognitive impairment and depression was chronic inflammation, which could be reflected by the dietary inflammatory index (DII). However, the effect of cognitive impairment on the association between DII and depression was not clear. Therefore, in this study, we hypothesized that cognitive impairment could mediate the association between dietary inflammation and depressive symptoms. A total of 2550 participants aged ≥60 from the National Health and Nutrition Examination Survey (NHANES) in 2011–2014 were involved in the serial, cross-sectional study. Proinflammatory and anti-inflammatory diets were measured by DII. Cognitive impairment was measured by four dimensions, CERAD-immediate, CERAN-delayed, animal fluency test, and DSST. Depressive symptoms were measured by PHQ-9 scores. We found that a proinflammatory diet and cognitive impairment were both risk factors for depressive symptoms. An interaction between an inflammatory diet and cognitive impairment was detected (P-interaction = 0.060). In addition, all four dimensions of cognition mediated the association between DII and depressive symptom scores. Part of the association between DII and depressive symptoms scores could be explained by different dimensions of cognitive function, and the proportion of mediation ranged from 10.0% to 36.7%. In conclusion, cognitive impairment levels partly mediated the association between DII and depressive symptoms.
A Culturally Sensitive and Theory-Based Intervention on Prevention and Management of Diabetes: A Cluster Randomized Control Trial
Authors: Githinji Phrashiah , Dawson John A. , Appiah Duke , Rethorst Chad D.
Published: December 2022

Type 2 diabetes is an emerging concern in Kenya. This clustered-randomized trial of peri-urban communities included a theory-based and culturally sensitive intervention to improve diabetes knowledge, health beliefs, dietary intake, physical activity, and weight status among Kenyan adults. Those in the intervention group (IG) received a culturally sensitive diabetes education intervention which applied the Health Belief Model in changing knowledge, health beliefs and behavior. Participants attended daily education sessions for 5 days, each lasting 3 h and received mobile phone messages for an additional 4 weeks. The control group (CG) received standard education on COVID-19. Data was collected at baseline, post-intervention (1 week), and follow-up assessment (5 weeks). Linear mixed effect analysis was performed to assess within and across group differences. Compared to the control, IG significantly increased diabetes knowledge (p < 0.001), health beliefs including perceived susceptibility (p = 0.05), perceived benefits (p = 0.04) and self-efficacy (p = 0.02). IG decreased consumption of oils (p = 0.03), refined grains (p = 0.01), and increased intake of fruits (p = 0.01). Perceived barriers, physical activity, and weight status were not significantly different between both groups. The findings demonstrate the potential of diabetes education in improving diabetes knowledge, health beliefs, and in changing dietary intake of among adults in Kenya.
Glucose and Fructose Supplementation and Their Acute Effects on Anaerobic Endurance and Resistance Exercise Performance in Healthy Individuals: A Double-Blind Randomized Placebo-Controlled Crossover Trial
Authors: Eckstein Max L. , Erlmann Maximilian P. , Aberer Felix , Haupt Sandra , Zimmermann Paul , Wachsmuth Nadine B. , Schierbauer Janis , Zimmer Rebecca T. , Herz Daniel , Obermayer-Pietsch Barbara , Moser Othmar
Published: December 2022

Background: The effects of glucose, fructose and a combination of these on physical performance have been subject of investigation, resulting in diverse findings. Objective: The aim of this study was to investigate how an individualized amount of glucose, fructose, and a combination of these compared to placebo (sucralose) alter endurance performance on a cycle ergometer, lower and upper body resistance exercise performance at individualized thresholds in healthy young individuals. Methods: A total of 16 healthy adults (9 females) with an age of 23.8 ± 1.6 years and a BMI of 22.6 ± 1.8 kg/m2 (body mass (BM) 70.9 ± 10.8 kg, height 1.76 ± 0.08 m) participated in this study. During the screening visit, the lactate turn point 2 (LTP2) was defined and the weights for chest-press and leg-press were determined. Furthermore, 30 min prior to each exercise session, participants received either 1 g/kg BM of glucose (Glu), 1 g/kg BM of fructose (Fru), 0.5 g/kg BM of glucose/fructose (GluFru) (each), or 0.2 g sucralose (placebo), respectively, which were dissolved in 300 mL of water. All exercises were performed until volitional exhaustion. Time until exhaustion (TTE) and cardio-pulmonary variables were determined for all cycling visits; during resistance exercise, repetitions until muscular failure were counted and time was measured. During all visits, capillary blood glucose and blood lactate concentrations as well as venous insulin levels were measured. Results: TTE in cycling was 449 ± 163 s (s) (Glu), 443 ± 156 s (Fru), 429 ± 160 s (GluFru) and 466 ± 162 s (Pla) (p = 0.48). TTE during chest-press sessions was 180 ± 95 s (Glu), 180 ± 92 s (Fru), 172 ± 78 s (GluFru) and 162 ± 66 s (Pla) (p = 0.25), respectively. Conclusions: Pre-exercise supplementation of Glu, Fru and a combination of these did not have an ergogenic effect on high-intensity anaerobic endurance performance and on upper and lower body moderate resistance exercise in comparison to placebo.
Molecular Cloning and Characterization of a Fasciola gigantica Nuclear Receptor Subfamily 1 (FgNR1)
Authors: Martviset Pongsakorn , Chantree Pathanin , Chaimon Salisa , Torungkitmangmi Nattaya , Prathaphan Parisa , Ruangtong Jittiporn , Sornchuer Phornphan , Thongsepee Nattaya , Sangpairoj Kant , Adisakwattana Poom
Published: December 2022

Fasciola gigantica, a giant liver fluke, causes tremendous loss to the livestock economy in several regions throughout the world. The situation of drug resistance has been emerging increasingly; therefore, novel drugs and drug targets need to be discovered. The adult F. gigantica inhabits the major bile ducts where bile salts accumulate—these are steroid-like molecules that mediate several physiological processes in organisms through interacting with their specific nuclear receptors. However, the molecular mechanism of the interaction in the parasitic organisms have not been clearly understood. In this study, putative nuclear receptor subfamily 1 of F. gigantica (FgNR1) was identified. Nucleotide and amino acid sequences of the FgNR1 homolog were obtained from the transcriptome of F. gigantica and predicted for properties and functions using bioinformatics. The full-length cDNA was cloned and expressed in the bacterial expression system and then used for immunization. Western analysis and immunolocalization suggested that FgNR1 could be detected in the crude worm antigens and was highly expressed in the caeca and testes of the adult parasite. Moreover, the bile could significantly activate the expression of FgNR1 in cultured parasites. Our results indicated that FgNR1 has high potential for the development of a novel anthelminthic drug in the future.
Micellar Curcumin Substantially Increases the Antineoplastic Activity of the Alkylphosphocholine Erufosine against TWIST1 Positive Cutaneous T Cell Lymphoma Cell Lines
Authors: Trochopoulos Antonios G. X. , Ilieva Yana , Kroumov Alexander D. , Dimitrova Lyudmila L. , Pencheva-El Tibi Ivanka , Philipov Stanislav , Berger Martin R. , Najdenski Hristo M. , Yoncheva Krassimira , Konstantinov Spiro M. , Zaharieva Maya M.
Published: December 2022

Cutaneous T-cell lymphoma (CTCL) is a rare form of cancer with local as well as systemic manifestations. Concomitant bacterial infections increase morbidity and mortality rates due to impaired skin barrier and immune deficiency. In the current study, we demonstrated that the in vitro anti-lymphoma potential of erufosine is diminished by TWIST1 expression and micellar curcumin substantially increases its antineoplastic activity. Pharmacokinetic analysis showed that the micellar curcumin (MCRM) used in our study was characterized by low zeta potential, slow release of curcumin, and fast cell membrane penetration. The combination ratio 1:4 [erufosine:MCRM] achieved strong synergism by inhibiting cell proliferation and clonogenicity. The combined antiproliferative effects were calculated using the symbolic mathematical software MAPLE 15. The synergistic combination strongly decreased the expression of TWIST1 and protein kinase B/Akt as proven by western blotting. Significant reductions in NF-κB activation, induction of apoptosis, and altered glutathione levels were demonstrated by corresponding assays. In addition, the synergistic combination enhanced the anti-staphylococcal activity and prevented biofilm formation, as shown by crystal violet staining. Taken together, the above results show that the development of nanotechnological treatment modalities for CTCL, based on rational drug combinations exhibiting parallel antineoplastic and antibacterial effects, may prove efficacious.
Suppressing of Src–Hic-5–JNK–AKT Signaling Reduced GAPDH Expression for Preventing the Progression of HuCCT1 Cholangiocarcinoma
Authors: Wu Wen-Sheng , Chen Rui-Fang , Cheng Chuan-Chu , Wei Jia-Ling , Lin Chen-Fang , You Ren-In , Chen Yen-Chang , Lee Ming-Che , Chen Yen-Cheng
Published: December 2022

Cholangiocarcinoma (CCA) is a malignant neoplasm of the bile ducts, being the second most common type of cancer in the liver, and most patients are diagnosed at a late stage with poor prognosis. Targeted therapy aiming at receptors tyrosine kinases (RTKs) such as c-Met or EGFR have been developed but with unsatisfactory outcomes. In our recent report, we found several oncogenic molecules downstream of RTKs, including hydrogen peroxide clone-5 (Hic-5), Src, AKT and JNK, were elevated in tissues of a significant portion of metastatic CCAs. By inhibitor studies and a knockdown approach, these molecules were found to be within the same signal cascade responsible for the migration of HuCCT1 cells, a conventionally used CCA cell line. Herein, we also found Src inhibitor dasatinib and Hic-5 siRNA corporately suppressed HuCCT1 cell invasion. Moreover, dasatinib inhibited the progression of the HuCCT1 tumor on SCID mice skin coupled with decreasing the expression of Hic-5 and EGFR and the activities of Src, AKT and JNK. In addition, we found a glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and several cytoskeletal molecules such as tubulin and cofilin were dramatically decreased after a long-term treatment of the HuCCT1 tumor with a high dose of dasatinib. Specifically, GAPDH was shown to be a downstream effector of the Hic-5/Src/AKT cascade involved in HuCCT1 cell migration. On the other hand, TFK1, another CCA cell line without Hic-5 expression, exhibited very low motility, whereas an ectopic Hic-5 expression enhanced the activation of Src and AKT and marginally increased TFK1 migration. In the future, it is tempting to investigate whether cotargeting Src, Hic-5 and/or GAPDH is efficient for preventing CCA progression in future clinical trials.