bluuebunny/crossref_metadata_2025 huggingface dataset:
Wearable Bio-Inspired Pulsating-Flow Cooling for Live Garments Based on a Novel Design of Ferrofluid Micro-Valve
Authors: Tang Jiawei , Luk Patrick
Published: November 2022

Temperature-related frustrations, such as heat exhaustion, heat stroke, hypothermia, and frost damage, are some of the most prevalent health risks encountered by humans. The aggravation may be lethal for individuals who reside or work in conditions of protracted and high temperature. Temperature-control technologies, such as underfloor heating and air conditioners, have been studied and applied to give individuals with a pleasant and, more crucially, an endurable temperature. However, it may be challenging to install these technologies in an exterior or enclosed space. In addition, they are inflexible for individual requirements, such as mobility and personal-temperature management. A wearable bio-inspired pulsing-flow (discontinuous) cooling system, which can significantly enhance cooling performance, is proposed in this work. The proposed system is implemented with valves to generate pulsating flows. Given that traditional mechanical-valve actuation systems continue to face limits in terms of switching frequency, interface wear loss, and size limitations for wearable-garment applications, a ferrofluid-based shape-controllable micro-valve is proposed to reduce the size and weight of the cooling system. An empirical approach is adopted to avoid the extensive computational simulation of the thermo fluidic dynamics involved, so that efforts can be focused on the design of an innovative scaled prototype built from ferrofluid valves positioned in a specific array of the cooling tubes. This allows the performance of continuous and pulsating cooling-flow systems to be compared on the same flow rate baseline. The results demonstrate that the proposed technology not only delivers superior cooling efficiency, but also has the potential to provide individualized temperature regulation in a “live” garment.
A Parameter Design Method for a Wireless Power Transmission System with a Uniform Magnetic Field
Authors: Ji Li , Zhang Chi , Ge Fuchen , Qian Buren , Sun Hongjun
Published: November 2022

In a wireless power transfer (WPT) system, misalignment on the transceiver side has a major impact on the transmission efficiency. However, a uniform magnetic field can mitigate the detrimental impact of offsets on the system performance. In this paper, an optimized double-D (DD) coil is proposed by dividing the wires into two groups. The parametric design approach proceeds from the outside to the inside of the coil. The uniformity of the magnetic field of the improved design is increased by 20.7% compared to that of a regular DD coil. The average transmission efficiency of the final test prototype can reach 85%, and the offset rates in the X and Y directions are only 3.21% and 3.43%, respectively, when misalignment occurs. This design can effectively improve the anti-offset ability of the system and can be generalized to the design of other types of coils.
Simulation-Based Investigations of the Load-Bearing Behavior of Concrete Hollow Sphere Slabs Exposed to Fire
Authors: Miller Olga , Gericke Oliver , Nigl David , Kovaleva Daria , Blandini Lucio
Published: November 2022

This paper concerns the investigations of the flexural capacity of concrete slabs with integrated concrete hollow spheres that are subjected to fire and their mass saving potential compared to solid slabs. (1) Background: The overuse of concrete in construction contributes considerably to global CO2 emissions; therefore, the potential for mass reduction in structural components must be fully exploited. However, the design regulations for weight-minimized components, particularly slabs with internal voids, are often not explicitly covered by standards, such as the fire design standard relevant to this paper. (2) Methods: Based on the design guidelines for statically determinate structures in Eurocode 2-2 and DIN 4102-4, a solid slab and a concrete slab with concrete hollow spheres are designed and evaluated with regard to their weight and flexural capacity when subjected to fire. The temperature profiles within the slab cross-section exposed to fire are simulated using ABAQUS finite element software, considering the physically nonlinear, temperature-dependent material behavior of concrete and steel. Using these results, the strain distribution corresponding to the maximum flexural moment is iteratively determined at the weakest cross-section, which exhibits the largest void. (3) Results: All components show sufficient flexural capacity for the target fire duration of 90 min. (4) Conclusion: In the context of this study, the design guidelines according to Eurocode 2-2 and DIN 4102-4 are proven to be fully applicable also for concrete hollow sphere slabs.
Uptake of Flaxseed Dietary Linusorbs Modulates Regulatory Genes Including Induction of Heat Shock Proteins and Apoptosis
Authors: Shim Youn Young , Tse Timothy J. , Saini AkalRachna K. , Kim Young Jun , Reaney Martin J. T.
Published: November 2022

Flaxseed (Linum usitatissimum L.) is gaining popularity as a superfood due to its health-promoting properties. Mature flax grain includes an array of biologically active cyclic peptides or linusorbs (LOs, also known as cyclolinopeptides) that are synthesized from three or more ribosome-derived precursors. Two flaxseed orbitides, [1–9-NαC]-linusorb B3 and [1–9-NαC]-linusorb B2, suppress immunity, induce apoptosis in a cell line derived from human epithelial cancer cells (Calu-3), and inhibit T-cell proliferation, but the mechanism of LO action is unknown. LO-induced changes in gene expression in both nematode cultures and human cancer cell lines indicate that LOs promoted apoptosis. Specific evidence of LO bioactivity included: (1) distribution of LOs throughout the organism after flaxseed consumption; (2) induction of heat shock protein (HSP) 70A, an indicator of stress; (3) induction of apoptosis in Calu-3 cells; and (4) modulation of regulatory genes (determined by microarray analysis). In specific cancer cells, LOs induced apoptosis as well as HSPs in nematodes. The uptake of LOs from dietary sources indicates that these compounds might be suitable as delivery platforms for a variety of biologically active molecules for cancer therapy.
Phenolic Profile, Antioxidant Activity and Amino Acid Composition of Moringa Leaves Fermented with Edible Fungal Strains
Authors: Starzyńska-Janiszewska Anna , Stodolak Bożena , Fernández-Fernández Carmen , Mickowska Barbara , Verardo Vito , Gómez-Caravaca Ana María
Published: November 2022

Solid-state fermentation (SSF) is widely recognised as a technique to increase the bioactive potential and nutritional value of plant materials. However, the effect of this biotreatment differs for individual substrates. This study aimed to evaluate the impact of SSF with filamentous fungi (Rhizopus, Aspergillus, and Neurospora) on a moringa leaf phenolic profile, antioxidant activity, and amino acid composition. A total of 43 phenolic compounds were determined in the dried leaves analysed by HPLC-ESI-TOF-MS. The leaves contained 11.79 mg/g of free phenolics: flavonols (80.6%, mainly quercetin and kaempferol glycosides), hydroxycinnamic acid derivatives (12.3%), vitexin and vicenin (6.9%), and a small amount of lignan (isolariciresinol isomers). The result of the 1-day fermentation was a slight enhancement in the concentration of individual free phenolics (flavones) and the antioxidant activity of the leaves. However, extending the incubation period caused a significant decrease in those parameters and cannot be recommended for obtaining a food fortificant from moringa leaves. In contrast, the 3-day fermentation with N. intermedia led to a 26% average accumulation of individual amino acids. Therefore, the SSF with Neurospora can be a promising method for improving the nutritional composition of moringa leaves and needs further investigation.
Enzyme-Linked Aptamer Kits for Rapid, Visual, and Sensitive Determination of Lactoferrin in Dairy Products
Authors: Zhang Fan , Du Hongxia , Li Linsen , Li Tengfei , Wang Jing , Chen Zilei , Yan Mengmeng , Zhu Chao , Qu Feng
Published: November 2022

Lactoferrin (Lf), as a popular nutritional fortification in dairy products, has the ability regulate the body’s immune system and function as a broad-spectrum antibacterial, which is of great significance to the growth and development of infants and children. Herein, an indirect competitive enzyme-linked aptamer assay (ELAA) kit was established for rapid, sensitive, and visual determination of Lf in dairy products. In the construction, the Lf aptamer was conjugated with horseradish peroxidase (HRP) as the recognition probe and aptamer complementary strand (cDNA) were anchored onto the microplate as the capture probe. The recognition probes were first mixed with a sample solution and specifically bound with the contained Lf, then added into the microplate in which the free recognition probes in the mixture were captured by the capture probe. After washing, the remaining complex of cDNA/Aptamer/HRP in the microplate was conducted with a chromogenic reaction through HRP, efficiently catalyzing the substrate 3, 3′, 5, 5′-tetramethylbenzidine (TMB), therefore the color shade would directly reflect Lf concentration. Under the optimization conditions, a good linear relationship (R2, 0.9901) was obtained in the wide range of 25–500 nM with the detection limit of 14.01 nM and a good specificity, as well as the reliable recoveries. Furthermore, the ELAA kits achieved the Lf determination with an accuracy of 79.71~116.99% in eleven samples, which consisted of three kinds of dairy products: including goat milk powder, cow milk powder, and nutrition drop. Moreover, the results were also validated by the high-performance capillary electrophoresis (HPCE) method. The ELAA kit provides a simple and convenient determination for Lf in dairy products, and it is highly expected to be commercialized.
Innovative Process for Dried Caper (Capparis spinosa L.) Powder Production
Authors: Cincotta Fabrizio , Merlino Maria , Verzera Antonella , Gugliandolo Enrico , Condurso Concetta
Published: November 2022

This research aimed to develop a new time, energy, and cost-saving production process for obtaining dried powder from Capparis spinosa floral buds. Four different trials, including dry salting with 40% NaCl (for 10 days and 40 days) and brine salting with 18% NaCl (at room temperature for 3 days and at 60 °C for 6 h), were carried out, and two different air-drying temperatures (40 and 50 °C) were used. The effects on chemical and sensory characteristics were investigated and compared with traditional undried caper samples. Spectroscopy and chromatographic techniques such as UV–VIS, GC-MS, and FTIR were used for chlorophylls, carotenoids, polyphenols, flavonoids, and volatile aroma compounds’ analyses. Moreover, a sensory descriptive analysis and acceptability were applied to individuate the product most appreciated by the consumers. Among the different trials, brine salting at 60 °C and drying at 50 °C constituted the fastest process that yielded an appreciated powder by consumers; the chemical analyses demonstrated that this process did not lead to the formation of extraneous aroma compounds that could influence the typical sensory properties of capers and maintained high levels of chlorophylls, carotenoids, and polyphenols. Altogether, the results could be of great significance to industrial production and potentiate positive impacts on the economy of production areas.
Effects of Tea Polyphenol and Its Combination with Other Antioxidants Added during the Extraction Process on Oxidative Stability of Antarctic Krill (Euphausia superba) Oil
Authors: Wang Ziwei , Liu Fujun , Luo Ying , Zeng Xiangbo , Pei Xuechen , Zhao Guanhua , Zhang Min , Zhou Dayong , Yin Fawen
Published: November 2022

Antarctic krill (Euphausia superba) oil contains high levels of marine omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In industrial production, krill oil is usually extracted from krill meals by using ethanol as a solvent. Water in the krill meal can be easily extracted by using ethanol as an extraction solvent. During the extraction process, the EPA and DHA are more easily oxidized and degraded when water exists in the ethanol extract of krill oil. Based on the analysis of peroxide value (POV), thiobarbituric acid-reactive substances (TBARS), fatty acid composition, and lipid class composition, the present study indicated that the composite antioxidants (TP-TPP) consist of tea polyphenol (TP) and tea polyphenol palmitate (TPP) had an excellent antioxidant effect. By contrast, adding TP-TPP into ethanol solvent during the extraction process is more effective than adding TP-TPP into krill oil after the extraction process.
Prospects for Plant-Based Meat: Current Standing, Consumer Perceptions, and Shifting Trends
Authors: Safdar Bushra , Zhou Haochun , Li He , Cao Jinnuo , Zhang Tianyu , Ying Zhiwei , Liu Xinqi
Published: November 2022

Dietary habits have a substantial influence on both planet and individual health. High intake of animal products has significant negative effects on the environment and on human health; hence, a reduction in meat consumption is necessary. The transition towards plant-based meat (PBM) is one of the potential solutions for environmental and health issues. To achieve this goal, it is important to understand the dietary habits and demands of consumers. This review was designed with a focus on PBM alternatives, dietary shifts during the COVID-19 pandemic, the drivers of consumers’ perceptions in various countries, and the measures that can promote the shift towards PBM. The PBM market is predicted to grow with rising awareness, familiarity, and knowledge in the coming years. Companies must focus on the categories of anticipated benefits to aid consumers in making the switch to a diet higher in PBM alternatives if they want to win over the target market.
A Comparative Study of Responses of Fractional Oscillator to Sinusoidal Excitation in the Weyl and Caputo Senses
Authors: Duan Jun-Sheng , Lan Yu-Jie , Li Ming
Published: November 2022

The fractional oscillator equation with the sinusoidal excitation mx″(t)+bDtαx(t)+kx(t)=Fsin(ωt), m,b,k,ω>0 and 0<α<2 is comparatively considered for the Weyl fractional derivative and the Caputo fractional derivative. In the sense of Weyl, the fractional oscillator equation is solved to be a steady periodic oscillation xW(t). In the sense of Caputo, the fractional oscillator equation is solved and subjected to initial conditions. For the fractional case α∈(0,1)∪(1,2), the response to excitation, S(t), is a superposition of three parts: the steady periodic oscillation xW(t), an exponentially decaying oscillation and a monotone recovery term in negative power law. For the two responses to initial values, S0(t) and S1(t), either of them is a superposition of an exponentially decaying oscillation and a monotone recovery term in negative power law. The monotone recovery terms come from the Hankel integrals which make the fractional case different from the integer-order case. The asymptotic behaviors of the solutions removing the steady periodic response are given for the four cases of the initial values. The Weyl fractional derivative is suitable for a describing steady-state problem, and can directly lead to a steady periodic solution. The Caputo fractional derivative is applied to an initial value problem and the steady component of the solution is just the solution in the corresponding Weyl sense.
Detection of Glaucoma on Fundus Images Using Deep Learning on a New Image Set Obtained with a Smartphone and Handheld Ophthalmoscope
Authors: Bragança Clerimar Paulo , Torres José Manuel , Soares Christophe Pinto de Almeida , Macedo Luciano Oliveira
Published: November 2022

Statistics show that an estimated 64 million people worldwide suffer from glaucoma. To aid in the detection of this disease, this paper presents a new public dataset containing eye fundus images that was developed for glaucoma pattern-recognition studies using deep learning (DL). The dataset, denoted Brazil Glaucoma, comprises 2000 images obtained from 1000 volunteers categorized into two groups: those with glaucoma (50%) and those without glaucoma (50%). All images were captured with a smartphone attached to a Welch Allyn panoptic direct ophthalmoscope. Further, a DL approach for the automatic detection of glaucoma was developed using the new dataset as input to a convolutional neural network ensemble model. The accuracy between positive and negative glaucoma detection, sensitivity, and specificity were calculated using five-fold cross-validation to train and refine the classification model. The results showed that the proposed method can identify glaucoma from eye fundus images with an accuracy of 90.0%. Thus, the combination of fundus images obtained using a smartphone attached to a portable panoptic ophthalmoscope and artificial intelligence algorithms yielded satisfactory results in the overall accuracy of glaucoma detection tests. Consequently, the proposed approach can contribute to the development of technologies aimed at massive population screening of the disease.
Georeferencing Accuracy Assessment of Historical Aerial Photos Using a Custom-Built Online Georeferencing Tool
Authors: Zhang Su , Barrett Hays A. , Baros Shirley V. , Neville Paul R. H. , Talasila Sandeep , Sinclair Lisa L.
Published: November 2022

As one of the earliest forms of remote sensing, aerial photography has been regarded as an important part of the mapmaking process. Aerial photos, especially historical aerial photos, provide significant amount of valuable information for many applications and fields. However, due to limited funding support, most historical aerial photos have not been digitized and georeferenced yet, which substantially limits their utility for today’s computer-based image processing and analysis. Traditionally, historical aerial photos are georeferenced with desktop GIS software applications. However, this method is expensive, time-consuming, and labor-intensive. To address these limitations, this research developed a custom-built online georeferencing tool to enable georeferencing digitized historical aerial photos in a web environment, which is able to georeference historical aerial photos in a rapid and cost-effective manner. To evaluate the georeferencing performance, a set of 50 historical aerial photos were georeferenced with not only the developed online georeferencing tool but also two commercial desktop software programs. Research results revealed the custom-built online georeferencing tool provided the highest degree of accuracy while maximizing its accessibility.
Genetic Variants Associated with Long-Terminal Repeats Can Diagnostically Classify Cannabis Varieties
Authors: Oultram Jackson M. J. , Pegler Joseph L. , Symons Greg M. , Bowser Timothy A. , Eamens Andrew L. , Grof Christopher P. L. , Korbie Darren J.
Published: November 2022

Cannabis sativa (Cannabis) has recently been legalized in multiple countries globally for either its recreational or medicinal use. This, in turn, has led to a marked increase in the number of Cannabis varieties available for use in either market. However, little information currently exists on the genetic distinction between adopted varieties. Such fundamental knowledge is of considerable value and underpins the accelerated development of both a nascent pharmaceutical industry and the commercial recreational market. Therefore, in this study, we sought to assess genetic diversity across 10 Cannabis varieties by undertaking a reduced representation shotgun sequencing approach on 83 individual plants to identify variations which could be used to resolve the genetic structure of the assessed population. Such an approach also allowed for the identification of the genetic features putatively associated with the production of secondary metabolites in Cannabis. Initial analysis identified 3608 variants across the assessed population with phylogenetic analysis of this data subsequently enabling the confident grouping of each variety into distinct subpopulations. Within our dataset, the most diagnostically informative single nucleotide polymorphisms (SNPs) were determined to be associated with the long-terminal repeat (LTRs) class of retroelements, with 172 such SNPs used to fully resolve the genetic structure of the assessed population. These 172 SNPs could be used to design a targeted resequencing panel, which we propose could be used to rapidly screen different Cannabis plants to determine genetic relationships, as well as to provide a more robust, scientific classification of Cannabis varieties as the field moves into the pharmaceutical sphere.
CRISPR/Cas9-Based Knock-Out of the PMR4 Gene Reduces Susceptibility to Late Blight in Two Tomato Cultivars
Authors: Li Ruiling , Maioli Alex , Yan Zhe , Bai Yuling , Valentino Danila , Milani Anna Maria , Pompili Valerio , Comino Cinzia , Lanteri Sergio , Moglia Andrea , Acquadro Alberto
Published: November 2022

Phytophthora infestans, the causal agent of late blight (LB) in tomato (Solanum lycopersicum L.), is a devastating disease and a serious concern for plant productivity. The presence of susceptibility (S) genes in plants facilitates pathogen proliferation; thus, disabling these genes may help provide a broad-spectrum and durable type of tolerance/resistance. Previous studies on Arabidopsis and tomato have highlighted that knock-out mutants of the PMR4 susceptibility gene are tolerant to powdery mildew. Moreover, PMR4 knock-down in potato has been shown to confer tolerance to LB. To verify the same effect in tomato in the present study, a CRISPR–Cas9 vector containing four single guide RNAs (sgRNAs: sgRNA1, sgRNA6, sgRNA7, and sgRNA8), targeting as many SlPMR4 regions, was introduced via Agrobacterium-tumefaciens-mediated transformation into two widely grown Italian tomato cultivars: ‘San Marzano’ (SM) and ‘Oxheart’ (OX). Thirty-five plants (twenty-six SM and nine OX) were selected and screened to identify the CRISPR/Cas9-induced mutations. The different sgRNAs caused mutation frequencies ranging from 22.1 to 100% and alternatively precise insertions (sgRNA6) or deletions (sgRNA7, sgRNA1, and sgRNA8). Notably, sgRNA7 induced in seven SM genotypes a −7 bp deletion in the homozygous status, whereas sgRNA8 led to the production of fifteen SM genotypes with a biallelic mutation (−7 bp and −2 bp). Selected edited lines were inoculated with P. infestans, and four of them, fully knocked out at the PMR4 locus, showed reduced disease symptoms (reduction in susceptibility from 55 to 80%) compared to control plants. The four SM lines were sequenced using Illumina whole-genome sequencing for deeper characterization without exhibiting any evidence of mutations in the candidate off-target regions. Our results showed, for the first time, a reduced susceptibility to Phytophtora infestans in pmr4 tomato mutants confirming the role of KO PMR4 in providing broad-spectrum protection against pathogens.
Effects of Corchorusoside C on NF-κB and PARP-1 Molecular Targets and Toxicity Profile in Zebrafish
Authors: Mirtallo Ezzone Nathan P. , Anaya-Eugenio Gerardo D. , Addo Ermias Mekuria , Ren Yulin , Kinghorn A. Douglas , Carcache de Blanco Esperanza J.
Published: November 2022

The present study aims to continue the study of corchorusoside C (1), a cardenolide isolated from Streptocaulon juventas, as a potential anticancer agent. A mechanistic study was pursued in a zebrafish model and in DU-145 prostate cancer cells to investigate the selectivity of 1 towards NF-κB and PARP-1 pathway elements. Compound 1 was found to inhibit the expression of IKKα and NF-κB p65 in TNF-α induced zebrafish and inhibit the expression of NIK in vitro. The protein expression levels of XRCC-1 were increased and p53 decreased in DU-145 cells. XIAP protein expression was initially decreased after treatment with 1, followed by an increase in expression at doses higher than the IC50 value. The activity of caspase-1 and the protein expression levels of IL-18 were both decreased following treatment of 1. The binding interactions for 1 to NIK, XRCC-1, p53, XIAP, and caspase-1 proteins were explored in molecular docking studies. Additionally, the toxicity profile of 1 in zebrafish was favorable in comparison to its analog digoxin and other anticancer drugs at the same MTD in zebrafish. Overall, 1 targets the noncanconical NF-κB pathway in vivo and in vitro, and is well tolerated in zebrafish supporting its potential in the treatment of prostate cancer.
Influence of Short and Long Hyperglycemia on Cardioprotection by Remote Ischemic Preconditioning—A Translational Approach
Authors: Feige Katharina , Roth Sebastian , M’Pembele René , Galow Anna , Koenig Sarah , Stroethoff Martin , Raupach Annika , Lurati Buse Giovanna , Mathes Alexander M. , Hollmann Markus W. , Huhn Ragnar , Torregroza Carolin
Published: November 2022

The adverse impact of common diseases like diabetes mellitus and acute hyperglycemia on morbidity and mortality from myocardial infarction (MI) has been well documented over the past years of research. In the clinical setting, the relationship between blood glucose and mortality appears linear, with amplifying risk associated with increasing blood glucose levels. Further, this seems to be independent of a diagnosis of diabetes. In the experimental setting, various comorbidities seem to impact ischemic and pharmacological conditioning strategies, protecting the heart against ischemia and reperfusion injury. In this translational experimental approach from bedside to bench, we set out to determine whether acute and/or prolonged hyperglycemia have an influence on the protective effect of transferred human RIPC-plasma and, therefore, might obstruct translation into the clinical setting. Control and RIPC plasma of young healthy men were transferred to isolated hearts of young male Wistar rats in vitro. Plasma was administered before global ischemia under either short hyperglycemic (HGs Con, HGs RIPC) conditions, prolonged hyperglycemia (HGl Con, HGl RIPC), or under normoglycemia (Con, RIPC). Infarct sizes were determined by TTC staining. Control hearts showed an infarct size of 55 ± 7%. Preconditioning with transferred RIPC plasma under normoglycemia significantly reduced infarct size to 25 ± 4% (p < 0.05 vs. Con). Under acute hyperglycemia, control hearts showed an infarct size of 63 ± 5%. Applying RIPC plasma under short hyperglycemic conditions led to a significant infarct size reduction of 41 ± 4% (p < 0.05 vs. HGs Con). However, the cardioprotective effect of RIPC plasma under normoglycemia was significantly stronger compared with acute hyperglycemic conditions (RIPC vs. HGs RIPC; p < 0.05). Prolonged hyperglycemia (HGl RIPC) completely abolished the cardioprotective effect of RIPC plasma (infarct size 60 ± 7%; p < 0.05 vs. HGl Con; HGl Con 59 ± 5%).
Developmental and Reproductive Impacts of Four Bisphenols in Daphnia magna
Authors: Qian Lingling , Chen Chen , Guo Liguo , Deng Junping , Zhang Xiangling , Zheng Jiexiang , Wang Genmei , Zhang Xiaofei
Published: November 2022

Bisphenol A (BPA) is a typical endocrine-disrupting chemical (EDC) used worldwide. Considering its adverse effects, BPA has been banned or strictly restricted in some nations, and many analogs have been introduced to the market. In this study, we selected three representative substitutes, BPS, BPF, and BPAF, along with BPA, to assess the developmental and reproductive effects on Daphnia magna. The F0 generation was exposed to bisphenols (BPs) at an environmentally relevant concentration (100 μg/L) for 21 d; then the embryo spawn at day 21 was collected. Behavior traits, the activity of antioxidant enzymes, and gene transcription were evaluated at three developmental stages (days 7, 14, and 21). Notably, body length, heart rate, and thoracic limb beating were significantly decreased, and D. magna behaved more sluggishly in the exposed group. Moreover, exposure to BPs significantly increased the antioxidant enzymatic activities, which indicated that BPs activated the antioxidant defense system. Additionally, gene expression indicated intergenerational effects in larvae, particularly in the BPAF group. In conclusion, BPA analogs such as BPF and BPAF showed similar or stronger reproductive and developmental toxicity than BPA in D. magna. These findings collectively deepen our understanding of the toxicity of BPA analogs and provide empirical evidence for screening safe alternatives to BPA.
Differential Expression of RSK4 Transcript Isoforms in Cancer and Its Clinical Relevance
Authors: Chen Sisi , Seckl Michael J. , Lorentzen Marc P. G. , Pardo Olivier E.
Published: November 2022

While we previously revealed RSK4 as a therapeutic target in lung and bladder cancers, the wider role of this kinase in other cancers remains controversial. Indeed, other reports instead proposed RSK4 as a tumour suppressor in colorectal and gastric cancers and are contradictory in breast malignancies. One explanation for these discrepancies may be the expression of different RSK4 isoforms across cancers. Four RNAs are produced from the RSK4 gene, with two being protein-coding. Here, we analysed the expression of the latter across 30 normal and 33 cancer tissue types from the combined GTEx/TCGA dataset and correlated it with clinical features. This revealed the expression of RSK4 isoforms 1 and 2 to be independent prognostic factors for patient survival, pathological stage, cancer metastasis, recurrence, and immune infiltration in brain, stomach, cervical, and kidney cancers. However, we found that upregulation of either isoform can equally be associated with good or bad prognosis depending on the cancer type, and changes in the expression ratio of isoforms fail to predict clinical outcome. Hence, differential isoform expression alone cannot explain the contradictory roles of RSK4 in cancers, and further research is needed to highlight the underlying mechanisms for the context-dependent function of this kinase.
The Quality and Fertilizing Potential of Red Deer (Cervus elaphus L.) Epididymal Spermatozoa Stored in a Liquid State
Authors: Dziekońska Anna , Koziorowska-Gilun Magdalena , Kordan Władysław , Neuman Nicoletta M. , Kotlarczyk Angelika M. , Korzekwa Anna J.
Published: November 2022

The aim of this study was to assess the quality and fertilizing potential of red deer epididymal spermatozoa stored in a liquid state for up to 11 days (D11). In Experiment 1, sperm quality was determined. In Experiment 2, the efficiency of in vitro fertilization (IVF) and artificial insemination (AI) of stored sperm were evaluated. An analysis of sperm quality on D5 of storage revealed a decrease (p < 0.05) in motility and morphology, and a higher proportion of apoptotic spermatozoa. On D1, D7 and D10, the total motility of sperm for IVF and AI was determined to be 82.6%, 71.0% and 64.8%, respectively. The results of IVF and AI demonstrated that the fertilizing potential of spermatozoa differs between days of storage. The percentage of blastocysts was higher when oocytes were fertilized on D1 (17.4 %) compared to D7 (8.5%) and D10 sperm (10.5%). Differences were noted in the pregnancy rates of inseminated hinds. The insemination with D1, D7 and D10 sperm led to live births (33% from D7 and D10). The results indicate that the quality of red deer epididymal spermatozoa remains satisfactory during ten days of storage in a liquid state, and that these spermatozoa maintain their fertility potential.
Perinatal Stem Cell Therapy to Treat Type 1 Diabetes Mellitus: A Never-Say-Die Story of Differentiation and Immunomodulation
Authors: Paris Francesca , Pizzuti Valeria , Marrazzo Pasquale , Pession Andrea , Alviano Francesco , Bonsi Laura
Published: November 2022

Human term placenta and other postpartum-derived biological tissues are promising sources of perinatal cells with unique stem cell properties. Among the massive current research on stem cells, one medical focus on easily available stem cells is to exploit them in the design of immunotherapy protocols, in particular for the treatment of chronic non-curable human diseases. Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells and perinatal cells can be harnessed both to generate insulin-producing cells for beta cell replenishment and to regulate autoimmune mechanisms via immunomodulation capacity. In this study, the strong points of cells derived from amniotic epithelial cells and from umbilical cord matrix are outlined and their potential for supporting cell therapy development. From a basic research and expert stem cell point of view, the aim of this review is to summarize information regarding the regenerative medicine field, as well as describe the state of the art on possible cell therapy approaches for diabetes.
The Downstaging Concept in Treatment-Resistant Depression: Spotlight on Ketamine
Authors: Wilkowska Alina , Cubała Wiesław Jerzy
Published: November 2022

Treatment-resistant depression is a pleomorphic phenomenon occurring in 30% of patients with depression. The chance to achieve remission decreases with every subsequent episode. It constitutes a significant part of the global disease burden, causes increased morbidity and mortality, and is associated with poor quality of life. It involves multiple difficult-to-treat episodes, with increasing resistance over time. The concept of staging captures the process of changes causing increasing treatment resistance and global worsening of functioning in all areas of life. Ketamine is a novel rapid-acting antidepressant with neuroplastic potential. Here, we argue that ketamine use as an add-on treatment of resistant major depressive disorder, based on its unique pharmacological properties, can reverse this process, give hope to patients, and prevent therapeutic nihilism.
Microglia-Derived Olfactomedin-like 3 Is a Potent Angiogenic Factor in Primary Mouse Brain Endothelial Cells: A Novel Target for Glioblastoma
Authors: Joseph Laila M. , Toedebusch Ryan G. , Debebe Eshetu , Bastian Aurelie H. , Lucchesi Christopher A. , Syed-Quadri Shafee , Wittenburg Luke A. , Chen Xinbin , Meyers Frederick J. , Toedebusch Christine M.
Published: November 2022

Neoangiogenesis, a hallmark feature of all malignancies, is robust in glioblastoma (GBM). Vascular endothelial growth factor (VEGF) has long been regarded as the primary pro-angiogenic molecule in GBM. However, anti-VEGF therapies have had little clinical efficacy, highlighting the need to explore VEGF-independent mechanisms of neoangiogenesis. Olfactomedin-like 3 (OLFML3), a secreted glycoprotein, is an established proangiogenic factor in many cancers, but its role in GBM neoangiogenesis is unknown. To gain insight into the role of OLFML3 in microglia-mediated angiogenesis, we assessed endothelial cell (EC) viability, migration and differentiation following (1) siRNA knockdown targeting endogenous EC Olfml3 and (2) EC exposure to human recombinant OLFML3 (rhOLFML3; 10 ng/mL, 48 h), and conditioned medium (CM) from isogenic control and Olfml3−/− microglia (48 h). Despite a 70% reduction in Olfml3 mRNA levels, EC angiogenic parameters were not affected. However, exposure to both rhOLFML3 and isogenic control microglial CM increased EC viability (p < 0.01), migration (p < 0.05) and differentiation (p < 0.05). Strikingly, these increases were abolished, or markedly attenuated, following exposure to Olfml3−/− microglial CM despite corresponding increased microglial secretion of VEGF-A (p < 0.0001). Consistent with reports in non-CNS malignancies, we have demonstrated that OLFML3, specifically microglia-derived OLFML3, promotes VEGF-independent angiogenesis in primary brain microvascular ECs and may provide a complementary target to mitigate neovascularization in GBM.
Molecular Insights and Clinical Outcomes of Drugs of Abuse Adulteration: New Trends and New Psychoactive Substances
Authors: Di Trana Annagiulia , Berardinelli Diletta , Montanari Eva , Berretta Paolo , Basile Giuseppe , Huestis Marilyn A. , Busardò Francesco Paolo
Published: November 2022

Adulteration is a well-known practice of drug manufacturers at different stages of drug production. The intentional addition of active ingredients to adulterate the primary drug may enhance or mask pharmacological effects or may produce more potent drugs to increase the number of available doses and the dealer’s profit. Adulterants found in different drugs change over time in response to different factors. A systematic literature search in PubMed and Scopus databases and official international organizations’ websites according to PRISMA guidelines was performed. A total of 724 studies were initially screened, with 145 articles from PubMed and 462 from Scopus excluded according to the criteria described in the Method Section. The remaining 117 records were further assessed for eligibility to exclude articles without sufficient data. Finally, 79 studies were classified as “non-biological” (n = 35) or “biological” (n = 35 case reports; n = 9 case series) according to the samples investigated. Although the seized samples analyses revealed the presence of well-established adulterants such as levamisole for cocaine or paracetamol/acetaminophen for heroin, the reported data disclosed new adulteration practices, such as the use of NPS as cutting agents for classic drugs of abuse and other NPS. For example, heroin adulterated with synthetic cannabinoids or cocaine adulterated with fentanyl/fentalogues raised particular concern. Notably, adulterants play a role in some adverse effects commonly associated with the primary drug, such as levamisole-adulterated cocaine that may induce vasculitis via an autoimmune process. It is essential to constantly monitor adulterants due to their changing availability that may threaten drug consumers’ health.
Investigating the Influence of Initial Water pH on Concrete Strength Gain Using a Sensors and Sclerometric Test Combination
Authors: Utepov Yelbek , Tulebekova Assel , Aldungarova Aliya , Mkilima Timoth , Zharassov Shyngys , Shakhmov Zhanbolat , Bazarbayev Daniyar , Tolkynbayev Temirkhan , Kaliyeva Zhanar
Published: November 2022

Concrete strength gain can be significantly affected by the initial characteristics of the raw materials. Unfortunately, information on the potential influence of the initial water pH on concrete strength gain is still scarce. In this study, the potential effects of the initial water pH on concrete strength gain were investigated using a combination of sensors and a sclerometric test. The impact of initial pH on the strength gain process was investigated using three distinct pH values (4.0, 7.0, and 12). The primary variables examined were pH variations over time, internal temperature, and strength gain. The problem was further examined using a number of statistical techniques, including Single-way Analysis of Variance, Scheffé’s approach, and Correlation Matrixes. When the temperature data from 4.0, 7.0, and 12 pH values were put through the Analysis of Variance, a p-value of 2.4 × 10−261 was retrieved. Additionally, when the strength gain data from 4.0, 7.0, and 12 pH values were subjected to the Analysis of Variance, a p-value of 2.9 × 10−168 was retrieved. The results showed that the differences in the list data retrieved from the investigated pH values were statistically significant. Based on the results, we can state that the initial pH level in the mixing water can have noticeably varied consequences in terms of the strength gain of the concrete and should be carefully considered during the preparation process of concrete. The findings retrieved from this study provide a piece of useful information in the construction field, especially with concrete strength management.
Hydrothermal Synthesis of Layered Double Hydroxides Doped with Holmium, Thulium and Lutetium
Authors: Golovin Sergei N. , Yapryntsev Maksim N. , Lebedeva Olga E.
Published: November 2022

For the first time, nickel-aluminum layered double hydroxides containing holmium, thulium or lutetium cations were successfully synthesized via the coprecipitation method followed by hydrothermal treatment. X-ray diffraction data show the formation of hydrotalcite-like structures with the absence of impurity phases. The presence of lanthanides is confirmed by energy-dispersive X-ray spectrometry. Assumed empirical formulae for these compounds are [Ni0.796Al0.193Ho0.011] [(NO3)0.204·yH2O], [Ni0.808Al0.178Tm0.015] [(NO3)0.193·yH2O] and [Ni0.765Al0.219Lu0.016] [(NO3)0.235·yH2O]. These novel layered compounds demonstrate the fundamental ability of doping hydrotalcite-like compounds with any lanthanide cation, which gives rise to the synthesis of new materials with specific properties.
Pharmacokinetics, Pharmacodynamics, and Dosing Considerations of Novel β-Lactams and β-Lactam/β-Lactamase Inhibitors in Critically Ill Adult Patients: Focus on Obesity, Augmented Renal Clearance, Renal Replacement Therapies, and Extracorporeal Membrane Oxygenation
Authors: Bakdach Dana , Elajez Reem , Bakdach Abdul Rahman , Awaisu Ahmed , De Pascale Gennaro , Ait Hssain Ali
Published: November 2022

Objective: Dose optimization of novel β-lactam antibiotics (NBLA) has become necessary given the increased prevalence of multidrug-resistant infections in intensive care units coupled with the limited number of available treatment options. Unfortunately, recommended dose regimens of NBLA based on PK/PD indices are not well-defined for critically ill patients presenting with special situations (i.e., obesity, extracorporeal membrane oxygenation (ECMO), augmented renal clearance (ARC), and renal replacement therapies (RRT)). This review aimed to discuss and summarize the available literature on the PK/PD attained indices of NBLA among critically ill patients with special circumstances. Data Sources: PubMed, MEDLINE, Scopus, Google Scholar, and Embase databases were searched for studies published between January 2011 and May 2022. Study selection and data extraction: Articles relevant to NBLA (i.e., ceftolozane/tazobactam, ceftazidime/avibactam, cefiderocol, ceftobiprole, imipenem/relebactam, and meropenem/vaborbactam) were selected. The MeSH terms of “obesity”, “augmented renal clearance”, “renal replacement therapy”, “extracorporeal membrane oxygenation”, “pharmacokinetic”, “pharmacodynamic” “critically ill”, and “intensive care” were used for identification of articles. The search was limited to adult humans’ studies that were published in English. A narrative synthesis of included studies was then conducted accordingly. Data synthesis: Available evidence surrounding the use of NBLA among critically ill patients presenting with special situations was limited by the small sample size of the included studies coupled with high heterogeneity. The PK/PD target attainments of NBLA were reported to be minimally affected by obesity and/or ECMO, whereas the effect of renal functionality (in the form of either ARC or RRT) was more substantial. Conclusion: Critically ill patients presenting with special circumstances might be at risk of altered NBLA pharmacokinetics, particularly in the settings of ARC and RRT. More robust, well-designed trials are still required to define effective dose regimens able to attain therapeutic PK/PD indices of NBLA when utilized in those special scenarios, and thus aid in improving the patients’ outcomes.
Corneal Aberrations and Thickness in Adults Born Small, Appropriate, or Large for Gestational Age at Term
Authors: Fieß Achim , Riedl Jana C. , Gißler Sandra , Mildenberger Eva , Urschitz Michael S. , Stoffelns Bernhard , Pfeiffer Norbert , Schuster Alexander K.
Published: November 2022

Background/Aims: This study investigated whether there are changes in corneal surface regularity and corneal thickness in adults born small, appropriate, or large for gestational age at term. Methods: This retrospective cohort study involved prospective Scheimpflug imaging of the cornea (Pentacam®) to compare the corneal thickness and aberrations between adults classified as small for gestational age (SGA), normal birth weight (BW), and large for gestational age (LGA). Multivariable linear regression was applied to analyze associations with gestational age, BW percentile, placental insufficiency, preeclampsia, and breastfeeding. Results: In total, 448 eyes of 261 individuals born full term (aged 29.9 ± 9.5 years, 140 females) were examined, including 29 severe SGA (BW < 3rd percentile), 32 moderate SGA (BW between 3rd and <10th percentile), 132 normal BW (BW between 10th and 90th percentile), 35 moderate LGA (BW between >90th and 97th percentile), and 33 severe LGA (BW > 97th percentile). There were no differences between groups in the corneal aberrations of the total cornea as well as of the corneal front surface, except for higher-order aberrations in the front of the cornea (p = 0.032). There was an association between the increased total root mean square of higher-order aberrations and lower birth weight percentile (p = 0.004), with increased higher-order aberrations correlating with lower visual acuity and spherical equivalent. Conclusion: Restricted prenatal growth is associated with increased higher-order aberrations in adulthood.
Running-Induced Metabolic and Physiological Responses Using New Zealand Blackcurrant Extract in a Male Ultra-Endurance Runner: A Case Study
Authors: Willems Mark E. T. , Briggs Andrew R.
Published: November 2022

Physical training for ultra-endurance running provides physiological adaptations for exercise-induced substrate oxidation. We examined the effects of New Zealand blackcurrant (NZBC) extract on running-induced metabolic and physiological responses in a male amateur ultra-endurance runner (age: 40 years, body mass: 65.9 kg, BMI: 23.1 kg·m−2, body fat: 14.7%, V˙O2max: 55.3 mL·kg−1·min−1, resting heart rate: 45 beats·min−1, running history: 6 years, marathons: 20, ultra-marathons: 28, weekly training distance: ~80 km, weekly running time: ~9 h). Indirect calorimetry was used and heart rate recorded at 15 min intervals during 120 min of treadmill running (speed: 10.5 km·h−1, 58% V˙O2max) in an environmental chamber (temperature: ~26 °C, relative humidity: ~70%) at baseline and following 7 days intake of NZBC extract (210 mg of anthocyanins·day−1) with constant monitoring of core temperature. The male runner had unlimited access to water and consumed a 100-kcal energy gel at 40- and 80 min during the 120 min run. There were no differences (mean of 8, 15 min measurements) for minute ventilation, oxygen uptake, carbon dioxide production and core temperature. With NZBC extract, the respiratory exchange ratio was 0.02 units lower, carbohydrate oxidation was 11% lower and fat oxidation was 23% higher (control: 0.39 ± 0.08, NZBC extract: 0.48 ± 0.12 g·min−1, p < 0.01). Intake of the energy gel did not abolish the enhanced fat oxidation by NZBC extract. Seven days’ intake of New Zealand blackcurrant extract altered exercise-induced substrate oxidation in a male amateur ultra-endurance runner covering a half-marathon distance in 2 h. More studies are required to address whether intake of New Zealand blackcurrant extract provides a nutritional ergogenic effect for ultra-endurance athletes to enhance exercise performance.