bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Formation Ability and Cell Viability Enhancement of MC3T3-E1 Cells by Ferrostatin-1 a Ferroptosis Inhibitor of Cancer Cells
Authors: Valanezhad Alireza , Odatsu Tetsurou , Abe Shigeaki , Watanabe Ikuya
Published: November 2021

Recently, ferroptosis has gained scientists’ attention as an iron-related regulated necrosis. However, not many reports have investigated the effect of ferroptosis on bone. Therefore, with the present study, we assessed the effect of ferroptosis inhibition using ferrostatin-1 on the MC3T3-E1 pre-osteoblast cell. Cell images, cell viability, alkaline phosphatase activity test, alizarin red staining, and RUNX2 gene expression using real-time PCR were applied to investigate the effects of ferrostatin and erastin on MC3T3-E1 osteoblast cells. Erastin was used as a well-known ferroptosis inducer reagent. Erastin with different concentrations ranging from 0 to 50 µmol/L was used for inducing cell death. The 25 µmol/L erastin led to controllable partial cell death on osteoblast cells. Ferrostatin-1 with 0 to 40 µmol/L was used for cell doping and cell death inhibition effect. Ferrostatin-1 also displayed a recovery effect on the samples, which had already received the partially artificial cell death by erastin. Cell differentiation, alizarin red staining, and RUNX2 gene expression confirmed the promotion of the bone formation ability effect of ferrostatin-1 on osteoblast cells. The objective of this study was to assess ferrostatin-1’s effect on the MC3T3-E1 osteoblast cell line based on its ferroptosis inhibitory property.
Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome
Authors: Bräuninger Hanna , Thottakara Tilo , Schön Jacob , Voss Svenja , Dhople Vishnu , Warnke Svenja , Scherschel Katharina , Schrage Benedikt , Kirchhof Paulus , Blankenberg Stefan , Völker Uwe , Westermann Dirk , Hammer Elke , Lindner Diana
Published: November 2021

Fibroblasts contribute to approximately 20% of the non-cardiomyocytic cells in the heart. They play important roles in the myocardial adaption to stretch, inflammation, and other pathophysiological conditions. Fibroblasts are a major source of extracellular matrix (ECM) proteins whose production is regulated by cytokines, such as TNF-α or TGF-β. The resulting myocardial fibrosis is a hallmark of pathological remodeling in dilated cardiomyopathy (DCM). Therefore, in the present study, the secretome and corresponding transcriptome of human cardiac fibroblasts from patients with DCM was investigated under normal conditions and after TNF-α or TGF-β stimulation. Secreted proteins were quantified via mass spectrometry and expression of genes coding for secreted proteins was analyzed via Affymetrix Transcriptome Profiling. Thus, we provide comprehensive proteome and transcriptome data on the human cardiac fibroblast’s secretome. In the secretome of quiescent fibroblasts, 58% of the protein amount belonged to the ECM fraction. Interestingly, cytokines were responsible for 5% of the total protein amount in the secretome and up to 10% in the corresponding transcriptome. Furthermore, cytokine gene expression and secretion were upregulated upon TNF-α stimulation, while collagen secretion levels were elevated after TGF-β treatment. These results suggest that myocardial fibroblasts contribute to pro-fibrotic and to inflammatory processes in response to extracellular stimuli.
On Placental Toxicology Studies and Cerium Dioxide Nanoparticles
Authors: Deval Gaëlle , Boland Sonja , Fournier Thierry , Ferecatu Ioana
Published: November 2021

The human placenta is a transient organ essential for pregnancy maintenance, fetal development and growth. It has several functions, including that of a selective barrier against pathogens and xenobiotics from maternal blood. However, some pollutants can accumulate in the placenta or pass through with possible repercussions on pregnancy outcomes. Cerium dioxide nanoparticles (CeO2 NPs), also termed nanoceria, are an emerging pollutant whose impact on pregnancy is starting to be defined. CeO2 NPs are already used in different fields for industrial and commercial applications and have even been proposed for some biomedical applications. Since 2010, nanoceria have been subject to priority monitoring by the Organization for Economic Co-operation and Development in order to assess their toxicity. This review aims to summarize the current methods and models used for toxicology studies on the placental barrier, from the basic ones to the very latest, as well as to overview the most recent knowledge of the impact of CeO2 NPs on human health, and more specifically during the sensitive window of pregnancy. Further research is needed to highlight the relationship between environmental exposure to CeO2 and placental dysfunction with its implications for pregnancy outcome.
New Bioactive Fused Triazolothiadiazoles as Bcl-2-Targeted Anticancer Agents
Authors: Hamdy Rania , Jones Arwyn T. , El-Sadek Mohamed , Hamoda Alshaimaa M. , Shakartalla Sarra B. , AL Shareef Zainab M. , Soliman Sameh S. M. , Westwell Andrew D.
Published: November 2021

A series of 3-(6-substituted phenyl-[1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazol-3-yl)-1H-indoles (5a–l) were designed, synthesized and evaluated for anti-apoptotic Bcl-2-inhibitory activity. Synthesis of the target compounds was readily accomplished through a reaction of acyl hydrazide (1) with carbon disulfide in the presence of alcoholic potassium hydroxide to afford the corresponding intermediate potassium thiocarbamate salt (2), which underwent cyclization reaction in the presence of excess hydrazine hydrate to the corresponding triazole thiol (3). Further cyclisation reaction with substituted benzoyl chloride derivatives in the presence of phosphorous oxychloride afforded the final 6-phenyl-indol-3-yl [1,2,4]-triazolo[3,4-b]-[1,3,4]-thiadiazole compounds (5a–l). The novel series showed selective sub-micromolar IC50 growth-inhibitory activity against Bcl-2-expressing human cancer cell lines. The most potent 6-(2,4-dimethoxyphenyl) substituted analogue (5k) showed selective IC50 values of 0.31–0.7 µM against Bcl-2-expressing cell lines without inhibiting the Bcl-2-negative cell line (Jurkat). ELISA binding affinity assay (interruption of Bcl-2-Bim interaction) showed potent binding affinity for (5k) with an IC50 value of 0.32 µM. Moreover, it fulfils drug likeness criteria as a promising drug candidate.
Dextromethorphan Reduces Oxidative Stress and Inhibits Uremic Artery Calcification
Authors: Liu En-Shao , Chen Nai-Ching , Jao Tzu-Ming , Chen Chien-Liang
Published: November 2021

Medial vascular calcification has emerged as a key factor contributing to cardiovascular mortality in patients with chronic kidney disease (CKD). Vascular smooth muscle cells (VSMCs) with osteogenic transdifferentiation play a role in vascular calcification. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors reduce reactive oxygen species (ROS) production and calcified-medium–induced calcification of VSMCs. This study investigates the effects of dextromethorphan (DXM), an NADPH oxidase inhibitor, on vascular calcification. We used in vitro and in vivo studies to evaluate the effect of DXM on artery changes in the presence of hyperphosphatemia. The anti-vascular calcification effect of DXM was tested in adenine-fed Wistar rats. High-phosphate medium induced ROS production and calcification of VSMCs. DXM significantly attenuated the increase in ROS production, the decrease in ATP, and mitochondria membrane potential during the calcified-medium–induced VSMC calcification process (p < 0.05). The protective effect of DXM in calcified-medium–induced VSMC calcification was not further increased by NADPH oxidase inhibitors, indicating that NADPH oxidase mediates the effect of DXM. Furthermore, DXM decreased aortic calcification in Wistar rats with CKD. Our results suggest that treatment with DXM can attenuate vascular oxidative stress and ameliorate vascular calcification.
ELF3 Is a Target That Promotes Therapeutic Efficiency in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Cells via Inhibiting PKCί
Authors: Lee Jeon-Soo , Choi Young Eun , Kim Sunshin , Han Ji-Youn , Goh Sung-Ho
Published: November 2021

(1) Background: Mutations in epidermal growth factor receptor (EGFR) proteins account for many non-small cell lung cancers (NSCLCs), and EGFR tyrosine kinase inhibitors (TKIs) are being used as targeted therapeutics. However, resistance to TKIs continues to increase owing to additional mutations in more than half of the patients receiving EGFR TKI therapy. In addition to targeting new mutations with next-generation therapeutics, it is necessary to find an alternative target to overcome the challenges associated with resistance. (2) Methods: To identify potential alternative targets in patients with NSCLC undergoing targeted therapy, putative targets were identified by transcriptome profiling and validated for their biological and therapeutic effects in vitro and in vivo. (3) Results: ELF3 was found to be differentially expressed in NSCLC, and ELF3 knockdown significantly increased cell death in K-Ras mutant as well as in EGFR L858R/T790M mutation harboring lung cancer cells. We also found that auranofin, an inhibitor of protein kinase C iota (PKCί), a protein upstream of ELF3, effectively induced cell death. (4) Conclusions: Our study suggests that blocking ELF3 is an effective way to induce cell death in NSCLC with K-Ras and EGFR T790M/L858R mutations and thus advocates the use of auranofin as an effective alternative drug to overcome EGFR TKI resistance.
The Role of Ancestral Duplicated Genes in Adaptation to Growth on Lactate, a Non-Fermentable Carbon Source for the Yeast Saccharomyces cerevisiae
Authors: Mattenberger Florian , Fares Mario , Toft Christina , Sabater-Muñoz Beatriz
Published: November 2021

The cell central metabolism has been shaped throughout evolutionary times when facing challenges from the availability of resources. In the budding yeast, Saccharomyces cerevisiae, a set of duplicated genes originating from an ancestral whole-genome and several coetaneous small-scale duplication events drive energy transfer through glucose metabolism as the main carbon source either by fermentation or respiration. These duplicates (~a third of the genome) have been dated back to approximately 100 MY, allowing for enough evolutionary time to diverge in both sequence and function. Gene duplication has been proposed as a molecular mechanism of biological innovation, maintaining balance between mutational robustness and evolvability of the system. However, some questions concerning the molecular mechanisms behind duplicated genes transcriptional plasticity and functional divergence remain unresolved. In this work we challenged S. cerevisiae to the use of lactic acid/lactate as the sole carbon source and performed a small adaptive laboratory evolution to this non-fermentative carbon source, determining phenotypic and transcriptomic changes. We observed growth adaptation to acidic stress, by reduction of growth rate and increase in biomass production, while the transcriptomic response was mainly driven by repression of the whole-genome duplicates, those implied in glycolysis and overexpression of ROS response. The contribution of several duplicated pairs to this carbon source switch and acidic stress is also discussed.
Molecular Mechanisms of Retinal Pigment Epithelium Dysfunction in Age-Related Macular Degeneration
Authors: Kim Jongmin , Lee Yeo Jin , Won Jae Yon
Published: November 2021

The retinal pigment epithelium (RPE), situated upon Bruch’s membrane, plays multiple roles in the ocular system by interacting with photoreceptors and. Therefore, dysfunction of the RPE causes diseases related to vision loss, such as age-related macular degeneration (AMD). Despite AMD being a global cause of blindness, the pathogenesis remains unclear. Understanding the pathogenesis of AMD is the first step for its prevention and treatment. This review summarizes the common pathways of RPE dysfunction and their effect in AMD. Potential treatment strategies for AMD based on targeting the RPE have also been discussed.
The Effect of Oxidative Stress and Memantine-Incorporated Reactive Oxygen Species-Sensitive Nanoparticles on the Expression of N-Methyl-d-aspartate Receptor Subunit 1 in Brain Cancer Cells for Alzheimer’s Disease Application
Authors: Park Jung Sun , Kim Taeyeon , Kim Dohoon , Jeong Young-IL
Published: November 2021

The aim of this study is to fabricate reactive oxygen species (ROS)-sensitive nanoparticles composed of succinyl β-cyclodextrin (bCDsu), memantine and thioketal linkages for application in Alzheimer’s disease, and to investigate the suppression of N-methyl-d-aspartate (NMDA) receptor 1 (NMDAR1) in cells. Thioketal diamine was attached to the carboxyl group of bCDsu to produce thioketal-decorated bCDsu conjugates (bCDsu-thioketal conjugates) and memantine was conjugated with thioketal dicarboxylic acid (memantine-thioketal carboxylic acid conjugates). Memantine-thioketal carboxylic acid conjugates were attached to bCDsu-thioketal conjugates to produce bCDsu-thioketal-memantine (bCDsuMema) conjugates. SH-SY5Y neuroblastoma cells and U87MG cells were used for NMDAR1 protein expression and cellular oxidative stress. Nanoparticles of bCDsuMema conjugates were prepared by means of a dialysis procedure. Nanoparticles of bCDsuMema conjugates had small particle sizes less than 100 nm and their morphology was found to be spherical in transmission electron microscopy observations (TEM). Nanoparticles of bCDsuMema conjugates responded to H2O2 and disintegrated or swelled in aqueous solution. Then, the nanoparticles rapidly released memantine according to the concentration of H2O2. In an in vivo animal imaging study, thioketal-decorated nanoparticles labelled with fluorescent dye such as chlorin e6 (Ce6) showed that the fluorescence intensity was stronger in the brain than in other organs, indicating that bCDsuMema nanoparticles can efficiently target the brain. When cells were exposed to H2O2, the viability of cells was time-dependently decreased. Memantine or bCDsuMema nanoparticles did not practically affect the viability of the cells. Furthermore, a western blot assay showed that the oxidative stress produced in cells using H2O2 increased the expression of NMDAR1 protein in both SH-SY5Y and U87MG cells. Memantine or bCDsuMema nanoparticles efficiently suppressed the NMDAR1 protein, which is deeply associated with Alzheimer’s disease. Fluorescence microscopy also showed that H2O2 treatment induced green fluorescence intensity, which represents intracellular ROS levels. Furthermore, H2O2 treatment increased the red fluorescence intensity, which represents the NMDAR1 protein, i.e., oxidative stress increases the expression of NMDAR1 protein level in both SH-SY5Y and U87MG cells. When memantine or bCDsuMema nanoparticles were treated in cells, the oxidative stress-mediated expression of NMDAR1 protein in cells was significantly decreased, indicating that bCDsuMema nanoparticles have the capacity to suppress NMDAR1 expression in brain cells, which has relevance in terms of applications in Alzheimer’s disease.
Cardiometabolic Alterations in the Interplay of COVID-19 and Diabetes: Current Knowledge and Future Avenues
Authors: Rizvi Ali A. , Janez Andrej , Rizzo Manfredi
Published: November 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) pandemic has raged for almost two years, with few signs of a sustained abatement or remission [...]
Incretins in the Therapy of Diabetic Kidney Disease
Authors: Przezak Agnieszka , Bielka Weronika , Pawlik Andrzej
Published: November 2021

Diabetic kidney disease is a microvascular complication that occurs in patients with diabetes. It is strongly associated with increased risk of kidney replacement therapy and all-cause mortality. Incretins are peptide hormones derived from the gastrointestinal tract, that besides causing enhancement of insulin secretion after oral glucose intake, participate in many other metabolic processes. Antidiabetic drug classes, such as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide receptor agonists, which way of action is based on incretins facility, not only show glucose-lowering properties but also have nephroprotective functions. The aim of this article is to present the latest information about incretin-based therapy and its influence on diabetic kidney disease appearance and progression, point its potential mechanisms of kidney protection and focus on future therapeutic possibilities bound with these two antidiabetic drug classes.
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1
Authors: Palicelli Andrea , Croci Stefania , Bisagni Alessandra , Zanetti Eleonora , De Biase Dario , Melli Beatrice , Sanguedolce Francesca , Ragazzi Moira , Zanelli Magda , Chaux Alcides , Cañete-Portillo Sofia , Bonasoni Maria Paola , Soriano Alessandra , Ascani Stefano , Zizzo Maurizio , Castro Ruiz Carolina , De Leo Antonio , Giordano Guido , Landriscina Matteo , Carrieri Giuseppe , Cormio Luigi , Berney Daniel M. , Gandhi Jatin , Nicoli Davide , Farnetti Enrico , Santandrea Giacomo , Bonacini Martina
Published: November 2021

Epigenetic alterations (including DNA methylation or miRNAs) influence oncogene/oncosuppressor gene expression without changing the DNA sequence. Prostate cancer (PC) displays a complex genetic and epigenetic regulation of cell-growth pathways and tumor progression. We performed a systematic literature review (following PRISMA guidelines) focused on the epigenetic regulation of PD-L1 expression in PC. In PC cell lines, CpG island methylation of the CD274 promoter negatively regulated PD-L1 expression. Histone modifiers also influence the PD-L1 transcription rate: the deletion or silencing of the histone modifiers MLL3/MML1 can positively regulate PD-L1 expression. Epigenetic drugs (EDs) may be promising in reprogramming tumor cells, reversing epigenetic modifications, and cancer immune evasion. EDs promoting a chromatin-inactive transcriptional state (such as bromodomain or p300/CBP inhibitors) downregulated PD-L1, while EDs favoring a chromatin-active state (i.e., histone deacetylase inhibitors) increased PD-L1 expression. miRNAs can regulate PD-L1 at a post-transcriptional level. miR-195/miR-16 were negatively associated with PD-L1 expression and positively correlated to longer biochemical recurrence-free survival; they also enhanced the radiotherapy efficacy in PC cell lines. miR-197 and miR-200a-c positively correlated to PD-L1 mRNA levels and inversely correlated to the methylation of PD-L1 promoter in a large series. miR-570, miR-34a and miR-513 may also be involved in epigenetic regulation.
Soft Surface Nanostructure with Semi-Free Polyionic Components for Sustainable Antimicrobial Plastic
Authors: Chan Shook Pui , Lim Diane S. W. , Armugam Arunmozhiarasi , Yi Guangshun , Zhang Yugen
Published: November 2021

Surface antimicrobial materials are of interest as they can combat the critical threat of microbial contamination without contributing to issues of environmental contamination and the development drug resistance. Most nanostructured surfaces are prepared by post fabrication modifications and actively release antimicrobial agents. These properties limit the potential applications of nanostructured materials on flexible surfaces. Here, we report on an easily synthesized plastic material with inherent antimicrobial activity, demonstrating excellent microbicidal properties against common bacteria and fungus. The plastic material did not release antimicrobial components as they were anchored to the polymer chains via strong covalent bonds. Time-kill kinetics studies have shown that bactericidal effects take place when bacteria come into contact with a material for a prolonged period, resulting in the deformation and rupture of bacteria cells. A scanning probe microscopy analysis revealed soft nanostructures on the submicron scale, for which the formation is thought to occur via surface phase separation. These soft nanostructures allow for polyionic antimicrobial components to be present on the surface, where they freely interact with and kill microbes. Overall, the new green and sustainable plastic is easily synthesized and demonstrates inherent and long-lasting activity without toxic chemical leaching.
Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus
Authors: Ma Yujia , Zhou Zechen , Li Xiaoyi , Yan Zeyu , Ding Kexin , Chen Dafang
Published: November 2021

We aim to compare the relative heritability contributed by variants of behavior-related environmental phenotypes and elucidate the role of these factors in the conundrum of “missing heritability” of type 2 diabetes. Methods: We used Linkage-Disequilibrium Adjusted Kinships (LDAK) and LDAK-Thin models to calculate the relative heritability of each variant and compare the relative heritability for each phenotype. Biological analysis was carried out for the phenotype whose variants made a significant contribution. Potential hub genes were prioritized based on topological parameters of the protein-protein interaction network. We included 16 behavior-related phenotypes and 2607 valid variants. In the LDAK model, we found the variants of alcohol consumption and caffeine intake were identified as contributing higher relative heritability than that of the random variants. Compared with the relative expected heritability contributed by the variants associated with type 2 diabetes, the relative expected heritability contributed by the variants associated with these two phenotypes was higher. In the LDAK-Thin model, the relative heritability of variants of 11 phenotypes was statistically higher than random variants. Biological function analysis showed the same distributions among type 2 diabetes and alcohol consumption. We eventually screened out 31 hub genes interacting intensively, four of which were validated and showed the upregulated expression pattern in blood samples seen in type 2 diabetes cases. Conclusion: We found that alcohol consumption contributed higher relative heritability. Hub genes may influence the onset of type 2 diabetes by a mediating effect or a pleiotropic effect. Our results provide new insight to reveal the role of behavior-related factors in the conundrum of “missing heritability” of type 2 diabetes.
NGAL as a Potential Target in Tumor Microenvironment
Authors: Crescenzi Elvira , Leonardi Antonio , Pacifico Francesco
Published: November 2021

The signaling network between cancer and stromal cells plays a crucial role in tumor microenvironment. The fate of tumor progression mainly depends on the huge amount of information that these cell populations exchange from the onset of neoplastic transformation. Interfering with such signaling has been producing exciting results in cancer therapy: just think of anti-PD-1/anti-PD-L1/anti-CTLA-4 antibodies that, acting as immune checkpoint inhibitors, interrupt the inhibitory signaling exerted by cancer cells on immune cells or the CAR-T technology that fosters the reactivation of anti-tumoral immunity in a restricted group of leukemias and lymphomas. Nevertheless, many types of cancers, in particular solid tumors, are still refractory to these treatments, so the identification of novel molecular targets in tumor secretome would benefit from implementation of current anti-cancer therapeutical strategies. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a secreted protein abundantly expressed in the secretome of various human tumors. It represents a promising target for the multiple roles that are played inside cancer and stromal cells, and also overall in their cross-talk. The review focuses on the different roles of NGAL in tumor microenvironment and in cancer senescence-associated secretory phenotype (SASP), highlighting the most crucial functions that could be eventually targetable in cancer therapy.
Partial Fractional Fourier Transform (PFrFT)-MIMO-OFDM for Known Underwater Acoustic Communication Channels
Authors: Chen Yixin , Clemente Carmine , Soraghan John J.
Published: November 2021

Communication over doubly selective channels (both time and frequency selective) suffers from significant intercarrier interference (ICI). This problem is severe in underwater acoustic communications. In this paper, a novel partial fractional (PFrFT)-MIMO-OFDM system is proposed and implemented to further mitigate ICI. A new iterative band minimum mean square error (BMMSE) weight combining based on LDLH factorization is used in a scenario of perfect knowledge of channel information. The proposed method is extended from SISO-OFDM configuration to MIMO-OFDM. Simulation results demonstrate that the proposed PFrFT-LDLH outperforms the other methods in the SISO-OFDM scenario and that its performance can be improved in MIMO-OFDM scenarios.
Usage and Temporal Patterns of Public Bicycle Systems: Comparison among Points of Interest
Authors: Yan Xingchen , Gao Liangpeng , Chen Jun , Ye Xiaofei
Published: November 2021

The public bicycle system is an important component of “mobility as a service” and has become increasingly popular in recent years. To provide a better understanding of the station activity and driving mechanisms of public bicycle systems, the study mainly compares the usage and temporal characteristics of public bicycles in the vicinity of the most common commuting-related points of interest and land use. It applies the peak hour factor, distribution fitting, and K-means clustering analysis on station-based data and performs the public bicycles usage and operation comparison among different points of interest and land use. The following results are acquired: (1) the demand type for universities and hospitals in peaks is return-oriented when that of middle schools is hire-oriented; (2) bike hire and return at metro stations and hospitals are frequent, while only the rental at malls is; (3) compared to middle schools and subway stations with the shortest bike usage duration, malls have the longest duration, valued at 18.08 min; and (4) medical and transportation land, with the most obvious morning return peak and the most concentrated usage in a whole day, respectively, both present a lag relation between bike rental and return. In rental-return similarity, the commercial and office lands present the highest level.
The First Described Nymphs and Detailed Imagoes of the Species Thalerosphyrus cingulatus Navás Revealing a New Mayfly Genus from Eastern China (Ephemeroptera: Heptageniidae, Ecdyonurinae)
Authors: Lei Zhiming , Gong Dewen , Zhang Wei , Zhou Changfa
Published: November 2021

The nymph and detailed imaginal morphology of the Chinese mayfly Thalerosphyrus cingulatus have not been reported since it was named by Navás in 1933. Here based on newly collected nymphal and associated imaginal materials of this species from eastern China, we find both nymphs and adults have several extraordinary characters. In adults, forewings have less crossveins in costal and subcostal sections, others crossveins arranged into five regular rows; tibiae and tarsi of midlegs and hindlegs subequal in length; male compound eyes widely separated and penes simple and fused. The nymphs have greatly extended lateral pronotum, round supracoxal spurs and extended dorsal lamellae of gills, especially those of the gills VII; maxillae have two independent distal dentisetae. These combined characters represent a new generic taxon. Therefore, Regulaneuria Zhou, gen. nov. is established here to include the species Regulaneuria cingulata (Navás, 1933) comb. nov. The forewing venation of the species R. cingulata is unique in the family Heptageniidae but similar to some counterparts of Leptophlebiidae and Baetidae.
Reproductive Potential Impacts Body Maintenance Parameters and Global DNA Methylation in Honeybee Workers (Apis mellifera L.)
Authors: Paleolog Jerzy , Kuszewska Karolina , Woyciechowski Michał , Strachecka Aneta
Published: November 2021

The widely accepted hypothesis in life history evolution about the trade-off between fecundity and longevity is not confirmed by long-living and highly fecund queens in eusocial insects. The fact that the queens and facultatively sterile workers usually arise from genetically identical eggs but differ in DNA methylation makes them a good model for studies on senescence, eusocial evolution, and epigenetics. Therefore, honeybees seem to be especially useful here because of long living rebel-workers (RW) with high reproductive potential recently described. Longevity, ovariole number, nosema tolerance, and global DNA methylation have been assayed in normal workers (NW) versus RW in hives and cages. RW always lived longer than NW and unexpectedly extended longevity of NW when they were together, similarly as the presence of a queen did. RW lived longer despite the fact that they had higher Nosema spore load; surprisingly they became infected more easily but tolerated the infection better. Global DNA methylation increased with age, being lower in RW than in NW. Therefore, RW are queen-like considering global DNA methylation and the link between fecundity, longevity, and body maintenance. Presented features of RW expands possibilities of the use of honeybees as a model for studies on senescence, nosemosis, eusocial evolution, and epigenetics.
Host Plants of the Immature Stages of the Invasive Longan Lanternfly, Pyrops candelaria (L.) (Hemiptera, Fulgoridae) in Taiwan
Authors: Hsu Meng-Hao , Yang Yueh-Lin , Wu Meng-Ling , Wang Liang-Jong
Published: November 2021

The longan lanternfly, Pyrops candelaria (L.), has been invading mainland Taiwan since 2018, but the distribution of the species has been confined to northern Taiwan until now. The manual removal of the adult insects from the longan is still the main control strategy because of the uncertainty around other key host plants, especially for eggs and nymphs. In this study, large numbers of eggs and nymphs were found on Triadica sebifera (L.) Small and Acacia confusa Merr. The occurrence of immature individuals on Triadica sebifera increased with developmental stage from eggs to the last instar from May to July 2021. On 30 April, the first egg mass was recorded. More egg masses were recorded in May, and some could be found in July. In May, only two younger instars were detected. Third and fourth instars began to appear from June, while the fifth instar was mainly recorded from July onwards. The results of this study provide great strategic value for decision-makers to allow for effective control of the target tree species. For now, we proved that longan and pomelo trees, preferred by adults, are not the key hosts for the immature stages of this insect, because few immature individuals were found on them. Therefore, we suggest that the existence of Triadica sebifera should be considered when analyzing possible spreading areas of this invasive lanternfly in Taiwan.
Aulacaspis yasumatsui Invasion Reduced Cycas micronesica Microstrobilus Size and Pollinator Brood Site Competence
Authors: Marler Thomas E. , Terry L. Irene
Published: November 2021

Aulacaspis yasumatsui Takagi invaded Guam in 2003, and the influence on survival and demography of the host Cycas micronesica K.D. Hill population has been well-studied. To more fully understand how A. yasumatsui has threatened the host cycad species, we determined the microstrobilus size and number of pollinators per microstrobilus from 2001 to 2021. The microstrobilus height and diameter were measured directly, and the volume was calculated. Microstrobili were 58 cm in height, 13 cm in diameter, and 4740 cm3 in volume prior to direct A. yasumatsui infestations. Microstrobili decreased in size immediately after direct infestations by A. yasumatsui, and then began to slowly increase in size until 2021. For example, the volume was 24% of pre-invasion volume in 2007, and was 57% of pre-invasion volume in 2021. Microstrobili were harvested; then, the number of pollinator pupae were counted after an incubation period. Pollinator pupae counts per microstrobilus declined to 66% of pre-invasion levels by 2007 and have remained similarly constrained through 2021. Our results revealed that A. yasumatsui damage to the host C. micronesica population is not limited to attrition of the extant plant population, but also includes a loss in male reproductive effort and the risk of coextinction of the insular pollinator.
The Fly Homologue of MFSD11 Is Possibly Linked to Nutrient Homeostasis and Has a Potential Role in Locomotion: A First Characterization of the Atypical Solute Carrier CG18549 in Drosophila Melanogaster
Authors: Ceder Mikaela M. , Lindberg Frida A. , Perland Emelie , Williams Michael J. , Fredriksson Robert
Published: November 2021

Cellular transport and function are dependent on substrate influx and efflux of various compounds. In humans, the largest superfamily of transporters is the SoLute Carriers (SLCs). Many transporters are orphans and little to nothing is known about their expression and/or function, yet they have been assigned to a cluster called atypical SLCs. One of these atypical SLCs is MFSD11. Here we present a first in-depth characterization of the MFSD11, CG18549. By gene expression and behavior analysis on ubiquitous and brain-specific knockdown flies. CG18549 knockdown flies were found to have altered adipokinetic hormone and adipokinteic hormone receptor expression as well as reduced vesicular monoamine transporter expression; to exhibit an altered locomotor behavior, and to have an altered reaction to stress stimuli. Furthermore, the gene expression of CG18549 in the brain was visualized and abundant expression in both the larvae and adult brain was observed, a result that is coherent with the FlyAtlas Anatomy microarray. The exact mechanism behind the observed behaviors is not fully understood, but this study provides new insights into the expression and function of CG18549. Clearly, these results provide a strong example as to why it is vital to fully characterize orphan transporters and through that gain knowledge about the body during normal condition and disease.
The Mitochondrial Genomes of 18 New Pleurosticti (Coleoptera: Scarabaeidae) Exhibit a Novel trnQ-NCR-trnI-trnM Gene Rearrangement and Clarify Phylogenetic Relationships of Subfamilies within Scarabaeidae
Authors: Ayivi Sam Pedro Galilee , Tong Yao , Storey Kenneth B. , Yu Dan-Na , Zhang Jia-Yong
Published: November 2021

The availability of next-generation sequencing (NGS) in recent years has facilitated a revolution in the availability of mitochondrial (mt) genome sequences. The mt genome is a powerful tool for comparative studies and resolving the phylogenetic relationships among insect lineages. The mt genomes of phytophagous scarabs of the subfamilies Cetoniinae and Dynastinae were under-represented in GenBank. Previous research found that the subfamily Rutelinae was recovered as a paraphyletic group because the few representatives of the subfamily Dynastinae clustered into Rutelinae, but the subfamily position of Dynastinae was still unclear. In the present study, we sequenced 18 mt genomes from Dynastinae and Cetoniinae using next-generation sequencing (NGS) to re-assess the phylogenetic relationships within Scarabaeidae. All sequenced mt genomes contained 37 sets of genes (13 protein-coding genes, 22 tRNAs, and two ribosomal RNAs), with one long control region, but the gene order was not the same between Cetoniinae and Dynastinae species. All mt genomes of Dynastinae species showed the same gene rearrangement of trnQ-NCR-trnI-trnM, whereas all mt genomes of Cetoniinae species showed the ancestral insect gene order of trnI-trnQ-trnM. Phylogenetic analyses (IQ-tree and MrBayes) were conducted using 13 protein-coding genes based on nucleotide and amino acid datasets. In the ML and BI trees, we recovered the monophyly of Rutelinae, Cetoniinae, Dynastinae, and Sericinae, and the non-monophyly of Melolonthinae. Cetoniinae was shown to be a sister clade to (Dynastinae + Rutelinae).
Combined Effect of Different Flower Stem Features on the Visiting Frequency of the Generalist Ant Lasius niger: An Experimental Study
Authors: Gorb Elena V. , Gorb Stanislav N.
Published: November 2021

In order to understand the effects of the morphology and surface texture of flower stems in Smyrnium rotundifolium on the visiting frequency of generalist ants, we conducted experiments with Lasius niger ants running on dry wooden sticks mimicking different types of stems: (1) intact (grooved) sticks; (2) sticks painted with slaked (hydrated) lime (calcium carbonate coverage) imitating plant epicuticular wax coverage; (3) intact sticks with smooth polyester plate-shaped cuffs imitating upper leaves; and (4) intact sticks bearing cuffs painted with slaked lime. Ants were attracted by the sweet sugar syrup droplets placed on a stick tip, and the number of ants visiting the drops was counted. Our data showed significant differences in the visiting frequencies between the different types of stem-mimicking samples. The number of recorded ants progressively decreased in the following order of samples: intact sticks—painted sticks—sticks with intact cuffs—sticks with painted cuffs. These results clearly demonstrated that micro/nanoscopic surface coverages and macroscopic physical barriers, especially if combined, have a negative impact on the attractiveness of stems to ants. This study provides further evidence for the hypothesis that having a diversity of plant stems in the field, generalist ants prefer substrates where their locomotion is less hindered by obstacles and/or surface slipperiness.
The Impact of Bedbug (Cimex spp.) Bites on Self-Rated Health and Average Hours of Sleep per Day: A Cross-Sectional Study among Hong Kong Bedbug Victims
Authors: Fung Eddy Hin Chung , Chiu Siu Wai , Lam Hon-Ming , Chung Roger Yat-Nork , Wong Samuel Yeung Shan , Chan Siu Ming , Dong Dong , Wong Hung
Published: November 2021

Bedbugs (Cimex spp.) are a nuisance public-health pest that is on the rise globally, particularly in crowded cities such as Hong Kong. To investigate the health impacts of bedbug infestations among bedbug victims, online surveys were distributed in Hong Kong between June 2019 to July 2020. Data on sociodemographics, self-rated health, average hours of sleep per day, and details of bedbug infestation were collected. Bivariate and multivariable analysis were performed using logistic regression. The survey identified 422 bedbug victims; among them, 223 (52.9%) experienced ≥five bites in the past month; most bites occurred on the arms (n = 202, 47.8%) and legs (n = 215, 51%), and the most common reaction to bites were itchiness (n = 322, 76.3%), redness, and swelling of the skin (n = 246, 58.1%), and difficulties sleeping or restlessness (n = 125, 29.6%). Bites usually occurred during sleep (n = 230, 54.5%). For impact on daily life in the past month, most bedbug victims reported moderate to severe impact on mental and emotional health (n = 223, 52.8%) and sleeping quality (n = 239, 56.6%). Lower self-rated health (aOR < 1) was independently associated with impact on physical appearance (p = 0.008), spending money on medication or doctor consultation (p = 0.04), number of bites in the past month (p = 0.023), and irregular time of bites (p = 0.003). Lower average hours of sleep per day (aOR < 1) was independently associated with impact on mental and emotional health (p = 0.016). This study brings attention to the neglected issue of bedbug infestation by considering bedbugs as an infectious agent instead of a vector and providing empirical evidence describing its health impacts.
Imaging of Gastric Carcinomatosis
Authors: Saiz Martínez Raquel , Dromain Clarisse , Vietti Violi Naik
Published: November 2021

Diagnosing the absence or presence of peritoneal carcinomatosis in patients with gastric cancer, including its extent and distribution, is an essential step in patients’ therapeutic management. Such diagnosis still remains a radiological challenge. In this article, we review the strengths and weaknesses of the different imaging techniques for the diagnosis of peritoneal carcinomatosis of gastric origin as well as the techniques’ imaging features. We also discuss the assessment of response to treatment and present recommendations for the follow-up of patients with complete surgical resection according to the presence of risk factors of recurrence, as well as discussing future directions for imaging improvement.
Bioinformatics Analysis Identifies Precision Treatment with Paclitaxel for Hepatocellular Carcinoma Patients Harboring Mutant TP53 or Wild-Type CTNNB1 Gene
Authors: Lin Jiunn-Chang , Liu Tsang-Pai , Andriani Vivin , Athoillah Muhammad , Wang Chih-Yang , Yang Pei-Ming
Published: November 2021

Hepatocellular carcinoma (HCC) is an aggressive and chemoresistant cancer type. The development of novel therapeutic strategies is still urgently needed. Personalized or precision medicine is a new trend in cancer therapy, which treats cancer patients with specific genetic alterations. In this study, a gene signature was identified from the transcriptome of HCC patients, which was correlated with the patients’ poorer prognoses. This gene signature is functionally related to mitotic cell cycle regulation, and its higher or lower expression is linked to the mutation in tumor protein p53 (TP53) or catenin beta 1 (CTNNB1), respectively. Gene–drug association analysis indicated that the taxanes, such as the clinically approved anticancer drug paclitaxel, are potential drugs targeting this mitotic gene signature. Accordingly, HCC cell lines harboring mutant TP53 or wild-type CTNNB1 genes are more sensitive to paclitaxel treatment. Therefore, our results imply that HCC patients with mutant TP53 or wild-type CTNNB1 genes may benefit from the paclitaxel therapy.
Beyond the Knife—Reviewing the Interplay of Psychosocial Factors and Peripheral Nerve Lesions
Authors: Heinzel Johannes C. , Dadun Lucy F. , Prahm Cosima , Winter Natalie , Bressler Michael , Lauer Henrik , Ritter Jana , Daigeler Adrien , Kolbenschlag Jonas
Published: November 2021

Peripheral nerve injuries are a common clinical problem. They not only affect the physical capabilities of the injured person due to loss of motor or sensory function but also have a significant impact on psychosocial aspects of life. The aim of this work is to review the interplay of psychosocial factors and peripheral nerve lesions. By reviewing the published literature, we identified several factors to be heavily influenced by peripheral nerve lesions. In addition to psychological factors like pain, depression, catastrophizing and stress, social factors like employment status and worker’s compensation status could be identified to be influenced by peripheral nerve lesions as well as serving as predictors of functional outcome themselves, respectively. This work sheds a light not only on the impact of peripheral nerve lesions on psychosocial aspects of life, but also on the prognostic values of these factors of functional outcome. Interdisciplinary, individualized treatment of patients is required to identify patient at risk for adverse outcomes and provide them with emotional support when adapting to their new life situation.
Morphology of the Myocardium after Experimental Bone Tissue Trauma and the Use of Extracellular Vesicles Derived from Mesenchymal Multipotent Stromal Cells
Authors: Maiborodin Igor , Klinnikova Marina , Kuzkin Sergey , Maiborodina Vitalina , Krasil’nikov Sergey , Pichigina Aleksandra , Lushnikova Elena
Published: November 2021

The effect of extracellular vesicles (EVs) of various origins on the heart structures in the time of health and disease has been well studied. At the same time, data on the distribution of EVs throughout the body after introduction into the tissues and the possibility of the influence of these EVs on organs distant from the injection site are practically absent. It is also necessary to note a certain inconsistency in the results of various researchers: from articles on the direct absorption of EVs derived from mesenchymal multipotent stromal cells (MSC EVs) by cardiomyocytes to the data that the heart is inherently immune to drug delivery mediated by nanoparticles. In this regard, the morphological changes in the myocardium of outbred rabbits of both sexes weighing 3–4 kg were studied at various times after experimental trauma of the bone tissue in the proximal condyle of the tibia (PCT) and the use of MSC EVs. As a result of modeling the PCT defect, rabbits develop myocardial edema in the heart muscle by the 3rd day, their lymphatic vessels expand, and then, on the 7th day, the blood vessels become dilated. In the myocardium, the relative and absolute contents of neutrophils, erythrocytes, and macrophages increase, but the percentage of lymphocytes decreases. By day 10, almost all of these changes return to their initial values. The detected transformations of the myocardium are most likely due to the ingress of detritus with the blood flow from the PCT. The use of MSC EVs to influence the regeneration of damaged tissue of PCT promotes earlier dilatation of the blood vessels of the heart with pronounced diapedesis of erythrocytes or even hemorrhages, prolongation of edema, the formation of blood clots in vessels with obliteration of their lumen, sclerotic transformation of vascular walls and paravascular tissues. In the myocardium, the number density of neutrophils, the percentage of lymphocytes, and neutrophils become smaller, with a simultaneous increase in the relative numbers of erythrocytes and macrophages, and changes in the content of macrophages remained until the end of the observation—up to 10 days after the surgery. The discovered effect of MSC EVs is most likely associated with the suppression of the activity of the inflammatory process in the PCT area, which, in turn, was caused by a longer ingress of detritus with blood flow into the myocardium. The absence of statistically significant differences between changes in the myocardium of the left and right ventricles may indicate that both detritus from the surgical site and MSC EVs affect the heart spreading through the coronary artery system.
Exploratory and Exploitative Internationalization: Effects of Social Capital Antecedents and Fit Moderators of Innovation Consequence
Authors: Wu Hang , Qu Yiying
Published: November 2021

Implementing international strategy is essential to enhance corporate innovation and achieve sustainable development. Existing research has theoretically illustrated the concept and importance of carrying out both exploratory and exploitative internationalization, yet our understanding of the antecedents and consequences of both activities remains unclear. Based on the data of Chinese international manufacturing firms, this paper examines the differential effects of business, government and knowledge network capital on exploratory and exploitative internationalization, and probes into how organizational, strategic, and environmental factors moderate the innovation effectiveness of exploratory and exploitative internationalization. Results indicate that business network capital has the same positive impact on exploratory and exploitative internationalization; government network capital influences the implementation of exploratory internationalization, whereas knowledge network capital influences the execution of exploitative internationalization. Furthermore, our findings reveal that, to maximize innovation performance, pursuing exploratory internationalization is more beneficial for firms with older age, firms entering into countries with low host–home country similarity, and operating in a more dynamic international environment. By contrast, pursuing exploitative internationalization is more effective for younger firms, firms entering into countries with high host–home country similarity, and in more stable international environment. Theoretical and managerial implications are discussed.