bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, Biosynthesis, and Biological Activity of Diels–Alder Adducts from Morus Genus: An Update
Authors: Tortora Carola , Pisano Luca , Vergine Valeria , Ghirga Francesca , Iazzetti Antonia , Calcaterra Andrea , Marković Violeta , Botta Bruno , Quaglio Deborah
Published: November 2022

The plants of the Moraceae family are producers of a great variety of polyphenolic natural products. Among these, the Diels–Alder type adducts (DAAs) are endowed with a unique cyclohexene scaffold, since they are biosynthesized from [4+2] cycloaddition of different polyphenolic precursors such as chalcones and dehydroprenyl polyphenols. To date, more than 150 DAAs have been isolated and characterized from Moraceous and related plants. The main source of DAAs is the mulberry root bark, also known as “Sang-Bai-Pi” in Traditional Chinese Medicine, but they have also been isolated from root bark, stem barks, roots, stems or twigs, leaves, and callus cultures of Moraceous and other related plants. Since 1980, many biological activities of DAAs have been identified, including anti-HIV, antimicrobial, anti-inflammatory, and anticancer ones. For these reasons, natural DAAs have been intensively investigated, and a lot of efforts have been made to study their biosynthesis and to establish practical synthetic access. In this review, we summarized all the updated knowledge on biosynthesis, chemoenzymatic synthesis, racemic and enantioselective total synthesis, and biological activity of natural DAAs from Moraceous and related plants.
Immobilization of Penicillin G Acylase on Vinyl Sulfone-Agarose: An Unexpected Effect of the Ionic Strength on the Performance of the Immobilization Process
Authors: da Rocha Thays N. , Morellon-Sterlling Roberto , Rocha-Martin Javier , Bolivar Juan M. , Gonçalves Luciana R. B. , Fernandez-Lafuente Roberto
Published: November 2022

Penicillin G acylase (PGA) from Escherichia coli was immobilized on vinyl sulfone (VS) agarose. The immobilization of the enzyme failed at all pH values using 50 mM of buffer, while the progressive increase of ionic strength permitted its rapid immobilization under all studied pH values. This suggests that the moderate hydrophobicity of VS groups is enough to transform the VS-agarose in a heterofunctional support, that is, a support bearing hydrophobic features (able to adsorb the proteins) and chemical reactivity (able to give covalent bonds). Once PGA was immobilized on this support, the PGA immobilization on VS-agarose was optimized with the purpose of obtaining a stable and active biocatalyst, optimizing the immobilization, incubation and blocking steps characteristics of this immobilization protocol. Optimal conditions were immobilization in 1 M of sodium sulfate at pH 7.0, incubation at pH 10.0 for 3 h in the presence of glycerol and phenyl acetic acid, and final blocking with glycine or ethanolamine. This produced biocatalysts with stabilities similar to that of the glyoxyl-PGA (the most stable biocatalyst of this enzyme described in literature), although presenting just over 55% of the initially offered enzyme activity versus the 80% that is recovered using the glyoxyl-PGA. This heterofuncionality of agarose VS beads opens new possibilities for enzyme immobilization on this support.
The Multi-Step Chain Extension for Waterborne Polyurethane Binder of Para-Aramid Fabrics
Authors: Ma Ge , Wang Qianshu , Ye Jun , He Lifan , Guo Longhai , Li Xiaoyu , Qiu Teng , Tuo Xinlin
Published: November 2022

The comprehensive balance of the mechanical, interfacial, and environmental requirements of waterborne polyurethane (WPU) has proved challenging, but crucial in the specific application as the binder for high-performance polymer fiber composites. In this work, a multi-step chain extension (MCE) method was demonstrated using three kinds of small extenders and one kind of macro-chain extender (CE) for different chain extension steps. One dihydroxyl blocked small molecular urea (1,3-dimethylolurea, DMU) was applied as one of the CEs and, through the hybrid macrodiol/diamine systems of polyether, polyester, and polysiloxane, the WPU was developed by the step-by-step optimization on each chain extending reaction via the characterization on the H-bonding association, microphase separation, and mechanical properties. The best performance was achieved when the ratio of polyether/polyester was controlled at 6:4, while 2% of DMU and 1% of polysiloxane diamine was incorporated in the third and fourth chain extension steps, respectively. Under the condition, the WPU exhibited not only excellent tensile strength of 30 MPa, elongation of break of about 1300%, and hydrophobicity indicated by the water contact angle of 98°, but also effective interfacial adhesion to para-aramid fabrics. The peeling strength of the joint based on the polysiloxane incorporated WPU after four steps of chain extension was 430% higher than that prepared through only two steps of chain extension. Moreover, about 44% of the peeling strength was sustained after the joint had been boiling for 40 min in water, suggesting the potential application for high-performance fabric composites.
Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells
Authors: Cecarini Valentina , Selmi Salima , Cuccioloni Massimiliano , Gong Chunmei , Bonfili Laura , Zheng Yadong , Cortese Manuela , Angeletti Mauro , Kilani Soumaya , Eleuteri Anna Maria
Published: November 2022

Background: Breast cancer is the most diagnosed cancer among women, and its incidence and mortality are rapidly growing worldwide. In this regard, plant-derived natural compounds have been shown to be effective as chemotherapeutic and preventative agents. Apricot kernels are a rich source of nutrients including proteins, lipids, fibers, and phenolic compounds and contain the aromatic cyanogenic glycoside amygdalin that has been shown to exert a cytotoxic effect on cancer cells by affecting the cell cycle, inducing apoptosis, and regulating the immune function. Methods: Here, we describe a previously unexplored proapoptotic mechanism of action of amygdalin in breast cancer (MCF7) cells that involves the modulation of intracellular proteolysis. For comparative purposes, the same investigations were also conducted upon cell treatment with two apricot kernel aqueous extracts from Prunus armeniaca L. Results: We observed that both the 20S and 26S proteasome activities were downregulated in the MCF7 cells upon 24 h treatments. Simultaneously, the autophagy cascade resulted in being impaired due to cathepsin B and L inhibition that also contributed to a reduction in cancer cell migration. The inhibition of these proteolytic systems finally promoted the activation of apoptotic events in the MCF7 cells. Conclusion: Collectively, our data unveil a novel mechanism of the anticancer activity of amygdalin, prompting further investigations for potential application in cancer preventative strategies.
Green Solvents for Eco-Friendly Synthesis of Dimethindene: A Forward-Looking Approach
Authors: Quivelli Andrea Francesca , Rossi Federico Vittorio , Alario Chiara , Sannicolò Francesco , Vitale Paola , García-Álvarez Joaquín , Perna Filippo Maria , Capriati Vito
Published: November 2022

Dimethindene is a selective histamine H1 antagonist and is commercially available as a racemate. Upon analyzing the synthetic pathways currently available for the industrial preparation of dimethindene, we set up a sustainable approach for the synthesis of this drug, switching from petroleum-based volatile organic compounds (VOCs) to eco-friendly solvents, such as 2-methyltetrahydrofuran (2-MeTHF) and cyclopentyl methyl ether (CPME) belonging to classes 3 and 2, respectively. Beyond decreasing the environmental impact of the synthesis (E-factor: 24.1–54.9 with VOCs; 12.2–22.1 with 2-MeTHF or CPME), this switch also improved the overall yield of the process (from 10% with VOCs to 21–22% with 2-MeTHF or CPME) and remarkably simplified the manual operations, working under milder conditions. Typical metrics applied at the first and second pass, according to the CHEM21 metrics toolkit, were also calculated for the whole synthetic procedure of dimethindene, and the results were compared with those of the classical procedure.
Synthesis, Characterization, and X-ray Crystallography, of the First Cyclohexadienyl Trifluoromethyl Metal Complex (η5-C6H7)Fe(CO)2CF3
Authors: Douvris Chris , Matatov David , Bussan Derek , Lampropoulos Christos , Wink Donald J.
Published: November 2022

Fluorochemistry is a field of tremendous developments and advances in several areas of science including materials, pharmaceuticals and agriculture. This makes the design and synthesis of fluorine-containing substances highly desirable research targets. The sub-area of synthetic perfluorinated chemistry proportionately attracts widespread interest by applying to all areas of chemistry including organic and inorganic. Particularly, the latter is much underdeveloped as metal complexes with perfluoroalkyl moieties are scarce, with the vast majority of perfluorinated analogs, of long known, halo and alkylated derivatives never having been synthesized. Focusing on the chemistry of trifluoromethyl group, which is the most important in the class of perfluoroalkyls, we set out to explore the possibility of synthesizing and completely characterizing a cyclohexadienyl metal complex. Upon utilizing a number of trifluorometylating reagents, we only arrived at an efficient preparation by the use of Morrison’s trifluormethylating reagent. As a result, the new, air- and moisture-sensitive complex (η5-C6H7)Fe(CO)2CF3, was prepared in 71% yield, using a nucleophilic iodo-for-trifluoromethyl substitution, and was completely characterized including by X-ray crystallography.
Synthesis, Structure and Molecular Docking of New 4,5-Dihydrothiazole Derivatives Based on 3,5-Dimethylpyrazole and Cytisine and Salsoline Alkaloids
Authors: Ibrayev Marat K. , Nurkenov Oralgazy A. , Rakhimberlinova Zhanar B. , Takibayeva Altynaray T. , Palamarchuk Irina V. , Turdybekov Dastan M. , Kelmyalene Assel A. , Kulakov Ivan V.
Published: November 2022

The interaction results of 1,2-dibromo-3-isothiocyanatopropane with some pyrazoles as well as cytisine and salsoline alkaloids were presented in this paper. It was shown that the reaction resulted in one one-step and rather mild method for the preparation of the corresponding 1,3-thiazoline bromomethyl derivatives. The yield of this reaction was affected by the presence of a base and an order in which reagents were added. Molecular docking of the synthesized 1,3-thiazoline derivatives for putative antibacterial activity was carried out using the penicillin-binding target protein (PBP4) of the bacteria E. coli “Homo sapiens” and S. aureus “Homo sapiens” as an example. Molecular docking demonstrated that the compounds had insignificant binding energies at the level of selected reference drugs (Cephalotin and Chloramphenicol). The presence of natural alkaloids in the structure of thiazoline derivatives somewhat increased the affinity of these substrates for target proteins selected.
Synthesis, Structure and Photochemistry of Dibenzylidenecyclobutanones
Authors: Fomina Marina V. , Freidzon Alexandra Y. , Kuz’mina Lyudmila G. , Moiseeva Anna A. , Starostin Roman O. , Kurchavov Nikolai A. , Nuriev Vyacheslav N. , Gromov Sergey P.
Published: November 2022

A series of symmetrical dibenzylidene derivatives of cyclobutanone were synthesized with the goal of studying the physicochemical properties of cross-conjugated dienones (ketocyanine dyes). The structures of the products were established and studied by X-ray diffraction and by NMR and electronic spectroscopy. All the products had E,E-geometry. The oxidation and reduction potentials of the dienones were determined by cyclic voltammetry. The potentials were shown to depend on the nature, position, and number of substituents in the benzene rings. A linear correlation was found between the difference of the electrochemical oxidation and reduction potentials and the energy of the long-wavelength absorption maximum. This correlation can be employed to analyze the properties of other compounds of this type. Quantum chemistry was used to explain the observed regularities in the electrochemistry, absorption, and fluorescence of the dyes. The results are in good agreement with the experimental redox potentials and spectroscopy data.
Determination of Mifepristone (RU-486) and Its Metabolites in Maternal Blood Sample after Pharmacological Abortion
Authors: Szpot Paweł , Wachełko Olga , Jurek Tomasz , Zawadzki Marcin
Published: November 2022

The aim of the study was the development and validation of the UHPLC-QqQ-MS/MS method for the determination of mifepristone in human blood as well as the identification and quantification of its metabolites after self-induced pharmacological abortion. The metabolic pathway in humans was proposed after examination of an authentic casework. The fast and simple preanalytical procedure was successfully applied (pH9, tert-butyl-methyl ether). The validation parameters of the method were as follows: limit of quantification: 0.5 ng/mL; coefficients of determination: >0.999 (R2), intra- and inter-day accuracy and precision values did not exceed ± 13.2%. The recovery and matrix effect were in the range of 96.3–114.7% and from −3.0 to 14.7%, respectively. Toxicological analysis of the mother’s blood (collected the day after the pregnancy termination) revealed the presence of five compounds: mifepristone (557.4 ng/mL), N-desmethyl-mifepristone (638.7 ng/mL), 22-OH-mifepristone (176.9 ng/mL), N,N-didesmethyl-mifepristone (144.5 ng/mL) and N-desmethyl-hydroxy-mifepristone (qualitatively). To our knowledge, the study presented in this paper is the first report on the concentrations of mifepristone and its metabolites in maternal blood samples after performing a self-induced abortion. The established UHPLC-QqQ-MS/MS method is suitable for forensic toxicological analysis as well as in terms of clinical toxicology in future investigations (examination of pharmacokinetics, bioavailability and metabolism of RU-486).
The Role of Graphene Oxide in the Exothermic Mechanism of Al/CuO Nanocomposites
Authors: Su Jiaxin , Hu Yan , Zhou Bin , Ye Yinghua , Shen Ruiqi
Published: November 2022

Metastable intermixed composites (MICs) have received increasing attention in the field of energy materials in recent years due to their high energy and good combustion performance. The exploration of ways of improving their potential release of heat is still underway. In this study, Al–CuO/graphene oxide (GO) nanocomposites were prepared using a combination of the self-assembly and in-suit synthesis methods. The formulation and experimental conditions were also optimized to maximize the exothermic heat. The DSC analysis shows that the addition of the GO made a significant contribution to the exothermic effect of the nanothermite. Compared with the Al–CuO nanothermite, the exothermic heat of the Al–CuO/GO nanocomposites increase by 306.9–1166.3 J/g and the peak temperatures dropped by 7.9–26.4 °C with different GO content. The reaction mechanism of the nanocomposite was investigated using a DSC and thermal reaction kinetics analysis. It was found that, compared with typical thermite reactions, the addition of the GO changed the reaction pathway of the nanothermite. The reaction products included CuAlO2. Moreover, the combustion properties of nanocomposite were investigated. This work reveals the unique mechanism of GO in thermite reactions, which may promote the application of carbon materials in nanothermite.
A Comparative Study between Screen-Printed and Solid-Contact Electrodes for the Stability-Indicating Determination of Bromazepam
Authors: Abdel-Gawad Sherif A. , Altharawi Ali
Published: November 2022

Stability-indicating methods are awesome tools to ensure the safety and efficacy of active pharmaceutical ingredients (APIs). An accurate comparative study involving the use of potentiometric sensors for the determination of bromazepam (BRZ) in the presence of its main product of degradation and impurity was performed by the fabrication of two membrane electrodes. A screen-printed electrode (SPE) and a solid-contact glassy carbon electrode (SCE) were fabricated and their performance optimized. The fabricated sensors showed a linear electrochemical response in the concentration range 1.0 × 10−6 M to 1.0 × 10−2 M. The electrodes exhibited Nernstian slopes of 59.70 mV/decade and 58.10 mV/decade for the BRZ-SPE and BRZ-SCE membrane electrodes, respectively. The electrochemical performance was greatly affected by the medium pH. They showed an almost ideal electrochemical performance between pH 3.0 and pH 6.0. The fabricated membranes were applied successfully for the quantification of BRZ in the presence of up to 90% of its degradation product. Moreover, a successful application of the fabricated electrodes was performed for the sensitive and selective quantification of BRZ in its tablet form without any pretreatment procedure.
Study on the Synergistic Molluscicidal Effect of Pedunsaponin A and Niclosamide
Authors: Yang Chunping , Zhou Yue , Wu Chuanlei , Yan Xiao , Cheng Pengcheng , Luo Liya , Qiu Xiaoyan , Zhang Min , Qin Guangwei , Zhang Yangyang , Chen Huabao
Published: November 2022

Niclosamide (NI) is the main molluscicide used to control Pomacea canaliculata (Lamarck) (Architaenioglossa: Ampullariidae). However, NI failed to inhibit snail climbing during the treatment process. In this study, we examined the effect of NI combined with pedunsaponin A at an ineffective concentration. The molluscicidal effect of Pedunsaponin A on NI was evidently synergistic after 48 h, and the synergism ratio (SR) was 1.82 after treatment for 72 h at 0.8 mg·L−1. Examination of the climbing adhesion effect showed that a high concentration of Pedunsaponin A (0.4 mg·L−1 and 0.8 mg·L−1) combined with NI significantly inhibited the climbing of P. canaliculata. We further studied the synergism mechanism; the results of histopathological observation showed that the siphon appeared cavities, the muscle fibers of the ventricular were severely dissolved, and kidney tubule arrangement was distorted after NI adding Pedunsaponin A. In addition, the hemocyte survival rate and the content of hemocyanin decreased significantly. According to the results of our study, the synergism mechanism may hinder oxygen transport of P. canaliculata, influencing the supply of energy; the ability of immune defense and excretion and metabolic detoxification decreased, prolonging the action time of NI in the body.
Ultrafast-Laser Micro-Structuring of LiNi0.8Mn0.1Co0.1O2 Cathode for High-Rate Capability of Three-Dimensional Li-ion Batteries
Authors: Tran Minh Xuan , Smyrek Peter , Park Jihun , Pfleging Wilhelm , Lee Joong Kee
Published: November 2022

Femtosecond ultrafast-laser micro-patterning was employed to prepare a three-dimensional (3D) structure for the tape-casting Ni-rich LiNi0.8Mn0.1Co0.1O2 (NMC811) cathode. The influences of laser structuring on the electrochemical performance of NMC811 were investigated. The 3D-NMC811 cathode retained capacities of 77.8% at 2 C of initial capacity at 0.1 C, which was thrice that of 2D-NMC811 with an initial capacity of 27.8%. Cyclic voltammetry (CV) and impedance spectroscopy demonstrated that the 3D electrode improved the Li+ ion transportation at the electrode–electrolyte interface, resulting in a higher rate capability. The diffusivity coefficient DLi+, calculated by both CV and electrochemical impedance spectroscopy, revealed that 3D-NMC811 delivered faster Li+ ion transportation with higher DLi+ than that of 2D-NMC811. The laser ablation of the active material also led to a lower charge–transfer resistance, which represented lower polarization and improved Li+ ion diffusivity.
Surface Functionalization of Nanofibers: The Multifaceted Approach for Advanced Biomedical Applications
Authors: Kulkarni Deepak , Musale Shubham , Panzade Prabhakar , Paiva-Santos Ana Cláudia , Sonwane Pratiksha , Madibone Monika , Choundhe Puja , Giram Prabhanjan , Cavalu Simona
Published: November 2022

Nanocarriers are gaining significant importance in the modern era of drug delivery. Nanofiber technology is one of the prime paradigms in nanotechnology for various biomedical and theranostic applications. Nanofibers obtained after successful electrospinning subjected to surface functionalized for drug delivery, biomedical, tissue engineering, biosensing, cell imaging and wound dressing application. Surface functionalization entirely changes physicochemical and biological properties of nanofibers. In physicochemical properties, wettability, melting point, glass transition temperature, and initial decomposition temperature significantly change offer several advantageous for nanofibers. Similarly, biological properties include cell adhesion, biocompatibility, and proliferation, also changes by functionalization of nanofibers. Various natural and synthetic materials polymers, metals, carbon materials, functional groups, proteins, and peptides, are currently used for surface modification of nanofibers. Various research studies across the globe demonstrated the usefulness of surface functionalized nanofibers in tissue engineering, wound healing, skin cancers, melanoma, and disease diagnosis. The delivery of drug through surface functionalized nanofibers results in improved permeation and bioavailability of drug which is important for better targeting of disease and therapeutic efficacy. This review provides a comprehensive insight about various techniques of surface functionalization of nanofibers along with its biomedical applications, toxicity assessment and global patent scenario.
Bismuth Quantum Dot (Bi QD)/Polydimethylsiloxane (PDMS) Nanocomposites with Self-Cleaning and Antibacterial Activity for Dental Applications
Authors: Hu Yingzi , Xu Zhiliang , Hu Yi , Hu Lanping , Zi You , Wang Mengke , Feng Xingmei , Huang Weichun
Published: November 2022

In the oral microenvironment, bacteria colonies are easily aggregated on the tooth-restoration surface, in the manner of a biofilm, which usually consists of heterogeneous structures containing clusters of a variety of bacteria embedded in an extracellular matrix, leading to serious recurrent caries. In this contribution, zero-dimensional (0D) bismuth (Bi) quantum dots (QDs) synthesized by a facile solvothermal method were directly employed to fabricate a Bi QD/polydimethylsiloxane (PDMS)-modified tooth by simple curing treatment. The result demonstrates that the as-fabricated Bi QD/PDMS-modified tooth at 37 °C for 120 min not only showed significantly improved hydrophobic performance with a water contact angle of 103° and 115° on the tooth root and tooth crown, respectively, compared to that (~20° on the tooth root, and ~5° on the tooth crown) of the pristine tooth, but also exhibited excellent antibacterial activity against S. mutans, superior biocompatibility, and biosafety. In addition, due to the highly photothermal effect of Bi QDs, the antibacterial activity of the as-fabricated Bi QD/PDMS-modified tooth could be further enhanced under illumination, even at a very low power density (12 mW cm−2). Due to the facile fabrication, excellent hydrophobicity, superior antibacterial activity, and biocompatibility and biosafety of the Bi QD/PDMS-modified tooth, it is envisioned that the Bi QD/PDMS-modified tooth with a fascinating self-cleaning and antibacterial performance can pave the way to new designs of versatile multifunctional nanocomposites to prevent secondary caries in the application of dental restoration.
Automated Recognition of Nanoparticles in Electron Microscopy Images of Nanoscale Palladium Catalysts
Authors: Boiko Daniil A. , Sulimova Valentina V. , Kurbakov Mikhail Yu. , Kopylov Andrei V. , Seredin Oleg S. , Cherepanova Vera A. , Pentsak Evgeniy O. , Ananikov Valentine P.
Published: November 2022

Automated computational analysis of nanoparticles is the key approach urgently required to achieve further progress in catalysis, the development of new nanoscale materials, and applications. Analysis of nanoscale objects on the surface relies heavily on scanning electron microscopy (SEM) as the experimental analytic method, allowing direct observation of nanoscale structures and morphology. One of the important examples of such objects is palladium on carbon catalysts, allowing access to various chemical reactions in laboratories and industry. SEM images of Pd/C catalysts show a large number of nanoparticles that are usually analyzed manually. Manual analysis of a statistically significant number of nanoparticles is a tedious and highly time-consuming task that is impossible to perform in a reasonable amount of time for practically needed large amounts of samples. This work provides a comprehensive comparison of various computer vision methods for the detection of metal nanoparticles. In addition, multiple new types of data representations were developed, and their applicability in practice was assessed.
Organic Solar Cells Improved by Optically Resonant Silicon Nanoparticles
Authors: Sandzhieva Maria , Khmelevskaia Darya , Tatarinov Dmitry , Logunov Lev , Samusev Kirill , Kuchmizhak Alexander , Makarov Sergey V.
Published: November 2022

Silicon nanophotonics has become a versatile platform for optics and optoelectronics. For example, strong light localization at the nanoscale and lack of parasitic losses in infrared and visible spectral ranges make resonant silicon nanoparticles a prospect for improvement in such rapidly developing fields as photovoltaics. Here, we employed optically resonant silicon nanoparticles produced by laser ablation for boosting the power conversion efficiency of organic solar cells. Namely, we created colloidal solutions of spherical nanoparticles with a range of diameters (80–240 nm) in different solvents. We tested how the nanoparticles’ position in the device, their concentration, silicon doping, and method of deposition affected the final device efficiency. The best conditions optimization resulted in an efficiency improvement from 6% up to 7.5%, which correlated with numerical simulations of nanoparticles’ optical properties. The developed low-cost approach paves the way toward highly efficient and stable solution-processable solar cells.
The Impact of Antenatal Balanced Plate Nutrition Education for Pregnant Women on Birth Weight: A Cluster Randomised Controlled Trial in Rural Bangladesh
Authors: Chowdhury Morseda , Raynes-Greenow Camille , Kelly Patrick , Alam Neeloy Ashraful , Afsana Kaosar , Billah Sk Masum , Dibley Michael John
Published: November 2022

Low birth weight (LBW) is a global public health problem with the highest prevalence in South Asia. It is strongly associated with maternal undernutrition. In South Asia, intra-household food distribution is inequitable, with lower dietary adequacy in women. Evidence that nutrition education improves diet during pregnancy and reduces LBW is weak. We assessed the impact of nutrition education for pregnant women on birth weight in rural Bangladesh. We conducted a parallel, two-arm, cluster-randomised controlled trial, with 36 clusters allocated equally to intervention (n = 445) or standard care (n = 448). From their first trimester until delivery, intervention participants received education about eating balanced meals to meet daily dietary requirements with diverse food groups. The primary outcome of mean birth weight was 127.5 g higher in the intervention compared to control women, and the intervention reduced the risk of LBW by 57%. Post hoc analyses showed a significantly higher birth weight and a greater reduction in LBW amongst adolescent mothers. The mean number of food groups consumed was significantly higher in the intervention from the third month of pregnancy than in the control. A community-based balanced plate nutrition education intervention effectively increased mean birth weight and reduced LBW, and improved dietary diversity in rural Bangladeshi women.
Impact of Total Parenteral Nutrition on Gut Microbiota in Pediatric Population Suffering Intestinal Disorders
Authors: Cerdó Tomás , García-Santos José Antonio , Rodríguez-Pöhnlein Anna , García-Ricobaraza María , Nieto-Ruíz Ana , G. Bermúdez Mercedes , Campoy Cristina
Published: November 2022

Parenteral nutrition (PN) is a life-saving therapy providing nutritional support in patients with digestive tract complications, particularly in preterm neonates due to their gut immaturity during the first postnatal weeks. Despite this, PN can also result in several gastrointestinal complications that are the cause or consequence of gut mucosal atrophy and gut microbiota dysbiosis, which may further aggravate gastrointestinal disorders. Consequently, the use of PN presents many unique challenges, notably in terms of the potential role of the gut microbiota on the functional and clinical outcomes associated with the long-term use of PN. In this review, we synthesize the current evidence on the effects of PN on gut microbiome in infants and children suffering from diverse gastrointestinal diseases, including necrotizing enterocolitis (NEC), short bowel syndrome (SBS) and subsequent intestinal failure, liver disease and inflammatory bowel disease (IBD). Moreover, we discuss the potential use of pre-, pro- and/or synbiotics as promising therapeutic strategies to reduce the risk of severe gastrointestinal disorders and mortality. The findings discussed here highlight the need for more well-designed studies, and harmonize the methods and its interpretation, which are critical to better understand the role of the gut microbiota in PN-related diseases and the development of efficient and personalized approaches based on pro- and/or prebiotics.
Indolepropionic Acid, a Gut Bacteria-Produced Tryptophan Metabolite and the Risk of Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease
Authors: Sehgal Ratika , de Mello Vanessa D. , Männistö Ville , Lindström Jaana , Tuomilehto Jaakko , Pihlajamäki Jussi , Uusitupa Matti
Published: November 2022

An intricate relationship between gut microbiota, diet, and the human body has recently been extensively investigated. Gut microbiota and gut-derived metabolites, especially, tryptophan derivatives, modulate metabolic and immune functions in health and disease. One of the tryptophan derivatives, indolepropionic acid (IPA), is increasingly being studied as a marker for the onset and development of metabolic disorders, including type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). The IPA levels heavily depend on the diet, particularly dietary fiber, and show huge variations among individuals. We suggest that these variations could partially be explained using genetic variants known to be associated with specific diseases such as T2D. In this narrative review, we elaborate on the beneficial effects of IPA in the mitigation of T2D and NAFLD, and further study the putative interactions between IPA and well-known genetic variants (TCF7L2, FTO, and PPARG), known to be associated with the risk of T2D. We have investigated the long-term preventive value of IPA in the development of T2D in the Finnish prediabetic population and the correlation of IPA with phytosterols in obese individuals from an ongoing Kuopio obesity surgery study. The diversity in IPA-linked mechanisms affecting glucose metabolism and liver fibrosis makes it a unique small metabolite and a promising candidate for the reversal or management of metabolic disorders, mainly T2D and NAFLD.
Ileocolonic-Targeted JAK Inhibitor: A Safer and More Effective Treatment for Inflammatory Bowel Disease
Authors: Yadav Vipul , House Aileen , Matiz Silvia , McCoubrey Laura E. , Bettano Kimberly A. , Bhave Leena , Wang Meiyao , Fan Peter , Zhou Siqun , Woodhouse Janice D. , Poimenidou Eirini , Dou Liu , Basit Abdul W. , Moy Lily Y. , Saklatvala Robert , Hegde Laxminarayan G. , Yu Hongshi
Published: November 2022

Janus kinase (JAK) inhibitors, such as tofacitinib (Xeljanz) and filgotinib (Jyseleca), have been approved for treatment of ulcerative colitis with several other JAK inhibitors in late-stage clinical trials for inflammatory bowel disease (IBD). Despite their impressive efficacy, the risk of adverse effects accompanying the use of JAK inhibitors has brought the entire class under scrutiny, leading to them receiving an FDA black box warning. In this study we investigated whether ileocolonic-targeted delivery of a pan-JAK inhibitor, tofacitinib, can lead to increased tissue exposure and reduced systemic exposure compared to untargeted formulations. The stability of tofacitinib in the presence of rat colonic microbiota was first confirmed. Next, in vivo computed tomography imaging was performed in rats to determine the transit time and disintegration site of ileocolonic-targeted capsules compared to gastric release capsules. Pharmacokinetic studies demonstrated that systemic drug exposure was significantly decreased, and colonic tissue exposure increased at 10 mg/kg tofacitinib dosed in ileocolonic-targeted capsules compared to gastric release capsules and an oral solution. Finally, in a rat model of LPS-induced colonic inflammation, targeted tofacitinib capsules significantly reduced concentrations of proinflammatory interleukin 6 in colonic tissue compared to a vehicle-treated control (p = 0.0408), unlike gastric release tofacitinib capsules and orally administered dexamethasone. Overall, these results support further development of ileocolonic-targeted tofacitinib, and potentially other specific JAK inhibitors in pre-clinical and clinical development, for the treatment of IBD.
Multivariate Data Analysis and Central Composite Design-Oriented Optimization of Solid Carriers for Formulation of Curcumin-Loaded Solid SNEDDS: Dissolution and Bioavailability Assessment
Authors: Corrie Leander , Kaur Jaskiran , Awasthi Ankit , Vishwas Sukriti , Gulati Monica , Saini Sumant , Kumar Bimlesh , Pandey Narendra Kumar , Gupta Gaurav , Dureja Harish , Chellapan Dinesh Kumar , Dua Kamal , Tewari Devesh , Singh Sachin Kumar
Published: November 2022

The study was initiated with two major purposes: investigating the role of isomalt (GIQ9) as a pharmaceutical carrier for solid self-nanoemulsifying drug delivery systems (S-SNEDDSs) and improving the oral bioavailability of lipophilic curcumin (CUN). GIQ9 has never been explored for solidification of liquid lipid-based nanoparticles such as a liquid isotropic mixture of a SNEDDS containing oil, surfactant and co-surfactant. The suitability of GIQ9 as a carrier was assessed by calculating the loading factor, flow and micromeritic properties. The S-SNEDDSs were prepared by surface adsorption technique. The formulation variables were optimized using central composite design (CCD). The optimized S-SNEDDS was evaluated for differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), microscopy, dissolution and pharmacokinetic studies. The S-SNEDDS showed a particle size, zeta potential and PDI of 97 nm, −26.8 mV and 0.354, respectively. The results of DSC, XRD, FTIR and microscopic studies revealed that the isotropic mixture was adsorbed onto the solid carrier. The L-SNEDDS and S-SNEDDS showed no significant difference in drug release, indicating no change upon solidification. The optimized S-SNEDDS showed 5.1-fold and 61.7-fold enhancement in dissolution rate and oral bioavailability as compared to the naïve curcumin. The overall outcomes of the study indicated the suitability of GIQ9 as a solid carrier for SNEDDSs.
Microbubble–Nanoparticle Complexes for Ultrasound-Enhanced Cargo Delivery
Authors: Chapla Rachel , Huynh Katherine T. , Schutt Carolyn E.
Published: November 2022

Targeted delivery of therapeutics to specific tissues is critically important for reducing systemic toxicity and optimizing therapeutic efficacy, especially in the case of cytotoxic drugs. Many strategies currently exist for targeting systemically administered drugs, and ultrasound-controlled targeting is a rapidly advancing strategy for externally-stimulated drug delivery. In this non-invasive method, ultrasound waves penetrate through tissue and stimulate gas-filled microbubbles, resulting in bubble rupture and biophysical effects that power delivery of attached cargo to surrounding cells. Drug delivery capabilities from ultrasound-sensitive microbubbles are greatly expanded when nanocarrier particles are attached to the bubble surface, and cargo loading is determined by the physicochemical properties of the nanoparticles. This review serves to highlight and discuss current microbubble–nanoparticle complex component materials and designs for ultrasound-mediated drug delivery. Nanocarriers that have been complexed with microbubbles for drug delivery include lipid-based, polymeric, lipid–polymer hybrid, protein, and inorganic nanoparticles. Several schemes exist for linking nanoparticles to microbubbles for efficient nanoparticle delivery, including biotin–avidin bridging, electrostatic bonding, and covalent linkages. When compared to unstimulated delivery, ultrasound-mediated cargo delivery enables enhanced cell uptake and accumulation of cargo in target organs and can result in improved therapeutic outcomes. These ultrasound-responsive delivery complexes can also be designed to facilitate other methods of targeting, including bioactive targeting ligands and responsivity to light or magnetic fields, and multi-level targeting can enhance therapeutic efficacy. Microbubble–nanoparticle complexes present a versatile platform for controlled drug delivery via ultrasound, allowing for enhanced tissue penetration and minimally invasive therapy. Future perspectives for application of this platform are also discussed in this review.
Implementation of a Health Risk Assessment into Workflow of the Appointment-Based Model at an Independent Community Pharmacy
Authors: Jackson Erica , McGrath Stephanie Harriman , Carroll Joni C. , McGivney Melissa Somma , Pitzarella Samantha , Coley Kim C.
Published: November 2022

Health risk assessments (HRAs) are tools used to collect information on patients’ current health conditions, personal and family medical history, and lifestyle factors that can impact their overall health. The objectives of this pilot project were to implement an HRA as part of the appointment-based model workflow and to assess the resulting pharmacy-patient-care service opportunities. Sixteen HRA questions from a single health plan were incorporated into the appointment-based model workflow at an independent community pharmacy. Questions were administered either telephonically or in person over two patient encounters. Pharmacy staff were trained on how to administer the HRA, what to do if patients needed immediate assistance, how to provide referrals, and how to document of responses. Forty-nine patients were contacted and 38 (77.6%) completed the HRA. The median time for HRA completion was 19 min and the identified opportunities were vaccination (49), smoking cessation (15), diabetes prevention program (14), asthma control assessments (8), and substance use disorder screening and referral (3). This pilot project demonstrates that community pharmacies can implement HRAs and utilize the results to identify new pharmacy-patient-care service opportunities that can contribute to improved patient care and practice sustainability.
Influences of Crystallinity and Crosslinking Density on the Shape Recovery Force in Poly(ε-Caprolactone)-Based Shape-Memory Polymer Blends
Authors: Fulati Ailifeire , Uto Koichiro , Ebara Mitsuhiro
Published: November 2022

Shape-memory polymers (SMPs) show great potential in various emerging applications, such as artificial muscles, soft actuators, and biomedical devices, owing to their unique shape recovery-induced contraction force. However, the factors influencing this force remain unclear. Herein, we designed a simple polymer blending system using a series of tetra-branched poly(ε-caprolactone)-based SMPs with long and short branch-chain lengths that demonstrate decreased crystallinity and increased crosslinking density gradients. The resultant polymer blends possessed mechanical properties manipulable across a wide range in accordance with the crystallinity gradient, such as stretchability (50.5–1419.5%) and toughness (0.62–130.4 MJ m−3), while maintaining excellent shape-memory properties. The experimental results show that crosslinking density affected the shape recovery force, which correlates to the SMPs’ energy storage capacity. Such a polymer blending system could provide new insights on how crystallinity and crosslinking density affect macroscopic thermal and mechanical properties as well as the shape recovery force of SMP networks, improving design capability for future applications.
Using PVA and Attapulgite for the Stabilization of Clayey Soil
Authors: He Chengzong , Hu Guochang , Mei Hong , Zhu Xiaoyong , Xue Jian , Liu Jin , Zhang Faming , Che Wenyue , Chen Zhihao , Song Zezhuo
Published: November 2022

Considering that, in the context of the ecological restoration of a large number of exposed rock slopes, it is difficult for existing artificial soil to meet the requirements of mechanical properties and ecological construction at the same time, this paper investigates the stabilization benefits of polyvinyl acetate and attapulgite-treated clayey soil through a series of laboratory experiments. To study the effectiveness of polyvinyl acetate (PVA) and attapulgite as soil stabilizer, a triaxial strength test, an evaporation test and a vegetation growth test were carried out on improved soil with different amounts of PVA content (0, 1%, 2%, 3%, and 4%) and attapulgite replacement (0, 2%, 4%, 6%, and 8%). The results show that the single and composite materials of polyvinyl acetate and attapulgite can increase the peak deviator stress of the sample. The addition of polyvinyl acetate can improve the soil strength by increasing the cohesion of the sample; the addition of attapulgite improves the soil strength mainly by increasing the internal friction angle of the sample. The strength of the composite is greatly improved by increasing the cohesion and internal friction angle of the sample at the same time. The effect of adding materials increased significantly with increasing curing age. Moreover, polyvinyl acetate and attapulgite improve the soil water retention of the soil by improving the water-holding capacity, so that the soil can still ensure the good growth of vegetation under long-term drought conditions. The scanning electron microscopy (SEM) images indicated that the PVA and attapulgite of soil affect the strength characteristics of soil specimens by the reaction of PVA and water, which changes the structure of the soil and, by the interweaving of attapulgite soil particles, acts as the skeleton of the aggregate. Overall, PVA and attapulgite can effectively increase clayey soil stability by improving the cohesive force and internal friction angle of clayey soil.
Chitosan-Boric Acid Scaffolds for Doxorubicin Delivery in the Osteosarcoma Treatment
Authors: Dornjak Luka , Kovačić Marin , Ostojić Karla , Angaits Ange , Szpunar Joanna , Urlić Inga , Rogina Anamarija
Published: November 2022

Biologically compatible chitosan-based scaffolds have been considered a promising platform for tissue regeneration, tumor treatment, and targeted drug delivery. Chitosan-based scaffolds can be utilized as pH-sensitive drug carriers with targeted drug delivery resulting in less invasive tumor treatments. Further improvement with bioactive ions, such as borate ions, can result in the dual functionality of chitosan carriers provided by simultaneous antitumor efficacy and tissue regeneration. Here, boric acid-containing crosslinked chitosan scaffolds were prepared as delivery systems of doxorubicin, a chemotherapy drug used in the treatment of osteosarcoma. The encapsulation of boric acid was indicated by FTIR spectroscopy, while the ICP-MS analysis indicated the rapid release of boron in phosphate buffer (pH 6.0) and phosphate-buffered saline solution (pH 7.4). The obtained chitosan-boric acid scaffolds exhibit a highly porous and interconnected structure responsible for high swelling capacity, while enzymatic degradation indicated good scaffolds stability during four weeks of incubation at pH 6.0 and 7.4. Furthermore, the release of doxorubicin investigated in phosphate buffers indicated lower doxorubicin concentrations at pH 7.4 with respect to pH 6.0. Finally, the cytotoxicity of prepared doxorubicin-encapsulated scaffolds was evaluated on human sarcoma cells indicating the scaffolds’ potential as cytostatic agents.
Multicomponent Comminution within a Stirred Media Mill and Its Application for Processing a Lithium-Ion Battery Slurry
Authors: Nöske Markus , Müller Jannes , Nowak Christine , Li Kangqi , Xu Xiaolu , Breitung-Faes Sandra , Kwade Arno
Published: November 2022

This study presents an approach for targeted comminution of component mixtures within a wet-operated stirred media mill. In the first step, a general understanding of the interactions between individual components on the grinding result with mixtures could be gained with basic experiments and following our former research work. In particular, a protective effect of the coarser particles on the fines could be elucidated. These findings were used to develop a process for the production of a battery slurry containing fine ground silicon particles as well as dispersed carbon black and graphite particles. By a tailored sample preparation applying a combination of particle dissolution and separation, the particle size distributions of carbon black and graphite particles were analyzed separately within the produced battery slurries. Based on the selective particle size analysis, the slurry preparation could be transferred from a complex multistage batch process using a dissolver to a stirred media mill, which was finally operated in a continuous one-passage mode. The prepared slurries were subsequently further processed to silicon-rich anodes using a pilot scale coating and drying plant. Afterward, the produced anodes were electrochemically characterized in full cells. The cell results prove a comparable electrochemical behavior of anode coatings derived from a dissolver- or mill-based slurry production process. Therefore, we could demonstrate that it is possible to integrate the mixing process for the production of multicomponent slurries into the comminution process for the preparation of individual materials upstream. Even with nearly identical starting sizes of their feed materials, the targeted particle size distributions of the single components can be reached, taking into account the different material-dependent particle strengths and sequential addition of single components to the multicomponent comminution process.
Monitoring Asbestos Mine Remediation Using Airborne Hyperspectral Imaging System: A Case Study of Jefferson Lake Mine, US
Authors: Jeong Yongsik , Yu Jaehyung , Wang Lei , Huynh Huy Hoa , Kim Hyun-Cheol
Published: November 2022

This study investigated an asbestos mine restoration project using Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) hyperspectral data. The distribution of an abandoned asbestos mine (AAM) and treatment area were analyzed before and after the remediation based on the spectral indices for detecting naturally occurring asbestos (NOA) indicators and encapsulation. The spectral indices were developed for NOA, host rock, and encapsulation by logistic regression models using spectral bands extracted from the random forest algorithm. The detection models mostly used VNIR spectra rather than SWIR and were statistically significant. The overall accuracy of the detection models was approximately 84%. Notably, the detection accuracy of non-treated and treated areas was increased to about 96%, excluding the host rock index. The NOA index detected asbestos in the mine area as well as those in outcrops outside of the mine. It has been confirmed that the NOA index can be efficiently applied to all cases of asbestos occurrence. The remote sensing data revealed that the mine area was increased by ~5% by the remediation, and the treatment activity reduced asbestos exposure by ~32%. Moreover, the integrative visualization between the detection results and 3D high-resolution images provided an intuitive and realistic understanding of the reclamation project.