bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling CD59-Antibody Interactions to Design Paratope-Mimicking Peptides for Complement Modulation
Authors: Sandomenico Annamaria , Ruggiero Alessia , Iaccarino Emanuela , Oliver Angela , Squeglia Flavia , Moreira Miguel , Esposito Luciana , Ruvo Menotti , Berisio Rita
Published: May 2023

CD59 is an abundant immuno-regulatory human protein that protects cells from damage by inhibiting the complement system. CD59 inhibits the assembly of the Membrane Attack Complex (MAC), the bactericidal pore-forming toxin of the innate immune system. In addition, several pathogenic viruses, including HIV-1, escape complement-mediated virolysis by incorporating this complement inhibitor in their own viral envelope. This makes human pathogenic viruses, such as HIV-1, not neutralised by the complement in human fluids. CD59 is also overexpressed in several cancer cells to resist the complement attack. Consistent with its importance as a therapeutical target, CD59-targeting antibodies have been proven to be successful in hindering HIV-1 growth and counteracting the effect of complement inhibition by specific cancer cells. In this work, we make use of bioinformatics and computational tools to identify CD59 interactions with blocking antibodies and to describe molecular details of the paratope–epitope interface. Based on this information, we design and produce paratope-mimicking bicyclic peptides able to target CD59. Our results set the basis for the development of antibody-mimicking small molecules targeting CD59 with potential therapeutic interest as complement activators.
Multiscale Model of CVD Growth of Graphene on Cu(111) Surface
Authors: Esmaeilpour Meysam , Bügel Patrick , Fink Karin , Studt Felix , Wenzel Wolfgang , Kozlowska Mariana
Published: May 2023

Due to its outstanding properties, graphene has emerged as one of the most promising 2D materials in a large variety of research fields. Among the available fabrication protocols, chemical vapor deposition (CVD) enables the production of high quality single-layered large area graphene. To better understand the kinetics of CVD graphene growth, multiscale modeling approaches are sought after. Although a variety of models have been developed to study the growth mechanism, prior studies are either limited to very small systems, are forced to simplify the model to eliminate the fast process, or they simplify reactions. While it is possible to rationalize these approximations, it is important to note that they have non-trivial consequences on the overall growth of graphene. Therefore, a comprehensive understanding of the kinetics of graphene growth in CVD remains a challenge. Here, we introduce a kinetic Monte Carlo protocol that permits, for the first time, the representation of relevant reactions on the atomic scale, without additional approximations, while still reaching very long time and length scales of the simulation of graphene growth. The quantum-mechanics-based multiscale model, which links kinetic Monte Carlo growth processes with the rates of occurring chemical reactions, calculated from first principles makes it possible to investigate the contributions of the most important species in graphene growth. It permits the proper investigation of the role of carbon and its dimer in the growth process, thus indicating the carbon dimer to be the dominant species. The consideration of hydrogenation and dehydrogenation reactions enables us to correlate the quality of the material grown within the CVD control parameters and to demonstrate an important role of these reactions in the quality of the grown graphene in terms of its surface roughness, hydrogenation sites, and vacancy defects. The model developed is capable of providing additional insights to control the graphene growth mechanism on Cu(111), which may guide further experimental and theoretical developments.
Mechanobiology in Cells and Tissues
Authors: Martino Sabata
Published: May 2023

This Editorial is a comment on the success of the Special Issue “Mechanobiology in Cells and Tissues” published in the International Journal of Molecular Sciences [...]
Neuronal Differentiation and Outgrowth Effect of Thymol in Trachyspermum ammi Seed Extract via BDNF/TrkB Signaling Pathway in Prenatal Maternal Supplementation and Primary Hippocampal Culture
Authors: Timalsina Binod , Haque Md Nazmul , Dash Raju , Choi Ho Jin , Ghimire Nisha , Moon Il Soo
Published: May 2023

Reviving the neuronal functions in neurodegenerative disorders requires the promotion of neurite outgrowth. Thymol, which is a principal component of Trachyspermum ammi seed extract (TASE), is reported to have neuroprotective effects. However, the effects of thymol and TASE on neuronal differentiation and outgrowth are yet to be studied. This study is the first report investigating the neuronal growth and maturation effects of TASE and thymol. Pregnant mice were orally supplemented with TASE (250 and 500 mg/kg), thymol (50 and 100 mg/kg), vehicle, and positive controls. The supplementation significantly upregulated the expression of brain-derived neurotrophic factor (BDNF) and early neuritogenesis markers in the pups’ brains at post-natal day 1 (P1). Similarly, the BDNF level was significantly upregulated in the P12 pups’ brains. Furthermore, TASE (75 and 100 µg/mL) and thymol (10 and 20 µM) enhanced the neuronal polarity, early neurite arborization, and maturation of hippocampal neurons in a dose-dependent manner in primary hippocampal cultures. The stimulatory activities of TASE and thymol on neurite extension involved TrkB signaling, as evidenced by attenuation via ANA-12 (5 µM), which is a specific TrkB inhibitor. Moreover, TASE and thymol rescued the nocodazole-induced blunted neurite extension in primary hippocampal cultures, suggesting their role as a potent microtubule stabilizing agent. These findings demonstrate the potent capacities of TASE and thymol in promoting neuronal development and reconstruction of neuronal circuitry, which are often compromised in neurodegenerative diseases and acute brain injuries.
Potential Modulation of Inflammation and Physical Function by Combined Probiotics, Omega-3 Supplementation and Vitamin D Supplementation in Overweight/Obese Patients with Chronic Low-Grade Inflammation: A Randomized, Placebo-Controlled Trial
Authors: Kopp Lena , Schweinlin Anna , Tingö Lina , Hutchinson Ashley N. , Feit Viktoria , Jähnichen Tabea , Lehnert Katja , Vetter Walter , Rings Andreas , Jensen Morten G. , Brummer Robert J. , Bischoff Stephan C.
Published: May 2023

Obesity is characterized by low-grade inflammation and increased gut permeability. Here, we aim to evaluate the effect of a nutritional supplement on these parameters in subjects with overweight and obesity. A double-blinded, randomized clinical trial was conducted in 76 adults with overweight or obesity (BMI 28 to 40) and low-grade inflammation (high-sensitivity C-reactive protein (hs-CRP) between 2 and 10 mg/L). The intervention consisted of a daily intake of a multi-strain probiotic of Lactobacillus and Bifidobacterium, 640 mg of omega-3 fatty acids (n-3 FAs), and 200 IU of vitamin D (n = 37) or placebo (n = 39), administered for 8 weeks. hs-CRP levels did not change post-intervention, other than an unexpected slight increase observed in the treatment group. Interleukin (IL)-6 levels decreased in the treatment group (p = 0.018). The plasma fatty acid (FA) levels of the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio and n-6/n-3 ratio (p < 0.001) decreased, and physical function and mobility improved in the treatment group (p = 0.006). The results suggest that hs-CRP may not be the most useful inflammatory marker, but probiotics, n-3 FAs, and vitamin D, as non-pharmaceutical supplements, may exert modest effects on inflammation, plasma FA levels, and physical function in patients with overweight and obesity and associated low-grade inflammation.
6-Polyaminosteroid Squalamine Analogues Display Antibacterial Activity against Resistant Pathogens
Authors: Vergoz Delphine , Nilly Flore , Desriac Florie , Barreau Magalie , Géry Antoine , Lepetit Charlie , Sichel François , Jeannot Katy , Giard Jean-Christophe , Garon David , Chevalier Sylvie , Muller Cécile , Dé Emmanuelle , Brunel Jean Michel
Published: May 2023

A series of 6-polyaminosteroid analogues of squalamine were synthesized with moderate to good yields and evaluated for their in vitro antimicrobial properties against both susceptible and resistant Gram-positive (vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus) and Gram-negative (carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa) bacterial strains. Minimum inhibitory concentrations against Gram-positive bacteria ranged from 4 to 16 µg/mL for the most effective compounds, 4k and 4n, and showed an additive or synergistic effect with vancomycin or oxacillin. On the other hand, the derivative 4f, which carries a spermine moiety like that of the natural trodusquemine molecule, was found to be the most active derivative against all the resistant Gram-negative bacteria tested, with an MIC value of 16 µg/mL. Our results suggest that 6-polyaminosteroid analogues of squalamine are interesting candidates for Gram-positive bacterial infection treatments, as well as potent adjuvants to fight Gram-negative bacterial resistance.
Comprehensive Analysis of Microbiome, Metabolome, and Transcriptome Revealed the Mechanisms of Intestinal Injury in Rainbow Trout under Heat Stress
Authors: Zhou Changqing , Gao Pan , Wang Jianlin
Published: May 2023

Global warming is one of the most common environmental challenges faced by cold-water fish farming. Intestinal barrier function, gut microbiota, and gut microbial metabolites are significantly altered under heat stress, posing serious obstacles to the healthy artificial culture of rainbow trout. However, the molecular mechanisms underlying intestinal injury in rainbow trout under heat stress remain unclear. In the present study, the optimal growth temperature for rainbow trout (16 °C) was used for the control group, and the maximum temperature tolerated by rainbow trout (24 °C) was used for the heat stress group, which was subjected to heat stress for 21 days. The mechanism of intestinal injury in rainbow trout under heat stress was explored by combining animal histology, 16S rRNA gene amplicon sequencing, ultra-high performance liquid chromatography-mass spectrometry, and transcriptome sequencing. The results showed that the antioxidant capacity of rainbow trout was enhanced under heat stress, the levels of stress-related hormones were significantly increased, and the relative expression of genes related to heat stress proteins was significantly increased, indicating that the heat stress model of rainbow trout was successfully established. Secondly, the intestinal tract of rainbow trout showed inflammatory pathological characteristics under heat stress, with increased permeability, activation of the inflammatory factor signaling pathway, and increased relative expression of inflammatory factor genes, suggesting that the intestinal barrier function was impaired. Thirdly, heat stress caused an imbalance of intestinal commensal microbiota and changes in intestinal metabolites in rainbow trout, which participated in the stress response mainly by affecting lipid metabolism and amino acid metabolism. Finally, heat stress promoted intestinal injury in rainbow trout by activating the peroxisome proliferator-activated receptor-α signaling pathway. These results not only expand the understanding of fish stress physiology and regulation mechanisms, but also provide a scientific basis for healthy artificial culture and the reduction of rainbow trout production costs.
The Influence of Spirodi(Iminohydantoin) on Charge Transfer through ds-DNA Containing 8-OXO-dG: A Theoretical Approach
Authors: Karwowski Boleslaw T.
Published: May 2023

Genetic information stored in a DNA base sequence is continuously exposed to harmful factors. It has been determined that 9 × 104 different DNA damage events occur in a single human cell every 24 h. Of these, 7,8-dihydro-8-oxo-guanosine (OXOG) is one of the most abundant and can undergo further transformations towards spirodi(iminohydantoin) (Sp). Sp is highly mutagenic in comparison to its precursor if not repaired. In this paper, the influence of both Sp diastereomers 4R and 4S as well as their anti and syn conformers on charge transfer through the double helix was taken into theoretical consideration. In addition, the electronic properties of four modelled double-stranded oligonucleotides (ds-oligos) were also discussed, i.e., d[A1Sp2A3oxoG4A5] * [T5C4T3C2T1]. Throughout the study, the M06—2X/6—31++G** level theory was used. Solvent–solute non-equilibrated and equilibrated interactions were also considered. The subsequent results elucidated that the 7,8-dihydro-8-oxo-guanosine:cytidine (OXOGC) base pair is the settled point of a migrated radical cation in each of the discussed cases, due to its low adiabatic ionization potential, i.e., ~5.55 [eV]. The opposite was noted for excess electron transfer through ds-oligos containing anti (R)-Sp or anti (S)-Sp. The radical anion was found on the OXOGC moiety, whereas in the presence of syn (S)-Sp or syn (R)-Sp, an excess electron was found on the distal A1T5 or A5T1 base pair, respectively. Furthermore, a spatial geometry analysis of the discussed ds-oligos revealed that the presence of syn (R)-Sp in the ds-oligo caused only a slight deformation to the double helix, while syn (S)-Sp formed an almost ideal base pair with a complementary dC. The above results are in strong agreement with the final charge transfer rate constant, as calculated according to Marcus’ theory. In conclusion, DNA damage such as spirodi(iminohydantoin), especially when becoming part of clustered DNA damage, can affect the effectiveness of other lesion recognition and repair processes. This can lead to the acceleration of undesired and deleterious processes such as carcinogenesis or aging. However, in terms of anticancer radio-/chemo- or combined therapy, the slowing down of the repair machinery can result in increased effectiveness. With this in mind, the influence of clustered damage on charge transfer and its subsequent effect on single-damage recognition by glycosylases justifies future investigation.
Mutations in the Vicinity of the IRAK3 Guanylate Cyclase Center Impact Its Subcellular Localization and Ability to Modulate Inflammatory Signaling in Immortalized Cell Lines
Authors: Turek Ilona , Nguyen Trang H. , Galea Charles , Abad Isaiah , Freihat Lubna , Manallack David T. , Velkov Tony , Irving Helen
Published: May 2023

Interleukin-1 receptor-associated kinase 3 (IRAK3) modulates the magnitude of cellular responses to ligands perceived by interleukin-1 receptors (IL-1Rs) and Toll-like receptors (TLRs), leading to decreases in pro-inflammatory cytokines and suppressed inflammation. The molecular mechanism of IRAK3’s action remains unknown. IRAK3 functions as a guanylate cyclase, and its cGMP product suppresses lipopolysaccharide (LPS)-induced nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) activity. To understand the implications of this phenomenon, we expanded the structure–function analyses of IRAK3 through site-directed mutagenesis of amino acids known or predicted to impact different activities of IRAK3. We verified the capacity of the mutated IRAK3 variants to generate cGMP in vitro and revealed residues in and in the vicinity of its GC catalytic center that impact the LPS-induced NFκB activity in immortalized cell lines in the absence or presence of an exogenous membrane-permeable cGMP analog. Mutant IRAK3 variants with reduced cGMP generating capacity and differential regulation of NFκB activity influence subcellular localization of IRAK3 in HEK293T cells and fail to rescue IRAK3 function in IRAK3 knock-out THP-1 monocytes stimulated with LPS unless the cGMP analog is present. Together, our results shed new light on the mechanism by which IRAK3 and its enzymatic product control the downstream signaling, affecting inflammatory responses in immortalized cell lines.
Enhancing SARS-CoV-2 Surveillance through Regular Genomic Sequencing in Spain: The RELECOV Network
Authors: Vázquez-Morón Sonia , Iglesias-Caballero María , Lepe José , Garcia Federico , Melón Santiago , Marimon José , García de Viedma Darío , Folgueira Maria , Galán Juan , López-Causapé Carla , Benito-Ruesca Rafael , Alcoba-Florez Julia , Gonzalez Candelas Fernando , Toro María , Fajardo Miguel , Ezpeleta Carmen , Lázaro Fernando , Pérez Castro Sonia , Cuesta Isabel , Zaballos Angel , Pozo Francisco , Casas Inmaculada , on behalf of RELECOV Network Members
Published: May 2023

Millions of SARS-CoV-2 whole genome sequences have been generated to date. However, good quality data and adequate surveillance systems are required to contribute to meaningful surveillance in public health. In this context, the network of Spanish laboratories for coronavirus (RELECOV) was created with the main goal of promoting actions to speed up the detection, analyses, and evaluation of SARS-CoV-2 at a national level, partially structured and financed by an ECDC-HERA-Incubator action (ECDC/GRANT/2021/024). A SARS-CoV-2 sequencing quality control assessment (QCA) was developed to evaluate the network’s technical capacity. QCA full panel results showed a lower hit rate for lineage assignment compared to that obtained for variants. Genomic data comprising 48,578 viral genomes were studied and evaluated to monitor SARS-CoV-2. The developed network actions showed a 36% increase in sharing viral sequences. In addition, analysis of lineage/sublineage-defining mutations to track the virus showed characteristic mutation profiles for the Delta and Omicron variants. Further, phylogenetic analyses strongly correlated with different variant clusters, obtaining a robust reference tree. The RELECOV network has made it possible to improve and enhance the genomic surveillance of SARS-CoV-2 in Spain. It has provided and evaluated genomic tools for viral genome monitoring and characterization that make it possible to increase knowledge efficiently and quickly, promoting the genomic surveillance of SARS-CoV-2 in Spain.
Special Issue “The Role of Mesenchymal Stem Cells on Inflammatory and Fibrotic Diseases”
Authors: Di Vincenzo Mariangela , Orciani Monia
Published: May 2023

This Special Issue focused on the complex role played by MSCs in the onset and development of inflammatory diseases: MSCs can support or counteract inflammation and, in turn, the onset of disease [...]
Correction: Ying et al. Dynamic Change in Starch Biosynthetic Enzymes Complexes during Grain-Filling Stages in BEIIb Active and Deficient Rice. Int. J. Mol. Sci. 2022, 23, 10714
Authors: Ying Yining , Xu Feifei , Zhang Zhongwei , Tappiban Piengtawan , Bao Jinsong
Published: May 2023

In the original publication [...]
Plasma Clearance of Coagulation Factor VIII and Extension of Its Half-Life for the Therapy of Hemophilia A: A Critical Review of the Current State of Research and Practice
Authors: Sarafanov Andrey G.
Published: May 2023

Factor VIII (FVIII) is an important component of blood coagulation as its congenital deficiency results in life-threatening bleeding. Current prophylactic therapy of the disease (hemophilia A) is based on 3–4 intravenous infusions of therapeutic FVIII per week. This poses a burden on patients, demanding reduction of infusion frequency by using FVIII with extended plasma half-life (EHL). Development of these products requires understanding FVIII plasma clearance mechanisms. This paper overviews (i) an up-to-date state of the research in this field and (ii) current EHL FVIII products, including recently approved efanesoctocog alfa, for which the plasma half-life exceeds a biochemical barrier posed by von Willebrand factor, complexed with FVIII in plasma, which results in ~1 per week infusion frequency. We focus on the EHL FVIII products’ structure and function, in particular related to the known discrepancy in results of one-stage clotting (OC) and chromogenic substrate (CS) assays used to assign the products’ potency, dosing, and for clinical monitoring in plasma. We suggest a possible root cause of these assays’ discrepancy that is also pertinent to EHL factor IX variants used to treat hemophilia B. Finally, we discuss approaches in designing future EHL FVIII variants, including those to be used for hemophilia A gene therapy.
Asymmetric Presynaptic Depletion of Dopamine Neurons in a Drosophila Model of Parkinson’s Disease
Authors: Zhang Jiajun , Lentz Lucie , Goldammer Jens , Iliescu Jessica , Tanimura Jun , Riemensperger Thomas Dieter
Published: May 2023

Parkinson’s disease (PD) often displays a strong unilateral predominance in arising symptoms. PD is correlated with dopamine neuron (DAN) degeneration in the substantia nigra pars compacta (SNPC), and in many patients, DANs appear to be affected more severely on one hemisphere than the other. The reason for this asymmetric onset is far from being understood. Drosophila melanogaster has proven its merit to model molecular and cellular aspects of the development of PD. However, the cellular hallmark of the asymmetric degeneration of DANs in PD has not yet been described in Drosophila. We ectopically express human α-synuclein (hα-syn) together with presynaptically targeted syt::HA in single DANs that innervate the Antler (ATL), a symmetric neuropil located in the dorsomedial protocerebrum. We find that expression of hα-syn in DANs innervating the ATL yields asymmetric depletion of synaptic connectivity. Our study represents the first example of unilateral predominance in an invertebrate model of PD and will pave the way to the investigation of unilateral predominance in the development of neurodegenerative diseases in the genetically versatile invertebrate model Drosophila.
The Immunosuppressive Roles of PD-L1 during Influenza A Virus Infection
Authors: Ning Hongya , Chiu Shih-Hsin , Xu Xiaodong , Ma Yanmei , Chen Ji-Long , Yang Guihong
Published: May 2023

The clinical benefits of targeting programmed death-ligand 1 (PD-L1) in various cancers represent a strategy for the treatment of immunosuppressive diseases. Here, it was demonstrated that the expression levels of PD-L1 in cells were greatly upregulated in response to H1N1 influenza A virus (IAV) infection. Overexpression of PD-L1 promoted viral replication and downregulated type-I and type-III interferons and interferon-stimulated genes. Moreover, the association between PD-L1 and Src homology region-2, containing protein tyrosine phosphatase (SHP2), during IAV/H1N1 infection was analyzed by employing the SHP2 inhibitor (SHP099), siSHP2, and pNL-SHP2. The results showed that the expressions of PD-L1 mRNA and protein were decreased under SHP099 or siSHP2 treatment, whereas the cells overexpressing SHP2 exhibited the opposite effects. Additionally, the effects of PD-L1 on the expression of p-ERK and p-SHP2 were investigated in PD-L1-overexpressed cells following WSN or PR8 infection, determining that the PD-L1 overexpression led to the decreased expression of p-SHP2 and p-ERK induced by WSN or PR8 infection. Taken together, these data reveal that PD-L1 could play an important role in immunosuppression during IAV/H1N1 infection; thus, it may serve as a promising therapeutic target for development of novel anti-IAV drugs.
The Role of Krüppel-like Factors in Pancreatic Physiology and Pathophysiology
Authors: Giarrizzo Michael , LaComb Joseph F. , Bialkowska Agnieszka B.
Published: May 2023

Krüppel-like factors (KLFs) belong to the family of transcription factors with three highly conserved zinc finger domains in the C-terminus. They regulate homeostasis, development, and disease progression in many tissues. It has been shown that KLFs play an essential role in the endocrine and exocrine compartments of the pancreas. They are necessary to maintain glucose homeostasis and have been implicated in the development of diabetes. Furthermore, they can be a vital tool in enabling pancreas regeneration and disease modeling. Finally, the KLF family contains proteins that act as tumor suppressors and oncogenes. A subset of members has a biphasic function, being upregulated in the early stages of oncogenesis and stimulating its progression and downregulated in the late stages to allow for tumor dissemination. Here, we describe KLFs’ function in pancreatic physiology and pathophysiology.
Assessing the Differential Methylation Analysis Quality for Microarray and NGS Platforms
Authors: Budkina Anna , Medvedeva Yulia A. , Stupnikov Alexey
Published: May 2023

Differential methylation (DM) is actively recruited in different types of fundamental and translational studies. Currently, microarray- and NGS-based approaches for methylation analysis are the most widely used with multiple statistical models designed to extract differential methylation signatures. The benchmarking of DM models is challenging due to the absence of gold standard data. In this study, we analyze an extensive number of publicly available NGS and microarray datasets with divergent and widely utilized statistical models and apply the recently suggested and validated rank-statistic-based approach Hobotnica to evaluate the quality of their results. Overall, microarray-based methods demonstrate more robust and convergent results, while NGS-based models are highly dissimilar. Tests on the simulated NGS data tend to overestimate the quality of the DM methods and therefore are recommended for use with caution. Evaluation of the top 10 DMC and top 100 DMC in addition to the not-subset signature also shows more stable results for microarray data. Summing up, given the observed heterogeneity in NGS methylation data, the evaluation of newly generated methylation signatures is a crucial step in DM analysis. The Hobotnica metric is coordinated with previously developed quality metrics and provides a robust, sensitive, and informative estimation of methods’ performance and DM signatures’ quality in the absence of gold standard data solving a long-existing problem in DM analysis.
Brown Adipose Tissue: A New Potential Target for Glucagon-like Peptide 1 Receptor Agonists in the Treatment of Obesity
Authors: Hropot Tim , Herman Rok , Janez Andrej , Lezaic Luka , Jensterle Mojca
Published: May 2023

Adipose tissue can be divided into white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue, according to the differences in morphology. WAT acts as a buffer for increased energy intake and decreased energy expenditure during the development of obesity, resulting in visceral and ectopic WAT accumulation. These WAT depots are strongly associated with chronic systemic inflammation, insulin resistance, and cardiometabolic risk related to obesity. They represent a primary weight loss target in anti-obesity management. Second-generation anti-obesity medications glucagon-like peptide-1 receptor agonists (GLP-1RAs) cause weight loss and improve body composition by reducing visceral and ectopic fat depots of WAT, resulting in improved cardiometabolic health. Recently, the understanding of the physiological significance of BAT beyond its primary function in generating heat through non-shivering thermogenesis has been expanded. This has raised scientific and pharmaceutical interest in the manipulation of BAT to further enhance weight reduction and body weight maintenance. This narrative review focuses on the potential impact of GLP-1 receptor agonism on BAT, particularly in human clinical studies. It provides an overview of the role of BAT in weight management and highlights the need for further research to elucidate the mechanisms by which GLP-1RAs affect energy metabolism and weight loss. Despite encouraging preclinical data, limited clinical evidence supports the notion that GLP-1RAs contribute to BAT activation.
Anion Exchange Membrane Based on BPPO/PECH with Net Structure for Acid Recovery via Diffusion Dialysis
Authors: Shen Haiyang , Gong Yifei , Chen Wei , Wei Xianbiao , Li Ping , Cheng Congliang
Published: May 2023

In order to improve the performance of the anion exchange membrane (AEM) used in acid recovery from industrial wastewater, this study adopted a new strategy in which brominated poly (2,6-dimethyl-1,4-phenyleneoxide) (BPPO) and polyepichlorohydrin (PECH) were used as the polymer backbone of the prepared membrane. The new anion exchange membrane with a net structure was formed by quaternizing BPPO/PECH with N,N,N,N-tetramethyl-1,6-hexanediamine (TMHD). The application performance and physicochemical property of the membrane were adjusted by changing the content of PECH. The experimental study found that the prepared anion exchange membrane had good mechanical performance, thermostability, acid resistance and an appropriate water absorption and expansion ratio. The acid dialysis coefficient (UH+) of anion exchange membranes with different contents of PECH and BPPO was 0.0173–0.0262 m/h at 25 °C. The separation factors (S) of the anion exchange membranes were 24.6 to 27.0 at 25 °C. Compared with the commercial BPPO membrane (DF-120B), the prepared membrane had higher values of UH+ and S in this paper. In conclusion, this work indicated that the prepared BPPO/PECH anion exchange membrane had the potential for acid recovery using the DD method.
Chemical, Physical, and Toxicological Properties of V-Agents
Authors: Pampalakis Georgios , Kostoudi Stavroula
Published: May 2023

V-agents are exceedingly toxic organophosphate nerve agents. The most widely known V-agents are the phosphonylated thiocholines VX and VR. Nonetheless, other V-subclasses have been synthesized. Here, a holistic overview of V-agents is provided, where these compounds have been categorized based on their structures to facilitate their study. A total of seven subclasses of V-agents have been identified, including phospho(n/r)ylated selenocholines and non-sulfur-containing agents, such as VP and EA-1576 (EA: Edgewood Arsenal). Certain V-agents have been designed through the conversion of phosphorylated pesticides to their respective phosphonylated analogs, such as EA-1576 derived from mevinphos. Further, this review provides a description of their production, physical properties, toxicity, and stability during storage. Importantly, V-agents constitute a percutaneous hazard, while their high stability ensures the contamination of the exposed area for weeks. The danger of V-agents was highlighted in the 1968 VX accident in Utah. Until now, VX has been used in limited cases of terrorist attacks and assassinations, but there is an increased concern about potential terrorist production and use. For this reason, studying the chemistry of VX and other less-studied V-agents is important to understand their properties and develop potential countermeasures.
Trade-Offs between Temperature and Fitness in Euschistus heros (Fabricius) (Hemiptera: Pentatomidae): Implications for Mass Rearing and Field Management
Authors: Barrufaldi Ana Paula Frugeri , Hayashida Rafael , Hoback William Wyatt , Higley Leon G. , Carvalho Jose Romario de , Oliveira Regiane Cristina de
Published: May 2023

The brown stink bug, Euschistus heros (Fabricius, 1798) (Hemiptera: Pentatomidae), is one of the most abundant soybean stink bug pests in Brazil. Temperature is a key factor that affects its development and reproduction, and fluctuating temperatures may impact the development and reproduction of E. heros differently from those under constant temperatures. The objective of this study was to evaluate the influence of constant and fluctuating temperature on the biological characteristics of E. heros in three successive generations. Treatments consisted of six constant temperatures (19 °C, 22 °C, 25 °C, 28 °C, 31 °C and 34 °C) and four fluctuating temperatures (25:21 °C, 28:24 °C, 31:27 °C, and 34:30 °C) evaluated for three successive generations. Second-stage nymphs were evaluated daily, and after they reached the adult stage, they were separated by sex, and the individual weight (mg) and pronotum size (mm) were recorded. After pair formation, eggs were collected to evaluate the pre-oviposition period, total number of eggs, and egg viability. The duration of the nymphal stage was reduced with an increase in both constant and fluctuating temperatures; however, at constant temperatures of 19 °C, 31 °C and 34 °C and fluctuating temperatures of 28:24 °C, there was no reproduction in adults. The base temperature and total degree day requirement for nymphal development were 15.5 °C and 197.4 dd, respectively. Pre-oviposition period (d), number of eggs per female, and viability of eggs (%) were affected by temperature across the generations. The multiple decrement life table analysis revealed that mortality was highest during the molting of the second-stage nymphs. These findings have important implications for E. heros’ laboratory mass-rearing programs and for its management in fields.
Five Surfaces Treated with d-Tetramethrin plus Acetamiprid for the Management of Tenebrio molitor and Alphitobius diaperinus: Which Is the Best?
Authors: Kavallieratos Nickolas G. , Nika Erifili P. , Gounari Penelope D.
Published: May 2023

Tenebrio molitor L. (Coleoptera: Tenebrionidae) and Alphitobius diaperinus Panzer (Coleoptera: Tenebrionidae) are two common tenebrionids occurring in grain storages. In this study, we assessed the immediate and delayed mortalities caused by d-tetramethrin plus acetamiprid on five different surfaces, i.e., plastic, glass, metal, wood, and ceramic, against adults of the two species. The tests included two label doses of the insecticide (minimum and maximum) and two food scenarios (food and no food). Generally, the maximum dose was more efficient than the minimum dose, and the presence of food resulted in lower observed mortalities than when food was absent. Tenebrio molitor was more susceptible than A. diaperinus, at all dose, food, and surface scenarios. At delayed bioassays, both doses killed all T. molitor on plastic, while on wood, mortality ranged between 80.6 and 100.0%, regardless of the food scenario. Concerning A. diaperinus, delayed mortalities ranged among treated surfaces, food scenarios, and dose from 58.3 to 100.0%. The insecticide killed the most individuals when it was treated on glass, while when it was applied on wood caused the death of the least individuals. Concerning plastic, metal, and ceramic surfaces, no general trend was observed. The maximum dose of the tested insecticide provides elevated mortalities for both species when food is absent.
Transvenous Pulmonary Chemoembolization and Optional Microwave Ablation for Colorectal Lung Metastases
Authors: Vogl Thomas J. , Hammann Lars , Adwan Hamzah
Published: May 2023

(1) Purpose: To evaluate tumor response and survival of patients with colorectal pulmonary metastases treated by transvenous pulmonary chemoembolization (TPCE) alone with palliative intent or TPCE followed by microwave ablation (MWA) with potentially curative intent. (2) Material and methods: A total of 164 patients (64 women and 100 men; mean age: 61.8 ± 12.7 years) with unresectable colorectal lung metastases and not responding to systemic chemotherapy, who either received repetitive TPCE (Group A) or TPCE followed by MWA (Group B), were retrospectively enrolled. The revised response evaluation criteria in solid tumors were used to assess treatment response in Group A. The oncological response in Group B was divided into local tumor progression (LTP) and intrapulmonary distant recurrence (IDR) after MWA. (3) Results: The 1-, 2-, 3-, and 4-year survival rates were 70.4%, 41.4%, 22.3%, and 5%, respectively, for all patients. In Group A; the rates of stable disease; progressive disease; and partial response were at 55.4%, 41.9%, and 2.7%, respectively. The rates of LTP and IDR were 3.8%, and 63.5%, respectively, in Group B. Conclusion: TPCE is an effective treatment for colorectal lung metastases, which can be performed alone or combined with MWA.
Arrhythmic Risk Stratification among Patients with Hypertrophic Cardiomyopathy
Authors: Santoro Francesco , Mango Federica , Mallardi Adriana , D’Alessandro Damiano , Casavecchia Grazia , Gravina Matteo , Correale Michele , Brunetti Natale Daniele
Published: May 2023

Hypertrophic cardiomyopathy (HCM) is a cardiac muscle disorder characterized by generally asymmetric abnormal hypertrophy of the left ventricle without abnormal loading conditions (such as hypertension or valvular heart disease) accounting for the left ventricular wall thickness or mass. The incidence of sudden cardiac death (SCD) in HCM patients is about 1% yearly in adults, but it is far higher in adolescence. HCM is the most frequent cause of death in athletes in the Unites States of America. HCM is an autosomal-dominant genetic cardiomyopathy, and mutations in the genes encoding sarcomeric proteins are identified in 30–60% of cases. The presence of this genetic mutation carries more than 2-fold increased risk for all outcomes, including ventricular arrhythmias. Genetic and myocardial substrate, including fibrosis and intraventricular dispersion of conduction, ventricular hypertrophy and microvascular ischemia, increased myofilament calcium sensitivity and abnormal calcium handling, all play a role as arrhythmogenic determinants. Cardiac imaging studies provide important information for risk stratification. Transthoracic echocardiography can be helpful to evaluate left ventricular (LV) wall thickness, LV outflow-tract gradient and left atrial size. Additionally, cardiac magnetic resonance can evaluate the prevalence of late gadolinium enhancement, which when higher than 15% of LV mass is a prognostic maker of SCD. Age, family history of SCD, syncope and non-sustained ventricular tachycardia at Holter ECG have also been validated as independent prognostic markers of SCD. Arrhythmic risk stratification in HCM requires careful evaluation of several clinical aspects. Symptoms combined with electrocardiogram, cardiac imaging tools and genetic counselling are the modern cornerstone for proper risk stratification.
Multilayer External Enclosing Wall Structures with Air Gaps or Channels
Authors: Zhangabay Nurlan , Tagybayev Askhat , Baidilla Islambek , Sapargaliyeva Bayan , Shakeshev Bekbulat , Baibolov Kanat , Duissenbekov Bolat , Utelbayeva Akmaral , Kolesnikov Alexandr , Izbassar Aizhan , Kozlov Pavel
Published: May 2023

Precise meanings of thermophysical processes taking place in air gaps have decisive importance in composite cladding structure systems’ calculation and modeling. The climatic load conditions in Kazakhstan can significantly affect the microclimate of premises in general. In this work, a review study is carried out to obtain the relevant scientific literature on enclosing structures with air gaps under various climatic conditions. The review mainly covers research institutes from Sweden, Norway, France, Saudi Arabia, Russia, and China. On the issue of the air gap parameter’s influence on thermophysical processes, 16 papers were analyzed, and on the issue of air infiltration, 12 papers were analyzed. However, the review shows a lack of research in this area under various climatic conditions. At the same time, experience has shown that the principle of multilayer protection from climatic influences creates a favorable microclimate in buildings, but due to a possible temperature drop, wall structures made of composite building materials can be quite favorable under some conditions, and under others they may be less favorable. Therefore, working out a new energy-saving design with air gaps for climatic conditions with large temperature fluctuations during summer and winter is an urgent task.
Computational-Simulation-Based Behavioral Analysis of Chemical Compounds
Authors: Pushpalatha  , Ramadevi  , Chandra Kishore Somasundaram , Bellucci Stefano
Published: May 2023

This research focuses on obtaining the behavior of chemical compounds with respect to their molecular weight and optimization energy based on the variation in properties in organic carbon links. Here, behavioral analysis of compounds is used in the application of a metal organic framework to denote the high-grade compounds. The grade was selected based on the essential measure of optimization energy and molecular weight, and in turn, depicts the stability of material. Computation of the optimization energy and molecular weight of chemical compounds was performed with Avogadro software. Several force fields can be considered to compute optimized energy. Exclusively, three force fields, namely, the Universal Force Field (UFF), the General Amber Force Field (GAFF), and the Ghemical force field (Ghemical) were selected from Avogadro as these were more relevant to compounds considered in this research. The various chemical compounds examined in this work are Aluminum (Al), Boron (Br), Calcium (Ca), Chlorine (Cl), Indium (In), Potassium (K), Scandium (Sc), Silicon (Si), and Tungsten (W). Hence, molecular modeling of different compounds incorporated with three different force fields was evaluated in this work. In this study, we found that the In structure has more energy reduction, of 22.673 kJ mol−1 in UFF, when compared with the other two force fields. Thus, In has higher potential with more stability.
Natural-Fibre-Reinforced Composite-Based Micro-Size Wind Turbines: Numerical Analysis and Feasibility Study
Authors: Raj E. Fantin Irudaya , Appadurai M. , Ram Vishal , Gnaniah Augustine Mathu , Salkuti Surender Reddy
Published: May 2023

Due to their inherent advantages, micro-sized horizontal axis wind turbines (HAWT) are preferred over vertical axis wind turbines (VAWT) for urban applications. Typically, HAWTs on the market are constructed using steel, alloys, or fibre-reinforced composites, with the latter being the most economical and stable in comparison to steel and alloy-based HAWTs. Nevertheless, in light of the increased emphasis on cost savings and environmental sustainability, natural-fibre composites have become more desirable. This study focuses on the implementation of flax-fibre-reinforced HAWT wind blades designed for urban applications in particular. The proposed wind blades were designed using CATIA and their feasibility and performance were evaluated via numerical analyses in ANSYS. Structural, modal, and harmonic analyses were conducted under various loading conditions. The results indicate that flax-fibre-reinforced wind blades possess higher natural frequencies, greater stability, and lower deflection amplitudes at resonance frequencies than other materials.
The Structure of Cognitive Abilities and Associations with Problem Behaviors in Early Adolescence: An Analysis of Baseline Data from the Adolescent Brain Cognitive Development Study
Authors: Moore Dawn Michele , Conway Andrew R. A.
Published: May 2023

Using baseline data (n = 9875) from the Adolescent Brain Cognitive Development (ABCD) Study examining children aged 9 to 10 years, the current analyses included: (1) exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) of neurocognitive measures administered during baseline collection, and (2) linear regression analyses on the Child Behavior Checklist (CBCL), controlling for demographic and socioeconomic factors. The neurocognitive tasks measured episodic memory, executive function (EF; attention), language skills, processing speed, working memory, visuospatial ability, and reasoning. The CBCL included composite scores of parent-reported internalizing, externalizing, and stress-related behavior problems. The study reported here serves as an extension of prior research using a principal components analysis (PCA) of the ABCD baseline data. We propose an alternative solution using factor analysis. Analyses revealed a three-factor structure: verbal ability (VA), executive function/processing speed (EF/PS), and working memory/episodic memory (WM/EM). These factors were significantly correlated with the CBCL scores, albeit with small effect sizes. These findings provide a novel three-factor solution to the structure of cognitive abilities measured in the ABCD Study, offering new insights into the association between cognitive function and problem behaviors in early adolescence.
Thin-Walled Part Properties in Powder Bed Fusion of Polymers—A Comparative Study on Temperature Development and Part Performance Depending on Part Thickness and Orientation
Authors: Jaksch Andreas , Cholewa Simon , Drummer Dietmar
Published: May 2023

To develop new areas of application for laser-based powder bed fusion of polymers (PBF-LB/P), a deeper process understanding of the resulting mechanical properties, particularly for thin-walled and complex structures, is needed. This work addresses the influence of part thickness and orientation in detail. For a general understanding, two PBF systems were used. For comparison, the normalized energy density was determined for specimens of various thicknesses and orientations. It could be seen that the normalized energy density exhibited opposing trends for the two systems for progressively thinner samples. During the process, the exposure temperature development was observed using an infrared camera for a greater understanding of the developing part properties. To further investigate the fracture behavior, an infrared camera was used during tensile testing, which revealed various patterns depending on the PBF-System used. The results showed a machine-dependent difference in the exposure temperatures and elongation at break for z-oriented parts. While the surface roughness was independent of the thickness, the density, porosity, and the mechanical properties were affected significantly by the part thickness. The parts showed a brittle breaking behavior with a crack initiation from the short side of the tensile bar. These results improved process expertise, and in particular the mechanical performance of thin-walled structures caused by temperature variations in PBF-LB/P.
Multimodal Transduction and Translanguaging in Deaf Pedagogy
Authors: Skyer Michael E.
Published: May 2023

Multimodal transduction is an interaction of teaching and learning. It traverses changes in epistemology and ontology through judgements about axiology. Using multimodal transduction (MT), students and teachers transcend languages and employ nonlanguage and quasi-language modes (e.g., drawing, color, line, math, infographics, and even sculptures). This study uses qualitative empirical data via grounded theory and case study designs to make theoretical claims about MT in a deaf higher-educational context. The data for this multi-year project were sourced through interviews, document analysis, observations, and stimulated recall with six university professors who are deaf. My analysis shows that these deaf faculty-members employ MT to convert inaccessible modes to become accessible for deaf learners. By changing modalities through MT, deaf faculty enhance comprehensibility and equity for deaf learners. This theoretical account of MT contends, extends, and clarifies aspects of translanguaging theory. As I argue, both operations transform power relations in the classroom by addressing ethics through deaf-centric aesthetics. In deaf education, MT is equally important for faculty in teaching and students’ learning. MT is widely and creatively used, owing to its flexibility and adaptivity. MT is useful for all deaf agents, regardless of additional disabilities, language competencies, or language deprivation. The MT process is inexplicit and undertheorized in the literature about deaf pedagogy and in translanguaging research. My study provides empirical support for theoretical claims about underlying mechanisms of translanguaging. One focus is to explore how MT and translanguaging (and similar theories) align or diverge. I argue that MT is a core mechanism that supports changes between all modes of discourse that enable information exchange, including but surpassing languages and translanguaging. In sum, MT is an interaction whereby deaf agents change the forms of knowledge; meanwhile, new realities and new power relations are manifested.