bluuebunny/crossref_metadata_2025 huggingface dataset:
The Urine Metabolome of R6/2 and zQ175DN Huntington’s Disease Mouse Models
Authors: Speziale Roberto , Montesano Camilla , Di Pietro Giulia , Cicero Daniel Oscar , Summa Vincenzo , Monteagudo Edith , Orsatti Laura
Published: August 2023

Huntington’s disease (HD) is caused by the expansion of a polyglutamine (polyQ)-encoding tract in exon 1 of the huntingtin gene to greater than 35 CAG repeats. It typically has a disease course lasting 15–20 years, and there are currently no disease-modifying therapies available. Thus, there is a need for faithful mouse models of HD to use in preclinical studies of disease mechanisms, target validation, and therapeutic compound testing. A large variety of mouse models of HD were generated, none of which fully recapitulate human disease, complicating the selection of appropriate models for preclinical studies. Here, we present the urinary liquid chromatography–high-resolution mass spectrometry analysis employed to identify metabolic alterations in transgenic R6/2 and zQ175DN knock-in mice. In R6/2 mice, the perturbation of the corticosterone metabolism and the accumulation of pyrraline, indicative of the development of insulin resistance and the impairment of pheromone excretion, were observed. Differently from R6/2, zQ175DN mice showed the accumulation of oxidative stress metabolites. Both genotypes showed alterations in the tryptophan metabolism. This approach aims to improve our understanding of the molecular mechanisms involved in HD neuropathology, facilitating the selection of appropriate mouse models for preclinical studies. It also aims to identify potential biomarkers specific to HD.
Automatic Assignment of Molecular Ion Species to Elemental Formulas in Gas Chromatography/Methane Chemical Ionization Accurate Mass Spectrometry
Authors: Wang Shunyang , Valdiviez Luis , Ye Honglian , Fiehn Oliver
Published: August 2023

Gas chromatography–mass spectrometry (GC-MS) usually employs hard electron ionization, leading to extensive fragmentations that are suitable to identify compounds based on library matches. However, such spectra are less useful to structurally characterize unknown compounds that are absent from libraries, due to the lack of readily recognizable molecular ion species. We tested methane chemical ionization on 369 trimethylsilylated (TMS) derivatized metabolites using a quadrupole time-of-flight detector (QTOF). We developed an algorithm to automatically detect molecular ion species and tested SIRIUS software on how accurate the determination of molecular formulas was. The automatic workflow correctly recognized 289 (84%) of all 345 detected derivatized standards. Specifically, strong [M − CH3]+ fragments were observed in 290 of 345 derivatized chemicals, which enabled the automatic recognition of molecular adduct patterns. Using Sirius software, correct elemental formulas were retrieved in 87% of cases within the top three hits. When investigating the cases for which the automatic pattern analysis failed, we found that several metabolites showed a previously unknown [M + TMS]+ adduct formed by rearrangement. Methane chemical ionization with GC-QTOF mass spectrometry is a suitable avenue to identify molecular formulas for abundant unknown peaks.
A Solid-Phase Microextraction—Liquid Chromatography-Mass Spectrometry Method for Analyzing Serum Lipids in Psoriatic Disease
Authors: Koussiouris John , Looby Nikita , Kulasingam Vathany , Chandran Vinod
Published: August 2023

Approximately 25% of psoriasis patients have an inflammatory arthritis termed psoriatic arthritis (PsA). There is strong interest in identifying and validating biomarkers that can accurately and reliably predict conversion from psoriasis to PsA using novel technologies such as metabolomics. Lipids, in particular, are of key interest in psoriatic disease. We sought to develop a liquid chromatography-mass spectrometry (LC-MS) method to be used in conjunction with solid-phase microextraction (SPME) for analyzing fatty acids and similar molecules. A total of 25 chromatographic methods based on published lipid studies were tested on two LC columns. As a proof of concept, serum samples from psoriatic disease patients (n = 27 psoriasis and n = 26 PsA) were processed using SPME and run on the selected LC-MS method. The method that was best for analyzing fatty acids and fatty acid-like molecules was optimized and applied to serum samples. A total of 18 tentatively annotated features classified as fatty acids and other lipid compounds were statistically significant between psoriasis and PsA groups using both multivariate and univariate approaches. The SPME-LC-MS method developed and optimized was capable of detecting fatty acids and similar lipids that may aid in differentiating psoriasis and PsA patients.
An Analytical Model of Dynamic Power Losses in eGaN HEMT Power Devices
Authors: Lei Jianming , Liu Yangyi , Yang Zhanmin , Chen Yalin , Chen Dunjun , Xu Liang , Yu Jing
Published: August 2023

In this work, we present an analytical model of dynamic power losses for enhancement-mode AlGaN/GaN high-electron-mobility transistor power devices (eGaN HEMTs). To build this new model, the dynamic on-resistance (Rdson) is first accurately extracted via our extraction circuit based on a double-diode isolation (DDI) method using a high operating frequency of up to 1 MHz and a large drain voltage of up to 600 V; thus, the unique problem of an increase in the dynamic Rdson is presented. Then, the impact of the current operation mode on the on/off transition time is evaluated via a dual-pulse-current-mode test (DPCT), including a discontinuous conduction mode (DCM) and a continuous conduction mode (CCM); thus, the transition time is revised for different current modes. Afterward, the discrepancy between the drain current and the real channel current is qualitative investigated using an external shunt capacitance (ESC) method; thus, the losses due to device parasitic capacitance are also taken into account. After these improvements, the dynamic model will be more compatible for eGaN HEMTs. Finally, the dynamic power losses calculated via this model are found to be in good agreement with the experimental results. Based on this model, we propose a superior solution with a quasi-resonant mode (QRM) to achieve lossless switching and accelerated switching speeds.
Study on the Effect of Cold Deformation and Heat Treatment on the Properties of Cu-Ag Alloy Wire
Authors: Wu Xuefeng , Jia Hewei , Fan Junling , Cao Jun , Su Chenghao
Published: August 2023

The effects of various drawing parameters and annealing processes on the structure and properties of Cu-Ag wires, containing 1 wt% silver, were investigated using specialized equipment including fine wire-drawing machines, very fine wire-drawing machines, heat treatment equipment, tensile testing machines, microcomputer-controlled electronic universal testers, resistance testers, and scanning electron microscopes. The results revealed that continuous drawing of Cu-1%Ag alloy wires led to elongation of the grains, resulting in a uniform and tightly fibrous microstructure. Moreover, the tensile strength of the alloy wire increased from 670 MPa to 783.9 MPa after a single pass with a deformation of 14%. Subsequently, when the wire was drawn at a speed of 500 m/min, the tensile strength further increased to 820.1 MPa. After annealing the Փ0.08 mm Cu-1% Ag alloy wire, an increase in annealing temperature up to 500 °C resulted in the wire’s tensile strength decreasing from 820.1 MPa to 377.5 MPa. Simultaneously, the elongation increased from 1.94% to 15.21%, and the resistivity decreased from 1.931 × 10−8 Ω·m to 1.723 × 10−8 Ω·m. Additionally, when annealing was conducted at a rate of 80 m/min, the wire resistivity dropped to 1.635 × 10−8 Ω·m.
Junction Temperature Optical Sensing Techniques for Power Switching Semiconductors: A Review
Authors: Isa Ridwanullahi , Mirza Jawad , Ghafoor Salman , Mustafa Khan Mohammed Zahed , Qureshi Khurram Karim
Published: August 2023

Recent advancements in power electronic switches provide effective control and operational stability of power grid systems. Junction temperature is a crucial parameter of power-switching semiconductor devices, which needs monitoring to facilitate reliable operation and thermal control of power electronics circuits and ensure reliable performance. Over the years, various junction temperature measurement techniques have been developed, engaging both non-optical and optical-based methods, highlighting their advancements and challenges. This review focuses on several optical sensing-based junction temperature measuring techniques used for power-switching devices such as metal-oxide-semiconductor field-effect transistors (MOSFETs) and insulated-gate bipolar transistors (IGBTs). A comprehensive summary of recent developments in infrared camera (IRC), thermal sensitive optical parameter (TSOP), and fiber Bragg grating (FBG) temperature sensing techniques is provided, shedding light on their merits and challenges while providing a few possible future solutions. In addition, calibration methods and remedies for obtaining accurate measurements are discussed, thus providing better insight and directions for future research.
Flexible and Stretchable Pressure Sensors: From Basic Principles to State-of-the-Art Applications
Authors: Seesaard Thara , Wongchoosuk Chatchawal
Published: August 2023

Flexible and stretchable electronics have emerged as highly promising technologies for the next generation of electronic devices. These advancements offer numerous advantages, such as flexibility, biocompatibility, bio-integrated circuits, and light weight, enabling new possibilities in diverse applications, including e-textiles, smart lenses, healthcare technologies, smart manufacturing, consumer electronics, and smart wearable devices. In recent years, significant attention has been devoted to flexible and stretchable pressure sensors due to their potential integration with medical and healthcare devices for monitoring human activity and biological signals, such as heartbeat, respiratory rate, blood pressure, blood oxygen saturation, and muscle activity. This review comprehensively covers all aspects of recent developments in flexible and stretchable pressure sensors. It encompasses fundamental principles, force/pressure-sensitive materials, fabrication techniques for low-cost and high-performance pressure sensors, investigations of sensing mechanisms (piezoresistivity, capacitance, piezoelectricity), and state-of-the-art applications.
Biohybrid Soft Robots Powered by Myocyte: Current Progress and Future Perspectives
Authors: Yuan Zheng , Guo Qinghao , Jin Delu , Zhang Peifan , Yang Wenguang
Published: August 2023

Myocyte-driven robots, a type of biological actuator that combines myocytes with abiotic systems, have gained significant attention due to their high energy efficiency, sensitivity, biocompatibility, and self-healing capabilities. These robots have a unique advantage in simulating the structure and function of human tissues and organs. This review covers the research progress in this field, detailing the benefits of myocyte-driven robots over traditional methods, the materials used in their fabrication (including myocytes and extracellular materials), and their properties and manufacturing techniques. Additionally, the review explores various control methods, robot structures, and motion types. Lastly, the potential applications and key challenges faced by myocyte-driven robots are discussed and summarized.
Surface Characteristics Affect the Properties of PLGA Nanoparticles as Photothermal Agents
Authors: Kovalenko Vera L. , Kolesnikova Olga A. , Nikitin Maxim P. , Shipunova Victoria O. , Komedchikova Elena N.
Published: August 2023

Photothermal therapy is one of the most promising and rapidly developing fields in modern oncology due to its high efficiency, localized action, and minimal invasiveness. Polymeric nanoparticles (NPs) incorporating low molecular-weight photothermal dyes are capable of delivering therapeutic agents to the tumor site, releasing them in a controlled manner, and providing tumor treatment under external light irradiation. The nanoparticle synthesis components are critically important factors that influence the therapeutically significant characteristics of polymeric NPs. Here, we show the impact of stabilizers and solvents used for synthesis on the properties of PLGA NPs for photothermal therapy. We synthesized PLGA nanocarriers using the microemulsion method and varied the nature of the solvent and the concentration of the stabilizer—namely, chitosan oligosaccharide lactate. A phthalocyanine-based photosensitizer, which absorbs light in the NIR window, was encapsulated in the PLGA NPs. When mQ water was used as a solvent and chitosan oligosaccharide lactate was used at a concentration of 1 g/L, the PLGA NPs exhibited highly promising photothermal properties. The final composite of the nanocarriers demonstrated photoinduced cytotoxicity against EMT6/P cells under NIR laser irradiation in vitro and was suitable for bioimaging.
Construction of Recombinant Escherichia coli with a High L-Phenylalanine Production Yield from Glucose
Authors: Gu Pengfei , Zhao Shuo , Li Chengwei , Jiang Shuixing , Zhou Hao , Li Qiang
Published: August 2023

L-phenylalanine is an important aromatic amino acid that is widely used in the area of feed, food additives, and pharmaceuticals. Among the different strategies of L-phenylalanine synthesis, direct microbial fermentation from raw substrates has attracted more and more attention due to its environment friendly process and low-cost raw materials. In this study, a rational designed recombinant Escherichia coli was constructed for L-phenylalanine production. Based on wild type E. coli MG1655, multilevel engineering strategies were carried out, such as directing more carbon flux into the L-phenylalanine synthetic pathway, increasing intracellular level of precursors, blocking by-product synthesis pathways and facilitating the secretion of L-phenylalanine. During 5 L fed batch fermentation, recombinant E. coli MPH-3 could produce 19.24 g/L of L-phenylalanine with a yield of 0.279 g/g glucose. To the best of our knowledge, this is one of the highest yields of L-phenylalanine producing E. coli using glucose as the sole carbon source in fed-batch fermentation.
Heat-Labile Enterotoxin Decreases Macrophage Phagocytosis of Enterotoxigenic Escherichia coli
Authors: Hollifield Ian E. , Motyka Natalya I. , Fernando Kaylynn A. , Bitoun Jacob P.
Published: August 2023

Enterotoxigenic E. coli (ETEC) are endemic in low-resource settings and cause robust secretory diarrheal disease in children less than five years of age. ETEC cause secretory diarrhea by producing the heat-stable (ST) and/or heat-labile (LT) enterotoxins. Recent studies have shown that ETEC can be carried asymptomatically in children and adults, but how ETEC subvert mucosal immunity to establish intestinal residency remains unclear. Macrophages are innate immune cells that can be exploited by enteric pathogens to evade mucosal immunity, so we interrogated the ability of ETEC and other E. coli pathovars to survive within macrophages. Using gentamicin protection assays, we show that ETEC H10407 is phagocytosed more readily than other ETEC and non-ETEC isolates. Furthermore, we demonstrate that ETEC H10407, at high bacterial burdens, causes nitrite accumulation in macrophages, which is indicative of a proinflammatory macrophage nitric oxide killing response. However, at low bacterial burdens, ETEC H10407 remains viable within macrophages for an extended period without nitrite accumulation. We demonstrate that LT, but not ST, intoxication decreases the number of ETEC phagocytosed by macrophages. Furthermore, we now show that macrophages exposed simultaneously to LPS and LT produce IL-33, which is a cytokine implicated in promoting macrophage alternative activation, iron recycling, and intestinal repair. Lastly, iron restriction using deferoxamine induces IL-33 receptor (IL-33R) expression and allows ETEC to escape macrophages. Altogether, these data demonstrate that LT provides ETEC with the ability to decrease the perceived ETEC burden and suppresses the initiation of inflammation. Furthermore, these data suggest that host IL-33/IL-33R signaling may augment pathways that promote iron restriction to facilitate ETEC escape from macrophages. These data could help explain novel mechanisms of immune subversion that may contribute to asymptomatic ETEC carriage.
Pediatric Osteoarticular Kingella kingae Infections of the Hand and Wrist: A Retrospective Study
Authors: Cochard Blaise , Gurbanov Elvin , Bazin Ludmilla , De Marco Giacomo , Vazquez Oscar , Di Laura Frattura Giorgio , Steiger Christina N. , Dayer Romain , Ceroni Dimitri
Published: August 2023

Our understanding of pediatric osteoarticular infections (OAIs) has improved significantly in recent decades. Kingella kingae is now recognized as the most common pathogen responsible for OAIs in pediatric populations younger than 4 years old. Research has provided a better understanding of the specific types, clinical characteristics, biological repercussions, and functional outcomes of these infections. Hands and wrists are rarely infected, with few reports available in the literature. The present study aimed to examine this specific condition in a large patient cohort, explore the implications for each anatomical area using magnetic resonance imaging (MRI), and critically evaluate the evolution of therapeutic management.
Investigating the Formation of Hot-Dry Rock in Gonghe Basin, Qinghai, China
Authors: Yang Yang , Chen Fangbo , Yu Siliu , Zheng Yubin , He Sujie , Zeng Yan , Xie Xiaoli , Zhu Jie , Luo Nan
Published: August 2023

The Gonghe Basin, Qinghai Province, China, has rich geothermal and hot-dry rock resources. Through a magnetotelluric survey line with 400 points, combined with regional geology data, the deep geoelectrical structural background and thermal source mechanisms of the Gonghe Basin were explored. The results showed that (1) a deep structure with high conductivity may exist at a depth of 15 km in the basin, and could be compared to the layer-shaped, low-velocity, high-conductivity structure in the eastern part of the Qinghai–Tibet Plateau; (2) the rushing reverse fault played a crucial role in heat control and conduction from the hot field; and (3) high-temperature heat storage existed, including four layers of geothermal resources. This study proposed a triple-polymorphism model of hot-dry rock in the area; that is, the high-conductivity layer in the Middle–Late Cenozoic crust was the principal heat source; the Middle–Late Triassic granite was the essential heat-storing body, as well as a parent rock to the hot-dry rock; and the Cenozoic sedimentary rock was the effective caprock. This model is critical to understanding geothermal causes, predicting geothermal resources, and planning, on the Qinghai–Tibet Plateau.
A Comparative Study of Malonic and l-Glutamic Acids for Metal Leaching from Spent Lithium-Ion Batteries: Kinetic and Optimization Analysis
Authors: Sohbatzadeh Laleh , Shafaei Tonkaboni Sied , Noaparast Mohammad , Entezari-Zarandi Ali
Published: August 2023

In this research, two different hydrometallurgical processes were introduced for recycling the cathodes of lithium-ion batteries (LIBs) from spent LIBs. The cathode materials were leached by malonic acid (MOA), as a leaching agent, and ascorbic acid (AA), as a reducing agent, in the first process, and by l-Glutamic acid (l-Glu), as a leaching agent, and AA, as a reducing agent, in the second process. The results of the tests showed that, with a similar solid-to-liquid (S/L) ratio of 10 g/L and a recovery time of 2 h for both processes, when using MOA of 0.25 M and AA of 0.03 M at 88 °C, 100% lithium (Li), 80% cobalt (Co), 99% nickel (Ni), and 98% manganese (Mn) were extracted, and when using l-Glu of 0.39 M and AA of 0.04 M at 90 °C, 100% Li, 79% Co, 91% Ni, and 92% Mn were extracted. The kinetics of the leaching process for the two systems were well justified by the Avrami equation, which was diffusion-controlled in the MOA + AA system, with the apparent activation energy of 3.23, 14.72, 7.77, and 7.36 kJ/mol for Mn, Ni, Co, and Li, respectively. The l-Glu + AA involved chemical-diffusion kinetic control, with the apparent activation energy for Mn, Ni, Co, and Li of 9.95, 29.42, 20.15, and 16.08 kJ/mol, respectively. Various characterization techniques were used to explain the observed synergistic effect in the l-Glu + AA system, which resulted in reduced acid consumption and enhanced recovery compared to the case of MOA + AA. This occurred because l-Glu is not able to reduce and recover metals without a reductant, while MOA has reductant properties.
Ancient Metasomatism in the Lithospheric Mantle, Eastern North China Craton: Insights from In-Situ Major and Trace Elements in Garnet Xenocrysts, Mengyin District
Authors: Wang Hao-Shuai , Yang Li-Qiang , Chu Zhi-Yuan , Zhang Liang , Li Nan , He Wen-Yan , Zhang Ya-Nan , Wang Yi-Qi
Published: August 2023

Mantle metasomatism refers to the interaction between mantle melt, fluid, and mantle rock. It not only affects the physical and chemical properties of the lithospheric mantle but also plays an important role in the process of metal and gem mineralization. In order to explore the nature and evolution of metasomatism in the lithospheric mantle of the Mengyin area in the eastern part of the North China Craton, this paper combines the previous data of garnet inclusions in diamonds and analyzes the major and trace elements of garnet xenocrysts in the Shengli No. 1 kimberlite pipe from the EPMA and LA-ICP-MS experiments. The experiments show that the garnet xenocrysts of the Shengli No. 1 kimberlite pipe are mainly lherzolitic and harzburgitic garnets. The content of Zr and TiO2 in some garnets are low, which are the characteristics of depleted garnets. Conversely, another group of garnets display high Zr and TiO2 contents, indicative of high-temperature melt metasomatism. When comparing the Ti/Eu ratio of the depleted garnets to that of the primary mantle, a significantly lower value is observed. Additionally, the (Sm/Er)N value undergoes minimal changes, while the Zr/Hf value exceeds that of the primary mantle. These characteristics are indicators of carbonatite melt metasomatism. Garnets that are affected by high-temperature melt metasomatism exhibit low (Sm/Er)N content, a significant variation in the Ti/Eu ratio, and a Zr/Hf value greater than that of the primary mantle. These characteristics indicate the influence of kimberlite melt metasomatism. Garnets impacted by carbonatite melt metasomatism display a strong sinusoidal distribution pattern of rare earth elements (REE) and are often found as lherzolitic garnet xenocrysts and garnet inclusions in diamond. On the other hand, garnets influenced by kimberlite melt metasomatism exhibit a slight sinusoidal REE distribution pattern in harzburgitic garnets and a slight sinusoidal REE distribution or a flat pattern from medium rare earth elements (MREEs) to heavy rare earth elements (HREEs) in lherzolitic garnet xenocrysts. Based on these findings, it is evident that there are at least two types of metasomatism occurring in the lithospheric mantle of the Mengyin area in the eastern part of the North China Craton. The first type involves the metasomatism of early carbonatite melt to the mantle peridotite. Garnets formed under this condition exhibit high Sr and LREE contents, as well as low Zr, Hf, Ti, Y, and HREE contents, indicating depletion characteristics. The second type entails the metasomatism of late kimberlite melts affecting the mantle peridotite. Garnets formed under this process display high Zr, Hf, Ti, Y, and HREE contents.
Synthesis and Biological Evaluation of Novel 2-Amino-1,4-Naphthoquinone Amide-Oxime Derivatives as Potent IDO1/STAT3 Dual Inhibitors with Prospective Antitumor Effects
Authors: Huang Ri-Zhen , Liang Qiao-Ling , Jing Xiao-Teng , Wang Ke , Zhang Hui-Yong , Wang Heng-Shan , Ma Xian-Li , Wei Jian-Hua , Zhang Ye
Published: August 2023

Indoleamine-2,3-dioxygenase 1 (IDO1) and signal transducer and activator of transcription 3 (STAT3) have emerged as significant targets in the tumor microenvironment for cancer therapy. In this study, we synthesized three novel 2-amino-1,4-naphthoquinone amide-oxime derivatives and identified them as dual inhibitors of IDO1 and STAT3. The representative compound NK3 demonstrated effective binding to IDO1 and exhibited good inhibitory activity (hIDO1 IC50 = 0.06 μM), leading to its selection for further investigation. The direct interactions between compound NK3 and IDO1 and STAT3 proteins were confirmed through surface plasmon resonance analysis. A molecular docking study of compound NK3 revealed key interactions between NK3 and IDO1, with the naphthoquinone-oxime moiety coordinating with the heme iron. In the in vitro anticancer assay, compound NK3 displayed potent antitumor activity against selected cancer cell lines and effectively suppressed nuclear translocation of STAT3. Moreover, in vivo assays conducted on CT26 tumor-bearing Balb/c mice and an athymic HepG2 xenograft model revealed that compound NK3 exhibited potent antitumor activity with low toxicity relative to 1-methyl-L-tryptophan (1-MT) and doxorubicin (DOX). Overall, these findings provided evidence that the dual inhibitors of IDO1 and STAT3 may offer a promising avenue for the development of highly effective drug candidates for cancer therapy.
Chemical Investigations in Kelussia odoratissima Mozaff. Leaves Based on Comprehensive Analytical Methods: LC-MS, SPME, and GC-MS Analyses
Authors: Rahimmalek Mehdi , Szumny Antoni , Gharibi Shima , Pachura Natalia , Miroliaei Mehran , Łyczko Jacek
Published: August 2023

Kelussia odoratissima Mozaff. is a species of Apiaceae endemic to the Zagros Mountains in Iran. In the present investigation, for the first time, the polyphenolic compounds and flavonoids of its leaves were determined by liquid chromatography-mass spectrometry (LC-MS). As a result, p-coumaric acid, ferulic acid, caffeic acid, chlorogenic acid, acetyl phloroglucinol, vanillic acid, m-coumaric acid, and 4-methylsiringol were determined as the main phenolic compounds, while 3-hydroxyflavone, flavone, quercetin, rutin, neohesperidin, polydatin, and diosmin were the main flavonoid components, of which chlorogenic acid (303.08 µL/gDW), neohesperidin (38.37 µL/gDw), and diosmin (28.62 µL/gDW) were the most abundant. Solid-phase microextraction (SPME) was also used to determine the chemical compounds. Based on SPME, (Z)-undec-6-en-2-one (17.48%) and (Z)-butylidenephthalide (4.348%) were the major components. Based on GC-MS analyses, (Z)-ligustilide was the main compound; however, some new compounds were also determined, including 3-ethylisobenzofuran-1 (3H)-one, (E)-ligugustilide, and E-n-butylidene phthalide. Also, for the first time, we have identified EOs ethyl and isobutyl phthalides on the basis of the obtained EI-MS spectra. Finally, the fragmentation of phthalides is also discussed in this research.
Glycyrrhiza glabra L. Extracts and Other Therapeutics against SARS-CoV-2 in Central Eurasia: Available but Overlooked
Authors: Zhurinov Murat Zh. , Miftakhova Alfira F. , Keyer Viktoriya , Shulgau Zarina T. , Solodova Elena V. , Kalykberdiyev Maxat K. , Abilmagzhanov Arlan Z. , Talgatov Eldar T. , Ait Sauyk , Shustov Alexandr V.
Published: August 2023

In Central Eurasia, the availability of drugs that are inhibitors of the SARS-CoV-2 virus and have proven clinical efficacy is still limited. The aim of this study was to evaluate the activity of drugs that were available in Kazakhstan during the acute phase of the epidemic against SARS-CoV-2. Antiviral activity is reported for Favipiravir, Tilorone, and Cridanimod, which are registered drugs used for the treatment of respiratory viral infections in Kazakhstan. A licorice (Glycyrrhiza glabra) extract was also incorporated into this study because it offered an opportunity to develop plant-derived antivirals. The Favipiravir drug, which had been advertised in local markets as an anti-COVID cure, showed no activity against SARS-CoV-2 in cell cultures. On the contrary, Cridanimod showed impressive high activity (median inhibitory concentration 66 μg/mL) against SARS-CoV-2, justifying further studies of Cridanimod in clinical trials. Tilorone, despite being in the same pharmacological group as Cridanimod, stimulated SARS-CoV-2 replication in cultures. The licorice extract inhibited SARS-CoV-2 replication in cultures, with a high median effective concentration of 16.86 mg/mL. Conclusions: The synthetic, low-molecular-weight compound Cridanimod suppresses SARS-CoV-2 replication at notably low concentrations, and this drug is not toxic to cells at therapeutic concentrations. In contrast to its role as an inducer of interferons, Cridanimod is active in cells that have a genetic defect in interferon production, suggesting a different mechanism of action. Cridanimod is an attractive drug for inclusion in clinical trials against SARS-CoV-2 and, presumably, other coronaviruses. The extract from licorice shows low activity against SARS-CoV-2. At the same time, high doses of 2 g/kg of this plant extract show little or no acute toxicity in animal studies; for this reason, licorice products can still be considered for further development as a safe, orally administered adjunctive therapy.
Structural Studies of Monounsaturated and ω-3 Polyunsaturated Free Fatty Acids in Solution with the Combined Use οf NMR and DFT Calculations—Comparison with the Liquid State
Authors: Venianakis Themistoklis , Siskos Michael G. , Papamokos George , Gerothanassis Ioannis P.
Published: August 2023

Molecular structures, in chloroform and DMSO solution, of the free fatty acids (FFAs) caproleic acid, oleic acid, α-linolenic acid, eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) are reported with the combined use of NMR and DFT calculations. Variable temperature and concentration chemical shifts of the COOH protons, transient 1D NOE experiments and DFT calculations demonstrate the major contribution of low molecular weight aggregates of dimerized fatty acids through intermolecular hydrogen bond interactions of the carboxylic groups, with parallel and antiparallel interdigitated structures even at the low concentration of 20 mM in CDCl3. For the dimeric DHA, a structural model of an intermolecular hydrogen bond through carboxylic groups and an intermolecular hydrogen bond between the carboxylic group of one molecule and the ω-3 double bond of a second molecule is shown to play a role. In DMSO-d6 solution, NMR and DFT studies show that the carboxylic groups form strong intermolecular hydrogen bond interactions with a single discrete solvation molecule of DMSO. These solvation species form parallel and antiparallel interdigitated structures of low molecular weight, as in chloroform solution. This structural motif, therefore, is an intrinsic property of the FFAs, which is not strongly affected by the length and degree of unsaturation of the chain and the hydrogen bond ability of the solvent.
Novel Derivatives of Nitrobenzofurazan with Chromogenic and Fluorogenic Properties
Authors: Bujor Alexandru , Hanganu Anamaria , Baratoiu Rodica , Hristea Elena N. , Tudose Madalina , Tecuceanu Victorita , Madalan Augustin M. , Ionita Petre
Published: August 2023

Five new derivatives were obtained utilizing 4-chloro-7-nitrobenzofurazan (NBD-chloride) in combination with furfurylamine, adamantylamine, aminohippuric acid, phenylalanine, and dehydroabietylamine. These derivatives were then subjected to a comparative analysis of their physical, chemical, and certain biological properties alongside two analogous and known compounds derived from the glycine and 4-amino-TEMPO free radical.
Design, Synthesis and Biological Evaluation of Novel PEG-Rakicidin B1 Hybrid as Clostridium difficile (CD) Targeted Anti-Bacterial Agent
Authors: Xie Lijun , Chen Li , Wei Yongbo , Chen Nannan , Wu Tong , Zhou Jingming , Jiang Hong , Lin Feng
Published: August 2023

Rakicidin B1 was isolated and purified from the culture broth of a marine Streptomyces sp. as a potent anti-cancer agent, and lately the compound and its derivatives have firstly been found to possess anti-Clostridium difficile (CD) activity but with high cytotoxicity. Herein, following our previous discovery on anti-CD activity of Rakicidin B1, structure modification was performed at the OH position of Rakicidin B1 and a new Rakicidin B1-PEG hybrids FIMP2 was facilely designed and synthesized by conjugating the PEG2000 with the scaffolds of Rakicidin B1 via the linkage of carbamate. The cytotoxicity of the FIMP2 was first evaluated against three different cancer cell lines, including HCT-8 cells, PANC-1, and Caco-2, with IC50 values at 0.519 μM, 0.815 μM, and 0.586 μM, respectively. Obviously, as compared with a positive control group treated with Rakicidin B1, the IC50 value of FIMP2 increased by nearly 91-fold, 50-fold, and 67-fold, suggesting that the PEGylation strategy significantly reduced the cytotoxicity of FIMP2. Thus, this preliminary result may be beneficial to increase its safety index (SI) value due to the decreased cytotoxicity of FIMP2. In addition, this decreased cytotoxicity of FIMP2 was further confirmed based on a zebrafish screening model in vivo. Thereafter, the anti-CD activity of FIMP2 was evaluated in vivo, and its efficacy to treat CDI was found to be better than that of vancomycin. The mortality and recurrence rate of FIMP2 is not as low compared with that of vancomycin; these results demonstrated that compound FIMP2 is a new, promising anti-CD agent with significant efficacy against CD recurrence with low cytotoxicity towards bodies.
Quantitative Insight into PCA Formation following Different Chlorhexidine Activation Methods in Endodontic Treatment
Authors: Czopik Barbara , Woźniakiewicz Aneta , Świętoniowska Natalia , Zarzecka Joanna , Woźniakiewicz Michał
Published: August 2023

The aim of the study was a quantitative analysis of p-chloroaniline (PCA) formation during 2% CHX activation with US and MDI methods in a root canal-like environment with the HPLC-DAD method and, thus, a safety assessment of US and MDI agitation of CHX in endodontic treatment. Two percent CHX was activated with the US method using ISO 30 and 35 K-file, and the MDI method using ISO 30.06 and 35.06 GP cones for 15, 30, 60, and 90 s. PCA concentration was assessed with the HPLC-DAD method. PCA concentration was also assessed for 2% CHX after 0, 3, 18, and 21 days of storage in ambient conditions. PCA was detected in all samples in all methods of activation. The concentration of PCA was dependent on time of activation in US ISO 30 and ISO 35 group (p < 0.05). In the MDI ISO 30.06 and ISO 35.06 groups, a similar trend was observed but without statistical significance (p > 0.05). PCA was detected in shelf-stored 2% CHX and the concentration was related to the time of storage. PCA is released after CHX activation with US and MDI, but mean concentrations are not higher than those observed from self-degradation of shelf-stored 2% CHX.
Electron Beam Irradiation Alters the Physicochemical Properties of Chickpea Proteins and the Peptidomic Profile of Its Digest
Authors: Zhang Yaqi , Kong Yunfei , Xu Wanjun , Yang Zhen , Bao Yulong
Published: August 2023

Irradiation can be used for the preservation of chickpea protein as it can destroy microorganisms, bacteria, virus, or insects that might be present. However, irradiation may provoke oxidative stress, and therefore modify the functionality and nutritional value of chickpea protein. In order to study the effects of irradiation on the physicochemical properties and digestion behaviour of chickpea protein, chickpea protein concentrate (CPC) was treated with electron beam irradiation (EBI) at doses of 5, 10, 15, and 20 kGy. After irradiation, protein solubility first increased at 10 kGy and 15 kGy, and then decreased at the higher dose of 20 kGy. This was supported by SDS-PAGE, where the intensity of major protein bands first increased and then decreased. Increased doses of EBI generally led to greater oxidative modification of proteins in CPC, indicated by reduced sulfhydryls and increased carbonyls. In addition, the protein structure was modified by EBI as shown by Fourier transform infrared spectroscopy analysis, where α-helix generally decreased, and β-sheet increased. Although the protein digestibility was not significantly affected by EBI, the peptidomic analysis of the digests revealed significant differences among CPC irradiated with varying doses. A total of 337 peptides were identified from CPC irradiated with 0 kGy, 10 kGy, and 20 kGy, with 18 overlapping peptides and 60, 29, and 40 peptides specific to the groups of 0, 10, and 20 kGy respectively. Theoretical calculation showed that the distribution of peptide length, hydrophobicity, net charge, and C-terminal residues were affected by irradiation. The 2, 2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity showed a marginal decrease with an increasing dose of irradiation. In conclusion, EBI led to oxidative modification and structural changes in chickpea protein, which subsequently affected the physicochemical properties of peptides obtained from in-vitro digestion of CPC, despite similar digestibility.
Exploring the Influence of Chemical Conditions on Nanoparticle Graphene Oxide Adsorption onto Clay Minerals
Authors: Ibrahim Marwa I. M. , Awad Elsayed A. M. , Dahdouh Salah M. M. , El-Etr Wafaa M. T. , Marey Samy A. , Hatamleh Ashraf Atef , Mahmood Mohsin , Elrys Ahmed S.
Published: August 2023

High concentrations of graphene oxide (GO), a nanoparticle substance with rapid manufacturing development, have the ability to penetrate the soil surface down to the mineral-rich subsurface layers. The destiny and distribution of such an unusual sort of nanomaterial in the environment must therefore be fully understood. However, the way the chemistry of solutions impacts GO nanoparticle adsorption on clay minerals is still unclear. Here, the adsorption of GO on clay minerals (e.g., bentonite and kaolinite) was tested under various chemical conditions (e.g., GO concentration, soil pH, and cation valence). Non-linear Langmuir and Freundlich models have been applied to describe the adsorption isotherm by comparing the amount of adsorbed GO nanoparticle to the concentration at the equilibrium of the solution. Our results showed fondness for GO in bentonite and kaolinite under similar conditions, but the GO nanoparticle adsorption with bentonite was superior to kaolinite, mainly due to its higher surface area and surface charge. We also found that increasing the ionic strength and decreasing the pH increased the adsorption of GO nanoparticles to bentonite and kaolinite, mainly due to the interaction between these clay minerals and GO nanoparticles’ surface oxygen functional groups. Experimental data fit well to the non-linear pseudo-second-order kinetic model of Freundlich. The model of the Freundlich isotherm was more fitting at a lower pH and higher ionic strength in the bentonite soil while the lowest R2 value of the Freundlich model was recorded at a higher pH and lower ionic strength in the kaolinite soil. These results improve our understanding of GO behavior in soils by revealing environmental factors influencing GO nanoparticle movement and transmission towards groundwater.
Chiral Metal Halide Perovskites: Focus on Lead-Free Materials and Structure-Property Correlations
Authors: Coccia Clarissa , Moroni Marco , Malavasi Lorenzo
Published: August 2023

Hybrid organic–inorganic perovskites (HOIPs) are promising materials in several fields related to electronics, offering long carrier-diffusion lengths, high absorption coefficients, tunable band gaps, and long spin lifetimes. Recently, chiral perovskites have attracted huge interest thanks to the possibility of further widening the applications of HOIPs. Chiral materials, being intrinsically non-centrosymmetric, display several attractive physicochemical properties, including circular dichroism, circularly polarized photoluminescence, nonlinear optics, ferroelectricity, and spin-related effects. Recent studies have shown that chirality can be transferred from the chiral organic ligands into the inorganic perovskite framework, resulting in materials combining the advantages of both chirality and perovskite superior optoelectronic characteristics. As for HOIPs for photovoltaics, strong interest is currently devoted towards the development of lead-free chiral perovskites to overcome any toxicity issue. While considering the basic and general features of chiral HOIPs, this review mainly focuses on lead-free materials. It highlights the first attempts to understand the correlation between the crystal structure characteristics and the chirality-induced functional properties in lead and lead-free chiral perovskites.
Assembling a Cinnamyl Pharmacophore in the C3-Position of Substituted Isatins via Microwave-Assisted Synthesis: Development of a New Class of Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson’s Disease
Authors: Manoharan Amritha , Oh Jong Min , Benny Feba , Kumar Sunil , Abdelgawad Mohamed A. , Ghoneim Mohammed M. , Shaker Mohamed E. , El-Sherbiny Mohamed , Almohaimeed Hailah M. , Gahtori Prashant , Kim Hoon , Mathew Bijo
Published: August 2023

Monoamine oxidase (MAO, EC 1.4.3.4) is responsible for the oxidative breakdown of both endogenous and exogenous amines and exists in MAO-A and MAO-B isomers. Eighteen indole-based phenylallylidene derivatives were synthesized via nucleophilic addition reactions comprising three sub-series, IHC, IHMC, and IHNC, and were developed and examined for their ability to inhibit MAO. Among them, compound IHC3 showed a strong MAO-B inhibitory effect with an IC50 (half-maximal inhibitory concentration) value of 1.672 μM, followed by IHC2 (IC50 = 16.934 μM). Additionally, IHC3 showed the highest selectivity index (SI) value of >23.92. The effectiveness of IHC3 was lower than the reference pargyline (0.14 μM); however, the SI value was higher than pargyline (17.16). Structurally, the IHC (-H in the B-ring) sub-series exhibited relatively stronger MAO-B inhibition than the others. In the IHC series, IHC3 (-F in the A-ring) exhibited stronger MAO-B suppression than the other substituted derivatives in the order -F > -Br > -Cl > -OCH3, -CH3, and -H at the 2-position in the A-ring. In the reversibility and enzyme kinetics experiments, IHC3 was a reversible inhibitor with a Ki value of 0.51 ± 0.15 μM for MAO-B. Further, it was observed that IHC3 greatly decreased the cell death caused by rotenone in SH-SY5Y neuroblastoma cells. A molecular docking study of the lead molecule was also performed to determine hypothetical interactions in the enzyme-binding cavity. These findings suggest that IHC3 is a strong, specific, and reversible MAO-B inhibitor that can be used to treat neurological diseases.
Impact of Static-Oriented Electric Fields on the Kinetics of Some Representative Suzuki–Miyaura and Metal-Cluster Mediated Reactions
Authors: Arepalli Navya , Mondal Sukanta , Chakraborty Debdutta , Chattaraj Pratim Kumar
Published: August 2023

In order to examine the effect of oriented (static) electric fields (OEF) on the kinetics of some representative Suzuki–Miyaura and metal-cluster mediated reactions at ambient temperatures, density functional theory-based calculations are reported herein. Results indicate that, in general, OEF can facilitate the kinetics of the concerned reactions when applied along the suitable direction (parallel or anti-parallel with respect to the reaction axis). The reverse effect happens if the direction of the OEF is flipped. OEF (when applied along the ‘right’ direction) helps to polarize the transition states in the desired direction, thereby facilitating favorable bonding interactions. Given the growing need for finding appropriate catalysts among the scientific community, OEF can prove to be a vital route for the same.
A Combined Plasmonic and Electrochemical Aptasensor Based on Gold Nanopit Arrays for the Detection of Human Serum Albumin
Authors: Zhu Ruifeng , Figueroa-Miranda Gabriela , Zhou Lei , Hu Ziheng , Lenyk Bohdan , Ingebrandt Sven , Offenhäusser Andreas , Mayer Dirk
Published: August 2023

Electrochemical and optical platforms are commonly employed in designing biosensors. However, one signal readout can easily lead to inaccuracies due to the effect of nonstandard test procedures, different operators, and experimental environments. We have developed a dual-signal protocol that combined two transducer principles in one aptamer-based biosensor by simultaneously performing electrochemical- and extraordinary optical transmission (EOT)-based plasmonic detection using gold nanopit arrays (AuNpA). Compared with full hole structures, we found that nanopits, that did not fully penetrate the gold film, not only exhibited a better plasmonic bandwidth and refractive index sensitivity both in the finite-difference time-domain simulation and in experiments by shielding the gold/quartz mode but also enlarged the electrochemical active surface area. Therefore, the periodic non-fully penetrating AuNpA were modified with ferrocene-labeled human serum albumin aptamer receptors. The formation of the receptor layer and human serum albumin binding complex induced a conformational change, which resulted in variation in the electron transfer between the electro-active ferrocene units and the AuNpA surface. Simultaneously, the binding event caused a surface plasmon polaritons wavelength shift corresponding to a change in the surface refractive index. Interestingly, although both transducers recorded the same binding process, they led to different limits of detection, dynamic ranges, and sensitivities. The electrochemical transducer showed a dynamic detection range from 1 nM to 600 μM, while the optical transducer covered high concentrations from 100 μM to 600 μM. This study not only provides new insights into the design of plasmonic nanostructures but also potentially opens an exciting avenue for dual-signal disease diagnosis and point-of-care testing applications.
Silicon-Nanowire-Type Polarization-Diversified CWDM Demultiplexer for Low Polarization Crosstalk
Authors: Jeong Seok-Hwan , Park Heuk , Lee Joon Ki
Published: August 2023

Coarse wavelength division multiplexing (CWDM)-targeted novel silicon (Si)-nanowire-type polarization-diversified optical demultiplexers were numerically analyzed and experimentally verified. The optical demultiplexer comprised a hybrid mode conversion-type polarization splitter rotator (PSR) and a delayed Mach–Zehnder interferometric demultiplexer. Si-nanowire-based devices were fabricated using a commercially available Si photonics foundry process, exhibiting nearly identical spectral responses regardless of the polarization states of the input signals under the PSR. The experiment demonstrated a low insertion loss of 1.0 dB and a polarization-dependent loss of 1.0 dB, effectively suppressing spectral crosstalk from other channels by less than −15 dB. Furthermore, a TM-mode rejection-filter-integrated optical demultiplexer was designed and experimentally validated to mitigate unwanted TM-mode-related polarization crosstalk that arose from the PSR. It exhibited an improved polarization crosstalk rejection efficiency of −25 dB to −50 dB within the whole CWDM spectral range.