bluuebunny/crossref_metadata_2025 huggingface dataset:
The Therapeutic Potential of Zinc-Alpha2-Glycoprotein (AZGP1) in Fibrotic Kidney Disease
Authors: Sörensen-Zender Inga , Rong Song , Haller Hermann , Schmitt Roland
Published: January 2022

Chronic kidney disease (CKD) is characterized by a long-term loss of kidney function and, in most cases, by progressive fibrosis. Zinc-alpha2-glycoprotein (AZGP1) is a secreted protein, which is expressed in many different tissues and has been associated with a variety of functions. In a previous study, we have shown in cell culture and in AZGP1 deficient mice that AZGP1 has protective anti-fibrotic effects. In the present study, we tested the therapeutic potential of an experimental increase in AZGP1 using two different strategies. (1) C57Bl/6J mice were treated systemically with recombinant AZGP1, and (2) a transgenic mouse strain was generated to overexpress AZGP1 conditionally in proximal tubular cells. Mice underwent unilateral uretic obstruction as a pro-fibrotic kidney stress model, and kidneys were examined after 14 days. Recombinant AZGP1 treatment was accompanied by better preservation of tubular integrity, reduced collagen deposition, and lower expression of injury and fibrosis markers. Weaker but similar tendencies were observed in transgenic AZGP1 overexpressing mice. Higher AZGP1 levels led to a significant reduction in stress-induced accumulation of tubular lipid droplets, which was paralleled by improved expression of key players in lipid metabolism and fatty acid oxidation. Together these data show beneficial effects of elevated AZGP1 levels in fibrotic kidney disease and highlight a novel link to tubular cell lipid metabolism, which might open up new opportunities for CKD treatment.
Genome Wide Identification of Respiratory Burst Oxidase Homolog (Rboh) Genes in Citrus sinensis and Functional Analysis of CsRbohD in Cold Tolerance
Authors: Zhang Yueliang , Zhang Yiwu , Luo Li , Lu Chunyi , Kong Weiwen , Cheng Libao , Xu Xiaoyong , Liu Jihong
Published: January 2022

Respiratory burst oxidase homologs (Rbohs) are critical enzymes involved in the generation of reactive oxygen species (ROS) that play an important role in plant growth and development as well as various biotic and abiotic stresses in plants. Thus far, there have been few reports on the characterization of the Rboh gene family in Citrus. In this study, seven Rboh genes (CsRbohA~CsRbohG) were identified in the Citrus sinensis genome. The CsRboh proteins were predicted to localize to the cell membrane. Most CsRbohs contained four conserved domains, an EF-hand domain, and a transmembrane region. Phylogenetic analysis demonstrated that the CsRbohs were divided into five groups, suggesting potential distinct functions and evolution. The expression profiles revealed that these seven CsRboh genes displayed tissue-specific expression patterns, and five CsRboh genes were responsive to cold stress. Fourteen putative cis-acting elements related to stress response, hormone response, and development regulation were present within the promoters of CsRboh genes. The in-silico microRNA target transcript analyses indicated that CsRbohE might be targeted by csi-miR164. Further functional and physiological analyses showed that the knockdown of CsRbohD in trifoliate orange impaired resistance to cold stress. As a whole, our results provide valuable information for further functional studies of the CsRboh genes in response to cold stress.
Heat Shock Protein 90 as Therapeutic Target for CVDs and Heart Ageing
Authors: Dabravolski Siarhei A. , Sukhorukov Vasily N. , Kalmykov Vladislav A. , Orekhov Nikolay A. , Grechko Andrey V. , Orekhov Alexander N.
Published: January 2022

Cardiovascular diseases (CVDs) are the leading cause of death globally, representing approximately 32% of all deaths worldwide. Molecular chaperones are involved in heart protection against stresses and age-mediated accumulation of toxic misfolded proteins by regulation of the protein synthesis/degradation balance and refolding of misfolded proteins, thus supporting the high metabolic demand of the heart cells. Heat shock protein 90 (HSP90) is one of the main cardioprotective chaperones, represented by cytosolic HSP90a and HSP90b, mitochondrial TRAP1 and ER-localised Grp94 isoforms. Currently, the main way to study the functional role of HSPs is the application of HSP inhibitors, which could have a different way of action. In this review, we discussed the recently investigated role of HSP90 proteins in cardioprotection, atherosclerosis, CVDs development and the involvements of HSP90 clients in the activation of different molecular pathways and signalling mechanisms, related to heart ageing.
Frequency and Spectrum of Mutations Induced by Gamma Rays Revealed by Phenotype Screening and Whole-Genome Re-Sequencing in Arabidopsis thaliana
Authors: Du Yan , Feng Zhuo , Wang Jie , Jin Wenjie , Wang Zhuanzi , Guo Tao , Chen Yuze , Feng Hui , Yu Lixia , Li Wenjian , Zhou Libin
Published: January 2022

Genetic variations are an important source of germplasm diversity, as it provides an allele resource that contributes to the development of new traits for plant breeding. Gamma rays have been widely used as a physical agent for mutation creation in plants, and their mutagenic effect has attracted extensive attention. However, few studies are available on the comprehensive mutation profile at both the large-scale phenotype mutation screening and whole-genome mutation scanning. In this study, biological effects on M1 generation, large-scale phenotype screening in M2 generation, as well as whole-genome re-sequencing of seven M3 phenotype-visible lines were carried out to comprehensively evaluate the mutagenic effects of gamma rays on Arabidopsis thaliana. A total of 417 plants with visible mutated phenotypes were isolated from 20,502 M2 plants, and the phenotypic mutation frequency of gamma rays was 2.03% in Arabidopsis thaliana. On average, there were 21.57 single-base substitutions (SBSs) and 11.57 small insertions and deletions (InDels) in each line. Single-base InDels accounts for 66.7% of the small InDels. The genomic mutation frequency was 2.78 × 10−10/bp/Gy. The ratio of transition/transversion was 1.60, and 64.28% of the C > T events exhibited the pyrimidine dinucleotide sequence; 69.14% of the small InDels were located in the sequence with 1 to 4 bp terminal microhomology that was used for DNA end rejoining, while SBSs were less dependent on terminal microhomology. Nine genes, on average, were predicted to suffer from functional alteration in each re-sequenced line. This indicated that a suitable mutation gene density was an advantage of gamma rays when trying to improve elite materials for one certain or a few traits. These results will aid the full understanding of the mutagenic effects and mechanisms of gamma rays and provide a basis for suitable mutagen selection and parameter design, which can further facilitate the development of more controlled mutagenesis methods for plant mutation breeding.
Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma
Authors: Win-Shwe Tin-Tin , Yanagisawa Rie , Lwin Thet-Thet , Kawakami Fumitaka , Koike Eiko , Takano Hirohisa
Published: January 2022

Tris (2-butoxyethyl) phosphate (TBEP) is an organophosphate flame retardant and used as a plasticizer in various household products such as plastics, floor polish, varnish, textiles, furniture, and electronic equipment. However, little is known about the effects of TBEP on the brain and behavior. We aimed to examine the effects of dietary exposure of TBEP on memory functions, their-related genes, and inflammatory molecular markers in the brain of allergic asthmatic mouse models. C3H/HeJSlc male mice were given diet containing TBEP (0.02 (TBEP-L), 0.2 (TBEP-M), or 2 (TBEP-H) μg/kg/day) and ovalbumin (OVA) intratracheally every other week from 5 to 11 weeks old. A novel object recognition test was conducted in each mouse at 11 weeks old. The hippocampi were collected to detect neurological, glia, and immunological molecular markers using the real-time RT-PCR method and immunohistochemical analyses. Mast cells and microglia were examined by toluidine blue staining and ionized calcium-binding adapter molecule (Iba)-1 immunoreactivity, respectively. Impaired discrimination ability was observed in TBEP-H-exposed mice with or without allergen. The mRNA expression levels of N-methyl-D aspartate receptor subunits Nr1 and Nr2b, inflammatory molecular markers tumor necrosis factor-α oxidative stress marker heme oxygenase 1, microglia marker Iba1, and astrocyte marker glial fibrillary acidic protein were significantly increased in TBEP-H-exposed mice with or without allergen. Microglia and mast cells activation were remarkable in TBEP-H-exposed allergic asthmatic mice. Our results indicate that chronic exposure to TBEP with or without allergen impaired object recognition ability accompanied with alteration of molecular expression of neuronal and glial markers and inflammatory markers in the hippocampus of mice. Neuron-glia-mast cells interaction may play a role in TBEP-induced neurobehavioral toxicity.
Differential Physio-Biochemical and Metabolic Responses of Peanut (Arachis hypogaea L.) under Multiple Abiotic Stress Conditions
Authors: Patel Jaykumar , Khandwal Deepesh , Choudhary Babita , Ardeshana Dolly , Jha Rajesh Kumar , Tanna Bhakti , Yadav Sonam , Mishra Avinash , Varshney Rajeev K. , Siddique Kadambot H. M.
Published: January 2022

The frequency and severity of extreme climatic conditions such as drought, salinity, cold, and heat are increasing due to climate change. Moreover, in the field, plants are affected by multiple abiotic stresses simultaneously or sequentially. Thus, it is imperative to compare the effects of stress combinations on crop plants relative to individual stresses. This study investigated the differential regulation of physio-biochemical and metabolomics parameters in peanut (Arachis hypogaea L.) under individual (salt, drought, cold, and heat) and combined stress treatments using multivariate correlation analysis. The results showed that combined heat, salt, and drought stress compounds the stress effect of individual stresses. Combined stresses that included heat had the highest electrolyte leakage and lowest relative water content. Lipid peroxidation and chlorophyll contents did not significantly change under combined stresses. Biochemical parameters, such as free amino acids, polyphenol, starch, and sugars, significantly changed under combined stresses compared to individual stresses. Free amino acids increased under combined stresses that included heat; starch, sugars, and polyphenols increased under combined stresses that included drought; proline concentration increased under combined stresses that included salt. Metabolomics data that were obtained under different individual and combined stresses can be used to identify molecular phenotypes that are involved in the acclimation response of plants under changing abiotic stress conditions. Peanut metabolomics identified 160 metabolites, including amino acids, sugars, sugar alcohols, organic acids, fatty acids, sugar acids, and other organic compounds. Pathway enrichment analysis revealed that abiotic stresses significantly affected amino acid, amino sugar, and sugar metabolism. The stress treatments affected the metabolites that were associated with the tricarboxylic acid (TCA) and urea cycles and associated amino acid biosynthesis pathway intermediates. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and heatmap analysis identified potential marker metabolites (pinitol, malic acid, and xylopyranose) that were associated with abiotic stress combinations, which could be used in breeding efforts to develop peanut cultivars that are resilient to climate change. The study will also facilitate researchers to explore different stress indicators to identify resistant cultivars for future crop improvement programs.
Glucocorticoid Regulates the Synthesis of Porcine Muscle Protein through m6A Modified Amino Acid Transporter SLC7A7
Authors: Xu Wei-Jing , Guo Kai , Shi Jia-Li , Guo Chang-Tong , Xu Jia-Le , Zheng Rong , Jiang Si-Wen , Chai Jin
Published: January 2022

The occurrence of stress is unavoidable in the process of livestock production, and prolonged stress will cause the decrease of livestock productivity. The stress response is mainly regulated by the hypothalamic-pituitary-adrenal axis (HPA axis), which produces a large amount of stress hormones, namely glucocorticoids (GCs), and generates a severe impact on the energy metabolism of the animal body. It is reported that m6A modification plays an important role in the regulation of stress response and also participates in the process of muscle growth and development. In this study, we explored the effect of GCs on the protein synthesis procession of porcine skeletal muscle cells (PSCs). We prove that dexamethasone affects the expression of SLC7A7, a main amino acid transporter for protein synthesis by affecting the level of m6A modification in PSCs. In addition, we find that SLC7A7 affects the level of PSC protein synthesis by regulating the conduction of the mTOR signaling pathway, which indicates that the reduction of SLC7A7 expression may alleviate the level of protein synthesis under stress conditions.
The Dual Role of the β2-Adrenoreceptor in the Modulation of IL-17 and IFN-γ Production by T Cells in Multiple Sclerosis
Authors: Melnikov Mikhail , Rogovskii Vladimir , Sviridova Anastasiya , Lopatina Anna , Pashenkov Mikhail , Boyko Alexey
Published: January 2022

Norepinephrine is a neurotransmitter that also has an immunomodulatory effect and is involved in multiple sclerosis (MS) pathogenesis. This study aimed to clarify the role of the β2-adrenoreceptor in the norepinephrine-mediated modulation of interleukin-17 (IL-17) and interferon-γ (IFN-γ) production, which play a critical pathogenetic role in MS. CD4+ T cells obtained from twenty-five relapsing-remitting MS patients and sixteen healthy subjects were cultured ex vivo with norepinephrine and/or β2-adrenoreceptor antagonist or agonist, followed by a cytokine production analysis using ELISA. Norepinephrine suppressed IL-17 and IFN-γ production by the anti-CD3/anti-CD28-microbead-stimulated CD4+ T cells in both groups. Blockade of the β2-adrenoreceptor with the specific antagonist ICI 118.551 enhanced norepinephrine-mediated IL-17 suppression but decreased its inhibitory effect on IFN-γ production in MS patients. In contrast, the β2-adrenoreceptor agonist formoterol did not influence norepinephrine’s inhibitory effect on cytokine production in both groups. The blockade of the β2-adrenoreceptor, even in the absence of exogenous norepinephrine, suppressed IL-17 production but did not influence IFN-γ production in both groups. Conversely, β2-adrenoreceptor activation by formoterol decreased IFN-γ production and did not affect IL-17 production in both groups. These data illustrate the inhibitory effect of norepinephrine on IL-17 and IFN-γ production by CD4+ T cells in MS. The inhibitory effect of norepinephrine on IFN-γ production by CD4+ T cells in MS could be mediated via β2-adrenoreceptor activation.
Mechanistic Insights Expatiating the Redox-Active-Metal-Mediated Neuronal Degeneration in Parkinson’s Disease
Authors: Behl Tapan , Madaan Piyush , Sehgal Aayush , Singh Sukhbir , Anwer Md Khalid , Makeen Hafiz A. , Albratty Mohammed , Mohan Syam , Bungau Simona
Published: January 2022

Parkinson’s disease (PD) is a complicated and incapacitating neurodegenerative malady that emanates following the dopaminergic (DArgic) nerve cell deprivation in the substantia nigra pars compacta (SN-PC). The etiopathogenesis of PD is still abstruse. Howbeit, PD is hypothesized to be precipitated by an amalgamation of genetic mutations and exposure to environmental toxins. The aggregation of α-synucelin within the Lewy bodies (LBs), escalated oxidative stress (OS), autophagy-lysosome system impairment, ubiquitin-proteasome system (UPS) impairment, mitochondrial abnormality, programmed cell death, and neuroinflammation are regarded as imperative events that actively participate in PD pathogenesis. The central nervous system (CNS) relies heavily on redox-active metals, particularly iron (Fe) and copper (Cu), in order to modulate pivotal operations, for instance, myelin generation, synthesis of neurotransmitters, synaptic signaling, and conveyance of oxygen (O2). The duo, namely, Fe and Cu, following their inordinate exposure, are viable of permeating across the blood–brain barrier (BBB) and moving inside the brain, thereby culminating in the escalated OS (through a reactive oxygen species (ROS)-reliant pathway), α-synuclein aggregation within the LBs, and lipid peroxidation, which consequently results in the destruction of DArgic nerve cells and facilitates PD emanation. This review delineates the metabolism of Fe and Cu in the CNS, their role and disrupted balance in PD. An in-depth investigation was carried out by utilizing the existing publications obtained from prestigious medical databases employing particular keywords mentioned in the current paper. Moreover, we also focus on decoding the role of metal complexes and chelators in PD treatment. Conclusively, metal chelators hold the aptitude to elicit the scavenging of mobile/fluctuating metal ions, which in turn culminates in the suppression of ROS generation, and thereby prelude the evolution of PD.
Hypoxia Inhibits Subretinal Inflammation Resolution Thrombospondin-1 Dependently
Authors: Touhami Sara , Béguier Fanny , Yang Tianxiang , Augustin Sébastien , Roubeix Christophe , Blond Frederic , Conart Jean Baptiste , Sahel José Alain , Bodaghi Bahram , Delarasse Cécile , Guillonneau Xavier , Sennlaub Florian
Published: January 2022

Hypoxia is potentially one of the essential triggers in the pathogenesis of wet age-related macular degeneration (wetAMD), characterized by choroidal neovascularization (CNV) which is driven by the accumulation of subretinal mononuclear phagocytes (MP) that include monocyte-derived cells. Here we show that systemic hypoxia (10% O2) increased subretinal MP infiltration and inhibited inflammation resolution after laser-induced subretinal injury in vivo. Accordingly, hypoxic (2% O2) human monocytes (Mo) resisted elimination by RPE cells in co-culture. In Mos from hypoxic mice, Thrombospondin 1 mRNA (Thbs1) was most downregulated compared to normoxic animals and hypoxia repressed Thbs-1 expression in human monocytes in vitro. Hypoxic ambient air inhibited MP clearance during the resolution phase of laser-injury in wildtype animals, but had no effect on the exaggerated subretinal MP infiltration observed in normoxic Thbs1−/−-mice. Recombinant Thrombospondin 1 protein (TSP-1) completely reversed the pathogenic effect of hypoxia in Thbs1−/−-mice, and accelerated inflammation resolution and inhibited CNV in wildtype mice. Together, our results demonstrate that systemic hypoxia disturbs TSP-1-dependent subretinal immune suppression and promotes pathogenic subretinal inflammation and can be therapeutically countered by local recombinant TSP-1.
Where Are We with RPE Replacement Therapy? A Translational Review from the Ophthalmologist Perspective
Authors: Raimondi Raffaele , Zollet Piero , De Rosa Francesco Paolo , Tsoutsanis Panagiotis , Stravalaci Matteo , Paulis Marianna , Inforzato Antonio , Romano Mario R.
Published: January 2022

The retinal pigmented epithelium (RPE) plays a pivotal role in retinal homeostasis. It is therefore an interesting target to fill the unmet medical need of different retinal diseases, including age-related macular degeneration and Stargardt disease. RPE replacement therapy may use different cellular sources: induced pluripotent stem cells or embryonic stem cells. Cells can be transferred as suspension on a patch with different surgical approaches. Results are promising although based on very limited samples. In this review, we summarize the current progress of RPE replacement and provide a comparative assessment of different published approaches which may become standard of care in the future.
Maternal and Neonatal Polyunsaturated Fatty Acid Intake and Risk of Neurodevelopmental Impairment in Premature Infants
Authors: Heath Rory J. , Klevebro Susanna , Wood Thomas R.
Published: January 2022

The N3 and N6 long chain polyunsaturated fatty acids (LCPUFA) docosahexaenoic acid (DHA) and arachidonic acid (AA) are essential for proper neurodevelopment in early life. These fatty acids are passed from mother to infant via the placenta, accreting into fetal tissues such as brain and adipose tissue. Placental transfer of LCPUFA is highest in the final trimester, but this transfer is abruptly severed with premature birth. As such, efforts have been made to supplement the post-natal feed of premature infants with LCPUFA to improve neurodevelopmental outcomes. This narrative review analyzes the current body of evidence pertinent to neurodevelopmental outcomes after LCPUFA supplementation in prematurely born infants, which was identified via the reference lists of systematic and narrative reviews and PubMed search engine results. This review finds that, while the evidence is weakened by heterogeneity, it may be seen that feed comprising 0.3% DHA and 0.6% AA is associated with more positive neurodevelopmental outcomes than LCPUFA-deplete feed. While no new RCTs have been performed since the most recent Cochrane meta-analysis in 2016, this narrative review provides a wider commentary; the wider effects of LCPUFA supplementation in prematurely born infants, the physiology of LCPUFA accretion into preterm tissues, and the physiological effects of LCPUFA that affect neurodevelopment. We also discuss the roles of maternal LCPUFA status as a modifiable factor affecting the risk of preterm birth and infant neurodevelopmental outcomes. To better understand the role of LCPUFAs in infant neurodevelopment, future study designs must consider absolute and relative availabilities of all LCPUFA species and incorporate the LCPUFA status of both mother and infant in pre- and postnatal periods.
ERK1/2 Activity Is Critical for the Outcome of Ischemic Stroke
Authors: Schanbacher Constanze , Bieber Michael , Reinders Yvonne , Cherpokova Deya , Teichert Christina , Nieswandt Bernhard , Sickmann Albert , Kleinschnitz Christoph , Langhauser Friederike , Lorenz Kristina
Published: January 2022

Ischemic disorders are the leading cause of death worldwide. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are thought to affect the outcome of ischemic stroke. However, it is under debate whether activation or inhibition of ERK1/2 is beneficial. In this study, we report that the ubiquitous overexpression of wild-type ERK2 in mice (ERK2wt) is detrimental after transient occlusion of the middle cerebral artery (tMCAO), as it led to a massive increase in infarct volume and neurological deficits by increasing blood–brain barrier (BBB) leakiness, inflammation, and the number of apoptotic neurons. To compare ERK1/2 activation and inhibition side-by-side, we also used mice with ubiquitous overexpression of the Raf-kinase inhibitor protein (RKIPwt) and its phosphorylation-deficient mutant RKIPS153A, known inhibitors of the ERK1/2 signaling cascade. RKIPwt and RKIPS153A attenuated ischemia-induced damages, in particular via anti-inflammatory signaling. Taken together, our data suggest that stimulation of the Raf/MEK/ERK1/2-cascade is severely detrimental and its inhibition is rather protective. Thus, a tight control of the ERK1/2 signaling is essential for the outcome in response to ischemic stroke.
Genetic Study of Four Candidate Holliday Junction Processing Proteins in the Thermophilic Crenarchaeon Sulfolobus acidocaldarius
Authors: Matsuda Ryo , Suzuki Shoji , Kurosawa Norio
Published: January 2022

Homologous recombination (HR) is thought to be important for the repair of stalled replication forks in hyperthermophilic archaea. Previous biochemical studies identified two branch migration helicases (Hjm and PINA) and two Holliday junction (HJ) resolvases (Hjc and Hje) as HJ-processing proteins; however, due to the lack of genetic evidence, it is still unclear whether these proteins are actually involved in HR in vivo and how their functional relation is associated with the process. To address the above questions, we constructed hjc-, hje-, hjm-, and pina single-knockout strains and double-knockout strains of the thermophilic crenarchaeon Sulfolobus acidocaldarius and characterized the mutant phenotypes. Notably, we succeeded in isolating the hjm- and/or pina-deleted strains, suggesting that the functions of Hjm and PINA are not essential for cellular growth in this archaeon, as they were previously thought to be essential. Growth retardation in Δpina was observed at low temperatures (cold sensitivity). When deletion of the HJ resolvase genes was combined, Δpina Δhjc and Δpina Δhje exhibited severe cold sensitivity. Δhjm exhibited severe sensitivity to interstrand crosslinkers, suggesting that Hjm is involved in repairing stalled replication forks, as previously demonstrated in euryarchaea. Our findings suggest that the function of PINA and HJ resolvases is functionally related at lower temperatures to support robust cellular growth, and Hjm is important for the repair of stalled replication forks in vivo.
eDNA Inactivation and Biofilm Inhibition by the PolymericBiocide Polyhexamethylene Guanidine Hydrochloride (PHMG-Cl)
Authors: Moshynets Olena V. , Baranovskyi Taras P. , Iungin Olga S. , Kysil Nadiia P. , Metelytsia Larysa O. , Pokholenko Ianina , Potochilova Viktoria V. , Potters Geert , Rudnieva Kateryna L. , Rymar Svitlana Y. , Semenyuta Ivan V. , Spiers Andrew J. , Tarasyuk Oksana P. , Rogalsky Sergiy P.
Published: January 2022

The choice of effective biocides used for routine hospital practice should consider the role of disinfectants in the maintenance and development of local resistome and how they might affect antibiotic resistance gene transfer within the hospital microbial population. Currently, there is little understanding of how different biocides contribute to eDNA release that may contribute to gene transfer and subsequent environmental retention. Here, we investigated how different biocides affect the release of eDNA from mature biofilms of two opportunistic model strains Pseudomonas aeruginosa ATCC 27853 (PA) and Staphylococcus aureus ATCC 25923 (SA) and contribute to the hospital resistome in the form of surface and water contaminants and dust particles. The effect of four groups of biocides, alcohols, hydrogen peroxide, quaternary ammonium compounds, and the polymeric biocide polyhexamethylene guanidine hydrochloride (PHMG-Cl), was evaluated using PA and SA biofilms. Most biocides, except for PHMG-Cl and 70% ethanol, caused substantial eDNA release, and PHMG-Cl was found to block biofilm development when used at concentrations of 0.5% and 0.1%. This might be associated with the formation of DNA–PHMG-Cl complexes as PHMG-Cl is predicted to bind to AT base pairs by molecular docking assays. PHMG-Cl was found to bind high-molecular DNA and plasmid DNA and continued to inactivate DNA on surfaces even after 4 weeks. PHMG-Cl also effectively inactivated biofilm-associated antibiotic resistance gene eDNA released by a pan-drug-resistant Klebsiella strain, which demonstrates the potential of a polymeric biocide as a new surface-active agent to combat the spread of antibiotic resistance in hospital settings.
GLP-1a: Going beyond Traditional Use
Authors: Laurindo Lucas Fornari , Barbalho Sandra Maria , Guiguer Elen Landgraf , da Silva Soares de Souza Maricelma , de Souza Gabriela Achete , Fidalgo Thiago Marques , Araújo Adriano Cressoni , de Souza Gonzaga Heron F. , de Bortoli Teixeira Daniel , de Oliveira Silva Ullmann Thais , Sloan Katia Portero , Sloan Lance Alan
Published: January 2022

Glucagon-like peptide-1 (GLP-1) is a human incretin hormone derived from the proglucagon molecule. GLP-1 receptor agonists are frequently used to treat type 2 diabetes mellitus and obesity. However, the hormone affects the liver, pancreas, brain, fat cells, heart, and gastrointestinal tract. The objective of this study was to perform a systematic review on the use of GLP-1 other than in treating diabetes. PubMed, Cochrane, and Embase were searched, and the PRISMA guidelines were followed. Nineteen clinical studies were selected. The results showed that GLP-1 agonists can benefit defined off-medication motor scores in Parkinson’s Disease and improve emotional well-being. In Alzheimer’s disease, GLP-1 analogs can improve the brain’s glucose metabolism by improving glucose transport across the blood–brain barrier. In depression, the analogs can improve quality of life and depression scales. GLP-1 analogs can also have a role in treating chemical dependency, inhibiting dopaminergic release in the brain’s reward centers, decreasing withdrawal effects and relapses. These medications can also improve lipotoxicity by reducing visceral adiposity and decreasing liver fat deposition, reducing insulin resistance and the development of non-alcoholic fatty liver diseases. The adverse effects are primarily gastrointestinal. Therefore, GLP-1 analogs can benefit other conditions besides traditional diabetes and obesity uses.
Preliminary Design Guidelines for Considering the Vibration and Noise of Low-Speed Axial Fans Due to Profile Vortex Shedding
Authors: Daku Gábor , Vad János
Published: January 2022

This paper presents a critical overview on worst-case design scenarios for which low-speed axial flow fans may exhibit an increased risk of blade resonance due to profile vortex shedding. To set up a design example, a circular-arc-cambered plate of 8% relative curvature is investigated in twofold approaches of blade mechanics and aerodynamics. For these purposes, the frequency of the first bending mode of a plate of arbitrary circular camber is expressed by modeling the fan blade as a cantilever beam. Furthermore, an iterative blade design method is developed for checking the risky scenarios for which spanwise and spatially coherent shed vortices, stimulating pronounced vibration and noise, may occur. Coupling these two approaches, cases for vortex-induced blade resonance are set up. Opposing this basis, design guidelines are elaborated upon for avoiding such resonance. Based on the approach presented herein, guidelines are also developed for moderating the annoyance due to the vortex shedding noise.
Automated Intracranial Hematoma Classification in Traumatic Brain Injury (TBI) Patients Using Meta-Heuristic Optimization Techniques
Authors: V Vidhya , Raghavendra U. , Gudigar Anjan , Kasula Praneet , Chakole Yashas , Hegde Ajay , R Girish Menon , Ooi Chui Ping , Ciaccio Edward J. , Acharya U. Rajendra
Published: January 2022

Traumatic Brain Injury (TBI) is a devastating and life-threatening medical condition that can result in long-term physical and mental disabilities and even death. Early and accurate detection of Intracranial Hemorrhage (ICH) in TBI is crucial for analysis and treatment, as the condition can deteriorate significantly with time. Hence, a rapid, reliable, and cost-effective computer-aided approach that can initially capture the hematoma features is highly relevant for real-time clinical diagnostics. In this study, the Gray Level Occurrence Matrix (GLCM), the Gray Level Run Length Matrix (GLRLM), and Hu moments are used to generate the texture features. The best set of discriminating features are obtained using various meta-heuristic algorithms, and these optimal features are subjected to different classifiers. The synthetic samples are generated using ADASYN to compensate for the data imbalance. The proposed CAD system attained 95.74% accuracy, 96.93% sensitivity, and 94.67% specificity using statistical and GLRLM features along with KNN classifier. Thus, the developed automated system can enhance the accuracy of hematoma detection, aid clinicians in the fast interpretation of CT images, and streamline triage workflow.
Novel Fluoridoaluminates from Ammonothermal Synthesis: Two Modifications of K2AlF5 and the Elpasolite Rb2KAlF6
Authors: Bäucker Christian , Becker Peter , Morell Keshia J. , Niewa Rainer
Published: January 2022

Two new modifications of the pentafluoridoaluminate K2AlF5 were obtained from ammonothermal synthesis at 753 K, 224 MPa and 773 K, 220 MPa, respectively. Both crystallize in the orthorhombic space group type Pbcn, with close metric relations and feature kinked chains of cis-vertex-connected AlF6 octahedra resulting in the Niggli formula ∞1{[AlF2/2eF4/1t]2−}. The differences lie in the number of octahedra necessary for repetition within the chains, which for K2AlF5-2 is realized after four and for K2AlF5-3 after eight octahedra. As a result, the orthorhombic unit cell for K2AlF5-3 is doubled in chain prolongation direction [001] as compared to K2AlF5-2 (1971.18(4) pm versus 988.45(3) pm, respectively), while the unit cell parameters within the other two directions are virtually identical. Moreover, the new elpasolite Rb2KAlF6 is reported, crystallizing in the cubic space group Fm3¯m with a = 868.9(1) pm and obtained under ammonothermal conditions at 723 K and 152 MPa.
Aqueous Solution Equilibria and Spectral Features of Copper Complexes with Tripeptides Containing Glycine or Sarcosine and Leucine or Phenylalanine
Authors: Vicatos Giselle M. , Hammouda Ahmed N. , Alnajjar Radwan , Bonomo Raffaele P. , Valora Gabriele , Bourne Susan A. , Jackson Graham E.
Published: January 2022

Copper(II) complexes of glycyl-L-leucyl-L-histidine (GLH), sarcosyl-L-leucyl-L-histidine (Sar-LH), glycyl-L-phenylalanyl-L-histidine (GFH) and sarcosyl-L-phenylalanyl-L-histidine (Sar-FH) have potential anti-inflammatory activity, which can help to alleviate the symptoms associated with rheumatoid arthritis (RA). From pH 2–11, the MLH, ML, MLH-1 and MLH-2 species formed. The combination of species for each ligand was different, except at the physiological pH, where CuLH-2 predominated for all ligands. The prevalence of this species was supported by EPR, ultraviolet-visible spectrophotometry, and mass spectrometry, which suggested a square planar CuN4 coordination. All ligands have the same basicity for the amine and imidazole-N, but the methyl group of sarcosine decreased the stability of MLH and MLH-2 by 0.1–0.34 and 0.46–0.48 log units, respectively. Phenylalanine increased the stability of MLH and MLH-2 by 0.05–0.29 and 1.19–1.21 log units, respectively. For all ligands, 1H NMR identified two coordination modes for MLH, where copper(II) coordinates via the amine-N and neighboring carbonyl-O, as well as via the imidazole-N and carboxyl-O. EPR spectroscopy identified the MLH, ML and MLH-2 species for Cu-Sar-LH and suggested a CuN2O2 chromophore for ML. DFT calculations with water as a solvent confirmed the proposed coordination modes of each species at the B3LYP level combined with 6-31++G**.
Impacts of Non-Lethal High-Temperature Stress on the Development and Reproductive Organs of Bradysia odoriphaga
Authors: Hu Jingrong , Medison Rudoviko Galileya , Zhang Seng , Ma Peifang , Shi Caihua
Published: January 2022

Bradysia odoriphaga is an agricultural pest in China’s vegetable industry. In this study, pupae and adults were exposed to various non-lethal high-temperatures. The results demonstrated a decreased rate of eclosion once the pupae were exposed to temperatures exceeding 37 °C for 1 h. No effect on the lifespan of unmated female adults was observed after exposure to temperature stress, while unmated male adult lifespan decreased (>37 °C for 2 h). The size of the testis and ovaries for unmated male and female adults decreased, as did the fecundity and egg hatching rate for mated females. Compared with the control group (25 °C), the testis size of unmated male adults decreased after high-temperature stress followed by recovery at 25 °C for 1 h, though the size of the ovaries of female adults did not change. Additionally, the size of the testis and ovaries for unmated male and female adults decreased following high-temperature stress and 24 h of recovery at 25 °C. High temperatures affected males more than females; 37 °C is the critical temperature to control the population of B. odoriphaga. These results lay the foundation for the future development of environmentally friendly high-temperature prevention and pest-control strategies.
Experimental Determination of Excitation Function Curves through the Measurement of Thick Target Yields in Liquid Targets: The Examples of the 68Zn(p,n)68Ga and 64Zn(p,α)61Cu Nuclear Reactions
Authors: do Carmo Sergio J. C. , Alves Francisco
Published: January 2022

The present work describes a method to determine excitation function curves and, therefore, cross-sections, making use of the irradiation of liquid targets at distinct energies in a biomedical cyclotron. The method relies on the derivative of experimentally measured thick target yield curves to determine the corresponding excitation function curves. The technique is presented as a valid and practical alternative to the commonly used activation method combined with the stack monitor technique, whose implementation in liquid targets offers practical difficulties. The working principle is exemplified by presenting the results obtained for the clinically relevant 68Zn(p,n)68Ga and the 64Zn(p,α)61Cu nuclear reactions, obtained though the irradiation of liquid targets containing dissolved natural zinc.
Impact of the COVID-19 Pandemic on Non-COVID-19 Clinical Trials
Authors: Audisio Katia , Lia Hillary , Robinson Newell , Rahouma Mohamed , Soletti Giovanni , Cancelli Gianmarco , Perezgrovas Olaria Roberto , Chadow David , Tam Derrick , Vervoort Dominique , Farkouh Michael , Bhatt Deepak , Fremes Stephen , Gaudino Mario
Published: January 2022

Randomized controlled trials (RCT) were impacted by the COVID-19 pandemic, but no systematic analysis has evaluated the overall impact of COVID-19 on non-COVID-19-related RCTs. The ClinicalTrials.gov database was queried in February 2020. Eligible studies included all randomized trials with a start date after 1 January 2010 and were active during the period from 1 January 2015 to 31 December 2020. The effect of the pandemic period on non-COVID-19 trials was determined by piece-wise regression models using 11 March 2020 as the start of the pandemic and by time series analysis (models fitted using 2015–2018 data and forecasted for 2019–2020). The study endpoints were early trial stoppage, normal trial completion, and trial activation. There were 161,377 non-COVID-19 trials analyzed. The number of active trials increased annually through 2019 but decreased in 2020. According to the piece-wise regression models, trial completion was not affected by the pandemic (p = 0.56) whereas trial stoppage increased (p = 0.001). There was a pronounced decrease in trial activation early during the pandemic (p < 0.001) which then recovered. The findings from the time series models were consistent comparing forecasted and observed results (trial completion p = 0.22; trial stoppage p < 0.01; trial activation, p = 0.01). During the pandemic, there was an increase in non-COVID-19 RCTs stoppage without changes in RCT completion. There was a sharp decline in new RCTs at the beginning of the pandemic, which later recovered.
C-Reactive Protein Monitoring and Clinical Presentation of Fever as Predictive Factors of Prolonged Febrile Neutropenia and Blood Culture Positivity after Autologous Hematopoietic Stem Cell Transplantation—Single-Center Real-Life Experience
Authors: Carcò Daniela , Markovic Uros , Castorina Paolo , Iachelli Valeria , Pace Tecla , Guardo Paola , Amato Gabriella , Galbo Federica , Scirè Paola , Moschetti Gaetano
Published: January 2022

Background: Febrile neutropenia (FN) is a medical emergency that requires urgent evaluation, timely administration of empiric broad-spectrum antibiotics and careful monitoring in order to optimize the patient’s outcome, especially in the setting of both allogeneic and autologous hematopoietic stem cell transplant (ASCT). Methods: In this real-life retrospective study, a total of 49 consecutive episodes of FN were evaluated in 40 adult patients affected by either multiple myeloma (thirty-eight) or lymphoma (eleven), following ASCT, with nine patients having fever in both of the tandem transplantations. Results: Febrile neutropenia occurred a median of 7 days from ASCT. Median duration of FN was 2 days, with 25% of population that had fever for at least four days. Ten patients had at least one fever spike superior to 39 °C, while the median number of daily fever spikes was two. Twenty patients had positive blood cultures with XDR germs, namely Pseudomonas aeruginosa and Klebsiella pneumoniae, present in seven cases. ROC analysis of peak C-reactive protein (CRP) values was conducted based on blood culture positivity and a value of 12 mg/dL resulted significant. Onset of prolonged fever with a duration greater than 3 days was associated with the presence of both a peak number of three or more daily fever spikes (p = 0.02) and a body temperature greater than 39 °C (p = 0.04) based on odds ratio (OR). Blood culture positivity and peak CRP values greater than 12 mg/dL were also associated with prolonged fever duration, p = 0.04, and p = 0.03, respectively. The probability of blood culture positivity was also greater in association with fever greater than 39 °C (p = 0.04). Furthermore, peak CRP values below the cut-off showed less probability of positive blood culture (p = 0.02). Conclusions: In our study, clinical characteristics of fever along with peak CRP levels were associated with a higher probability of both prolonged fever duration and positive blood culture, needing extended antibiotic therapy.
Thermal Behavior of a Light Timber-Frame Wall vs. a Theoretical Simulation with Various Insulation Materials
Authors: Ninikas Konstantinos , Tallaros Porfyrios , Mitani Andromachi , Koutsianitis Dimitrios , Ntalos Georgios , Taghiyari Hamid R. , Papadopoulos Antonios N.
Published: January 2022

The objective of this paper is to compare the thermal behavior of a light frame timber wall by measuring 15 test samples with various insulation materials versus a theoretical simulation with the use of a software. This work establishes the variance between the two different methods to measure the thermal transmittance coefficient of timber walls. It is verified that the mean percentage alteration between the two methods is 4.25%. Furthermore, this approach proved that with the use of a simulation software, additional readings (humidity, vapor flux, heat flux, and vapor pressure) can also be considered and measured, enhancing the overall development of a timber wall. This can provide additional information regarding to the characteristics of the masonry’s elements assisting in an improved design of a timber wall with upgraded performance.
The Immunoglobulin Superfamily Members syg-2 and syg-1 Regulate Neurite Development in C. elegans
Authors: Tucker Dana K. , Adams Chloe S. , Prasad Gauri , Ackley Brian D.
Published: January 2022

Neurons form elaborate networks by guiding axons and dendrites to appropriate destinations. Neurites require information about the relative body axes during the initial projection from the cell body, and failure to receive or interpret those cues correctly can result in outgrowth errors. We identified a mutation in the Ig superfamily member syg-2 in a screen for animals with anterior/posterior (A/P) axon guidance defects. We found that syg-2 and its cognate Ig family member syg-1 appear to function in a linear genetic pathway to control the outgrowth of GABAergic axons. We determined that this pathway works in parallel to Wnt signaling. Specifically, mutations in syg-2 or syg-1 selectively affected the embryonically derived Dorsal D-type (DD) GABAergic neurons. We found no evidence that these mutations affected the Ventral D-type neurons (VD) that form later, during the first larval stage. In addition, mutations in syg-1 or syg-2 could result in the DD neurons forming multiple processes, becoming bipolar, rather than the expected pseudounipolar morphology. Given SYG-2′s essential function in synaptogenesis of the hermaphrodite-specific neurons (HSNs), we also examined DD neuron synapses in syg-2 mutants. We found syg-2 mutants had a decreased number of synapses formed, but synaptic morphology was largely normal. These results provide further evidence that the GABAergic motorneurons use multiple guidance pathways during development.
Exploring Visitors’ Visual Behavior Using Eye-Tracking: The Case of the “Studiolo Del Duca”
Authors: Mandolesi Serena , Gambelli Danilo , Naspetti Simona , Zanoli Raffaele
Published: January 2022

Although the understanding of cognitive disciplines has progressed, we know relatively little about how the human brain perceives art. Thanks to the growing interest in visual perception, eye-tracking technology has been increasingly used for studying the interaction between individuals and artworks. In this study, eye-tracking was used to provide insights into non-expert visitors’ visual behaviour as they move freely in the historical room of the “Studiolo del Duca” of the Ducal Palace in Urbino, Italy. Visitors looked for an average of almost two minutes. This study revealed which parts of the artefact captured visitors’ attention and also gives interesting information about the main patterns of fruition.
Research on the Performance of Pumpjet Propulsor of Different Scales
Authors: Yang Jun , Feng Dakui , Liu Liwei , Wang Xianzhou , Yao Chaobang
Published: January 2022

This study presents a numerical research on the open-water performance of a pumpjet propulsor at different scales. Simulations were performed by an in-house viscous CFD (Computational Fluid Dynamic) code. The Reynolds-averaged Navier–Stokes (RANS) method with SST k-ω turbulence model is employed. A dynamic overset grid is used to treat the relative motion between the rotor and other parts. The numerical results are compared with the model test data and they agree well. Comparisons for the open-water performance between the pumpjet propulsors with two scales are carried out. The results indicate that the total thrust coefficient of the large-scale pumpjet propulsor is greater than that of the small-scale one while the torque coefficient is smaller. Therefore, the efficiency of the large-scale pumpjet propulsor is about 8~10% higher than that of the small-scale pumpjet propulsor. The open-water performance of the rotor, pre-swirl stator and duct is obtained separately to estimate the discrepancies on the thrust and torque coefficients between different scales. To analyze the scale effect from different parts, the research on flow field and pressure distribution are carried out. The variation of total thrust and torque coefficient comes mainly from the rotor, which is caused by the flow field, influenced by the duct and stator.
Keeping a Clean Surface under Water: Nanoscale Nipple Array Decreases Surface Adsorption and Adhesion Forces
Authors: Uesugi Kaoru , Nagayama Kazuaki , Hirose Euichi
Published: January 2022

While nanoscale nipple arrays are expected to reduce light reflection and/or dust contamination in some insects, similar structures have been reported in various marine invertebrates. To evaluate the anti-contamination property of the structure in aquatic regimes, we measured the adsorption and adhesion forces on the flat surface and MOSMITE™ (Mitsubishi Chemical Corporation, Tokyo, Japan), a synthetic material mimicking the nipple array, under water. A small force toward the surface occurred when the probe approached the substrate surface. This adsorption force was significantly smaller on MOSMITE™ than on the flat surface. The adhesion force toward the surface occurred when the probe was detached from the surface, and it was also significantly smaller on MOSMITE™ than on the flat surface. The adhesion force in the air was much greater than the force under water, and the force was also significantly smaller on MOSMITE™ than on the flat surface. In the aquatic regime, the nipple array provides less adsorption/adhesion properties for the surface and thus, the organisms would have less contamination of microparticles on their body surface. As the adsorption and adhesion forces are also involved in the attachment of cells, tissue, and larvae, less adhesive body surfaces should be beneficial for survival in aquatic environments, as well as land environments.