bluuebunny/crossref_metadata_2025 huggingface dataset:
Ameliorative Potential of Donepezil with or without Prednisolone in Bleomycin-Induced Pulmonary Fibrosis in Rats: Involvement of the Anti-Inflammatory, Antioxidant, and the Antifibrotic Pathways
Authors: Mina Shery , Elfeky Dina M. , Kabel Ahmed M. , Hedya Sabeha E.
Published: May 2023

Background and Objectives: Bleomycin-induced pulmonary fibrosis is one of the serious complications that may limit the use of bleomycin in cancer therapy. To date, there is no effective remedy for the amelioration of this condition. Donepezil, an anti-Alzheimer’s medication, has recently been proven to exhibit potent anti-inflammatory, antioxidant, and antifibrotic effects. To the best of our knowledge, this study represents the first study designed to investigate the prophylactic effects of donepezil, either alone or in combination with the classic anti-inflammatory drug prednisolone, in bleomycin-induced pulmonary fibrosis. Methods: This study was carried out on fifty rats, which were divided into five equal groups: control (Saline) group; bleomycin group; bleomycin + prednisolone group; bleomycin + donepezil group; and bleomycin + prednisolone + donepezil group. At the end of the experiments, bronchoalveolar lavage was performed to evaluate the total and differential leucocytic counts. The right lung was processed to assess the oxidative stress markers, proinflammatory cytokines, NLRP3 inflammasome, and transforming growth factor–beta1. The left lung was subjected to histopathological and immunohistochemical examination. Results: The administration of donepezil and/or prednisolone induced a significant amelioration of oxidative stress, inflammation, and fibrosis. In addition, these animals showed a significant amelioration of the histopathological changes of fibrosis, together with a significant decline in nuclear factor kappa B (p65) immunoexpression, compared to the group treated with bleomycin alone. However, the rats treated with the donepezil/prednisolone combination showed non-significant effects on the aforementioned parameters compared to the group treated with prednisolone alone. Conclusions: Donepezil may emerge as a promising drug that shows significant prophylactic effects against bleomycin-induced pulmonary fibrosis.
Editorial for the Special Issue “Acute and Chronic Pancreatitis, Pancreatic Malignancies”
Authors: Gulbinas Antanas , Ignatavicius Povilas , Dambrauskas Zilvinas
Published: May 2023

Pancreatic diseases, especially acute pancreatitis and pancreatic cancer, are associated with high rates of complications, difficult treatment that may not always be effective, and high mortality in complex cases [...]
Challenges Women Experience in Leadership Careers: An Integrative Review
Authors: Galsanjigmed Enkhzul , Sekiguchi Tomoki
Published: May 2023

A part of diversity management is working to achieve gender equality and create a comfortable working environment for women. However, in many organizations, gender biases and stereotypes frequently occur, consciously or unconsciously, regardless of whether women take on leadership roles. In addition, women must overcome a variety of challenges when taking on leadership roles or aspiring to become leaders. Based on the above background, we review and integrate the literature on management and career studies related to the challenges that women face in the process of advancing to leadership positions in organizations. Specifically, we examine the external and internal factors that create the various obstacles that women who aspire to leadership positions in structured organizations face from a gender perspective. Based on the integrative review, we discuss the implications for practices to increase the number of female leaders.
Simulation Studies on Single-Event Effects and the Mechanisms of SiC VDMOS from a Structural Perspective
Authors: Liu Tao , Wang Yuan , Ma Rongyao , Wu Hao , Tao Jingyu , Yu Yiren , Cheng Zijun , Hu Shengdong
Published: May 2023

The single-event effect reliability issue is one of the most critical concerns in the context of space applications for SiC VDMOS. In this paper, the SEE characteristics and mechanisms of the proposed deep trench gate superjunction (DTSJ), conventional trench gate superjunction (CTSJ), conventional trench gate (CT), and conventional planar gate (CT) SiC VDMOS are comprehensively analyzed and simulated. Extensive simulations demonstrate the maximum SET current peaks of DTSJ−, CTSJ−, CT−, and CP SiC VDMOS, which are 188 mA, 218 mA, 242 mA, and 255 mA, with a bias voltage VDS of 300 V and LET = 120 MeV·cm2/mg, respectively. The total charges of DTSJ−, CTSJ−, CT−, and CP SiC VDMOS collected at the drain are 320 pC, 1100 pC, 885 pC, and 567 pC, respectively. A definition and calculation of the charge enhancement factor (CEF) are proposed. The CEF values of DTSJ−, CTSJ−, CT−, and CP SiC VDMOS are 43, 160, 117, and 55, respectively. Compared with CTSJ−, CT−, and CP SiC VDMOS, the total charge and CEF of the DTSJ SiC VDMOS are reduced by 70.9%, 62.4%, 43.6% and 73.1%, 63.2%, and 21.8%, respectively. The maximum SET lattice temperature of the DTSJ SiC VDMOS is less than 2823 K under the wide operating conditions of a drain bias voltage VDS ranging from 100 V to 1100 V and a LET value ranging from 1 MeV·cm2/mg to 120 MeV·cm2/mg, while the maximum SET lattice temperatures of the other three SiC VDMOS significantly exceed 3100 K. The SEGR LET thresholds of DTSJ−, CTSJ−, CT−, and CP SiC VDMOS are approximately 100 MeV·cm2/mg, 15 MeV·cm2/mg, 15 MeV·cm2/mg, and 60 MeV·cm2/mg, respectively, while the value of VDS = 1100 V.
Ultra-Fast Impedimetric Immunoassay for Detection of Streptococcus agalactiae Using Carbon Electrode with Nanodiamonds Film
Authors: Bigus Daniel , Lewandowska Wioleta , Bięga Ewelina , Grela Anna , Siedlar Aleksandra , Sosnowska Marta , Fabisiak Magdalena , Łęga Tomasz , Dashkievich Yanina , Nowacka-Dośpiał Joanna , Palka Katarzyna , Żołędowska Sabina , Nidzworski Dawid
Published: May 2023

This publication presents the results of work on the development of a quick and cheap electrochemical immunosensor for the diagnosis of infections with the pathogen Streptococcus agalactiae. The research was carried out on the basis of the modification of the well-known glassy carbon (GC) electrodes. The surface of the GC (glassy carbon) electrode was covered with a film made of nanodiamonds, which increased the number of sites for the attachment of anti-Streptococcus agalactiae antibodies. The GC surface was activated with EDC/NHS (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-Hydroxysuccinimide). Determination of electrode characteristics after each modification step, performed using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS).
Design of a Digital LAMP Detection Platform Based on Droplet Microfluidic Technology
Authors: Jiang Liying , Lan Xianghao , Ren Linjiao , Yang Mingzhu , Wei Bo , Wang Yang
Published: May 2023

Loop-mediated isothermal amplification (LAMP) is a rapid and high-yield amplification technology for specific DNA or RNA molecules. In this study, we designed a digital loop-mediated isothermal amplification (digital-LAMP)-functioning microfluidic chip to achieve higher sensitivity for detection of nucleic acids. The chip could generate droplets and collect them, based on which we could perform Digital-LAMP. The reaction only took 40 min at a constant temperature of 63 °C. The chip enabled highly accurate quantitative detection, with the limit of detection (LOD) down to 102 copies μL−1. For better performance while reducing the investment of money and time in chip structure iterations, we used COMSOL Multiphysics to simulate different droplet generation ways by including flow-focusing structure and T-junction structure. Moreover, the linear structure, serpentine structure, and spiral structure in the microfluidic chip were compared to study the fluid velocity and pressure distribution. The simulations provided a basis for chip structure design while facilitating chip structure optimization. The digital-LAMP-functioning chip proposed in the work provides a universal platform for analysis of viruses.
Ectothiorhodospira lacustris sp. nov., a New Purple Sulfur Bacterium from Low-Mineralized Soda Lakes That Contains a Unique Pathway for Nitric Oxide Reduction
Authors: Bryantseva Irina A. , Kyndt John A. , Gorlenko Vladimir M. , Imhoff Johannes F.
Published: May 2023

Several strains of a Gram-negative, anaerobic photoautotrophic, motile, rod-shaped bacterium, designated as B14B, A-7R, and A-7Y were isolated from biofilms of low-mineralized soda lakes in central Mongolia and Russia (southeast Siberia). They had lamellar stacks as photosynthetic structures and bacteriochlorophyll a as the major photosynthetic pigment. The strains were found to grow at 25–35 °C, pH 7.5–10.2 (optimum, pH 9.0), and with 0–8% (w/v) NaCl (optimum, 0%). In the presence of sulfide and bicarbonate, acetate, butyrate, yeast extract, lactate, malate, pyruvate, succinate, and fumarate promoted growth. The DNA G + C content was 62.9–63.0 mol%. While the 16S rRNA gene sequences confirmed that the new strains belonged to the genus Ectothiorhodospira of the Ectothiorhodospiraceae, comparison of the genome nucleotide sequences of strains B14B, A-7R, and A-7Y revealed that the new isolates were remote from all described Ectothiorhodospira species both in dDDH (19.7–38.8%) and in ANI (75.0–89.4%). The new strains are also genetically differentiated by the presence of a nitric oxide reduction pathway that is lacking from all other Ectiothiorhodospiraceae. We propose to assign the isolates to the new species, Ectothiorhodospira lacustris sp. nov., with the type strain B14BT (=DSM 116064T = KCTC 25542T = UQM 41491T).
Inclusive Urban Mining: An Opportunity for Engineering Education
Authors: Schlezak Sofia L. , Styer Jaime E.
Published: May 2023

With the understanding that the mining industry is an important and necessary part of the production chain, we argue that the future of mining must be sustainable and responsible when responding to the increasing material demands of the current and next generations. In this paper, we illustrate how concepts, such as inclusiveness and the circular economy, can come together in new forms of mining—what we call inclusive urban mining—that could be beneficial for not only the mining industry, but for the environmental and social justice efforts as well. Based on case studies in the construction and demolition waste and WEEE (or e-waste) sectors in Colombia and Argentina, we demonstrate that inclusive urban mining could present an opportunity to benefit society across multiple echelons, including empowering vulnerable communities and decreasing environmental degradation associated with extractive mining and improper waste management. Then, recognizing that most engineering curricula in this field do not include urban mining, especially from a community-based perspective, we show examples of the integration of this form of mining in engineering education in first-, third- and fourth-year design courses. We conclude by providing recommendations on how to make inclusive urban mining visible and relevant to engineering education.
In Silico Drug Design of Anti-Breast Cancer Agents
Authors: Rajagopal Kalirajan , Kalusalingam Anandarajagopal , Bharathidasan Anubhav Raj , Sivaprakash Aadarsh , Shanmugam Krutheesh , Sundaramoorthy Monall , Byran Gowramma
Published: May 2023

Cancer is a condition marked by abnormal cell proliferation that has the potential to invade or indicate other health issues. Human beings are affected by more than 100 different types of cancer. Some cancer promotes rapid cell proliferation, whereas others cause cells to divide and develop more slowly. Some cancers, such as leukemia, produce visible tumors, while others, such as breast cancer, do not. In this work, in silico investigations were carried out to investigate the binding mechanisms of four major analogs, which are marine sesquiterpene, sesquiterpene lactone, heteroaromatic chalcones, and benzothiophene against the target estrogen receptor-α for targeting breast cancer using Schrödinger suite 2021-4. The Glide module handled the molecular docking experiments, the QikProp module handled the ADMET screening, and the Prime MM-GB/SA module determined the binding energy of the ligands. The benzothiophene analog BT_ER_15f (G-score −15.922 Kcal/mol) showed the best binding activity against the target protein estrogen receptor-α when compared with the standard drug tamoxifen which has a docking score of −13.560 Kcal/mol. TRP383 (tryptophan) has the highest interaction time with the ligand, and hence it could act for a long time. Based on in silico investigations, the benzothiophene analog BT_ER_15f significantly binds with the active site of the target protein estrogen receptor-α. Similar to the outcomes of molecular docking, the target and ligand complex interaction motif established a high affinity of lead candidates in a dynamic system. This study shows that estrogen receptor-α targets inhibitors with better potential and low toxicity when compared to the existing market drugs, which can be made from a benzothiophene derivative. It may result in considerable activity and be applied to more research on breast cancer.
Influence of Different Rootstocks on Fruit Quality and Primary and Secondary Metabolites Content of Blood Oranges Cultivars
Authors: Forner-Giner María Ángeles , Ballesta-de los Santos Manuel , Melgarejo Pablo , Martínez-Nicolás Juan José , Núñez-Gómez Dámaris , Continella Alberto , Legua Pilar
Published: May 2023

Blood oranges have high concentrations of bioactive compounds that are beneficial to health. In Europe, the cultivation of blood oranges is increasing due to their excellent nutritional properties. In Citrus crops, rootstocks play an important role in juice and can increase the content of bioactive compounds. The morphological, qualitative and nutritional parameters were analyzed in cultivars ‘Tarocco Ippolito’, ‘Tarocco Lempso’, ‘Tarocco Tapi’ and ‘Tarocco Fondaconuovo’ grafted onto Citrus macrophylla and Citrus reshni. ‘Tarocco Lempso’ grafted onto Citrus macrophylla obtained the highest values of weight (275.78 g), caliber (81.37 mm and 76.79 mm) and juice content (162.11 g). ‘Tarocco Tapi’ grafted onto Citrus reshni obtained the most interesting qualitative parameters (15.40 °Brix; 12.0 MI). ‘Tarocco Lempso’ grafted onto Citrus reshni obtained the most intense red juice (a* = 9.61). Overall, the highest concentrations of primary metabolites were in proline, aspartate, citric acid, and sucrose. The results showed that ‘Tarocco Ippolito’ juice grafted onto Citrus reshni had the highest levels of total hydroxycinnamic acids (263.33 mg L−1), total flavones (449.74 mg L−1) and total anthocyanins (650.42 mg L−1). To conclude, ‘Tarocco Lempso’ grafted onto Citrus macrophylla obtained the best values of agronomic parameters, and the cultivars grafted onto Citrus reshni obtained significantly higher concentrations in primary and secondary metabolites.
Surfactant Additives Containing Hydrophobic Fluorocarbon Chains and Hydrophilic Sulfonate Anion for Highly Reversible Zn Anode
Authors: Huang Jinxian , Fu Zhao , Sun Chuan-Fu , Deng Wenzhuo
Published: May 2023

Aqueous zinc-ion batteries (AZIBs) show enormous potential as a large-scale energy storage technique. However, the growth of Zn dendrites and serious side reactions occurring at the Zn anode hinder the practical application of AZIBs. For the first time, we reported a fluorine-containing surfactant, i.e., potassium perfluoro-1-butanesulfonate (PPFBS), as an additive to the 2 M ZnSO4 electrolyte. Benefitting from its hydrophilic sulfonate anion and hydrophobic long fluorocarbon chain, PPFBS can promote the uniform distribution of Zn2+ flux at the anode/electrolyte interface, allowing the Zn/Zn cell to cycle for 2200 h. Furthermore, PPFBS could inhibit side reactions due to the existence of the perfluorobutyl sulfonate (C4F9SO3−) adsorption layer and the presence of C4F9SO3− in the solvation structure of Zn2+. The former can reduce the amount of H2O molecules and SO42− in contact with the Zn anode and C4F9SO3− entering the Zn2+-solvation structure by replacing SO42−. The Zn/Cu cell exhibits a superior average CE of 99.47% over 500 cycles. When coupled with the V2O5 cathode, the full cell shows impressive cycle stability. This work provides a simple, effective, and economical solution to the common issues of the Zn anode.
Opening a Band Gap in Biphenylene Monolayer via Strain: A First-Principles Study
Authors: Hou Yinlong , Ren Kai , Wei Yu , Yang Dan , Cui Zhen , Wang Ke
Published: May 2023

A biphenylene network is a novel 2D allotropy of carbon with periodic 4-6-8 rings, which was synthesized successfully in 2021. In recent years, although the mechanical properties and thermal transport received a lot of research attention, how to open the Dirac cone in the band structure of a biphenylene network is still a confused question. In this work, we utilized uniaxial and biaxial lattice strains to manipulate the electronic properties and phonon frequencies of biphenylene, and we found an indirect band gap under 10% biaxial strain through the first-principles calculations. This indirect band gap is caused by the competition between the band-edge state A and the Dirac cone for the conduction band minimum (CBM). Additionally, the lightest carrier’s effective mass in biphenylene is 0.184 m0 for electrons along x (Γ→X) direction, while the effective mass for holes shows a remarkable anisotropy, suggesting the holes in the tensile biphenylene monolayer are confined within a one-dimensional chain along x direction. For phonon dispersion, we discovered that the Raman-active Ag3 phonon mode shows a robust single phonon mode character under both compressive and tensile strain, but its frequency is sensitive to lattice strain, suggesting the lattice strain in biphenylene can be identified by Raman spectroscopy
Synthesis and Molecular Docking Studies of Alkoxy- and Imidazole-Substituted Xanthones as α-Amylase and α-Glucosidase Inhibitors
Authors: Aguila-Muñoz Dolores G. , Vázquez-Lira Gabriel , Sarmiento-Tlale Erika , Cruz-López María C. , Jiménez-Montejo Fabiola E. , López y López Víctor E. , Escalante Carlos H. , Andrade-Pavón Dulce , Gómez-García Omar , Tamariz Joaquín , Mendieta-Moctezuma Aarón
Published: May 2023

Current antidiabetic drugs have severe side effects, which may be minimized by new selective molecules that strongly inhibit α-glucosidase and weakly inhibit α-amylase. We have synthesized novel alkoxy-substituted xanthones and imidazole-substituted xanthones and have evaluated them for their in silico and in vitro α-glucosidase and α-amylase inhibition activity. Compounds 6c, 6e, and 9b promoted higher α-glucosidase inhibition (IC50 = 16.0, 12.8, and 4.0 µM, respectively) and lower α-amylase inhibition (IC50 = 76.7, 68.1, and >200 µM, respectively) compared to acarbose (IC50 = 306.7 µM for α-glucosidase and 20.0 µM for α-amylase). Contrarily, derivatives 10c and 10f showed higher α-amylase inhibition (IC50 = 5.4 and 8.7 µM, respectively) and lower α-glucosidase inhibition (IC50 = 232.7 and 145.2 µM, respectively). According to the structure–activity relationship, attaching 4-bromobutoxy or 4′-chlorophenylacetophenone moieties to the 2-hydroxy group of xanthone provides higher α-glucosidase inhibition and lower α-amylase inhibition. In silico studies suggest that these scaffolds are key in the activity and interaction of xanthone derivatives. Enzymatic kinetics studies showed that 6c, 9b, and10c are mainly mixed inhibitors on α-glucosidase and α-amylase. In addition, drug prediction and ADMET studies support that compounds 6c, 9b, and 10c are candidates with antidiabetic potential.
Characterization of the Nonpolar and Polar Extractable Components of Glanded Cottonseed for Its Valorization
Authors: He Zhongqi , Nam Sunghyun , Liu Shasha , Zhao Qi
Published: May 2023

Cottonseed is the second major product of cotton (Gossypium spp.) crops after fiber. Thus, the characterization and valorization of cottonseed are important parts of cotton utilization research. In this work, the nonpolar and polar fractions of glanded (Gd) cottonseed were sequentially extracted by 100% hexane and 80% ethanol aqueous solutions and subjected to 13C and 1H nuclear magnetic resonance (NMR) spectroscopy and Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS), respectively. The nonpolar (crude oil) extracts showed the characteristic NMR peak features of edible plant oils with the absence of ω-3 linolenic acid. Quantitative analysis revealed the percentage of polyunsaturated, monounsaturated, and saturated fatty acids as 48.7%, 16.9%, and 34.4%, respectively. Both general unsaturated fatty acid features and some specific olefinic compounds (e.g., oleic, linolenic, and gondonic acids) were found in the nonpolar fraction. In the polar extracts, FT-ICR MS detected 1673 formulas, with approximately 1/3 being potential phenolic compounds. Both the total and phenolic formulas fell mainly in the categories of lipid, peptide-like, carbohydrate, and lignin. A literature search and comparison further identifies some of these formulas as potential bioactive compounds. For example, one compound [2,5-dihydroxy-N′-(2,3,4-trihydroxybenzylidene) benzohydrazide] identified in the polar extracts is likely responsible for the anticancer function observed when used on human breast cancer cell lines. The chemical profile of the polar extracts provides a formulary for the exploration of bioactive component candidates derived from cottonseed for nutritive, health, and medical applications.
Coriander (Coriandrum sativum) Polyphenols and Their Nutraceutical Value against Obesity and Metabolic Syndrome
Authors: Scandar Samir , Zadra Claudia , Marcotullio Maria Carla
Published: May 2023

Coriander is a widely used plant for its medicinal and biological properties. Both coriander essential oil and extracts are interesting sources of bioactive compounds and are widely used as spices in culinary practice due to their exclusive aroma and flavour. We focus our attention on coriander extracts that are rich in polyphenols. It is well known that plant polyphenols possess different biological activities and several functional foods contain this class of compounds. The polyphenol profile in an extract can be influenced by the plant part studied, the method of extraction and other parameters. This study performs a literature review using the words “coriander”, “polyphenols” and “extraction” or “biological activity” in different databases such as PubMed, Google Scholar and Scopus. After that, we focus on the evidence of coriander polyphenols as protective agents against some inflammation-related diseases. Due to the bioactivities of coriander extract, this herb can be considered a valuable functional food against obesity, metabolic syndrome and diabetes.
Medicinal Plants of the Flora of Kazakhstan Used in the Treatment of Skin Diseases
Authors: Berganayeva Gulzat , Kudaibergenova Bates , Litvinenko Yuliya , Nazarova Irada , Sydykbayeva Sandugash , Vassilina Gulzira , Izdik Nazerke , Dyusebaeva Moldyr
Published: May 2023

The skin shows the physiological condition of the body’s organs and systems that prevent infections and physical damage. Throughout the ages, in folk medicine, phytotherapy was considered a primary form of treatment in all countries, including Kazakhstan, due to the abundance and availability of plant-based remedies. This paper discusses several medicinal plants that are traditionally used in the treatment of skin diseases in the Republic of Kazakhstan. The chemical composition of these plants was analyzed, with a particular focus on the biologically active basic compounds responsible for their therapeutic efficiency in treating skin ailments.
Effect of Indole-2-carboxylic Acid on the Self-Corrosion and Discharge Activity of Aluminum Alloy Anode in Alkaline Al–Air Battery
Authors: Guo Lei , Huang Yue , Ritacca Alessandra Gilda , Wang Kai , Ritacco Ida , Tan Yan , Qiang Yujie , Al-Zaqri Nabil , Shi Wei , Zheng Xingwen
Published: May 2023

Al–air battery has been regarded as a promising new energy source. However, the self-corrosion of aluminum anode leads to a loss of battery capacity and a decrease in battery longevity, limiting its commercial applications. Herein, indole-2-carboxylic acid (ICA) has been added to 4 M NaOH as a corrosion inhibitor. Its impact on the self-corrosion of aluminum alloy and the enhancement of the functionality of Al–air batteries at various concentrations have been investigated. X-ray photoelectron spectroscopy (XPS), attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM), and scanning electron microscopy (SEM) techniques have been used to examine the compositional and morphological alterations of aluminum alloy surfaces. Electrochemical and hydrogen evolution tests showed that indole-2-carboxylic acid is an efficient corrosion inhibitor in alkaline solutions, and its impact grows with concentration. Our findings demonstrated that when the inhibitor concentration is 0.07 M, the inhibition efficiency is 54.0%, the anode utilization rises from 40.2% to 79.9%, the capacity density increases from 1197.6 to 2380.9 mAh g−1, and the energy density increases from 1469.9 to 2951.8 Wh kg−1. In addition, theoretical calculations have been performed to support the experimental results.
Enhancement of Inhibitory Activity by Combining Allosteric Inhibitors Putatively Binding to Different Allosteric Sites on Cathepsin K
Authors: Sato Shun , Yamamoto Kana , Ito Moeno , Nishino Katsutoshi , Otsuka Takanao , Irie Kazuhiro , Nagao Masaya
Published: May 2023

Background: Cathepsin K, which is involved in bone resorption, is a good target for treating osteoporosis, but no clinically approved medicine has been developed. Recently, allosteric inhibitors with high specificity and few side effects have been attracting attention for use in new medicines. Methods: Cathepsin K inhibitors were isolated from the methanol extract of Chamaecrista nomame (Leguminosae) using cathepsin K inhibition activity-assisted multi-step chromatography. Standard kinetic analysis was employed to examine the mechanism of cathepsin K inhibition when an isolated inhibitor and its derivative were used. The allosteric binding of these cathepsin K inhibitors was supported by a docking study using AutoDock vina. Combinations of allosteric cathepsin K inhibitors expected to bind to different allosteric sites were examined by means of cathepsin K inhibition assay. Results: Two types of cathepsin K inhibitors were identified in the methanol extract of Chamaecrista nomame. One type consisted of cassiaoccidentalin B and torachrysone 8-β-gentiobioside, and inhibited both cathepsin K and B with similar inhibitory potential, while the other type of inhibitor consisted of pheophytin a, and inhibited cathepsin K but not cathepsin B, suggesting that pheophytin a binds to an allosteric site of cathepsin K. Kinetic analysis of inhibitory activity suggested that pheophytin a and its derivative, pheophorbide b, bind allosterically to cathepsin K. This possibility was supported by a docking study on cathepsin K. The cathepsin K inhibitory activity of pheophytin a and pheophorbide b was enhanced by combining them with the allosteric inhibitors NSC 13345 and NSC94914, which bind to other allosteric sites on cathepsin K. Conclusions: Different allosteric inhibitors that bind to different sites in combination, as shown in this study, may be useful for designing new allosteric inhibitory drugs with high specificity and few side effects.
Electronic, Structural, Optical, and Electrical Properties of CsPbX3 Powders (X = Cl, Br, and I) Prepared Using a Surfactant-Free Hydrothermal Approach
Authors: Echeverría-Arrondo Carlos , Alvarez Agustin O. , Masi Sofia , Fabregat-Santiago Francisco , Porta Felipe A. La
Published: May 2023

Recently, several strategies have been adopted for the cesium lead halide, CsPbX3 (X = Cl, Br, and/or I), crystal growth with a perovskite-type structure, paving the way for the further development of innovative optoelectronic and photovoltaic applications. The optoelectronic properties of advanced materials are controlled, in principle, by effects of morphology, particle size, structure, and composition, as well as imperfections in these parameters. Herein, we report a detailed investigation, using theoretical and experimental approaches to evaluate the structural, electronic, optical, and electrical properties of CsPbX3 microcrystals. The microcrystals are synthesized successfully using the hydrothermal method without surfactants. This synthetic approach also offers an easy upscaling for perovskite-related material synthesis from low-cost precursors. Lastly, in this direction, we believe that deeper mechanistic studies, based on the synergy between theory and practice, can guide the discovery and development of new advanced materials with highly tailored properties for applications in optoelectronic devices, as well as other emergent technologies.
“I Feel Like I Work Full-Time for Parkinson’s”: A Longitudinal Interpretative Phenomenological Analysis of the Experiences of Parkinson’s Informal Caregivers during COVID-19 in England
Authors: Garner Ian W. , Murray Craig D. , Eccles Fiona J. R. , Zarotti Nicolò , Simpson Jane
Published: May 2023

While the direct effects of COVID-19 caused widespread global suffering and death, the indirect impacts—via public health preventative measures and a reduction in health and social care services—were also devastating for many. More recently, it has also become increasingly apparent that such measures have had disproportionate effects, exacerbating existing health inequalities. For caregivers of individuals with chronic illness, the effects have been marked and particularly so for informal caregivers of individuals with complex neurodegenerative conditions such as Parkinson’s. Nine informal caregivers (all partners: three men and six women) of individuals with Parkinson’s in England took part in individual semi-structured interviews on two occasions (December 2021/January 2022 and May 2022). The interviews focused on their experiences of supporting their partner, their own challenges, and how these evolved and changed post-lockdown. Interpretative phenomenological analysis was used to inform the methodology and analysis. Four themes were identified: (i) lockdown-induced revolution and evolution of the relationship dynamic with partner; (ii) fighting to be seen, heard, and understood in healthcare encounters; (iii) making sense of, and adapting to, risk in a time of COVID-19; and (iv) managing isolation and need for support during and after lockdown. The negative effects from both the lockdowns and the depletion of usual health and support services were apparent for all participants. Existing vulnerabilities from being a carer of an individual with complex needs were also exacerbated. As caregivers worked hard to mitigate these effects for their partners as much as possible, the long-term impact of such intense psychological and practical effort was often considerable. Ultimately, a simple restoration of pre-lockdown support levels may be insufficient to facilitate a successful return to optimal levels of support and wellbeing.
Analysis of the Effects of Known Sleep-Support Supplements in Relation to Life Habits, Sleep Conditions, and Sleep Problems
Authors: Imafuku Fuminori , Yamamoto Kazuya , Tanaka Eiji , Aoki Ryo , Nishino Seiji
Published: May 2023

Sleep is a crucial component of health, and insomnia is among the most common and vexing of life-habit-related disorders. While dietary sleep-support supplements can improve sleep, choosing an effective dietary supplement can be challenging for users due to the wide variety of options available and the varying effects experienced by different individuals. In this study, to identify new criteria for estimating the effects of dietary supplements, we examined the relationships among the dietary supplements, the pre-conditions (PCs; defined as the life habits and sleep conditions before supplementation), and the sleep problems of subjects before supplementation. An open, randomized, cross-over intervention trial enrolling 160 subjects was conducted to test the efficacy of each dietary supplement (Analysis 1) and the relationships among dietary supplements, the PCs, and sleep problems (Analysis 2). To this end, l-theanine (200 mg/day), γ-aminobutyric acid (GABA) (111.1 mg/day), Apocynum venetum leaf extract (AVLE) (50 mg/day), and l-serine (300 mg/day) were administered to subjects. Before the first intervention period, life habits and sleep conditions were surveyed to identify each subject’s PCs. For each combination of supplements and sleep problems, PCs were compared between subjects whose sleep problems were improved and subjects whose sleep problems were not improved via supplementation. All the tested supplements were found to ameliorate sleep problems significantly (Analysis 1). In Analysis 2, the PCs specific to improved subjects were found to differ depending on the dietary supplements and sleep problems. In addition, subjects who consumed dairy products often showed improvement in their sleep problems with all the tested supplements. This study suggests the possibility of personalizing sleep-support supplementation based on personal life habits, sleep conditions, and sleep problems, in addition to the known efficacy of dietary supplements.
Intra-Amniotic Administration of Cashew Nut (Anacardium occidentale L.) Soluble Extract Improved Gut Functionality and Morphology In Vivo (Gallus gallus)
Authors: Meneguelli Talitha , Kolba Nikolai , Misra Arundhati , Dionísio Ana , Pelissari Kravchychyn Ana , Da Silva Bárbara , Stampini Duarte Martino Hercia , Hermsdorff Helen , Tako Elad
Published: May 2023

Cashew nuts are rich in dietary fibers, monounsaturated fatty acids, carotenoids, tocopherols, flavonoids, catechins, amino acids, and minerals that offer benefits for health. However, the knowledge of its effect on gut health is lacking. In this way, cashew nut soluble extract (CNSE) was assessed in vivo via intra-amniotic administration in intestinal brush border membrane (BBM) morphology, functionality, and gut microbiota. Four groups were evaluated: (1) no injection (control); (2) H2O injection (control); (3) 10 mg/mL CNSE (1%); and (4) 50 mg/mL CNSE (5%). Results related to CNSE on duodenal morphological parameters showed higher Paneth cell numbers, goblet cell (GC) diameter in crypt and villi, depth crypt, mixed GC per villi, and villi surface area. Further, it decreased GC number and acid and neutral GC. In the gut microbiota, treatment with CNSE showed a lower abundance of Bifidobacterium, Lactobacillus, and E. coli. Further, in intestinal functionality, CNSE upregulated aminopeptidase (AP) gene expression at 5% compared to 1% CNSE. In conclusion, CNSE had beneficial effects on gut health by improving duodenal BBM functionality, as it upregulated AP gene expression, and by modifying morphological parameters ameliorating digestive and absorptive capacity. For intestinal microbiota, higher concentrations of CNSE or long-term intervention may be necessary.
Association between Early Childhood Vitamin D Status and Age 6-Year Lung Function among Children with a History of Severe Bronchiolitis in Infancy
Authors: Doumat George , Mehta Geneva D. , Mansbach Jonathan M. , Hasegawa Kohei , Camargo Carlos A.
Published: May 2023

Improving lung health in children requires understanding the risk factors for decreased lung function. Our objective was to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) levels and lung function in children. We analyzed data from a prospective cohort of infants hospitalized with bronchiolitis (severe bronchiolitis), a group at high risk for developing childhood asthma. Children were followed longitudinally, and 25(OH)D and spirometry testing were conducted at ages 3 and 6, respectively. We used a multivariable linear regression adjusted for race/ethnicity, annual household income, premature birth, and secondhand smoke exposure to examine the association between serum 25(OH)D level and primary outcomes (percent predicted [pp] of forced expiratory volume in the first second (FEV1) and the forced vital capacity (FVC)) and secondary outcome (FEV1pp/FVCpp). Serum 25(OH)D level and age 6 spirometry were available for 363 children. In adjusted analyses comparing the highest quintile (Q5) of serum 25(OH)D (median 37 ng/mL) to the lowest quintile (Q1; median 18 ng/mL), FEV1pp was 6% lower (p = 0.03) in Q1. Likewise, FVCpp was 7% lower (p = 0.03) in Q1. There was no difference in FEV1pp/FVCpp across the serum 25(OH)D quintiles. Compared to children with higher vitamin D status at age 3, those with lower status had decreased FEV1pp and FVCpp at 6 years.
Pictolysin-III, a Hemorrhagic Type-III Metalloproteinase Isolated from Bothrops pictus (Serpentes: Viperidae) Venom, Reduces Mitochondrial Respiration and Induces Cytokine Secretion in Epithelial and Stromal Cell Lines
Authors: Vivas-Ruiz Dan E. , Rosas Paola , Proleón Alex , Torrejón Daniel , Lazo Fanny , Tenorio-Ricca Ana Belén , Guajardo Francisco , Almarza Cristopher , Andrades Víctor , Astorga Jessica , Oropesa Daniel , Toledo Jorge , Vera María Jesús , Martínez Jorge , Araya-Maturana Ramiro , Dubois-Camacho Karen , Hermoso Marcela A. , Alvarenga Valéria G. , Sanchez Eladio Flores , Yarlequé Armando , Oliveira Luciana Souza , Urra Félix A.
Published: May 2023

From the venom of the Bothrops pictus snake, an endemic species from Peru, we recently have described toxins that inhibited platelet aggregation and cancer cell migration. In this work, we characterize a novel P-III class snake venom metalloproteinase, called pictolysin-III (Pic-III). It is a 62 kDa proteinase that hydrolyzes dimethyl casein, azocasein, gelatin, fibrinogen, and fibrin. The cations Mg2+ and Ca2+ enhanced its enzymatic activity, whereas Zn2+ inhibited it. In addition, EDTA and marimastat were also effective inhibitors. The amino acid sequence deduced from cDNA shows a multidomain structure that includes a proprotein, metalloproteinase, disintegrin-like, and cysteine-rich domains. Additionally, Pic-III reduces the convulxin- and thrombin-stimulated platelet aggregation and in vivo, it has hemorrhagic activity (DHM = 0.3 µg). In epithelial cell lines (MDA-MB-231 and Caco-2) and RMF-621 fibroblast, it triggers morphological changes that are accompanied by a decrease in mitochondrial respiration, glycolysis, and ATP levels, and an increase in NAD(P)H, mitochondrial ROS, and cytokine secretion. Moreover, Pic-III sensitizes to the cytotoxic BH3 mimetic drug ABT-199 (Venetoclax) in MDA-MB-231 cells. To our knowledge, Pic-III is the first SVMP reported with action on mitochondrial bioenergetics and may offer novel opportunities for promising lead compounds that inhibit platelet aggregation or ECM–cancer-cell interactions.
Maximizing Postoperative Recovery: The Role of Functional Biomaterials as Nasal Packs—A Comprehensive Systematic Review without Meta-Analysis (SWiM)
Authors: Razali Rabiatul Adawiyah , Vijakumaran Ubashini , Fauzi Mh Busra , Lokanathan Yogeswaran
Published: May 2023

Numerous biomaterials have been developed over the years to enhance the outcomes of endoscopic sinus surgery (ESS) for patients with chronic rhinosinusitis. These products are specifically designed to prevent postoperative bleeding, optimize wound healing, and reduce inflammation. However, there is no singular material on the market that can be deemed the optimal material for the nasal pack. We systematically reviewed the available evidence to assess the functional biomaterial efficacy after ESS in prospective studies. The search was performed using predetermined inclusion and exclusion criteria, and 31 articles were identified in PubMed, Scopus, and Web of Science. The Cochrane risk-of-bias tool for randomized trials (RoB 2) was used to assess each study’s risk of bias. The studies were critically analyzed and categorized into types of biomaterial and functional properties, according to synthesis without meta-analysis (SWiM) guidelines. Despite the heterogeneity between studies, it was observed that chitosan, gelatin, hyaluronic acid, and starch-derived materials exhibit better endoscopic scores and significant potential for use in nasal packing. The published data support the idea that applying a nasal pack after ESS improves wound healing and patient-reported outcomes.
Cinchonain Ia Shows Promising Antitumor Effects in Combination with L-Asparaginase-Loaded Nanoliposomes
Authors: Nguyen Thi Nga , Do Thi Phuong , Nguyen Thi Cuc , Trieu Ha Phuong , Nguyen Thi Giang An , Do Thi Thao
Published: May 2023

Cancer is among the leading causes of death worldwide, with no effective and safe treatment to date. This study is the first to co-conjugate the natural compound cinchonain Ia, which has promising anti-inflammatory activity, and L-asparaginase (ASNase), which has anticancer potential, to manufacture nanoliposomal particles (CALs). The CAL nanoliposomal complex had a mean size of approximately 118.7 nm, a zeta potential of −47.00 mV, and a polydispersity index (PDI) of 0.120. ASNase and cinchonain Ia were encapsulated into liposomes with approximately 93.75% and 98.53% efficiency, respectively. The CAL complex presented strong synergistic anticancer potency, with a combination index (CI) < 0.32 in two-dimensional culture and 0.44 in a three-dimensional model, as tested on NTERA-2 cancer stem cells. Importantly, the CAL nanoparticles demonstrated outstanding antiproliferative efficiency on cell growth in NTERA-2 cell spheroids, with greater than 30- and 2.5-fold increases in cytotoxic activity compared to either cinchonain Ia or ASNase liposomes, respectively. CALs also presented extremely enhanced antitumor effects, reaching approximately 62.49% tumor growth inhibition. Tumorized mice under CALs treatment showed a survival rate of 100%, compared to 31.2% in the untreated control group (p < 0.01), after 28 days of the experiment. Thus, CALs may represent an effective material for anticancer drug development.
Immunometabolism Modulation by Extracts from Pistachio Stalks Formulated in Phospholipid Vesicles
Authors: Pani Simone , Pappalardo Ilaria , Santarsiero Anna , Vassallo Antonio , Radice Rosa Paola , Martelli Giuseppe , Siano Francesco , Todisco Simona , Convertini Paolo , Caddeo Carla , Infantino Vittoria
Published: May 2023

Several studies have demonstrated the effectiveness of plant extracts against various diseases, especially skin disorders; namely, they exhibit overall protective effects. The Pistachio (Pistacia vera L.) is known for having bioactive compounds that can effectively contribute to a person’s healthy status. However, these benefits may be limited by the toxicity and low bioavailability often inherent in bioactive compounds. To overcome these problems, delivery systems, such as phospholipid vesicles, can be employed. In this study, an essential oil and a hydrolate were produced from P. vera stalks, which are usually discarded as waste. The extracts were characterized by liquid and gas chromatography coupled with mass spectrometry and formulated in phospholipid vesicles intended for skin application. Liposomes and transfersomes showed small size (<100 nm), negative charge (approximately −15 mV), and a longer storage stability for the latter. The entrapment efficiency was determined via the quantification of the major compounds identified in the extracts and was >80%. The immune-modulating activity of the extracts was assayed in macrophage cell cultures. Most interestingly, the formulation in transfersomes abolished the cytotoxicity of the essential oil while increasing its ability to inhibit inflammatory mediators via the immunometabolic citrate pathway.
Carbon Nanomaterials (CNMs) in Cancer Therapy: A Database of CNM-Based Nanocarrier Systems
Authors: Mohan Hugh , Fagan Andrew , Giordani Silvia
Published: May 2023

Carbon nanomaterials (CNMs) are an incredibly versatile class of materials that can be used as scaffolds to construct anticancer nanocarrier systems. The ease of chemical functionalisation, biocompatibility, and intrinsic therapeutic capabilities of many of these nanoparticles can be leveraged to design effective anticancer systems. This article is the first comprehensive review of CNM-based nanocarrier systems that incorporate approved chemotherapy drugs, and many different types of CNMs and chemotherapy agents are discussed. Almost 200 examples of these nanocarrier systems have been analysed and compiled into a database. The entries are organised by anticancer drug type, and the composition, drug loading/release metrics, and experimental results from these systems have been compiled. Our analysis reveals graphene, and particularly graphene oxide (GO), as the most frequently employed CNM, with carbon nanotubes and carbon dots following in popularity. Moreover, the database encompasses various chemotherapeutic agents, with antimicrotubule agents being the most common payload due to their compatibility with CNM surfaces. The benefits of the identified systems are discussed, and the factors affecting their efficacy are detailed.
A Gold Nanocage Probe Targeting Survivin for the Diagnosis of Pancreatic Cancer
Authors: Song Lina , Ren Shuai , Yue Yali , Tian Ying , Wang Zhongqiu
Published: May 2023

In this paper, Au nanocages (AuNCs) loaded with the MRI contrast agent gadolinium (Gd) and capped with the tumor-targeting gene survivin (Sur–AuNC•Gd–Cy7 nanoprobes) were designed and applied as a targeted imaging agent for pancreatic cancer. With its capacity to transport fluorescent dyes and MR imaging agents, the gold cage is an outstanding platform. Furthermore, it has the potential to transport different drugs in the future, making it a unique carrier platform. The utilization of Sur–AuNC•Gd–Cy7 nanoprobes has proven to be an effective means of targeting and localizing survivin-positive BxPC-3 cells within their cytoplasm. By targeting survivin, an antiapoptotic gene, the Sur–AuNC•Gd–Cy7 nanoprobe was able to induce pro-apoptotic effects in BxPC-3 pancreatic cancer cells. The biocompatibility of AuNCs•Gd, AuNCs•Gd–Cy7 nanoparticles, and Sur–AuNC•Gd–Cy7 nanoprobes is evaluated through the hemolysis rate assay. The stability of AuNCs•Gd, AuNCs•Gd–Cy7 nanoparticles, and Sur–AuNC•Gd–Cy7 nanoprobes was evaluated by determining their hydrodynamic dimensions following storage in different pH solutions for a corresponding duration. Excellent biocompatibility and stability of the Sur–AuNC•Gd–Cy7 nanoprobes will facilitate their further utilization in vivo and in vitro. The surface-bound survivin plays a role in facilitating the Sur–AuNC•Gd–Cy7 nanoprobes’ ability to locate the BxPC-3 tumor. The probe was modified to incorporate Gd and Cy7, thereby enabling the simultaneous utilization of magnetic resonance imaging (MRI) and fluorescence imaging (FI) techniques. In vivo, the Sur–AuNC•Gd–Cy7 nanoprobes were found to effectively target and localize survivin-positive BxPC-3 tumors through the use of MRI and FI. After being injected via the caudal vein, the Sur–AuNC•Gd–Cy7 nanoprobes were found to accumulate effectively in an in situ pancreatic cancer model within 24 h. Furthermore, these nanoprobes were observed to be eliminated from the body through the kidneys within 72 h after a single injection. This characteristic is crucial for a diagnostic agent. Based on the aforementioned outcomes, the Sur–AuNC•Gd–Cy7 nanoprobes have significant potential advantages for the theranostic treatment of pancreatic cancer. This nanoprobe possesses distinctive characteristics, such as advanced imaging abilities and specific drug delivery, which offer the possibility of enhancing the precision of diagnosis and efficacy of treatment for this destructive illness.