bluuebunny/crossref_metadata_2025 huggingface dataset:
A Proposed Simulation Technique for Population Stability Testing in Credit Risk Scorecards
Authors: du Pisanie Johan , Allison James Samuel , Visagie Jaco
Published: January 2023

Credit risk scorecards are logistic regression models, fitted to large and complex data sets, employed by the financial industry to model the probability of default of potential customers. In order to ensure that a scorecard remains a representative model of the population, one tests the hypothesis of population stability; specifying that the distribution of customers’ attributes remains constant over time. Simulating realistic data sets for this purpose is nontrivial, as these data sets are multivariate and contain intricate dependencies. The simulation of these data sets are of practical interest for both practitioners and for researchers; practitioners may wish to consider the effect that a specified change in the properties of the data has on the scorecard and its usefulness from a business perspective, while researchers may wish to test a newly developed technique in credit scoring. We propose a simulation technique based on the specification of bad ratios, this is explained below. Practitioners can generally not be expected to provide realistic parameter values for a scorecard; these models are simply too complex and contain too many parameters to make such a specification viable. However, practitioners can often confidently specify the bad ratio associated with two different levels of a specific attribute. That is, practitioners are often comfortable with making statements such as “on average a new customer is 1.5 times as likely to default as an existing customer with similar attributes”. We propose a method which can be used to obtain parameter values for a scorecard based on specified bad ratios. The proposed technique is demonstrated using a realistic example, and we show that the simulated data sets adhere closely to the specified bad ratios. The paper provides a link to a Github project with the R code used to generate the results.
A Novel and Robust Wind Speed Prediction Method Based on Spatial Features of Wind Farm Cluster
Authors: Zhang Mumin , Wang Yuzhi , Zhang Haochen , Peng Zhiyun , Tang Junjie
Published: January 2023

Wind energy has been widely used in recent decades to achieve green and sustainable development. However, wind speed prediction in wind farm clusters remains one of the less studied areas. Spatial features of cluster data of wind speed are not fully exploited in existing work. In addition, missing data, which dramatically deteriorate the forecasting performance, have not been addressed thoroughly. To tackle these tough issues, a new method, termed input set based on wind farm cluster data–deep extreme learning machine (IWC-DELM), is developed herein. This model builds an input set based on IWC, which takes advantage of the historical data of relevant wind farms to utilize the spatial characteristics of wind speed sequences within such wind farm clusters. Finally, wind speed prediction is obtained after the training of DELM, which results in a better performance in forecasting accuracy and training speed. The structure IWC, complete with the multidimensional average method (MDAM), is also beneficial to make up the missing data, thus enhancing data robustness in comparison to the traditional method of the moving average approach (MAA). Experiments are conducted with some real-world data, and the results of gate recurrent unit (GRU), long- and short-term memory (LSTM) and sliced recurrent neural networks (SRNNs) are also taken for comparison. These comparative tests clearly verify the superiority of IWC-DELM, whose accuracy and efficiency both rank at the top among the four candidates.
Molecular Cloning and Characteristics of a Lectin from the Bivalve Glycymeris yessoensis
Authors: Mizgina Tatyana O. , Baldaev Sergey N. , Likhatskaya Galina N. , Molchanova Valentina I. , Kokoulin Maxim S. , Filshtein Alina P. , Rogozhin Eugene A. , Chikalovets Irina V. , Isaeva Marina P. , Chernikov Oleg V.
Published: January 2023

C-type lectins (CTLs) are a family of carbohydrate-binding proteins that mediate multiple biological events, including adhesion between cells, the turnover of serum glycoproteins, and innate immune system reactions to prospective invaders. Here, we describe the cDNA cloning of lectin from the bivalve Glycymeris yessoensis (GYL), which encodes 161 amino acids and the C-type carbohydrate recognition domain (CRD) with EPN and WND motifs. The deduced amino acid sequence showed similarity to other CTLs. GYL is a glycoprotein containing two N-glycosylation sites per subunit. N-glycans are made up of xylose, mannose, D-glucosamine, 3-O-methylated galactose, D-quinovoses, and 3-O-methylated 6-deoxy-D-glucose. The potential CRD tertiary structure of the GYL adopted CTL-typical long-form double-loop structure and included three disulfide bridges at the bases of the loops. Additionally, when confirming the GYL sequence, eight isoforms of this lectin were identified. This fact indicates the presence of a multigene family of GYL-like C-type lectins in the bivalve G. yessoensis. Using the glycan microarray approach, natural carbohydrate ligands were established, and the glycotope for GYL was reconstructed as “Galβ1–4GlcNAcβ obligatory containing an additional fragment”, like a sulfate group or a methyl group of fucose or N-acetylgalactosamine residues.
A Survey of Didemnin Depsipeptide Production in Tistrella
Authors: Stankey Robert , Johnson Don , Duggan Brendan , Mead David , La Clair James
Published: January 2023

As one of the first families of marine natural products to undergo clinical trials, the didemnin depsipeptides have played a significant role in inspiring the discovery of marine drugs. Originally developed as anticancer therapeutics, the recent re-evaluation of these compounds including synthetically derived dehydrodidemnin B or Aplidine, has led to their advancement towards antiviral applications. While conventionally associated with production in colonial tunicates of the family Didemnidae, recent studies have identified their biosynthetic gene clusters from the marine–derived bacteria Tistrella mobilis. While these studies confirm the production of didemnin X/Y, the low titer and general lack of understanding of their biosynthesis in Tistrella currently prevents the development of effective microbial or synthetic biological approaches for their production. To this end, we conducted a survey of known species of Tistrella and report on their ability to produce the didemnin depsipeptides. These data were used to develop conditions to produce didemnin B at titers over 15 mg/L.
Acknowledgment to the Reviewers of Medical Sciences in 2022
Authors:   Medical Sciences Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Therapeutic and Toxic Effects of Valproic Acid Metabolites
Authors: Shnayder Natalia A. , Grechkina Violetta V. , Khasanova Aiperi K. , Bochanova Elena N. , Dontceva Evgenia A. , Petrova Marina M. , Asadullin Azat R. , Shipulin German A. , Altynbekov Kuanysh S. , Al-Zamil Mustafa , Nasyrova Regina F.
Published: January 2023

Valproic acid (VPA) and its salts are psychotropic drugs that are widely used in neurological diseases (epilepsy, neuropathic pain, migraine, etc.) and psychiatric disorders (schizophrenia, bipolar affective disorder, addiction diseases, etc.). In addition, the indications for the appointment of valproate have been expanding in recent years in connection with the study of new mechanisms of action of therapeutic and toxic metabolites of VPA in the human body. Thus, VPA is considered a component of disease-modifying therapy for multiple tumors, neurodegenerative diseases (Huntington’s disease, Parkinson’s disease, Duchenne progressive dystrophy, etc.), and human immunodeficiency syndrome. The metabolism of VPA is complex and continues to be studied. Known pathways of VPA metabolism include: β-oxidation in the tricarboxylic acid cycle (acetylation); oxidation with the participation of cytochrome P-450 isoenzymes (P-oxidation); and glucuronidation. The complex metabolism of VPA explains the diversity of its active and inactive metabolites, which have therapeutic, neutral, or toxic effects. It is known that some active metabolites of VPA may have a stronger clinical effect than VPA itself. These reasons explain the relevance of this narrative review, which summarizes the results of studies of blood (serum, plasma) and urinary metabolites of VPA from the standpoint of the pharmacogenomics and pharmacometabolomics. In addition, a new personalized approach to assessing the cumulative risk of developing VPA-induced adverse reactions is presented and ways for their correction are proposed depending on the patient’s pharmacogenetic profile and the level of therapeutic and toxic VPA metabolites in the human body fluids (blood, urine).
Differential Effect of Fructose in the Presence or Absence of Fatty Acids on Circadian Metabolism in Hepatocytes
Authors: Tsameret Shani , Chapnik Nava , Froy Oren
Published: January 2023

We aimed to explore whether fructose in the absence or presence of fatty acids modulates circadian metabolism in AML-12 hepatocytes. Fructose treatment under steatosis conditions (FruFA) led to fat synthesis resulting in increased triglycerides and cholesterol content. Fructose led to reduced activity of the AMPK and mTOR-signaling pathway. However, FruFA treatment led to inhibition of the AMPK signaling pathway but activation of the mTOR pathway. Fructose also increased the expression of inflammatory markers, whereas the addition of fatty acids dampened their circadian expression. At the clock level, fructose or FruFA altered the expression of the core clock. More specifically, fructose led to altered expression of the BMAL1-RORα-REV-ERBα axis, together with reduced phosphorylated BMAL1 levels. In conclusion, our results show that hepatocytes treated with fructose respond differently if fatty acids are present, leading to a differential effect on metabolism and circadian rhythms. This is achieved by modulating BMAL1 activity and expression.
Compressed Natural Gas as an Alternative Vehicular Fuel in Tanzania: Implementation, Barriers, and Prospects
Authors: Gerutu Gerutu Bosinge , Greyson Kenedy Aliila , Chombo Pius Victor
Published: January 2023

This paper presents the implementation of natural gas vehicles (NGVs) in Tanzania’s road transportation sector. The peculiarity of this analysis is the evaluation of the technical and economic performance of the converted gasoline and diesel engines to use compressed natural gas (CNG) as the cleanest-burning hydrocarbon. The technical performance involved vehicle mileage (MiCNG), fuel consumption (Fcons), speed drop, engine fuel enhancement (Fenh), and fuel saving, while the economic performance involved conversion cost (Cc), fuel cost saving (FCsaving), and payback (PB). Considering the conversion of gasoline vehicles, the MiCNG could reach an average of 100 to 500 km per filling, depending on the CNG cylinder size. The Fenh and fuel saving were ranging between 1.9 and 3.9 and 71 and 78%. With a proportion of 30:70 diesel-CNG fuel, the heavy-duty truck with 180 kg of CNG could reach 1300 km, saving about 440 L, which is 78.6% per roundtrip, while the medium passenger car with 15 kg of CNG could reach 350 km, presenting a fuel saving of about 75%. From an economic point of view, gasoline retrofitted NGVs cost about 50 to 200 TZS/km, yielding a fuel cost saving of up to 79% and starting to pay off between 2 and 7 months or 10,000 and 40,000 km, depending on the engine capacity. Considering dual fuel, the heavy-duty truck consumes about 496 TZS/km, saving about 62.3% of diesel fuel and starting to pay off after 2.5 months or 29,304 km. To conclude, NGV technologies have been successfully implemented in Tanzania’s road transportation sector, presenting significant fuel savings and reducing reliance on imported oil. While taking measures, this study paves a way for Tanzania and other sub-Saharan countries to promote NGV growth.
Hybrid Silicon Substrate FinFET-Metal Insulator Metal (MIM) Memristor Based Sense Amplifier Design for the Non-Volatile SRAM Cell
Authors: Priya G. Lakshmi , Rawat Namita , Sanagavarapu Abhishek , Venkatesh M. , Andrew Roobert A.
Published: January 2023

Maintaining power consumption has become a critical hurdle in the manufacturing process as CMOS technologies continue to be downscaled. The longevity of portable gadgets is reduced as power usage increases. As a result, less-cost, high-density, less-power, and better-performance memory devices are in great demand in the electronics industry for a wide range of applications, including Internet of Things (IoT) and electronic devices like laptops and smartphones. All of the specifications for designing a non-volatile memory will benefit from the use of memristors. In addition to being non-volatile, memristive devices are also characterized by the high switching frequency, low wattage requirement, and compact size. Traditional transistors can be replaced by silicon substrate-based FinFETs, which are substantially more efficient in terms of area and power, to improve the design. As a result, the design of non-volatile SRAM cell in conjunction with silicon substrate-based FinFET and Metal Insulator Metal (MIM) based Memristor is proposed and compared to traditional SRAMs. The power consumption of the proposed hybrid design has outperformed the standard Silicon substrate FinFET design by 91.8% better. It has also been reported that the delay for the suggested design is actually quite a bit shorter, coming in at approximately 1.989 ps. The proposed architecture has been made significantly more practical for use as a low-power and high-speed memory system because of the incorporation of high-K insulation at the interface of metal regions. In addition, Monte Carlo (MC) simulations have been run for the reported 6T-SRAM designs in order to have a better understanding of the device stability.
Natural Organic Materials Based Memristors and Transistors for Artificial Synaptic Devices in Sustainable Neuromorphic Computing Systems
Authors: Tanim Md Mehedi Hasan , Templin Zoe , Zhao Feng
Published: January 2023

Natural organic materials such as protein and carbohydrates are abundant in nature, renewable, and biodegradable, desirable for the construction of artificial synaptic devices for emerging neuromorphic computing systems with energy efficient operation and environmentally friendly disposal. These artificial synaptic devices are based on memristors or transistors with the memristive layer or gate dielectric formed by natural organic materials. The fundamental requirement for these synaptic devices is the ability to mimic the memory and learning behaviors of biological synapses. This paper reviews the synaptic functions emulated by a variety of artificial synaptic devices based on natural organic materials and provides a useful guidance for testing and investigating more of such devices.
Deletions across the SARS-CoV-2 Genome: Molecular Mechanisms and Putative Functional Consequences of Deletions in Accessory Genes
Authors: Rogozin Igor B. , Saura Andreu , Bykova Anastassia , Brover Vyacheslav , Yurchenko Vyacheslav
Published: January 2023

The analysis of deletions may reveal evolutionary trends and provide new insight into the surprising variability and rapidly spreading capability that SARS-CoV-2 has shown since its emergence. To understand the factors governing genomic stability, it is important to define the molecular mechanisms of deletions in the viral genome. In this work, we performed a statistical analysis of deletions. Specifically, we analyzed correlations between deletions in the SARS-CoV-2 genome and repetitive elements and documented a significant association of deletions with runs of identical (poly-) nucleotides and direct repeats. Our analyses of deletions in the accessory genes of SARS-CoV-2 suggested that there may be a hypervariability in ORF7A and ORF8 that is not associated with repetitive elements. Such recurrent search in a “sequence space” of accessory genes (that might be driven by natural selection) did not yet cause increased viability of the SARS-CoV-2 variants. However, deletions in the accessory genes may ultimately produce new variants that are more successful compared to the viral strains with the conventional architecture of the SARS-CoV-2 accessory genes.
Escherichia coli O80 in Healthy Cattle: Absence of Shigatoxigenic and Enteropathogenic E. coli O80:H2 and (Phylo) Genomics of Non-Clonal Complex 165 E. coli O80
Authors: Ikeda Rie , Nakamura Keiji , Saulmont Marc , Habets Audrey , Duprez Jean-Noël , Korsak Nicolas , Hayashi Tetsuya , Thiry Damien , Mainil Jacques G.
Published: January 2023

The origin of human and calf infections by Shigatoxigenic (STEC) and enteropathogenic (EPEC) Escherichia coli O80:H2 is still unknown. The aim of this study was to identify E. coli O80 in healthy cattle with an emphasis on melibiose non-fermenting E. coli O80:H2. Faecal materials collected from 149 bulls at 1 slaughterhouse and 194 cows on 9 farms were tested with O80 antigen-encoding gene PCR after overnight growth in enrichment broths. The 53 O80 PCR-positive broths were streaked on different (semi-)selective agar plates. Five E. coli colonies from 3 bulls and 11 from 2 cows tested positive with the O80 PCR, but no melibiose non-fermenting E. coli was isolated. However, these 16 E. coli O80 were negative with PCR targeting the fliCH2, eae, stx1, stx2 and hlyF genes and were identified by WGS to serotypes and sequence types O80:H6/ST8619 and O80:H45/ST4175. They were phylogenetically related to E. coli O80:H6 and O80:H45 isolated from different animal species in different countries, respectively, but neither to STEC and EPEC O80:H2/ST301, nor to other serotypes of the clonal complex 165. As a conclusion, healthy adult cattle were not identified as a source of contamination of humans and calves by STEC or EPEC O80:H2.
Inferring Bacterial Community Interactions and Functionalities Associated with Osteopenia and Osteoporosis in Taiwanese Postmenopausal Women
Authors: Kuo Yi-Jie , Chen Chia-Jung , Hussain Bashir , Tsai Hsin-Chi , Hsu Gwo-Jong , Chen Jung-Sheng , Asif Aslia , Fan Cheng-Wei , Hsu Bing-Mu
Published: January 2023

Growing evidence suggests that the gut microbiota and their metabolites are associated with bone homeostasis and fragility. However, this association is limited to microbial taxonomic differences. This study aimed to explore whether gut bacterial community associations, composition, and functions are associated with osteopenia and osteoporosis. We compared the gut bacterial community composition and interactions of healthy postmenopausal women with normal bone density (n = 8) with those of postmenopausal women with osteopenia (n = 18) and osteoporosis (n = 21) through 16S rRNA sequencing coupled with network biology and statistical analyses. The results of this study showed reduced alpha diversity in patients with osteoporosis, followed by that in patients with osteopenia, then in healthy controls. Taxonomic analysis revealed that significantly enriched bacterial genera with higher abundance was observed in patients with osteoporosis and osteopenia than in healthy subjects. Additionally, a co-occurrence network revealed that, compared to healthy controls, bacterial interactions were higher in patients with osteoporosis, followed by those with osteopenia. Further, NetShift analysis showed that a higher number of bacteria drove changes in the microbial community structure of patients with osteoporosis than osteopenia. Correlation analysis revealed that most of these driver bacteria had a significant positive relationship with several significant metabolic pathways. Further, ordination analysis revealed that height and T-score were the primary variables influencing the gut microbial community structure. Taken together, this study evaluated that microbial community interaction is more important than the taxonomic differences in knowing the critical role of gut microbiota in postmenopausal women associated with osteopenia and osteoporosis. Additionally, the significantly enriched bacteria and functional pathways might be potential biomarkers for the prognosis and treatment of postmenopausal women with osteopenia and osteoporosis.
Effects of Dietary Isoleucine Supplementation on the Production Performance, Health Status and Cecal Microbiota of Arbor Acre Broiler Chickens
Authors: Liu Hengchen , Sun Jianli , Jiang Shuzhen , Jiao Ning , Huang Libo , Yuan Xuejun , Guan Qinglin , Li Yang , Yang Weiren
Published: January 2023

A total of 24,000 healthy 1-day-old Arbor Acres broilers with similar initial weights were used in this study and fed a basal diet supplemented with 0, 400 and 800 mg/kg isoleucine (Ile), denoted CON, ILE400 and ILE800, respectively. Results revealed that the final body weight, average daily weight gain, and eviscerated carcass rate, of broiler chickens in the ILE400 group were significantly higher than in other groups (p < 0.05). In addition, the ILE400 and ILE800 groups had a lower feed conversion rate and a higher survival rate and breast muscle rate (p < 0.05), while the abdominal fat rate was significantly lower than the CON group (p < 0.05). There were significantly lower serum concentrations of UREA, glucose (GLU) and total cholesterol (TCHO) in the ILE400 and ILE800 groups than in the CON group (p < 0.05); glutathione peroxidase (GSH-Px) activity was significantly higher in the ILE400 group than in the other groups, and tumor necrosis factor-alpha (TNF-α) concentration was considerably lower than in other groups (p < 0.05). Moreover, interleukin (IL)-10 concentration in the ILE800 group was significantly higher than in the other groups (p < 0.05). The ILE400 group significantly down-regulated the mRNA expressions of fatty-acid synthase (FASN) and solid alcohol regulatory element binding protein 1c (SREBP1c), and significantly up-regulated the mRNA expressions of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), lipoprotein lipase (LPL) and sirtuin1 (Sirt1) (p < 0.05). The ILE400 group had significantly higher intestinal villus height than the CON and ILE800 groups, while the ILE800 group had significantly lower intestinal villus height/crypt depth (p < 0.05). Furthermore, high-throughput sequencing showed that the Shannon index, and Verrucomicrobiota, Colidextribacter and Bacteroides abundances were significantly higher in the ILE400 group than in the CON group (p < 0.05). Interestingly, the ILE800 group reduced the Simpson index, phylum Firmicutes and Bacteroidota abundances (including genera Colidextribacter, Butyricicoccus, [Ruminococcus]_torques_group, Bacteroides, Alistipes, Barnesiella and Butyricimonas), and increased Proteobacteria and Cyanobacteria (including genera Dyella, Devosia, unidentified_Chloroplast and Hyphomicrobium) (p < 0.05). Overall, our study showed that adding 400 mg/kg Ile to the diet (diets total Ile levels at 1.01%, 0.90% and 0.87% during the starter, grower and finisher phases, respectively) increased production performance and improved the health status in broiler chickens.
Investigation on Segregation Granulation by Fuel and Flux in Coating
Authors: Wang Lin , Jiang Xin , Wang Qingyu , Ai Mingxing , Yin Xiaowei , Liu Jintao , Shen Fengman
Published: January 2023

The metallurgical property of sinter is an important factor affecting the smooth operation of blast furnaces (BF), because it has a great impact on the permeability of BF and solid fuel rate. In order to promote the combustion of solid fuel and the mineralization of flux in sintering process, and eventually improve the strength of sintered ore, a series of investigation on segregation granulation by fuel and flux in coating were carried out, including the sinter pot experiments, the morphology analysis, and the discussion combine with phase diagram. The experimental results show that, (1) as the CaO increased from 0% to 40% and coke breeze increased from 0% to 100%, the sintering indices were improved, the tumble strength of sinter increased from 65.8% to 68.4%, the rate of qualified products increased from 77.4% to 81.0%, and the micro-strength of sinter increased from 68.7% to 75.9%. (2) There are three reasons for the high strength of sinter by segregation granulation of fuel and flux in coating, (a) the complete combustion of solid fuel and release the heat, (b) the effective absorb heat and mineralization of flux, and (c) the improvement of fluidity of bonding phase. The outcomes of the present work may provide a new method to improve the strength of sintered ore and give some reference for better understanding segregation granulation process and using it in actual operation.
Plant Essential Oils as Healthy Functional Ingredients of Nutraceuticals and Diet Supplements: A Review
Authors: Matera Riccardo , Lucchi Elena , Valgimigli Luca
Published: January 2023

Essential oils (EOs) are mixtures of volatile molecules endowed with health-promoting biological activities that go beyond their role as aromas and natural preservatives and can be exploited to develop functional foods and diet supplements. Their composition is briefly addressed along with regulatory aspects. The potential health benefit of human diet supplementation with EOs is outlined through a review of the recent literature on available clinical trials and preclinical research concerning EOs activity towards: (1) irritable bowel syndrome; (2) inflammatory bowel disease; (3) regulation of microbiota; (4) gastroprotection; (5) hepatoprotection; (6) protection of the urinary tract and diuresis; (7) management of metabolic disorders including hyperglycemia and hyperlipidemia; (8) anti-inflammatory and pain control; (9) immunomodulation and protection from influenza; and (10) neuroprotection and modulation of mood and cognitive performance. The emerging potential in such activities of selected EOs is given focus, particularly green and black cumin, bergamot, orange, myrtle, peppermint, sage, eucalyptus, lavender, thyme, lemon balm, ginger, and garlic.
Fluoropolymer: A Review on Its Emulsion Preparation and Wettability to Solid-Liquid Interface
Authors: Liang Lei , Wen Tao , Xin Jun , Su Chao , Song Ke , Zhao Wei , Liu Hongwu , Su Gui
Published: January 2023

In the preparation of a superamphiphobic surface, the most basic method is to reduce the surface free energy of the interface. The C—F bond has a very low surface free energy, which can significantly change the wettability of the solid–liquid interface and make it a hydrophobic or oleophobic, or even superamphiphobic surface. Based on the analysis of a large number of research articles, the preparation and application progress in fluoropolymer emulsion were summarized. After that, some corresponding thoughts were put forward combined with our professional characteristics. According to recent research, the status of the fluoropolymer emulsion preparation system was analyzed. In addition, all related aspects of fluoropolymer emulsion were systematically classified in varying degrees. Furthermore, the interaction between fluoropolymer structure and properties, especially the interaction with nanomaterials, was also explored. The aim of this review is to try to attract more scholars’ attention to fluorocarbon interfacial materials. It is expected that it will make a certain theoretical and practical significance in the preparation and application of fluoropolymer.
New Bicyclic Pyridine-Based Hybrids Linked to the 1,2,3-Triazole Unit: Synthesis via Click Reaction and Evaluation of Neurotropic Activity and Molecular Docking
Authors: Sirakanyan Samvel N. , Spinelli Domenico , Petrou Anthi , Geronikaki Athina , Kartsev Victor G. , Hakobyan Elmira K. , Yegoryan Hasmik A. , Zuppiroli Luca , Zuppiroli Riccardo , Ayvazyan Armen G. , Paronikyan Ruzanna G. , Arakelyan Tatevik A. , Hovakimyan Anush A.
Published: January 2023

The synthesis of new original bicyclic pyridine-based hybrids linked to the 1,2,3-triazole unit was described via a click reaction. The anticonvulsant activity and some psychotropic properties of the new compounds were evaluated. The biological assays demonstrated that some of the studied compounds showed high anticonvulsant and psychotropic properties. The five most active compounds (7a, d, g, j, and m) contain a pyrano [3,4-c]pyridine cycle with a methyl group in the pyridine ring in their structures. Furthermore, molecular docking studies were performed, and their results are in agreement with experimental data.
Dess–Martin Periodinane-Mediated Oxidative Coupling Reaction of Isoquinoline with Benzyl Bromide
Authors: Yang Chunmei , Zhang Guoqing , Tang Senling , Pan Yang , Shao Huawu , Jiao Wei
Published: January 2023

Dess–Martin periodinane (DMP) is a broadly applicable oxidant in chemical synthesis. In this work, an efficient and convenient synthesis of N-substituted isoquinolinone derivatives mediated by DMP was achieved through the oxidative coupling reaction of functionalized isoquinoline with readily available benzyl bromide, which is a metal-free, mild, and practical method for synthesizing isoquinoline-1,3-dione or isoquinoline-1,3,4-trione derivatives in excellent yields. The H2O18-labeling experiment was performed to gain insight into the possible mechanism for this reaction.
Inhibition of Klf10 Attenuates Oxidative Stress-Induced Senescence of Chondrocytes via Modulating Mitophagy
Authors: Shang Jie , Lin Nan , Peng Rong , Jiang Ning , Wu Biao , Xing Baizhou , Lin Shiyuan , Xu Xianghe , Lu Huading
Published: January 2023

Osteoarthritis (OA) is the most prevalent degenerative joint disease in the elderly. Accumulation of evidence has suggested that chondrocyte senescence plays a significant role in OA development. Here, we show that Krüppel-like factor 10 (Klf10), also named TGFβ inducible early gene-1 (TIEG1), is involved in the pathology of chondrocyte senescence. Knocking down the Klf10 in chondrocytes attenuated the tert-butyl hydroperoxide (TBHP)-induced senescence, inhibited generation of reactive oxygen species (ROS), and maintained mitochondrial homeostasis by activating mitophagy. These findings suggested that knocking down Klf10 inhibited senescence-related changes in chondrocytes and improved cartilage homeostasis, indicating that Klf10 may be a therapeutic target for protecting cartilage against OA.
Wnt Signaling Pathway Collapse upon β-Catenin Destruction by a Novel Antimicrobial Peptide SKACP003: Unveiling the Molecular Mechanism and Genetic Activities Using Breast Cancer Cell Lines
Authors: Selvarathinam Kanitha , Subramani Prabhu , Thekkumalai Malarvili , Vilwanathan Ravikumar , Selvarajan Ramganesh , Abia Akebe Luther King
Published: January 2023

Despite progress in breast cancer treatment, the survival rate for patients with metastatic breast cancer remains low due to chemotherapeutic agent resistance and the lack of specificity of the current generation of cancer drugs. Our previous findings indicated that the antimicrobial peptide SKACP003 exhibited anticancer properties, particularly against the MCF-7, MDA-MB-231, and MDA-MB-453 breast cancer cell lines. However, the mechanism of SKACP003-induced cancer cell death is unknown. Here, we investigated the molecular mechanism by which SKACP003 inhibits the cell cycle, cell proliferation, and angiogenesis in breast cancer cell lines. The results revealed that all the breast cancer cell lines treated at their IC50 values significantly inhibited the replicative phase of the cell cycle. The SKACP003-induced growth inhibition induced apoptosis, as evidenced by a decrease in BCL-2 and an increase in BAX and caspase gene (Cas-3, Cas-8, and Cas-9) expression. Reduced expression of the β-Catenin signaling pathway was associated with the SKACP003-induced apoptosis. SKACP003-treated breast cancer cells showed decreased expression of Wnt/β-Catenin targeting genes such as C-Myc, P68, and COX-2 and significant downregulation of CDK-4 and CDK-6 genes. Furthermore, cytoplasmic β-catenin protein levels in SKACP003-treated cell lines were significantly lower than in control cell lines. The results of the current study suggest that the newly identified antimicrobial peptide SKACP003 has great potential as a candidate for specifically targeting the β-catenin and thus significantly reducing the progression and prognosis of breast cancer cell lines.
Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo
Authors: Markelić Milica , Mojić Marija , Bovan Dijana , Jelača Sanja , Jović Zorana , Purić Milica , Koruga Djuro , Mijatović Sanja , Maksimović-Ivanić Danijela
Published: January 2023

In our recent study, we showed that in vitro treatment of melanoma cells with hyperpolarized light (HPL) as well as with the second derivative of fullerene, hyper-harmonized hydroxylated fullerene water complex (3HFWC) reduced viability of cells by decreasing their proliferative capacity and inducing senescence and reprogramming towards a normal, melanocytic phenotype. Therefore, we wanted to determine whether these effects persisted in vivo in the syngeneic mouse melanoma model with a combined treatment of HPL irradiation and 3HFWC per os. Our results demonstrated the potent antitumor effects of 3HFWC nanosubstance assisted by HPL irradiation. These effects were primarily driven by the stimulation of melanoma cell growth arrest, the establishment of a senescent phenotype, and melanocytic differentiation on the one hand, and the awakening of the antitumor immune response on the other. In addition, the combined treatment reduced the protumorigenic activity of immune cells by depleting T regulatory cells, myeloid-derived suppressors, and M2 macrophages. The support of the 3HFWC substance by HPL irradiation may be the axis of the new approach design based on tumor cell reprogramming synchronized with the mobilization of the host’s protective immune response.
Asymmetrical Dimer Photonic Crystals Enabling Outstanding Optical Sensing Performance
Authors: Mangach Hicham , El Badri Youssef , Hmima Abdelhamid , Bouzid Abdenbi , Achaoui Younes , Zeng Shuwen
Published: January 2023

The exploration of the propensity of engineered materials to bring forward innovations predicated on their periodic nanostructured tailoring rather than the features of their individual compounds is a continuous pursuit that has propelled optical sensors to the forefront of ultra-sensitive bio-identification. Herein, a numerical analysis based on the Finite Element Method (FEM) was used to investigate and optimize the optical properties of a unidirectional asymmetric dimer photonic crystal (PhC). The proposed device has many advantages from a nanofabrication standpoint compared to conventional PhCs sensors, where integrating defects within the periodic array is imperative. The eigenvalue and transmission analysis performed indicate the presence of a protected, confined mode within the structure, resulting in a Fano-like response in the prohibited states. The optical sensor demonstrated a promising prospect for monitoring the DNA hybridization process, with a quality factor (QF) of roughly 1.53×105 and a detection limit (DL) of 4.4×10−5 RIU. Moreover, this approach is easily scalable in size while keeping the same attributes, which may potentially enable gaze monitoring.
Copeptin Implementation on Stroke Prognosis
Authors: Karatzetzou Stella , Tsiptsios Dimitrios , Sousanidou Anastasia , Fotiadou Styliani , Christidi Foteini , Kokkotis Christos , Gkantzios Aimilios , Stefas Eleftherios , Vlotinou Pinelopi , Kaltsatou Antonia , Aggelousis Nikolaos , Vadikolias Konstantinos
Published: January 2023

Predicting functional outcome following stroke is considered to be of key importance in an attempt to optimize overall stroke care. Although clinical prognostic tools have been widely implemented, optimal blood biomarkers might be able to yield additional information regarding each stroke survivor’s propensity for recovery. Copeptin seems to have interesting prognostic potential poststroke. The present review aims to explore the prognostic significance of copeptin in stroke patients. Literature research of two databases (MEDLINE and Scopus) was conducted to trace all relevant studies published between 16 February 2012 and 16 February 2022 that focused on the utility of copeptin as a prognostic marker in acute stroke setting. 25 studies have been identified and included in the present review. The predictive ability of copeptin regarding both functional outcome and mortality appears to be in the range of established clinical variables, thus highlighting the added value of copeptin evaluation in stroke management. Apart from acute ischemic stroke, the discriminatory accuracy of the biomarker was also demonstrated among patients with transient ischemic attack, intracerebral hemorrhage, and subarachnoid hemorrhage. Overall, copeptin represents a powerful prognostic tool, the clinical implementation of which is expected to significantly facilitate the individualized management of stroke patients.
Optimizing the Relationship between Regulation and Innovation in Dietary Supplements: A Case Study of Food with Function Claims in Japan
Authors: Sato Keigo , Kodama Kota , Sengoku Shintaro
Published: January 2023

Regulation has long been a counterpart of innovation in the health care industry, and recent cases have demonstrated that appropriately designed regulations can both coexist with and promote innovation. This study is the first study to explore how the regulatory environment affected the innovation process during the transition of the regulations for functional foods in Japan by examining quantitatively the impact of the foods with function claims (FFC) system on industry, companies, and products. Based on a dataset of Japanese dietary supplement manufacturing companies (n = 169) and their products (n = 731) in 2019, we found that companies that have newly entered the FFC system are smaller in scale than existing companies (p < 0.01, Wilcoxon rank sum test). We also found that companies with FFC products have larger revenue growth (p = 0.01). A multiple regression analysis revealed that FFC product sales increased with in-house clinical testing (coefficient: 26.8, p < 0.0001), diverse active ingredients (coefficient: 7.6, p < 0.001), and the claim of new functions (coefficient: 10.2, p < 0.05). These results suggested that the FFC system facilitated the market entry of small and mid-size enterprises and promoted the creation of high-value products through innovative company efforts.
Evaluation of WIC Online Ordering during the COVID-19 Pandemic: Evidence from an Oklahoma Grocery Store Chain
Authors: Zhang Qi , Zhang Junzhou , Park Kayoung , Tang Chuanyi
Published: January 2023

The COVID-19 pandemic is worsening the disparities in food access in the United States. As consumers have been increasingly using grocery online ordering services to limit their exposure to the COVID-19 virus, participants of federal nutrition assistance programs lack the online benefit redemption option. With the support of the US Department of Agriculture (USDA), retailers are pilot-testing online food benefit ordering in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). By combining the Oklahoma WIC administrative data, the online ordering data from a grocery store chain in Oklahoma, and the COVID-19 data in Oklahoma, this study examines how WIC participants responded to the online food benefit ordering option and how their adoption of online ordering was associated with the COVID-19 incidence. Results show that from July to December 2020, 15,171 WIC households redeemed WIC benefits at an Oklahoma chain store, but only 819 of them adopted online ordering. They together completed 102,227 online orders, which accounted for 2.7% of the store visits and 2.6% of the monetary value of WIC redemptions at these stores. There was no significant relationship between WIC online ordering adoption and COVID-19 incidence in Oklahoma.
Moderate and Severe Congenital Heart Diseases Adversely Affect the Growth of Children in Italy: A Retrospective Monocentric Study
Authors: Palleri Daniela , Bartolacelli Ylenia , Balducci Anna , Bonetti Simone , Zanoni Rossana , Ciuca Cristina , Gesuete Valentina , Bulgarelli Ambra , Hasan Tammam , Ragni Luca , Angeli Emanuela , Gargiulo Gaetano Domenico , Donti Andrea
Published: January 2023

Children with congenital heart disease (CHD) are at increased risk for undernutrition. The aim of our study was to describe the growth parameters of Italian children with CHD compared to healthy children. We performed a cross-sectional study collecting the anthropometric data of pediatric patients with CHD and healthy controls. WHO and Italian z-scores for weight for age (WZ), length/height for age (HZ), weight for height (WHZ) and body mass index (BMIZ) were collected. A total of 657 patients (566 with CHD and 91 healthy controls) were enrolled: 255 had mild CHD, 223 had moderate CHD and 88 had severe CHD. Compared to CHD patients, healthy children were younger (age: 7.5 ± 5.4 vs. 5.6 ± 4.3 years, p = 0.0009), taller/longer (HZ: 0.14 ± 1.41 vs. 0.62 ± 1.20, p < 0.002) and heavier (WZ: −0,07 ± 1.32 vs. 0.31 ± 1.13, p = 0.009) with no significant differences in BMIZ (−0,14 ± 1.24 vs. –0.07 ± 1.13, p = 0.64) and WHZ (0.05 ± 1.47 vs. 0.43 ± 1.07, p = 0.1187). Moderate and severe CHD patients presented lower z-scores at any age, with a more remarkable difference in children younger than 2 years (WZ) and older than 5 years (HZ, WZ and BMIZ). Stunting and underweight were significantly more present in children affected by CHD (p < 0.01). In conclusion, CHD negatively affects the growth of children based on the severity of the disease, even in a high-income country, resulting in a significant percentage of undernutrition in this population.
Acknowledgment to the Reviewers of Nutraceuticals in 2022
Authors:   Nutraceuticals Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
White Photoluminescence in Dy-Doped Oxyfluoride Glasses
Authors: Chen Xianmei , Khamenok Artemiy V. , Khusainov Shaukat G. , Shestakov Mikhail V. , Moshchalkov Victor V.
Published: January 2023

Dy3+-doped, Ag and Dy3+-co-doped, and Tm3+ and Dy3+-co-doped oxyfluoride glasses have been prepared by a conventional melt-quenching method. White and yellowish light emissions were generated in the glasses under excitation in the range from 350 to 390 nm. Changes in the excitation wavelength in the ultraviolet (UV) range do not significantly alter the emission tint of the Dy and Ag and Dy-co-doped glasses. On the contrary, the tint of the Tm and Dy co-doped glasses considerably varies under excitation in the same range.
Acoustic Aerosol Delivery: Assessing of Various Nasal Delivery Techniques and Medical Devices on Intrasinus Drug Deposition
Authors: Leclerc Lara , Prévôt Nathalie , Hodin Sophie , Delavenne Xavier , Mentzel Heribert , Schuschnig Uwe , Pourchez Jérémie
Published: January 2023

This study aims to evaluate the impact of the nasal delivery technique and nebulizing technologies (using different frequencies of oscillating airflow) for acoustic aerosol targeting of maxillary sinuses. Sodium fluoride (chemical used as a marker), tobramycin (drug used as a marker) and 99mTc-DTPA (radiolabel aerosol) were used to assess the intrasinus aerosol deposition on a nasal cast. Two commercial medical devices (PARI SINUS nebulizer and NL11SN ATOMISOR nebulizer) and various nasal delivery techniques (one or two nostrils connected to the aerosol inlet, the patient with the soft palate closed or open during the acoustic administration of the drug, the presence or not of flow resistance in the nostril opposite to the one allowing the aerosol to be administered) were evaluated. The closed soft palate condition showed a significant increase in drug deposition even though no significant difference in the rest of the nasal fossae was noticed. Our results clearly demonstrated a higher intrasinus aerosol deposition (by a factor 2–3; respectively 0.03 ± 0.007% vs. 0.003 ± 0.0002% in the right maxillary sinus and 0.027 ± 0.006% vs. 0.013 ± 0.004% in the left maxillary sinus) using the acoustic airflow generated by the PARI SINUS compared to the NL11SN ATOMISOR. The results clearly demonstrated that the optimal conditions for aerosol deposition in the maxillary sinuses were obtained with a closed soft palate. Thus, the choice of the nebulizing technology (and mainly the frequency of the pulsating aerosol generated) and also the recommendation of the best nasal delivery technique are key factors to improve intrasinus aerosol deposition.
Synthesis and Biological Evaluation of 6-O-Sucrose Monoester Glycolipids as Possible New Antifungal Agents
Authors: Verboni Michele , Sisti Maurizio , Campana Raffaella , Benedetti Serena , Palma Francesco , Potenza Lucia , Lucarini Simone , Duranti Andrea
Published: January 2023

A small library of 6-O-sucrose monoester surfactants has been synthesized and tested against various microorganisms. The synthetic procedure involved a modified Mitsunobu reaction, which showed improved results compared to those present in the literature (higher yields and larger scope). The antifungal activities of most of these glycolipids were satisfactory. In particular, sucrose palmitoleate (URB1537) showed good activity against Candida albicans ATCC 10231, Fusarium spp., and Aspergillus fumigatus IDRAH01 (MIC value: 16, 32, 64 µg/mL, respectively), and was further characterized through radical scavenging, anti-inflammatory, and biocompatibility tests. URB1537 has been shown to control the inflammatory response and to have a safe profile.
Lipid Liquid Crystal Nanoparticles: Promising Photosensitizer Carriers for the Treatment of Infected Cutaneous Wounds
Authors: Awad Muhammed , Kopecki Zlatko , Barnes Timothy J. , Wignall Anthony , Joyce Paul , Thomas Nicky , Prestidge Clive A.
Published: January 2023

Cutaneous chronic wounds impose a silent pandemic that affects the lives of millions worldwide. The delayed healing process is usually complicated by opportunistic bacteria that infect wounds. Staphylococcus aureus is one of the most prevalent bacteria in infected cutaneous wounds, with the ability to form antibiotic-resistant biofilms. Recently, we have demonstrated the potential of gallium protoporphyrin lipid liquid crystalline nanoparticles (GaPP-LCNP) as a photosensitizer against S. aureus biofilms in vitro. Herein, we investigate the potential of GaPP-LCNP using a pre-clinical model of infected cutaneous wounds. GaPP-LCNP showed superior antibacterial activity compared to unformulated GaPP, reducing biofilm bacterial viability by 5.5 log10 compared to 2.5 log10 in an ex vivo model, and reducing bacterial viability by 1 log10 in vivo, while unformulated GaPP failed to reduce bacterial burden. Furthermore, GaPP-LCNP significantly promoted wound healing through reduction in the bacterial burden and improved early collagen deposition. These findings pave the way for future pre-clinical investigation and treatment optimizations to translate GaPP-LCNP towards clinical application.
Novel Collagen-Polyphenols-Loaded Silica Composites for Topical Application
Authors: Deaconu Mihaela , Prelipcean Ana-Maria , Brezoiu Ana-Maria , Mitran Raul-Augustin , Isopencu Gabriela , Matei Cristian , Berger Daniela
Published: January 2023

Lesions can affect skin functions and cause a simple issue, such as dehydration, or more challenging complications, such as bacterial infections. The purpose of this study was to design composites for topical application that can prevent and/or assist in bacterial infections and support cell regeneration using natural components. A polyphenolic extract obtained from Salvia officinalis was embedded in functionalized mesoporous silica nanoparticles for better stability, followed by their distribution into a collagen porous scaffold. The resulting polyphenols-loaded MSN exhibited enhanced antibacterial activity and good cytocompatibility. Improved thermal stability of the collagen porous scaffold was obtained due to the presence of the functionalized MSN. For the first time, collagen-polyphenols-loaded silica composites were reported in the literature as potential wound dressings. The newly developed composites showed excellent sterility.