bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization in Inhibitory Effectiveness of Carbamazepine in Voltage-Gated Na+ and Erg-Mediated K+ Currents in a Mouse Neural Crest-Derived (Neuro-2a) Cell Line
Authors: Wu Po-Ming , Cho Hsin-Yen , Chiang Chi-Wu , Chuang Tzu-Hsien , Wu Sheng-Nan , Tu Yi-Fang
Published: July 2022

Carbamazepine (CBZ, Tegretol®) is an anticonvulsant used in the treatment of epilepsy and neuropathic pain; however, several unwanted effects of this drug have been noticed. Therefore, the regulatory actions of CBZ on ionic currents in electrically excitable cells need to be reappraised, although its efficacy in suppressing voltage-gated Na+ current (INa) has been disclosed. This study was undertaken to explore the modifications produced by CBZ on ionic currents (e.g., INa and erg-mediated K+ current [IK(erg)]) measured from Neuro-2a (N2a) cells. In these cells, we found that this drug differentially suppressed the peak (transient, INa(T)) and sustained (late, INa(L)) components of INa in a concentration-dependent manner with effective IC50 of 56 and 18 μM, respectively. The overall current–voltage relationship of INa(T) with or without the addition of CBZ remained unchanged; however, the strength (i.e., ∆area) in the window component of INa (INa(W)) evoked by the short ascending ramp pulse (Vramp) was overly lessened in the CBZ presence. Tefluthrin (Tef), a synthetic pyrethroid, known to stimulate INa, augmented the strength of the voltage-dependent hysteresis (Hys(V)) of persistent INa (INa(P)) in response to the isosceles-triangular Vramp; moreover, further application of CBZ attenuated Tef-mediated accentuation of INa(P)’s Hys(V). With a two-step voltage protocol, the recovery of INa(T) inactivation seen in Neuro-2a cells became progressively slowed by adding CBZ; however, the cumulative inhibition of INa(T) evoked by pulse train stimulation was enhanced during exposure to this drug. Neuro-2a-cell exposure to CBZ (100 μM), the magnitude of erg-mediated K+ current measured throughout the entire voltage-clamp steps applied was mildly inhibited. The docking results regarding the interaction of CBZ and voltage-gate Na+ (NaV) channel predicted the ability of CBZ to bind to some amino-acid residues in NaV due to the existence of a hydrogen bond or hydrophobic contact. It is conceivable from the current investigations that the INa (INa(T), INa(L), INa(W), and INa(P)) residing in Neuro-2a cells are susceptible to being suppressed by CBZ, and that its block on INa(L) is larger than that on INa(T). Collectively, the magnitude and gating of NaV channels produced by the CBZ presence might have an impact on its anticonvulsant and analgesic effects occurring in vivo.
PbUGT72AJ2-Mediated Glycosylation Plays an Important Role in Lignin Formation and Stone Cell Development in Pears (Pyrus bretschneideri)
Authors: Wang Han , Feng Xiaofeng , Zhang Yingjie , Wei Dongyi , Zhang Yang , Jin Qing , Cai Yongping
Published: July 2022

Glycosylation is necessary for many processes of plant secondary metabolism. It can maintain plant homeostasis and is of great significance to normal plant growth and development. At present, the significance of glycosylation for lignin biosynthesis has been proven in some plants, but it has not yet been reported in pears. We used in situ hybridization, in vitro expression, substrate catalysis, transgenic Arabidopsisthaliana, and transient transformation of pear fruit in our investigation, which was predicated on the identification of a gene PbUGT72AJ2 that may be involved in lignin monolignol glycosylation according to our previous work. These results revealed that PbUGT72AJ2 transcripts were localized to some pulp cell walls, lignin deposition, and stone cell areas of pear fruit. The recombinant PbUGT72AJ2-pGEX4T-1 protein had activity against coniferyl alcohol and sinapyl alcohol, and its catalytic efficiency against coniferyl alcohol was higher than that against sinapyl alcohol. When PbUGT72AJ2 was transferred into Arabidopsisthaliana mutants, it was found that some characteristics of Arabidopsisthalianaugt72e3 mutants were restored. In Arabidopsisthaliana, overexpression of PbUGT72AJ2 enhanced the contents of coniferin and syringin, whereas lignification did not change significantly. Transient transformation of pear fruit showed that when PbUGT72AJ2 in pear fruit was silenced by RNA interference, the content of lignin and stone cells in pear fruit increased, whereas the gene PbUGT72AJ2 was overexpressed in pear fruit, and there was almost no change in the pear fruit compared with the control. Lignin deposition in pear fruit was closely related to stone cell development. In this study, we proved that PbUGT72AJ2 plays an important role in lignin deposition and stone cell development in pear fruit, which provides a molecular biological basis for improving pear fruit quality at the molecular level.
The Intracellular Distribution of the Small GTPase Rho5 and Its Dimeric Guanidine Nucleotide Exchange Factor Dck1/Lmo1 Determine Their Function in Oxidative Stress Response
Authors: Bischof Linnet , Schweitzer Franziska , Sterk Carolin C. , Heinisch Jürgen J.
Published: July 2022

Rho5, the yeast homolog of human Rac1, is a small GTPase which regulates the cell response to nutrient and oxidative stress by inducing mitophagy and apoptosis. It is activated by a dimeric GEF composed of the subunits Dck1 and Lmo1. Upon stress, all three proteins rapidly translocate from the cell surface (Rho5) and a diffuse cytosolic distribution (Dck1 and Lmo1) to mitochondria, with translocation of the GTPase depending on both GEF subunits. We here show that the latter associate with mitochondria independent from each other and from Rho5. The trapping of Dck1-GFP or GFP-Lmo1 to the mitochondrial surface by a specific nanobody fused to the transmembrane domain (TMD) of Fis1 results in a loss of function, mimicking the phenotypes of the respective gene deletions, dck1 or lmo1. Direct fusion of Rho5 to Fis1TMD, i.e., permanent attachment to the mitochondria, also mimics the phenotypes of an rho5 deletion. Together, these data suggest that the GTPase needs to be activated at the plasma membrane prior to its translocation in order to fulfill its function in the oxidative stress response. This notion is substantiated by the observation that strains carrying fusions of Rho5 to the cell wall integrity sensor Mid2, confining the GTPase to the plasma membrane, retained their function. We propose a model in which Rho5 activated at the plasma membrane represses the oxidative stress response under standard growth conditions. This repression is relieved upon its GEF-mediated translocation to mitochondria, thus triggering mitophagy and apoptosis.
Prediction of Response to Cisplatin-Based Neoadjuvant Chemotherapy of Muscle-Invasive Bladder Cancer Patients by Molecular Subtyping including KRT and FGFR Target Gene Assessment
Authors: Ecke Thorsten H. , Voß Paula Carolin , Schlomm Thorsten , Rabien Anja , Friedersdorff Frank , Barski Dimitri , Otto Thomas , Waldner Michael , Veltrup Elke , Linden Friederike , Hake Roland , Eidt Sebastian , Roggisch Jenny , Heidenreich Axel , Rieger Constantin , Kastner Lucas , Hallmann Steffen , Koch Stefan , Wirtz Ralph M.
Published: July 2022

Patients with muscle-invasive urothelial carcinoma achieving pathological complete response (pCR) upon neoadjuvant chemotherapy (NAC) have improved prognosis. Molecular subtypes of bladder cancer differ markedly regarding sensitivity to cisplatin-based chemotherapy and harbor FGFR treatment targets to various content. The objective of the present study was to evaluate whether preoperative assessment of molecular subtype as well as FGFR target gene expression is predictive for therapeutic outcome—rate of ypT0 status—to justify subsequent prospective validation within the “BladderBRIDGister”. Formalin-fixed paraffin-embedded (FFPE) tissue specimens from transurethral bladder tumor resections (TUR) prior to neoadjuvant chemotherapy and corresponding radical cystectomy samples after chemotherapy of 36 patients were retrospectively collected. RNA from FFPE tissues were extracted by commercial kits, Relative gene expression of subtyping markers (e.g., KRT5, KRT20) and target genes (FGFR1, FGFR3) was analyzed by standardized RT-qPCR systems (STRATIFYER Molecular Pathology GmbH, Cologne). Spearman correlation, Kruskal–Wallis, Mann–Whitney and sensitivity/specificity tests were performed by JMP 9.0.0 (SAS software). The neoadjuvant cohort consisted of 36 patients (median age: 69, male 83% vs. female 17%) with 92% of patients being node-negative during radical cystectomy after 1 to 4 cycles of NAC. When comparing pretreatment with post-treatment samples, the median expression of KRT20 dropped most significantly from DCT 37.38 to 30.65, which compares with a 128-fold decrease. The reduction in gene expression was modest for other luminal marker genes (GATA3 6.8-fold, ERBB2 6.3-fold). In contrast, FGFR1 mRNA expression increased from 33.28 to 35.88 (~6.8-fold increase). Spearman correlation revealed positive association of pretreatment KRT20 mRNA levels with achieving pCR (r = 0.3072: p = 0.0684), whereas pretreatment FGFR1 mRNA was associated with resistance to chemotherapy (r = −0.6418: p < 0.0001). Hierarchical clustering identified luminal tumors of high KRT20 mRNA expression being associated with high pCR rate (10/16; 63%), while the double-negative subgroup with high FGFR1 expression did not respond with pCR (0/9; 0%). Molecular subtyping distinguishes patients with high probability of response from tumors as resistant to neoadjuvant chemotherapy. Targeting FGFR1 in less-differentiated bladder cancer subgroups may sensitize tumors for adopted treatments or subsequent chemotherapy.
Impact of Exogenous Application of Potato Virus Y-Specific dsRNA on RNA Interference, Pattern-Triggered Immunity and Poly(ADP-ribose) Metabolism
Authors: Samarskaya Viktoriya O. , Spechenkova Nadezhda , Markin Nikolay , Suprunova Tatyana P. , Zavriev Sergey K. , Love Andrew J. , Kalinina Natalia O. , Taliansky Michael
Published: July 2022

In this work we developed and exploited a spray-induced gene silencing (SIGS)-based approach to deliver double-stranded RNA (dsRNA), which was found to protect potato against potato virus Y (PVY) infection. Given that dsRNA can act as a defence-inducing signal that can trigger sequence-specific RNA interference (RNAi) and non-specific pattern-triggered immunity (PTI), we suspected that these two pathways may be invoked via exogeneous application of dsRNA, which may account for the alterations in PVY susceptibility in dsRNA-treated potato plants. Therefore, we tested the impact of exogenously applied PVY-derived dsRNA on both these layers of defence (RNAi and PTI) and explored its effect on accumulation of a homologous virus (PVY) and an unrelated virus (potato virus X, PVX). Here, we show that application of PVY dsRNA in potato plants induced accumulation of both small interfering RNAs (siRNAs), a hallmark of RNAi, and some PTI-related gene transcripts such as WRKY29 (WRKY transcription factor 29; molecular marker of PTI), RbohD (respiratory burst oxidase homolog D), EDS5 (enhanced disease susceptibility 5), SERK3 (somatic embryogenesis receptor kinase 3) encoding brassinosteroid-insensitive 1-associated receptor kinase 1 (BAK1), and PR-1b (pathogenesis-related gene 1b). With respect to virus infections, PVY dsRNA suppressed only PVY replication but did not exhibit any effect on PVX infection in spite of the induction of PTI-like effects in the presence of PVX. Given that RNAi-mediated antiviral immunity acts as the major virus resistance mechanism in plants, it can be suggested that dsRNA-based PTI alone may not be strong enough to suppress virus infection. In addition to RNAi- and PTI-inducing activities, we also showed that PVY-specific dsRNA is able to upregulate production of a key enzyme involved in poly(ADP-ribose) metabolism, namely poly(ADP-ribose) glycohydrolase (PARG), which is regarded as a positive regulator of biotic stress responses. These findings offer insights for future development of innovative approaches which could integrate dsRNA-induced RNAi, PTI and modulation of poly(ADP-ribose) metabolism in a co-ordinated manner, to ensure a high level of crop protection.
Structure Prediction, Evaluation, and Validation of GPR18 Lipid Receptor Using Free Programs
Authors: Michalik Ilona , Kuder Kamil J. , Kieć-Kononowicz Katarzyna , Handzlik Jadwiga
Published: July 2022

The GPR18 receptor, often referred to as the N-arachidonylglycine receptor, although assigned (along with GPR55 and GPR119) to the new class A GPCR subfamily-lipid receptors, officially still has the status of a class A GPCR orphan. While its signaling pathways and biological significance have not yet been fully elucidated, increasing evidence points to the therapeutic potential of GPR18 in relation to immune, neurodegenerative, and cancer processes to name a few. Therefore, it is necessary to understand the interactions of potential ligands with the receptor and the influence of particular structural elements on their activity. Thus, given the lack of an experimentally solved structure, the goal of the present study was to obtain a homology model of the GPR18 receptor in the inactive state, meeting all requirements in terms of protein structure quality and recognition of active ligands. To increase the reliability and precision of the predictions, different contemporary protein structure prediction methods and software were used and compared herein. To test the usability of the resulting models, we optimized and compared the selected structures followed by the assessment of the ability to recognize known, active ligands. The stability of the predicted poses was then evaluated by means of molecular dynamics simulations. On the other hand, most of the best-ranking contemporary CADD software/platforms for its full usability require rather expensive licenses. To overcome this down-to-earth obstacle, the overarching goal of these studies was to test whether it is possible to perform the thorough CADD experiments with high scientific confidence while using only license-free/academic software and online platforms. The obtained results indicate that a wide range of freely available software and/or academic licenses allow us to carry out meaningful molecular modelling/docking studies.
Autotaxin Has a Negative Role in Systemic Inflammation
Authors: Nikitopoulou Ioanna , Katsifa Aggeliki , Kanellopoulou Paraskevi , Jahaj Edison , Vassiliou Alice G. , Mastora Zafeiria , Dimopoulou Ioanna , Orfanos Stylianos E. , Aidinis Vassilis , Kotanidou Anastasia
Published: July 2022

The pathogenesis of sepsis involves complex interactions and a systemic inflammatory response leading eventually to multiorgan failure. Autotaxin (ATX, ENPP2) is a secreted glycoprotein largely responsible for the extracellular production of lysophosphatidic acid (LPA), which exerts multiple effects in almost all cell types through its at least six G-protein-coupled LPA receptors (LPARs). Here, we investigated a possible role of the ATX/LPA axis in sepsis in an animal model of endotoxemia as well as in septic patients. Mice with 50% reduced serum ATX levels showed improved survival upon lipopolysaccharide (LPS) stimulation compared to their littermate controls. Similarly, mice bearing the inducible inactivation of ATX and presenting with >70% decreased ATX levels were even more protected against LPS-induced endotoxemia; however, no significant effects were observed upon the chronic and systemic transgenic overexpression of ATX. Moreover, the genetic deletion of LPA receptors 1 and 2 did not significantly affect the severity of the modelled disease, suggesting that alternative receptors may mediate LPA effects upon sepsis. In translation, ATX levels were found to be elevated in the sera of critically ill patients with sepsis in comparison with their baseline levels upon ICU admission. Therefore, the results indicate a role for ATX in LPS-induced sepsis and suggest possible therapeutic benefits of pharmacologically targeting ATX in severe, systemic inflammatory disorders.
Maternal Acetate Supplementation Reverses Blood Pressure Increase in Male Offspring Induced by Exposure to Minocycline during Pregnancy and Lactation
Authors: Hsu Chien-Ning , Yu Hong-Ren , Chan Julie Y. H. , Lee Wei-Chia , Wu Kay L. H. , Hou Chih-Yao , Chang-Chien Guo-Ping , Lin Sufan , Tain You-Lin
Published: July 2022

Emerging evidence supports that hypertension can be programmed or reprogrammed by maternal nutrition. Maternal exposures during pregnancy, such as maternal nutrition or antibiotic use, could alter the offspring’s gut microbiota. Short-chain fatty acids (SCFAs) are the major gut microbiota-derived metabolites. Acetate, the most dominant SCFA, has shown its antihypertensive effect. Limited information exists regarding whether maternal acetate supplementation can prevent maternal minocycline-induced hypertension in adult offspring. We exposed pregnant Sprague Dawley rats to normal diet (ND), minocycline (MI, 50 mg/kg/day), magnesium acetate (AC, 200 mmol/L in drinking water), and MI + AC from gestation to lactation period. At 12 weeks of age, four groups (n = 8/group) of male progeny were sacrificed. Maternal acetate supplementation protected adult offspring against minocycline-induced hypertension. Minocycline administration reduced plasma acetic acid level, which maternal acetate supplementation prevented. Additionally, acetate supplementation increased the protein level of SCFA receptor G protein-coupled receptor 41 in the offspring kidneys. Further, minocycline administration and acetate supplementation significantly altered gut microbiota composition. Maternal acetate supplementation protected minocycline-induced hypertension accompanying by the increases in genera Roseburia, Bifidobacterium, and Coprococcus. In sum, our results cast new light on targeting gut microbial metabolites as early interventions to prevent the development of hypertension, which could help alleviate the global burden of hypertension.
miR-10 and Its Negative Correlation with Serum IL-35 Concentration and Positive Correlation with STAT5a Expression in Patients with Rheumatoid Arthritis
Authors: Paradowska-Gorycka Agnieszka , Wajda Anna , Rzeszotarska Ewa , Kmiolek Tomasz , Stypinska Barbara , Dudek Ewa , Romanowska-Prochnicka Katarzyna , Syrowka Piotr
Published: July 2022

Circulating free-cell miRNAs are increasingly important as potential non-invasive biomarkers due to the easy accessibility of clinical materials. Moreover, their epigenetic role may provide insight into the mechanisms of pathogenesis. Nevertheless, these aspects are mostly studied in the area of oncological diseases. Therefore, this research aimed to find the potential association of selected miRNAs in serum with the expression of Th17/Treg transcription factors and clinical features in RA patients. Accordingly, experiments was conducted on rheumatoid arthritis (RA), osteoarthritis (OA) and healthy subjects (HC). Analysis of miRNAs level in serum was performed using LNA miRNA PCR assays. mir-10 was detected only in RA patients. Furthermore, its expression was correlated with IL-35 serum concentration and the mRNA level of STAT5a in whole blood in RA. Additionally, a tendency of the raised level of miR-10 was noted in RA patients with high activity disease. miR-326 was significantly upregulated in RA patients with rheumatoid factor presence. In HC the correlation between miR-26 and IL-21 serum levels and expression of SMAD3 have been found. In OA patients, correlations between miR-126 and HIF1 expression and between miR-146 and RORc have been noted. The differential association of transcription factor expression with serum miRNA levels may be important in the diagnosis and progression of RA and OA.
Influencer Marketing on Instagram: A Sequential Mediation Model of Storytelling Content and Audience Engagement via Relatability and Trust
Authors: Atiq Madiha , Abid Ghulam , Anwar Aizza , Ijaz Muhammad Fazal
Published: July 2022

Storytelling content is where the facts are conveyed by emotion and that make people more engaged and want to take action or change their surroundings. Stories fascinate people and can easily be remembered compared to the facts alone. The much-hyped feature “stories” of Instagram, a trendy social media platform, has become a game-changer for influencer marketing. The present study extends reactance theory in the context of Instagram’s millennial users. Previous researchers have tested the effectiveness of the stories feature of this particular social media platform. Therefore, in line with the earlier studies, we propose a sequential mediation model that investigates the effect of storytelling content (made by Instagram Influencers) on audience engagement using two sequential mediation mechanisms of relatability and trust. Data were obtained using a cross-sectional study design from 273 millennial users of Instagram. Our results justify the direct and indirect hypothesized relationship through Process Macros. We found that relatability and trust play a significant role in building a strong relationship between storytelling content and audience engagement. Ultimately, the research findings suggest that professionals should be more creative while making the content on Instagram to engage the millennial market. Moreover, this research has tried to fill the gap in the literature on Instagram “stories” as an advertising platform.
Resistance to Extreme Stresses by a Newly Discovered Japanese Tardigrade Species, Macrobiotus kyoukenus (Eutardigrada, Macrobiotidae)
Authors: Cesari Michele , Giovannini Ilaria , Altiero Tiziana , Guidetti Roberto , Cornette Richard , Kikawada Takahiro , Rebecchi Lorena
Published: July 2022

Tardigrades are small micrometazoans able to resist several environmental stresses in any stage of their life cycle. An integrated analysis of tardigrade specimens collected in Tsukuba (Japan) revealed a peculiar morphology and a new sensory field in the cloaca. Molecular taxonomy and phylogenetic analysis on different genes (COI, ITS2, 18S and 28S) confirmed that this population is a new species, Macrobiotus kyoukenus sp. nov., belonging to the widespread Macrobiotus hufelandi group. The stress resistance capabilities of M. kyoukenus sp. nov. have been tested by submitting animals to extreme desiccation, rapid freezing, and high levels of ultraviolet radiations (UVB and UVC). Animals were able to survive desiccation (survivorship 95.71 ± 7.07%) and freezing up to −80 °C (82.33 ± 17.11%). Both hydrated and desiccated animals showed a high tolerance to increasing UV radiations: hydrated animals survived to doses up to 152.22 kJ m−2 (UVB) and up to 15.00 kJ m−2 (UVC), while desiccated specimens persisted to radiations up to 165.12 kJ m−2 (UVB) and up to 35.00 kJ m−2 (UVC). Present data contribute to the discovery of a larger tardigrade biodiversity in Japan, and the tolerance capabilities of M. kyoukenus sp. nov. show that it could become a new emerging model for stress resistance studies.
Reproductive Apparatus, Gonadic Maturation, and Allometry of Cyclocephala barrerai Martínez (Coleoptera: Melolonthidae: Dynastinae)
Authors: Sanchez-Cruz Abraham , Tapia-Maruri Daniel , Jiménez-Pérez Alfredo
Published: July 2022

The Order Coleoptera provides good examples of morphological specializations in the reproductive apparatus, gonadic maturation, and allometry differing between the sexes. The female and male reproductive apparatus has been modified to ensure reproduction between individuals of the same species. The genus Cyclocephala has more than 500 species distributed in America, and Cyclocephala barrerai Martínez is an economically important species in the central part of Mexico. The objective of this work was to study the reproductive system, gonadic maturation, and allometry of C. barrerai. We used light, scanning electron, and laser scanning confocal microscopy to describe the reproductive apparatus and gonadic maturation of females and males. The relationship between adult weight and different parts of the body was established by linear regression. Regardless, the reproductive apparatuses of C. barrerai are like those of other Melolonthidae: the genital chamber, the type II accessory glands, and the ventral plaques of the female and the ejaculator bulb and genital capsule of the males are specific to C. barrerai. The gonads are fully developed when 18 d old. The weight of adult C. barrerai has a positive linear relationship with distinct parts of its body, while the antennae of males are larger than those of the females.
Proteomic Response of Aedes aegypti Larvae to Silver/Silver Chloride Nanoparticles Synthesized Using Bacillus thuringiensis subsp. israelensis Metabolites
Authors: Chimkhan Nantipat , Thammasittirong Sutticha Na-Ranong , Roytrakul Sittiruk , Krobthong Sucheewin , Thammasittirong Anon
Published: July 2022

Silver/silver chloride nanoparticles (Ag/AgCl NPs) are an alternative approach to control the larvae of Aedes aegypti, a vector of mosquito-borne diseases. However, the molecular mechanisms of Ag/AgCl NPs to A. aegypti have not been reported. In this work, Ag/AgCl NPs were synthesized using supernatant, mixed toxins from Bacillus thuringiensis subsp. israelensis (Bti), and heterologously expressed Cry4Aa and Cry4Ba toxins. The images from scanning electron microscopy revealed that the Ag/AgCl NPs were spherical in shape with a size range of 25–100 nm. The larvicidal activity against A. aegypti larvae revealed that the Ag/AgCl NPs synthesized using the supernatant of Bti exhibited higher toxicity (LC50 = 0.133 μg/mL) than the Ag/AgCl NPs synthesized using insecticidal proteins (LC50 = 0.148–0.217 μg/mL). The proteomic response to Ag/AgCl NPs synthesized using the supernatant of Bti in A. aegypti larvae was compared to the ddH2O-treated control. Two-dimensional gel electrophoresis analysis revealed 110 differentially expressed proteins, of which 15 were selected for identification using mass spectrometry. Six upregulated proteins (myosin I heavy chain, heat shock protein 70, the F0F1-type ATP synthase beta subunit, methyltransferase, protein kinase, and condensin complex subunit 3) that responded to Ag/AgCl NP treatment in A. aegypti were reported for NP treatments in different organisms. These results suggested that possible mechanisms of action of Ag/AgCl NPs on A. aegypti larvae are: mitochondrial dysfunction, DNA and protein damage, inhibition of cell proliferation, and cell apoptosis. The findings from this work provide greater insight into the action of green synthesized Ag/AgCl NPs on the control of A. aegypti larvae.
Nutritional Composition of Bombyx mori Pupae: A Systematic Review
Authors: Tassoni Luca , Cappellozza Silvia , Dalle Zotte Antonella , Belluco Simone , Antonelli Pietro , Marzoli Filippo , Saviane Alessio
Published: July 2022

As insects have started to enter the eating habits of Western countries, an increasing amount of literature regarding the mulberry silkworm (Bombyx mori) prospective application as food has been published. Despite this growing interest, there is currently no systematic review of silkworm nutritional composition available. In this paper, we performed a systematic review of the recent available literature on the nutrient composition of mulberry silkworm pupae. After screening the titles and abstracts of 14,008 studies retrieved from three scientific databases, data about nutrients was extracted from 29 selected papers, together with their related variables. This systematic review provides an overview of the variety of data reported in the literature and highlights that many elements contribute to hindering a sound comparison of the different nutritional values reported for silkworm pupae. The observed variability of the composition data reported could be due to differences in diet, strains, pretreatments, and origin of the silkworm analyzed. However, all these variables were not always available and should be reported in future studies to simplify the data comparison.
Transcriptome Analysis Reveals Early Hemocyte Responses upon In Vivo Stimulation with LPS in the Stick Insect Bacillus rossius (Rossi, 1788)
Authors: Bidoli Carlotta , Miccoli Andrea , Buonocore Francesco , Fausto Anna Maria , Gerdol Marco , Picchietti Simona , Scapigliati Giuseppe
Published: July 2022

Despite a growing number of non-model insect species is being investigated in recent years, a greater understanding of their physiology is prevented by the lack of genomic resources. This is the case of the common European stick insect Bacillus rossius (Rossi, 1788): in this species, some knowledge is available on hemocyte-related defenses, but little is known about the physiological changes occurring in response to natural or experimental challenges. Here, the transcriptional signatures of adult B. rossius hemocytes were investigated after a short-term (2 h) LPS stimulation in vivo: a total of 2191 differentially expressed genes, mostly involved in proteolysis and carbohydrate and lipid metabolic processes, were identified in the de novo assembled transcriptome and in-depth discussed. Overall, the significant modulation of immune signals—such as C-type lectins, ML domain-containing proteins, serpins, as well as Toll signaling-related molecules—provide novel information on the early progression of LPS-induced responses in B. rossius.
Predatory and Parasitic Insects Associated with Urophora cardui L. (Diptera: Tephritidae) Galls on Canada Thistle, Cirsium arvense L. (Asterales, Asteraceae) in North Dakota
Authors: Swenson Stephanie J. , Bell-Clement Jonathan , Schroeder Sarah , Prischmann-Voldseth Deirdre A.
Published: July 2022

We surveyed the insect fauna associated with Urophora cardui L. (Diptera: Tephritidae) galls on Canada thistle, Cirsium arvense L. (Asterales, Asteraceae), in parts of the northern Great Plains, U.S., by field-collecting galls and rearing or dissecting out the insects. We also examined the relationships between gall biomass and insect density and biomass. Urophora cardui were widespread, and the gall biomass was positively correlated with fly density and fly biomass. We recovered Isohydnocera tabida (LeConte) (Coleoptera: Cleridae) from galls in two counties, which represents a new host record and provides vital information on the little-known immatures of this predatory species. Pteromalus elevatus (Walker) (Hymenoptera: Pteromalidae) was the dominant parasitoid that emerged from the U. cardui galls. Individual galls typically only had one insect species, and occasionally both U. cardui and P. elevatus were present, but it was rare for other insects to be present in galls housing I. tabida. This study adds to the taxonomic literature of gall-inhabiting insect species and provides new information on the predators of U. cardui, specifically a little-known clerid beetle species.
Evolution of the Colocasiomyia gigantea Species Group (Diptera: Drosophilidae): Phylogeny, Biogeography and Shift of Host Use
Authors: Xiao Ling , Li Nan-Nan , Yang Long-Kun , Li Jia-Ling , Gao Jian-Jun
Published: July 2022

The gigantea species group of the genus Colocasiomyia de Meijere (Diptera: Drosophilidae) is among the four aroid-breeding species groups in this genus; however, it differs from the remaining three groups in the host use: all the flies in this group use plants from the subfamily Monsteroideae instead of from the subfamily Aroideae. So far, we have not resolved the phylogenetic relationship within this group, making it difficult to trace its geographical origin, pattern of species diversification and history of host plant use. In this study, we reconstructed the phylogenetic relationships within the C. gigantea group using DNA sequences of eight (two mitochondrial and six nuclear) gene markers, and we inferred the ancestral areas and host plants of the group based on the resulting phylogeny. According to the results, the C. gigantea group may have diverged from its sister group (i.e., the C. cristata group) through vicariance between the northeastern Oriental region and Sundaland + Wallacea, and the subsequent diversification of the C. gigantea group occurred mostly in the northeastern Oriental region, although an Oriental-to-Sundaland dispersal was followed by vicariance between these two areas, which finally gave rise to the C. gigantea-C. scindapsae lineage in the latter area. We inferred the most likely ancestral host plant of the C. gigantea group to be of the genus Rhaphidophora Hassk, with possible subsequent shifts to Scindapsus Schott and/or Epipremnum Schott plants. We discuss the potential for the egg filaments in the C. gigantea group to be used as a model system for comparative studies in pollination mutualism and developmental genetics concerning tubulogenesis.
Frailty Index and Cardiovascular Disease among Middle-Aged and Older Chinese Adults: A Nationally Representative Cross-Sectional and Follow-Up Study
Authors: Liu Xinyao , Dai Guolin , He Qile , Ma Hao , Hu Hongpu
Published: July 2022

Evidence for the association between the frailty index and cardiovascular disease (CVD) is inconclusive, and this association has not been evaluated in Chinese adults. We aim to examine the association between the frailty index and CVD among middle-aged and older Chinese adults. We conducted cross-sectional and cohort analyses using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). From 2011 to 2018, 17,708 participants aged 45 years and older were included in the CHARLS. The primary outcome was CVD events (composite of heart disease and stroke). Multivariable adjusted logistic regression and Cox proportional hazards models were used to estimate the association between the frailty index and CVD in cross-sectional and follow-up studies, respectively. A restricted cubic spline model was used to characterize dose–response relationships. A total of 16,293 and 13,580 participants aged 45 years and older were included in the cross-sectional and cohort analyses, respectively. In the cross-sectional study, the prevalence of CVD in robust, pre-frailty and frailty was 7.83%, 18.70% and 32.39%, respectively. After multivariable adjustment, pre-frailty and frailty were associated with CVD; ORs were 2.54 (95% confidence interval [CI], 2.28–2.84) and 4.76 (95% CI, 4.10–5.52), respectively. During the 7 years of follow-up, 2122 participants without previous CVD developed incident CVD; pre-frailty and frailty were associated with increased risk of CVD events; HRs were 1.53 (95% CI, 1.39–1.68) and 2.17 (95% CI, 1.88–2.50), respectively. Furthermore, a stronger association of the frailty index with CVD was observed in participants aged <55, men, rural community-dwellers, BMI ≥ 25, without hypertension, diabetes or dyslipidemia. A clear nonlinear dose–response pattern between the frailty index and CVD was widely observed (p < 0.001 for nonlinearity), the frailty index was above 0.08, and the hazard ratio per standard deviation was 1.18 (95% CI 1.13–1.25). We observed the association between the frailty index and CVD among middle-aged and elderly adults in China, independent of chronological age and other CVD risk factors. Our findings are important for prevention strategies aimed at reducing the growing burden of CVD in older adults.
Primary Thrombophilia XVII: A Narrative Review of Sticky Platelet Syndrome in México
Authors: Minutti-Zanella Claudia , Villarreal-Martínez Laura , Ruiz-Argüelles Guillermo J.
Published: July 2022

Sticky Platelet Syndrome (SPS) is a disorder characterized by platelet hyperaggregability, diagnosed by studying in vitro platelet aggregation with ADP and epinephrine. It is the second most common cause of thrombophilia in Mexican Mestizos and manifests as an autosomal dominant trait which, combined with other coagulopathies, contributes significantly to the morbidity and mortality of patients with primary thrombophilia. It is easily treatable with antiplatelet drugs; however, the methods for diagnosis are not readily available in all clinical laboratories and the disorder is often overlooked by most clinicians. Herein, we present the results of more than 20 years of Mexican experience with the study of SPS in a Mestizo population.
Impact of Kinesiotherapy and Hydrokinetic Therapy on the Rehabilitation of Balance, Gait and Functional Capacity in Patients with Lower Limb Amputation: A Pilot Study
Authors: Cotrobas-Dascalu Vlad-Theodor , Badau Dana , Stoica Marius , Dreve Adina Andreea , Predescu Corina Michaela Lorenta , Gherghel Carmen Liliana , Bratu Mircea , Raducu Popescu , Oltean Antoanela , Badau Adela
Published: July 2022

The purpose of this pilot study was to identify impact differences in the rehabilitation of balance, gait and functional capacity in patients with lower limb amputation performing hydrokinetic therapy and kinesiotherapy programs during the pre-prosthetic and prosthetic phases. The study included 16 male patients aged 40–60 years with amputated lower limbs for 6 to 12 months, which involved transfemoral amputation (TFA), transtibial amputation (TTA), traumatic and vascular amputation, who were divided into the following two groups: the hydrokinetic therapy (HKT) group and the kinesiotherapy (KT) group, named after the content of the rehabilitation programs that were implemented for 2 weeks in the pre-prosthetic and prosthetic periods. The initial and final evaluation of the participants included the following tests: the Berg Scale and the four square test for the evaluation of the balance; the PodoSmart device for gait assessment; through the walking test over 6 min, we evaluated the functional capacity. The results were processed in SPSS 24. Analysis of the results on balance rehabilitation through the Berg Scale highlighted that the progress related to the mean of the total score was 7.62 points, p = 0.00 for the HKT group and 7.50 points, p = 0.00 for the KT group, while in the four square step test, the mean of progress was 6.125 s, p = 0.00 for the HKT group and 6 s, p = 0.000 for the KT group. The PodoSmart gait analysis revealed that the HKT group showed a progress mean of 4.875%, p = 0.00, for the foot symmetry parameter, which was 1.875% less than the score achieved by the KT group whose symmetry progress mean was 6.75%, p = 0.00, while the average progress mean for the cadence parameter was 2.75 steps/min higher for the KT group than the HKT group. The comparative analysis of the impact of these two programs on the patients’ functional capacity indicated that the score recorded by the KT group was a progress mean of 15.12 m, p = 0.00 better than the HKT group for the travelled distance parameter; the implementation of the hydrokinetic therapy program led to better exercise adaptation for the HKT group compared to the KT group at an average HR (HRavg) with 0.50 BPM, p = 0.00. After analyzing the results, it has been found that hydrokinetic therapy programs have a greater impact on balance rehabilitation and exercise adaptation, while kinesiotherapy programs have a greater impact on gait rehabilitation and functional capacity optimization for the travelled distance parameter.
Transapical Transcatheter Aortic Valve Replacement: A Real-World Early and Mid-Term Outcome of a Third-Level Centre
Authors: Francica Alessandra , Tonelli Filippo , Saran Alberto , Pesarini Gabriele , Vendramin Igor , Tabbì Rocco , Rossetti Cecilia , Luciani Giovanni Battista , Ribichini Flavio L. , Onorati Francesco
Published: July 2022

Background: Transapical transcatheter aortic valve replacement (TA-TAVR) is generally considered to be associated with higher morbidity compared with transfemoral-TAVR. However, TA-TAVR remains a feasible alternative for patients who are unsuitable for TF-TAVR. It has been shown that outcomes after TAVR are linked to the operator’s expertise. Therefore, the purpose of this study is to report short- and mid-term outcomes after TA-TAVR performed by an expert Heart-Team of a third-level centre. Methods: From 2015 to 2022, 154 consecutive patients underwent TA-TAVR. The outcomes were analysed according to the VARC-3 criteria. Kaplan–Meier curves were estimated for major clinical events at mid-term follow-up. Results: The mean age of the population was 79.3 years and the STS risk-score of mortality was 4.2 ± 3.6%. Periprocedural mortality was 1.9%. Acute kidney injury and prolonged ventilation occurred in 1.9%. Incidence of stroke was 0.6%. Pacemaker implantation rate was 1.9%. Freedom from cardiovascular mortality was 75.7%, and 60.2% at 3 and 5 years. Freedom from stroke was 92.3% and 88.9% at 3 and 5 years, respectively; freedom from endocarditis was 94.4% and 90.8% at 3 and 5 years, respectively. Conclusion: TA-TAVR may be considered a safe and effective alternative approach in patients unsuitable for TF-TAVR, especially when performed by a proficient Heart-Team.
Comprehensibility of Contraindications in German, UK and US Summaries of Product Characteristics/Prescribing Information—A Comparative Qualitative and Quantitative Analysis
Authors: Then Melanie I. , Andrikyan Wahram , Fromm Martin F. , Maas Renke
Published: July 2022

Contraindications (CIs) in Summaries of Product Characteristics (SmPCs)/Prescribing Information (PI) that lack clarity may pose a risk to medication safety and increase the risk for adverse drug reactions. We assessed and compared SmPCs/PI from three major drug markets regarding comprehensibility from the prescriber perspective, as well as usability in clinical decision support systems. 158 drugs met the following inclusion criteria: marketed in Germany (DE), United Kingdom (UK) and United States (US) and belonged to the 100 most recently FDA approved and/or 100 most frequently prescribed drugs in either country. In the 474 (3 × 158) SmPCs/PI all expressions for absolute CIs were identified, divided into 3999 stand-alone terms and evaluated according to ‘clarity’ and ‘codability’. The average number of absolute CIs per drug differed drastically between the three markets (DE: 11.7, UK: 9.0, US: 4.6). Expressions were frequently unclear (DE: 27.2% (95% CI 25.2–29.2%), UK: 28.5% (26.2–30.9%), US: 22.6% (19.7–25.8%)). Moreover, 60.9% (58.6–63.1%), 63.6% (61.0–66.0%), and 64.7% (61.2–68.1%) of the expressions were not codable in DE, UK, and US, respectively. Taken together, in three major drug markets, statements regarding CIs in SmPCs/PI substantially differ in frequency and frequently lack clarity and codability which poses an unnecessary obstacle to medication safety.
Far-Infrared Therapy Improves Arteriovenous Fistula Patency and Decreases Plasma Asymmetric Dimethylarginine in Patients with Advanced Diabetic Kidney Disease: A Prospective Randomized Controlled Trial
Authors: Chen Chun-Fan , Lee Chiu-Yang , Chen Fu-An , Yang Chih-Yu , Chen Tz-Heng , Ou Shuo-Ming , Lee Kuo-Hua , Li Ching-Po , Chan Chia-Hao , Lee Pui-Ching , Chen Yung-Tai , Lee Tsung-Lun , Ho Yang , Chen Fan-Yu , Ma Hao-Wei , Chen Jinn-Yang , Tan Ann Charis , Li Szu-Yuan , Lin Chih-Ching
Published: July 2022

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and plays a significant role in the pathogenesis of arteriovenous fistula (AVF) dysfunction. The aim of this study is to evaluate the effect of far-infrared (FIR) therapy on the maturation and patency of newly-created AVFs in patients with advanced diabetic kidney disease (DKD) as well as the concurrent change in plasma ADMA. The study enrolled 144 participants with advanced DKD where 101 patients were randomly allocated to the FIR therapy group (N = 50) and control group (N = 51). Patients receiving FIR therapy had a decreased AVF failure rate within 12 months (16% versus 35.3%; p = 0.027); decreased incremental change of ADMA concentration at the 3rd and 12th month; increased AVF blood flow at the 1st, 3rd, and 12th month; increased 3-month physiologic maturation rate (88% versus 68.6%; p = 0.034); increased 1-year unassisted AVF patency rate (84% versus 64.7%; p = 0.017); and increased clinical AVF maturation rate within 12 months (84% versus 62.7%; p = 0.029) compared to the control group. The study demonstrates that FIR therapy can reduce the incremental changes in plasma ADMA concentration, which may be associated with the improvement of AVF prognosis in patients with advanced DKD.
Study of Machinability in Drilling Operation of Enset–Sisal Hybrid Polyester Composite
Authors: Bekele Abera E. , Lemu Hirpa G. , Jiru Moera G.
Published: July 2022

Due to their light weight, low density, high-specificity strength, and ease of fiber surface treatment, natural-fiber-reinforced composites are recognized as the most suitable materials for interior part applications. Moreover, natural fibers are widely accessible and environmentally friendly. The fabricated parts are assembled predominantly by fastening using drilled holes, which makes drilling operations common machining processes for the composite parts. Damage occurs at the entry and exit surfaces of drilled holes. In this study, hand layup procedures are used to create unidirectional and woven forms of 1:1 ratio enset (false banana)/sisal hybrid polyester composites that have been treated with 5% NaOH. The drill operation was performed using a computer numerical control (CNC) drill machine with high-speed steel twist drill. A Taguchi design tool was used to complete the analysis. The experiments were conducted at different levels of drilling speeds: 600, 1200, and 1800 rpm. Feed rates of 0.1, 0.2, and 0.3 mm/rev and drill bit diameters of 6, 9, and 12 mm were used. These were determined to be the study parameters that influenced the delamination factors (Fd) and surface roughness (SR) of the hybrid composite drilled parts. Delamination occurred at the entry and exit surfaces of the drilled holes, and surface roughness occurred at the inner surface of the sectioned drilled hole. The quality of the drilled holes was compared based on the delamination factor and the surface roughness, as analyzed by the 3D optical surface profiles.
Prediction of Gaps in Automated Tape Laying and Their Influence on Porosity in Consolidated Laminates
Authors: Link Tobias , Rosenberg Philipp , Henning Frank
Published: July 2022

An efficient way to reduce direct operating costs in aerospace applications is to lower the overall weight. In this context, thermoplastic composites offer a high potential for weight reduction. However, their application requires time and cost-optimized process technologies. Thermoplastic tape laying with subsequent out-of-autoclave consolidation represents such a process technology. Typical process chains consist of several automated steps that can influence the component’s quality. Hence, a cross-process approach is applied to identify relevant process parameters. This paper focuses on minimizing the gaps between parallel-placed tapes and thereby reducing their influence on the laminate’s porosity. A geometrical model is developed and validated to predict the maximum gap sizes for a tape-laying process as a function of process accuracy, material accuracy, and process parameters. Based on this, a methodological approach is presented to minimize the influence of gaps on porosity. It is validated using automated tape laying and a novel low-pressure consolidation process. The findings make an important contribution to understanding the development of porosity along the process chain for the manufacture of thermoplastic composites for aerospace applications. It can be shown that the approach enables the prediction of gap sizes and allows to minimize their influence on porosity.