bluuebunny/crossref_metadata_2025 huggingface dataset:
9-O-Terpenyl-Substituted Berberrubine Derivatives Suppress Tumor Migration and Increase Anti-Human Non-Small-Cell Lung Cancer Activity
Authors: Chang Jia-Ming , Wu Jin-Yi , Chen Shu-Hsin , Chao Wen-Ying , Chuang Hsiang-Hao , Kam Kam-Hong , Zhao Pei-Wen , Li Yi-Zhen , Yen Yu-Pei , Lee Ying-Ray
Published: September 2021

Lung cancer is one of the most common cancers and the leading cause of death in humans worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases and is often diagnosed at a late stage. Among patients with NSCLC, 50% die within 1 year after diagnosis. Even with clinical intervention, the 5-year survival rate is only approximately 20%. Therefore, the development of an advanced therapeutic strategy or novel agent is urgently required for treating NSCLC. Berberine exerts therapeutic activity toward NSCLC; therefore, its activity as an antitumor agent needs to be explored further. In this study, three terpenylated-bromide derivatives of berberrubine were synthesized and their anti-NSCLC activities were evaluated. Each derivative had higher anti-NSCLCs activity than berberrubine and berberine. Among them, 9-O-gernylberberrubine bromide (B4) and 9-O-farnesylberberrubine bromide (B5) showed greater growth inhibition, cell-cycle regulation, in vitro tumorigenesis suppression, and tumor migration reduction. In addition, some degree of apoptosis and autophagic flux blocking was noted in the cells under B4 and B5 treatments. Our study demonstrates that the berberrubine derivatives, B4 and B5, exhibit impressive anti-NSCLC activities and have potential for use as chemotherapeutic agents against NSCLC.
Identification and Characterization of Short Crown Root 8, a Temperature-Sensitive Mutant Associated with Crown Root Development in Rice
Authors: Hu Peng , Wen Yi , Wang Yueying , Wu Hao , Wang Junge , Wu Kaixiong , Chai Bingze , Zhu Lixin , Zhang Guangheng , Gao Zhenyu , Ren Deyong , Zhu Li , Guo Longbiao , Zeng Dali , Xu Jing , Yan Song , Qian Qian , Rao Yuchun , Hu Jiang
Published: September 2021

Crown roots are essential for plants to obtain water and nutrients, perceive environmental changes, and synthesize plant hormones. In this study, we identified and characterized short crown root 8 (scr8), which exhibited a defective phenotype of crown root and vegetative development. Temperature treatment showed that scr8 was sensitive to temperature and that the mutant phenotypes were rescued when grown under low temperature condition (20 °C). Histological and EdU staining analysis showed that the crown root formation was hampered and that the root meristem activity was decreased in scr8. With map-based cloning strategy, the SCR8 gene was fine-mapped to an interval of 126.4 kb on chromosome 8. Sequencing analysis revealed that the sequence variations were only found in LOC_Os08g14850, which encodes a CC-NBS-LRR protein. Expression and inoculation test analysis showed that the expression level of LOC_Os08g14850 was significantly decreased under low temperature (20 °C) and that the resistance to Xanthomonas oryzae pv. Oryzae (Xoo) was enhanced in scr8. These results indicated that LOC_Os08g14850 may be the candidate of SCR8 and that its mutation activated the plant defense response, resulting in a crown root growth defect.
Tumor Necrosis Factor-Alpha Exacerbates Viral Entry in SARS-CoV2-Infected iPSC-Derived Cardiomyocytes
Authors: Lee Chiu-Yang , Huang Chih-Heng , Rastegari Elham , Rengganaten Vimalan , Liu Ping-Cheng , Tsai Ping-Hsing , Chin Yuan-Fan , Wu Jing-Rong , Chiou Shih-Hwa , Teng Yuan-Chi , Lee Chih-Wei , Liang Yanwen , Chen An-Yu , Hsu Shu-Chen , Hung Yi-Jen , Sun Jun-Ren , Chien Chian-Shiu , Chien Yueh
Published: September 2021

The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.
Angelman Syndrome and Angelman-like Syndromes Share the Same Calcium-Related Gene Signatures
Authors: Panov Julia , Kaphzan Hanoch
Published: September 2021

Angelman-like syndromes are a group of neurodevelopmental disorders that entail clinical presentation similar to Angelman Syndrome (AS). In our previous study, we showed that calcium signaling is disrupted in AS, and we identified calcium-target and calcium-regulating gene signatures that are able to differentiate between AS and their controls in different models. In the herein study, we evaluated these sets of calcium-target and calcium-regulating genes as signatures of AS-like and non-AS-like syndromes. We collected a number of RNA-seq datasets of various AS-like and non-AS-like syndromes and performed Principle Component Analysis (PCA) separately on the two sets of signature genes to visualize the distribution of samples on the PC1–PC2 plane. In addition to the evaluation of calcium signature genes, we performed differential gene expression analyses to identify calcium-related genes dysregulated in each of the studied syndromes. These analyses showed that the calcium-target and calcium-regulating signatures differentiate well between AS-like syndromes and their controls. However, in spite of the fact that many of the non-AS-like syndromes have multiple differentially expressed calcium-related genes, the calcium signatures were not efficient classifiers for non-AS-like neurodevelopmental disorders. These results show that features based on clinical presentation are reflected in signatures derived from bioinformatics analyses and suggest the use of bioinformatics as a tool for classification.
Points of View on the Tools for Genome/Gene Editing
Authors: Chuang Chin-Kai , Lin Wei-Ming
Published: September 2021

Theoretically, a DNA sequence-specific recognition protein that can distinguish a DNA sequence equal to or more than 16 bp could be unique to mammalian genomes. Long-sequence-specific nucleases, such as naturally occurring Homing Endonucleases and artificially engineered ZFN, TALEN, and Cas9-sgRNA, have been developed and widely applied in genome editing. In contrast to other counterparts, which recognize DNA target sites by the protein moieties themselves, Cas9 uses a single-guide RNA (sgRNA) as a template for DNA target recognition. Due to the simplicity in designing and synthesizing a sgRNA for a target site, Cas9-sgRNA has become the most current tool for genome editing. Moreover, the RNA-guided DNA recognition activity of Cas9-sgRNA is independent of both of the nuclease activities of it on the complementary strand by the HNH domain and the non-complementary strand by the RuvC domain, and HNH nuclease activity null mutant (H840A) and RuvC nuclease activity null mutant (D10A) were identified. In accompaniment with the sgRNA, Cas9, Cas9(D10A), Cas9(H840A), and Cas9(D10A, H840A) can be used to achieve double strand breakage, complementary strand breakage, non-complementary strand breakage, and no breakage on-target site, respectively. Based on such unique characteristics, many engineered enzyme activities, such as DNA methylation, histone methylation, histone acetylation, cytidine deamination, adenine deamination, and primer-directed mutation, could be introduced within or around the target site. In order to prevent off-targeting by the lasting expression of Cas9 derivatives, a lot of transient expression methods, including the direct delivery of Cas9-sgRNA riboprotein, were developed. The issue of biosafety is indispensable in in vivo applications; Cas9-sgRNA packaged into virus-like particles or extracellular vesicles have been designed and some in vivo therapeutic trials have been reported.
Procoagulant Extracellular Vesicles Alter Trophoblast Differentiation in Mice by a Thrombo-Inflammatory Mechanism
Authors: Markmeyer Paulina , Lochmann Franziska , Singh Kunal Kumar , Gupta Anubhuti , Younis Ruaa , Shahzad Khurrum , Biemann Ronald , Huebner Hanna , Ruebner Matthias , Isermann Berend , Kohli Shrey
Published: September 2021

Procoagulant extracellular vesicles (EV) and platelet activation have been associated with gestational vascular complications. EV-induced platelet-mediated placental inflammasome activation has been shown to cause preeclampsia-like symptoms in mice. However, the effect of EV-mediated placental thrombo-inflammation on trophoblast differentiation remains unknown. Here, we identify that the EV-induced thrombo-inflammatory pathway modulates trophoblast morphology and differentiation. EVs and platelets reduce syncytiotrophoblast differentiation while increasing giant trophoblast and spongiotrophoblast including the glycogen-rich cells. These effects are platelet-dependent and mediated by the NLRP3 inflammasome. In humans, inflammasome activation was negatively correlated with trophoblast differentiation marker GCM1 and positively correlated with blood pressure. These data identify a crucial role of EV-induced placental thrombo-inflammation on altering trophoblast differentiation and suggest platelet activation or inflammasome activation as a therapeutic target in order to achieve successful placentation.
Interplay of Immunometabolism and Epithelial–Mesenchymal Transition in the Tumor Microenvironment
Authors: Chou Ming-Yu , Yang Muh-Hwa
Published: September 2021

Epithelial–mesenchymal transition (EMT) and metabolic reprogramming in cancer cells are the key hallmarks of tumor metastasis. Since the relationship between the two has been well studied, researchers have gained increasing interest in the interplay of cancer cell EMT and immune metabolic changes. Whether the mutual influences between them could provide novel explanations for immune surveillance during metastasis is worth understanding. Here, we review the role of immunometabolism in the regulatory loop between tumor-infiltrating immune cells and EMT. We also discuss the challenges and perspectives of targeting immunometabolism in cancer treatment.
In Silico Study, Physicochemical, and In Vitro Lipase Inhibitory Activity of α,β-Amyrenone Inclusion Complexes with Cyclodextrins
Authors: Oliveira Luana Carvalho de , Menezes Danielle Lima Bezerra de , Silva Valéria Costa da , Lourenço Estela Mariana Guimarães , Miranda Paulo Henrique Santana , Silva Márcia de Jesus Amazonas da , Lima Emerson Silva , Júnior Valdir Florêncio da Veiga , Marreto Ricardo Neves , Converti Attilio , Barbosa Euzébio Guimaraes , Lima Ádley Antonini Neves de
Published: September 2021

α,β-amyrenone (ABAME) is a triterpene derivative with many biological activities; however, its potential pharmacological use is hindered by its low solubility in water. In this context, the present work aimed to develop inclusion complexes (ICs) of ABAME with γ- and β-cyclodextrins (CD), which were systematically characterized through molecular modeling studies as well as FTIR, XRD, DSC, TGA, and SEM analyses. In vitro analyses of lipase activity were performed to evaluate possible anti-obesity properties. Molecular modeling studies indicated that the CD:ABAME ICs prepared at a 2:1 molar ratio would be more stable to the complexation process than those prepared at a 1:1 molar ratio. The physicochemical characterization showed strong evidence that corroborates with the in silico results, and the formation of ICs with CD was capable of inducing changes in ABAME physicochemical properties. ICs was shown to be a stronger inhibitor of lipase activity than Orlistat and to potentiate the inhibitory effects of ABAME on porcine pancreatic enzymes. In conclusion, a new pharmaceutical preparation with potentially improved physicochemical characteristics and inhibitory activity toward lipases was developed in this study, which could prove to be a promising ingredient for future formulations.
Stearoyl-CoA Desaturase (SCD) Induces Cardiac Dysfunction with Cardiac Lipid Overload and Angiotensin II AT1 Receptor Protein Up-Regulation
Authors: Abd Alla Joshua , Jamous Yahya F. , Quitterer Ursula
Published: September 2021

Heart failure is a major cause of death worldwide with insufficient treatment options. In the search for pathomechanisms, we found up-regulation of an enzyme, stearoyl-CoA desaturase 1 (Scd1), in different experimental models of heart failure induced by advanced atherosclerosis, chronic pressure overload, and/or volume overload. Because the pathophysiological role of Scd1/SCD in heart failure is not clear, we investigated the impact of cardiac SCD upregulation through the generation of C57BL/6-Tg(MHCSCD)Sjaa mice with myocardium-specific expression of SCD. Echocardiographic examination showed that 4.9-fold-increased SCD levels triggered cardiac hypertrophy and symptoms of heart failure at an age of eight months. Tg-SCD mice had a significantly reduced left ventricular cardiac ejection fraction of 25.7 ± 2.9% compared to 54.3 ± 4.5% of non-transgenic B6 control mice. Whole-genome gene expression profiling identified up-regulated heart-failure-related genes such as resistin, adiponectin, and fatty acid synthase, and type 1 and 3 collagens. Tg-SCD mice were characterized by cardiac lipid accumulation with 1.6- and 1.7-fold-increased cardiac contents of saturated lipids, palmitate, and stearate, respectively. In contrast, unsaturated lipids were not changed. Together with saturated lipids, apoptosis-enhancing p53 protein contents were elevated. Imaging by autoradiography revealed that the heart-failure-promoting and membrane-spanning angiotensin II AT1 receptor protein of Tg-SCD hearts was significantly up-regulated. In transfected HEK cells, the expression of SCD increased the number of cell-surface angiotensin II AT1 receptor binding sites. In addition, increased AT1 receptor protein levels were detected by fluorescence spectroscopy of fluorescent protein-labeled AT1 receptor-Cerulean. Taken together, we found that SCD promotes cardiac dysfunction with overload of cardiotoxic saturated lipids and up-regulation of the heart-failure-promoting AT1 receptor protein.
Renal Ischemia/Reperfusion Early Induces Myostatin and PCSK9 Expression in Rat Kidneys and HK-2 Cells
Authors: Barisione Chiara , Verzola Daniela , Garibaldi Silvano , Ferrari Pier Francesco , Garibotto Giacomo , Ameri Pietro , Pane Bianca , Spinella Giovanni , Pratesi Giovanni , Palombo Domenico
Published: September 2021

During visceral interventions, the transient clampage of supraceliac aorta causes ischemia/reperfusion (I/R) in kidneys, sometime resulting in acute renal failure; preclinical studies identified redox imbalance as the main driver of I/R injury. However, in humans, the metabolic/inflammatory responses seem to prevail on oxidative stress. We investigated myostatin (Mstn) and proprotein convertase subtilisin/kexin type 9 (PCSK9), proatherogenic mediators, during renal I/R. Compared to sham-operated animals, the kidneys of rats who had experienced ischemia (30 min) had higher Mstn and PCSK9 expression after 4 h of reperfusion. After 24 h, they displayed tubular necrosis, increased nitrotyrosine positivity, and nuclear peroxisome proliferator-activated receptor gamma coactivator-1alpha relocation, markers of oxidative stress and mitochondria imbalance. Mstn immunopositivity was increased in tubuli, while PCSK9 immunosignal was depleted; systemically, PCSK9 was higher in plasma from I/R rats. In HK-2 cells, both ischemia and reperfusion enhanced reactive oxygen species production and mitochondrial dysfunction. H2O2 upregulated Mstn and PCSK9 mRNA after 1 and 3.5 h, respectively. Accordingly, ischemia early induced Mstn and PCSK9 mRNA; during reperfusion Mstn was augmented and PCSK9 decreased. Mstn treatment early increased PCSK9 expression (within 8 h), to diminish over time; finally, Mstn silencing restrained ischemia-induced PCSK9. Our study demonstrates that renal I/R enhances Mstn and PCSK9 expression and that Mstn induces PCSK9, suggesting them as therapeutic targets for vascular protection during visceral surgery.
Populus euphratica Apyrases Increase Drought Tolerance by Modulating Stomatal Aperture in Arabidopsis
Authors: Zhang Yanli , Sun Yuanling , Liu Xiaojing , Deng Jiayin , Yao Jun , Zhang Yinan , Deng Shurong , Zhang Huilong , Zhao Nan , Li Jinke , Zhou Xiaoyang , Zhao Rui , Chen Shaoliang
Published: September 2021

Stomatal regulation is crucial to reduce water consumption under drought conditions. Extracellular ATP (eATP) serves as a signaling agent in stomatal regulation; however, it is less known whether the eATP mediation of stomatal aperture is linked to apyrases (APYs), the principal enzymes that control the concentration of eATP. To clarify the role of APYs in stomatal control, PeAPY1 and PeAPY2 were isolated from Populus euphratica and transferred into Arabidopsis. Compared with the wild-type Arabidopsis and loss-of-function mutants (Atapy1 and Atapy2), PeAPY1- and PeAPY2-transgenic plants decreased stomatal aperture under mannitol treatment (200 mM, 2 h) and reduced water loss during air exposure (90 min). The role of apyrase in stomatal regulation resulted from its control in eATP-regulated stomatal movements and increased stomatal sensitivity to ABA. The bi-phasic dose-responses to applied nucleotides, i.e., the low ATP (0.3–1.0 mM)-promoted opening and high ATP (>2.0 mM)-promoted closure, were both restricted by P. euphratica apyrases. It is noteworthy that eATP at a low concentration (0.3 mM) counteracted ABA action in the regulation of stomatal aperture, while overexpression of PeAPY1 or PeAPY2 effectively diminished eATP promotion in opening, and consequently enhanced ABA action in closure. We postulate a speculative model of apyrase signaling in eATP- and ABA-regulated stomatal movements under drought.
The Disruption of the Endothelial Barrier Contributes to Acute Lung Injury Induced by Coxsackievirus A2 Infection in Mice
Authors: Ji Wangquan , Hu Qiang , Zhang Mengdi , Zhang Chuwen , Chen Chen , Yan Yujie , Zhang Xue , Chen Shuaiyin , Tao Ling , Zhang Weiguo , Jin Yuefei , Duan Guangcai
Published: September 2021

Sporadic occurrences and outbreaks of hand, foot, and mouth disease (HFMD) caused by Coxsackievirus A2 (CVA2) have frequently reported worldwide recently, which pose a great challenge to public health. Epidemiological studies have suggested that the main cause of death in critical patients is pulmonary edema. However, the pathogenesis of this underlying comorbidity remains unclear. In this study, we utilized the 5-day-old BALB/c mouse model of lethal CVA2 infection to evaluate lung damage. We found that the permeability of lung microvascular was significantly increased after CVA2 infection. We also observed the direct infection and apoptosis of lung endothelial cells as well as the destruction of tight junctions between endothelial cells. CVA2 infection led to the degradation of tight junction proteins (e.g., ZO-1, claudin-5, and occludin). The gene transcription levels of von Willebrand factor (vWF), endothelin (ET), thrombomodulin (THBD), granular membrane protein 140 (GMP140), and intercellular cell adhesion molecule-1 (ICAM-1) related to endothelial dysfunction were all significantly increased. Additionally, CVA2 infection induced the increased expression of inflammatory cytokines (IL-6, IL-1β, and MCP-1) and the activation of p38 mitogen-activated protein kinase (MAPK). In conclusion, the disruption of the endothelial barrier contributes to acute lung injury induced by CVA2 infection; targeting p38-MAPK signaling may provide a therapeutic approach for pulmonary edema in critical infections of HFMD.
Analysis of SINE Families B2, Dip, and Ves with Special Reference to Polyadenylation Signals and Transcription Terminators
Authors: Vassetzky Nikita S. , Borodulina Olga R. , Ustyantsev Ilia G. , Kosushkin Sergei A. , Kramerov Dmitri A.
Published: September 2021

Short Interspersed Elements (SINEs) are eukaryotic non-autonomous retrotransposons transcribed by RNA polymerase III (pol III). The 3′-terminus of many mammalian SINEs has a polyadenylation signal (AATAAA), pol III transcription terminator, and A-rich tail. The RNAs of such SINEs can be polyadenylated, which is unique for pol III transcripts. Here, B2 (mice and related rodents), Dip (jerboas), and Ves (vespertilionid bats) SINE families were thoroughly studied. They were divided into subfamilies reliably distinguished by relatively long indels. The age of SINE subfamilies can be estimated, which allows us to reconstruct their evolution. The youngest and most active variants of SINE subfamilies were given special attention. The shortest pol III transcription terminators are TCTTT (B2), TATTT (Ves and Dip), and the rarer TTTT. The last nucleotide of the terminator is often not transcribed; accordingly, the truncated terminator of its descendant becomes nonfunctional. The incidence of complete transcription of the TCTTT terminator is twice higher compared to TTTT and thus functional terminators are more likely preserved in daughter SINE copies. Young copies have long poly(A) tails; however, they gradually shorten in host generations. Unexpectedly, the tail shortening below A10 increases the incidence of terminator elongation by Ts thus restoring its efficiency. This process can be critical for the maintenance of SINE activity in the genome.
The Mitigators of Ad Irritation and Avoidance of YouTube Skippable In-Stream Ads: An Empirical Study in Taiwan
Authors: Lin Hota Chia-Sheng , Lee Neil Chueh-An , Lu Yi-Chieh
Published: September 2021

On YouTube, skippable in-stream advertisements (ads) are critical income for both YouTube and content creators. However, ads inevitably irritate viewers, and as a result, they tend to avoid ads. Thus, this study attempts to identify potential mitigators—source attractiveness and reciprocal altruism—of ad irritation and avoidance in the context of YouTube skippable in-stream ads. Using an online survey (n = 512) in Taiwan, the proposed model is examined by a partial least squares structural equation modeling analysis. The findings show that while ad irritation has a positive effect on ad avoidance, reciprocal altruism can significantly reduce both ad irritation and avoidance. However, source attractiveness fails to mitigate ad irritation and avoidance. Theoretical and managerial implications of these findings are discussed, and several solutions for reducing ad irritation and avoidance are provided.
Effects of Selection to Diflubenzuron and Bacillus thuringiensis Var. Israelensis on the Overwintering Successes of Aedes albopictus (Diptera: Culicidae)
Authors: Ioannou Charalampos S. , Hadjichristodoulou Christos , Mouchtouri Varvara A. , Papadopoulos Nikos T.
Published: September 2021

Aedes albopictus is an invasive mosquito species responsible for local transmission of chikungunya and dengue viruses in Europe. In the absence of available treatments, insecticides-based control remains one of the most important viable strategies to prevent emerging problems. Diflubenzuron (DFB) and Bacillus thuringiensis var. israelensis (Bti) are among the most commonly used larvicides for Ae. albopictus control with consequent concerns for the potential development of resistance. Studies on the resistance emergence in Ae. albopictus and its persistence in the wild to both DFB and Bti are essential for the efficient and sustainable planning of the control programmes. In this context, larvae from a recently laboratory established population were subjected to increasing selective pressure for nine successive generations using both DFB and Bti. The resistance levels and the overwintering success of the selected populations relative to control (colonies that received no selection) were determined. Results revealed an 8.5- and 1.6-fold increase on the resistance levels following selection with DFB and Bti, respectively. The selection process to both larvicides had no apparent impacts on the overwintering capability relative to control, suggesting the successful persistence of the selected individuals in the wild on an annual base.
Multiple Mating of Aphelinus asychis Enhance the Number of Female Progeny but Shorten the Longevity
Authors: Wang Shengyin , Wang Libo , Liu Jiawen , Zhang Dayu , Liu Tongxian
Published: September 2021

The Aphelinus asychis female adult is an important arrhenotocous parthenogenesis parasitoid of Myzus persicae, and its reproductive mode is beneficial for the population continuation of A. asychis by way of multiple mating and backcross. To explore the effect of mating on the population fitness and control efficiency of A. asychis, its mating frequency and backcross were observed under laboratory conditions. The results showed that most matings in A. asychis involved four distinct stages: courtship, pre-copulatory, copulation, and post-copulatory behaviours. Only the duration of courtship increased significantly with an increase in copulation frequency for females, and the courtship duration of A. asychis females mated with different males were significantly shorter than those mated with the same male at the same mating times, which suggested that A. asychis females might prefer to mate with different males to enrich the genotype of their offspring. The total number of mummified aphids and the female and male longevity decreased significantly with an increase in mating frequency. On the contrary, female progenies increased significantly with an increase of mating frequency, suggesting that sperm limitation might occur in females when they only mated once. These results imply that females might prefer to receive more sperm by mating multiple times in their life span. In addition, we found that the intrinsic rate of increase (r) of A. asychis of the control group (0.2858 d−1) was significantly greater than that in the backcross treatment (0.2687 d−1). The finite killing rate (θ) of A. asychis of the control group was similar to that in the backcross treatment, which showed that this treatment had a negligible negative effect on the control efficiency of A. asychis. In conclusion, the results showed that multiple mating increased the number and proportion of A. asychis female progenies but shortened the longevity of female and male adults, while the negative effect of backcross on the control efficiency of A. asychis was negligible.
Bone Marrow Ts65Dn Trisomy-Induced Changes in Platelet Functionality and Lymphocytopenia Do Not Impact Atherosclerosis Susceptibility in Mice
Authors: Korporaal Suzanne J. A. , van der Sluis Ronald J. , Van Eck Miranda , Hoekstra Menno
Published: September 2021

The genetic disorder Down syndrome is associated with a decreased susceptibility for atherosclerotic cardiovascular disease. Hematological and immune abnormalities occur frequently in Down syndrome patients. We evaluated, in a preclinical setting, the impact of a Down syndrome-like hematological/immune phenotype on atherosclerosis susceptibility. Hereto, hypercholesterolemic low-density lipoprotein receptor knockout mice were transplanted with bone marrow from either a trisomic Ts65Dn mouse or euploid wild-type control and subsequently fed a Western-type diet to induce the development of atherosclerotic lesions. T and B cell concentrations were markedly reduced in blood of Ts65Dn bone marrow recipients (p < 0.001). Expression levels of the pro-atherogenic scavenger receptor CD36 were respectively 37% and 59% lower (p < 0.001) in trisomic monocytes and macrophages. However, these combined effects did not translate into an altered atherosclerosis susceptibility. Notably, blood platelet numbers were elevated in Ts65Dn bone marrow recipients (+57%; p < 0.001), which was paralleled by higher platelet GPVI protein expression (+35%; p < 0.001) and an enhanced collagen-induced platelet activation (p < 0.001). In conclusion, we have shown that providing mice with a Down syndrome-like hematological profile does not change the susceptibility to atherosclerosis. Furthermore, our studies have uncovered a novel effect of the trisomy on platelet functionality that may be relevant in human clinical settings.
Comprehensive Comparison of the Effect of Inotropes on Cardiorenal Syndrome in Patients with Advanced Heart Failure: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Chen Wei-Cheng , Lin Meng-Hsuan , Chen Chieh-Lung , Lai Yi-Ching , Chen Chih-Yu , Lin Yu-Chao , Hung Chin-Chuan
Published: September 2021

Prevention of cardiorenal syndrome through treatment with inotropic agents remains challenging. This network meta-analysis evaluated the safety and renoprotective effects of inotropes on patients with advanced heart failure (HF) using a frequentist random-effects model. A systematic database search was performed until 31 January 2021, and a total of 37 trials were included. Inconsistency, publication bias, and subgroup analyses were conducted. The levosimendan group exhibited significantly decreased mortality compared with the control (odds ratio (OR): 0.62; 95% confidence interval (CI): 0.46–0.84), milrinone (OR: 0.50; 95% CI: 0.30–0.84), and dobutamine (OR: 0.75; 95% CI: 0.57–0.97) groups. In terms of renal protection, levosimendan (standardized mean difference (SMD): 1.67; 95% CI: 1.17–2.18) and dobutamine (SMD: 1.49; 95% CI: 0.87–2.12) more favorably improved the glomerular filtration rate (GFR) than the control treatment did, but they did not significantly reduce the incidence of acute kidney injury. Furthermore, levosimendan had the highest P-score, indicating that it most effectively reduced mortality and improved renal function (e.g., GFR and serum creatinine level), even in patients with renal insufficiency. In conclusion, levosimendan is a safe alternative for protecting renal function on cardiorenal syndrome in patients with advanced HF.
Comparative Analysis of Stroke Patients with and without Sequelae: A Cross-Sectional Analysis Using the KOREA National Health and Nutrition Examination Survey (2016–2019)
Authors: Oh Chi Woong , Lee Sang Hyuk , Nam Taek Min , Jang Ji Hwan , Kim Young Zoon , Kim Kyu Hong , Kim Do-Hyung , Ko Nak Gyeong , Kim Seung Hwan
Published: September 2021

(1) Background: We aimed to evaluate the association between sociodemographic factors and mental health problems and the sequelae of stroke in South Korea by analyzing the annual Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2016 to 2019. (2) Methods: Data were obtained from 32,379 participants who participated in the KNHANES (2016–2019). A total of 567 participants diagnosed with stroke were included in this study. Patients were divided into two groups based on the presence of sequelae: (a) stroke patients with sequelae (n = 227, 40.0%) and (b) stroke patients without sequelae (n = 340, 60.0%). (3) Results: Compared to stroke patients without sequelae, those with sequelae were significantly associated with sex (male, 61.2% vs. 47.6%, p = 0.002), household income (lower half, 78.9% vs. 67.4%, p = 0.005), owning a house (60.4% vs. 68.5%, p = 0.048), marital status (unmarried, 7.05% vs. 1.76%, p < 0.001), depression (13.2% vs. 7.35%, p = 0.045), suicidal ideation (6.17% vs. 3.24%, p = 0.010), and suicide attempts (2.64% vs. 0.88%, p = 0.012). (4) Conclusions: Our study showed that poor sociodemographic factors and mental health problems were significantly associated with sequelae from stroke. Clinical physicians should therefore carefully screen for depression and suicidality in stroke patients with sequelae, especially in those with poor sociodemographic factors.
Alpha-1 Acid Glycoprotein and Podocin mRNA as Novel Biomarkers for Early Glomerular Injury in Obese Children
Authors: Medyńska Anna , Chrzanowska Joanna , Kościelska-Kasprzak Katarzyna , Bartoszek Dorota , Żabińska Marcelina , Zwolińska Danuta
Published: September 2021

Introduction: Obesity, which is a serious problem in children, has a negative impact on many organs, including kidneys, and obesity-related glomerulopathy (ORG) is an increasingly common cause of ESKD (end-stage kidney disease) in adults. Early-detected and -treated glomerular lesions are reversible, so it is important to find a useful marker of early damage. The study aimed to evaluate the albumin-to-creatinine ratio (ACR), urinary alpha-1-acid glycoprotein (α1-AGP), and mRNA of podocyte-specific proteins as indicators of glomerular injury and their relationship with the degree of obesity and metabolic disorders. Materials and Methods: A total of 125 obese children and 33 healthy peers were enrolled. Patients were divided into two groups, depending on SDS BMI values. ACR, α1-AGP, mRNA expression of nephrin, synaptopodin, podocin, and C2AP protein in urine sediment were measured. Results: ACR values did not differ between groups and were within the normal range. α1-AGP and mRNA expression were significantly higher in obese children compared with controls. mRNA expression of the remaining podocyte proteins was similar in both groups. No significant differences concerning all examined parameters were found depending on the degree of obesity. There was a positive significant correlation between α1-AGP and ACR. Conclusions: Increased α1-AGP before the onset of albuminuria suggests its usefulness as a biomarker of early glomerular damage in obese children. An increased podocin mRNA expression also indicates podocyte damage and may be linked to ORG development. The lack of increase in expression of other podocyte proteins suggests that podocin mRNA may be a more specific and sensitive biomarker. The degree of obesity has no impact on the tested parameters, but further studies are needed to confirm it.
Laser Butt Welding of Thin Ti6Al4V Sheets: Effects of Welding Parameters
Authors: Omoniyi Peter , Mahamood Rasheedat , Arthur Nana , Pityana Sisa , Skhosane Samuel , Okamoto Yasuhiro , Shinonaga Togo , Maina Martin , Jen Tien-Chien , Akinlabi Esther
Published: September 2021

Titanium and its alloys, particularly Ti6Al4V, which is widely utilized in the marine and aerospace industries, have played a vital role in different manufacturing industries. An efficient and cost-effective way of joining this metal is by laser welding. The effect of laser power and welding speed on the tensile, microhardness, and microstructure of Ti6Al4V alloy is investigated in this paper. Results show that the microhardness is highest at the fusion zone and reduces towards the base metal. The microstructure at the fusion zone shows a transformed needle-like lamellar α phase, with a martensitic α’ phase observed within the heat affected zone. Results of tensile tests show an improved tensile strength compared to the base metal.
Machine Learning Classification Algorithms for Predicting Karenia brevis Blooms on the West Florida Shelf
Authors: Li Marvin F. , Glibert Patricia M. , Lyubchich Vyacheslav
Published: September 2021

Harmful algal blooms (HABs), events that kill fish, impact human health in multiple ways, and contaminate water supplies, have increased in frequency, magnitude, and impacts in numerous marine and freshwaters around the world. Blooms of the toxic dinoflagellate Karenia brevis have resulted in thousands of tons of dead fish, deaths to many other marine organisms, numerous respiratory-related hospitalizations, and tens to hundreds of millions of dollars in economic damage along the West Florida coast in recent years. Four types of machine learning algorithms, Support Vector Machine (SVM), Relevance Vector Machine (RVM), Naïve Bayes classifier (NB), and Artificial Neural Network (ANN), were developed and compared in their ability to predict these blooms. Comparing the 21 year monitoring dataset of K. brevis abundance, RVM and NB were found to have better skills in bloom prediction than the other two approaches. The importance of upwelling-favorable northerly winds in increasing K. brevis probability, and of onshore westerly winds in preventing blooms from dispersing offshore, were quantified using RVM, and all models were used to explore the importance of large river flows and the nutrients they supply in regulating blooms. These models provide new tools for management of these devastating algal blooms.
Abundant Genetic Diversity and Extensive Differentiation among Geographic Populations of the Citrus Pathogen Diaporthe citri in Southern China
Authors: Xiong Tao , Zeng Yating , Wang Wen , Li Pudong , Gai Yunpeng , Jiao Chen , Zhu Zengrong , Xu Jianping , Li Hongye
Published: September 2021

The fungal pathogen Diaporthe citri is a major cause of diseases in citrus. One common disease is melanose, responsible for large economic losses to the citrus fruit industry. However, very little is known about the epidemiology and genetic structure of D. citri. In this study, we analyzed 339 isolates from leaves and fruits with melanose symptoms from five provinces in southern China at 14 polymorphic simple sequence repeat (SSR) loci and the mating type idiomorphs. The genetic variations were analyzed at three levels with separate samples: among provinces, among orchards within one county, and among trees within one orchard. The five provincial populations from Fujian, Zhejiang, Jiangxi, Hunan, and Guizhou were significantly differentiated, while limited differences were found among orchards from the same county or among trees from the same orchard. STRUCTURE analysis detected two genetic clusters in the total sample, with different provincial subpopulations showing different frequencies of isolates in these two clusters. Mantel analysis showed significant positive correlation between genetic and geographic distances, consistent with geographic separation as a significant barrier to gene flow in D. citri in China. High levels of genetic diversity were found within individual subpopulations at all three spatial scales of analyses. Interestingly, most subpopulations at all three spatial scales had the two mating types in similar frequencies and with alleles at the 14 SSR loci not significantly different from linkage equilibrium. Indeed, strains with different mating types and different multilocus genotypes were frequently isolated from the same leaves and fruits. The results indicate that sexual reproduction plays an important role in natural populations of D. citri in southern China and that its ascospores likely represent an important contributor to citrus disease.
Diagnostic Allele-Specific PCR for the Identification of Candida auris Clades
Authors: Carolus Hans , Jacobs Stef , Lobo Romero Celia , Deparis Quinten , Cuomo Christina A. , Meis Jacques F. , Van Dijck Patrick
Published: September 2021

Candida auris is an opportunistic pathogenic yeast that emerged worldwide during the past decade. This fungal pathogen poses a significant public health threat due to common multidrug resistance (MDR), alarming hospital outbreaks, and frequent misidentification. Genomic analyses have identified five distinct clades that are linked to five geographic areas of origin and characterized by differences in several phenotypic traits such as virulence and drug resistance. Typing of C. auris strains and the identification of clades can be a powerful tool in molecular epidemiology and might be of clinical importance by estimating outbreak and MDR potential. As C. auris has caused global outbreaks, including in low-income countries, typing C. auris strains quickly and inexpensively is highly valuable. We report five allele-specific polymerase chain reaction (AS-PCR) assays for the identification of C. auris and each of the five described clades of C. auris based on conserved mutations in the internal transcribed spacer (ITS) rDNA region and a clade-specific gene cluster. This PCR method provides a fast, cheap, sequencing-free diagnostic tool for the identification of C. auris, C. auris clades, and potentially, the discovery of new clades.
Simulated Microgravity Promotes Horizontal Gene Transfer of Antimicrobial Resistance Genes between Bacterial Genera in the Absence of Antibiotic Selective Pressure
Authors: Urbaniak Camilla , Grams Tristan , Mason Christopher E. , Venkateswaran Kasthuri
Published: September 2021

Bacteria are able to adapt and survive in harsh and changing environments through many mechanisms, with one of them being horizontal gene transfer (HGT). This process is one of the leading culprits in the spread of antimicrobial resistance (AMR) within bacterial communities and could pose a significant health threat to astronauts if they fell ill, especially on long-duration space missions. In order to better understand the degree of HGT activity that could occur in space, biosafety level-2, donor and recipient bacteria were co-cultured under simulated microgravity (SMG) on Earth with concomitant 1G controls. Two AMR genes, blaOXA-500 and ISAba1, from the donor Acinetobacter pittii, were tracked in four recipient strains of Staphylococcus aureus (which did not harbor those genes) using polymerase chain reaction. All four S. aureus strains that were co-cultured with A. pittii under SMG had a significantly higher number of isolates that were now blaOXA-500- and ISAba1-positive compared to growth at 1G. The acquisition of these genes by the recipient induced a phenotypic change, as these isolates were now resistant to oxacillin, which they were previously susceptible to. This is a novel study, presenting, for the first time, increased HGT activity under SMG and the potential impact of the space environment in promoting increased gene dissemination within bacterial communities.
Enhanced Microglia Activation and Glioma Tumor Progression by Inflammagen Priming in Mice with Tumor Necrosis Factor Receptor Type 2 Deficiency
Authors: Liao Chih-Kai , Fang Kuan-Min , Huang Hui-Ting , Chang Wen-Ruei , Chuang Chao-Chi , Tzeng Shun-Fen
Published: September 2021

Despite the fact that accumulation of microglia, the resident macrophages of the central nervous system (CNS) are the main feature of glioblastoma, the role of microglia in the progression of glioma is still arguable. Based on the correlation of inflammation with tumor progression, in this study, we attempt to determine if peripheral inflammation aggravates glioma expansion and the activation of microglia associated with the tumor. Experimental animals were administered intraperitoneally by inflammagen lipopolysaccharide (LPS) for 7 days (LPS priming) before intracerebral implantation of glioma cells. Moreover, a reduced level of tumor necrosis factor receptor type 2 (TNFR2) that is restricted to immune cells, neurons, and microglia has been found in patients with glioblastoma through the clinic analysis of monocyte receptor expression. Thus, in addition to wildtype (WT) mice, heterogeneous TNFR2 gene deficiency (TNFR2+/−) mice and homogeneous TNFR2 gene knockout (TNFR2−/−) mice were used in this study. The results show that peripheral challenge by LPS, Iba1+- or CD11b+-microglia increase in numbers in the cortex and hippocampus of TNFR2−/− mice, when compared to WT or TNFR2+/− mice. We further conducted the intracerebral implantation of rodent glioma cells into the animals and found that the volumes of tumors formed by rat C6 glioma cells or mouse GL261 glioma cells were significantly larger in the cortex of TNFR2−/− mice when compared to that measured in LPS-primed WT or LPS-primed TNFR2+/− mice. Ki67+-cells were exclusively clustered in the tumor of LPS-primed TNFR2−/− mice. Microglia were also extensively accumulated in the tumor formed in LPS-primed TNFR2−/− mice. Accordingly, our findings demonstrate that aggravation of microglia activation by peripheral inflammatory challenge and a loss of TNFR2 function might lead to the promotion of glioma growth.
Influence of Ultrasonication of Functionalized Carbon Nanotubes on the Rheology, Hydration, and Compressive Strength of Portland Cement Pastes
Authors: Silvestro Laura , Ruviaro Artur , Lima Geannina , de Matos Paulo , de Azevedo Afonso R. G. , Monteiro Sérgio Neves , Gleize Philippe
Published: September 2021

The functionalization process usually increases the localized defects of carbon nanotubes (CNT). Thus, the ultrasonication parameters used for dispersing non-functionalized CNT should be carefully evaluated to verify if they are adequate in dispersing functionalized CNT. Although ultrasonication is widely used for non-functionalized CNT, the effect of this dispersing process of functionalized CNT has not been thoroughly investigated. Thus, this work investigated the effect of ultrasonication on functionalized CNT + superplasticizer (SP) aqueous dispersions by ultraviolet-visible (UV-Vis) spectroscopy, dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR). Furthermore, Portland cement pastes with additions of 0.05% and 0.1% CNT by cement weight and ultrasonication amplitudes of 0%, 50% and 80% were evaluated through rheometry, isothermal calorimetry, compressive strength at 1, 7 and 28 days, X-ray diffraction (XRD), and thermogravimetric analysis (TGA). FTIR results from CNT + SP dispersions indicated that ultrasonication may negatively affect SP molecules and CNT graphene structure. The increase in CNT content and amplitude of ultrasonication gradually increased the static and dynamic yield stress of paste but did not significantly affect its hydration kinetics. Compressive strength results indicated that the optimum CNT content was 0.05% by cement weight, which increased the strength of composite by up to 15.8% compared with the plain paste. CNT ultrasonication neither increases the degree of hydration of cement nor the mechanical performance of composite when compared with mixes containing unsonicated CNT. Overall, ultrasonication of functionalized CNT is not efficient in improving the fresh and hardened performance of cementitious composites.
Synergistic Enhanced Thermal Conductivity and Dielectric Constant of Epoxy Composites with Mesoporous Silica Coated Carbon Nanotube and Boron Nitride Nanosheet
Authors: Hao Yutao , Li Qihan , Pang Xianhai , Gong Bohong , Wei Chengmei , Ren Junwen
Published: September 2021

Dielectric materials with high thermal conductivity and outstanding dielectric properties are highly desirable for advanced electronics. However, simultaneous integration of those superior properties for a material remains a daunting challenge. Here, a multifunctional epoxy composite is fulfilled by incorporation of boron nitride nanosheets (BNNSs) and mesoporous silica coated multi-walled carbon nanotubes (MWCNTs@mSiO2). Owing to the effective establishment of continuous thermal conductive network, the obtained BNNSs/MWCNTs@mSiO2/epoxy composite exhibits a high thermal conductivity of 0.68 W m−1 K−1, which is 187% higher than that of epoxy matrix. In addition, the introducing of mesoporous silica dielectric layer can screen charge movement to shut off leakage current between MWCNTs, which imparts BNNSs/MWCNTs@mSiO2/epoxy composite with high dielectric constant (8.10) and low dielectric loss (<0.01) simultaneously. It is believed that the BNNSs/MWCNTs@mSiO2/epoxy composites with admirable features have potential applications in modern electronics.