bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative Role of 14-3-3ε in Sleep Regulation
Authors: Wei Yu , Du Juan , Zhao Zhangwu
Published: September 2021

Sleep is a crucial factor for health and survival in all animals. In this study, we found by proteomic analysis that some cancer related proteins were impacted by the circadian clock. The 14-3-3ε protein, expression of which is activated by the circadian transcription factor Clock, regulates adult sleep of Drosophila independent of circadian rhythm. Detailed analysis of the sleep regulatory mechanism shows that 14-3-3ε directly targets the Ultrabithorax (Ubx) gene to activate transcription of the pigment dispersing factor (PDF). The dopamine receptor (Dop1R1) and the octopamine receptor (Oamb), are also involved in the 14-3-3ε pathway, which in 14-3-3ε mutant flies causes increases in the dopR1 and OAMB, while downregulation of the DopR1 and Oamb can restore the sleep phenotype caused by the 14-3-3ε mutation. In conclusion, 14-3-3ε is necessary for sleep regulation in Drosophila.
Paricalcitol Improves Hypoxia-Induced and TGF-β1-Induced Injury in Kidney Pericytes
Authors: Lim Jeong-Hoon , Yook Ju-Min , Oh Se-Hyun , Jeon Soo-Jee , Noh Hee Won , Jung Hee-Yeon , Choi Ji-Young , Cho Jang-Hee , Kim Chan-Duck , Kim Yong-Lim , Park Sun-Hee
Published: September 2021

Recently, the role of kidney pericytes in kidney fibrosis has been investigated. This study aims to evaluate the effect of paricalcitol on hypoxia-induced and TGF-β1-induced injury in kidney pericytes. The primary cultured pericytes were pretreated with paricalcitol (20 ng/mL) for 90 min before inducing injury, and then they were exposed to TGF-β1 (5 ng/mL) or hypoxia (1% O2 and 5% CO2). TGF-β1 increased α-SMA and other fibrosis markers but reduced PDGFRβ expression in pericytes, whereas paricalcitol reversed the changes. Paricalcitol inhibited the TGF-β1-induced cell migration of pericytes. Hypoxia increased TGF-β1, α-SMA and other fibrosis markers but reduced PDGFRβ expression in pericyte, whereas paricalcitol reversed them. Hypoxia activated the HIF-1α and downstream molecules including prolyl hydroxylase 3 and glucose transporter-1, whereas paricalcitol attenuated the activation of the HIF-1α-dependent molecules and TGF-β1/Smad signaling pathways in hypoxic pericytes. The gene silencing of HIF-1α vanished the hypoxia-induced TGF-β1, α-SMA upregulation, and PDGFRβ downregulation. The effect of paricalcitol on the HIF-1α-dependent changes of fibrosis markers was not significant after the gene silencing of HIF-1α. In addition, hypoxia aggravated the oxidative stress in pericytes, whereas paricalcitol reversed the oxidative stress by increasing the antioxidant enzymes in an HIF-1α-independent manner. In conclusion, paricalcitol improved the phenotype changes of pericyte to myofibroblast in TGF-β1-stimulated pericytes. In addition, paricalcitol improved the expression of fibrosis markers in hypoxia-exposed pericytes both in an HIF-1α-dependent and independent manner.
Dehydrocostus Lactone Attenuates Methicillin-Resistant Staphylococcus aureus-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization
Authors: Wu Ya-Xian , Jiang Feng-Juan , Liu Gang , Wang Ying-Ying , Gao Zhi-Qi , Jin Si-Hao , Nie Yun-Juan , Chen Dan , Chen Jun-Liang , Pang Qing-Feng
Published: September 2021

Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs Saussurea lappa and Inula helenium L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria.
Interactions of Truncated Menaquinones in Lipid Monolayers and Bilayers
Authors: Van Cleave Cameron , Koehn Jordan T. , Pereira Caroline Simões , Haase Allison A. , Peters Benjamin J. , Croslow Seth W. , McLaughlin Kyle G. , Werst Katarina R. , Goach Audra L. , Crick Dean C. , Arantes Guilherme Menegon , Crans Debbie C.
Published: September 2021

Menaquinones (MK) are hydrophobic molecules that consist of a naphthoquinone headgroup and a repeating isoprenyl side chain and are cofactors used in bacterial electron transport systems to generate cellular energy. We have previously demonstrated that the folded conformation of truncated MK homologues, MK-1 and MK-2, in both solution and reverse micelle microemulsions depended on environment. There is little information on how MKs associate with phospholipids in a model membrane system and how MKs affect phospholipid organization. In this manuscript, we used a combination of Langmuir monolayer studies and molecular dynamics (MD) simulations to probe these questions on truncated MK homologues, MK-1 through MK-4 within a model membrane. We observed that truncated MKs reside farther away from the interfacial water than ubiquinones are are located closer to the phospholipid tails. We also observed that phospholipid packing does not change at physiological pressure in the presence of truncated MKs, though a difference in phospholipid packing has been observed in the presence of ubiquinones. We found through MD simulations that for truncated MKs, the folded conformation varied, but MKs location and association with the bilayer remained unchanged at physiological conditions regardless of side chain length. Combined, this manuscript provides fundamental information, both experimental and computational, on the location, association, and conformation of truncated MK homologues in model membrane environments relevant to bacterial energy production.
Identification of Abundant and Functional dodecaRNAs (doRNAs) Derived from Ribosomal RNA
Authors: Lambert Marine , Benmoussa Abderrahim , Diallo Idrissa , Ouellet-Boutin Katheryn , Dorval Véronique , Majeau Nathalie , Joly-Beauparlant Charles , Droit Arnaud , Bergeron Alain , Têtu Bernard , Fradet Yves , Pouliot Frédéric , Provost Patrick
Published: September 2021

Using a modified RNA-sequencing (RNA-seq) approach, we discovered a new family of unusually short RNAs mapping to ribosomal RNA 5.8S, which we named dodecaRNAs (doRNAs), according to the number of core nucleotides (12 nt) their members contain. Using a new quantitative detection method that we developed, we confirmed our RNA-seq data and determined that the minimal core doRNA sequence and its 13-nt variant C-doRNA (doRNA with a 5′ Cytosine) are the two most abundant doRNAs, which, together, may outnumber microRNAs. The C-doRNA/doRNA ratio is stable within species but differed between species. doRNA and C-doRNA are mainly cytoplasmic and interact with heterogeneous nuclear ribonucleoproteins (hnRNP) A0, A1 and A2B1, but not Argonaute 2. Reporter gene activity assays suggest that C-doRNA may function as a regulator of Annexin II receptor (AXIIR) expression. doRNAs are differentially expressed in prostate cancer cells/tissues and may control cell migration. These findings suggest that unusually short RNAs may be more abundant and important than previously thought.
In Vivo Study of the Efficacy and Safety of 5-Aminolevulinic Radiodynamic Therapy for Glioblastoma Fractionated Radiotherapy
Authors: Takahashi Junko , Nagasawa Shinsuke , Doi Motomichi , Takahashi Masamichi , Narita Yoshitaka , Yamamoto Junkoh , Ikemoto Mitsushi J. , Iwahashi Hitoshi
Published: September 2021

To treat malignant glioma, standard fractionated radiotherapy (RT; 60 Gy/30 fractions over 6 weeks) was performed post-surgery in combination with temozolomide to improve overall survival. Malignant glioblastoma recurrence rate is extremely high, and most recurrent tumors originate from the excision cavity in the high-dose irradiation region. In our previous study, protoporphyrin IX physicochemically enhanced reactive oxygen species generation by ionizing radiation and combined treatment with 5-aminolevulinic acid (5-ALA) and ionizing radiation, while radiodynamic therapy (RDT) improved tumor growth suppression in vivo in a melanoma mouse model. We examined the effect of 5-ALA RDT on the standard fractionated RT protocol using U251MG- or U87MG-bearing mice. 5-ALA was orally administered at 60 or 120 mg/kg, 4 h prior to irradiation. In both models, combined treatment with 5-ALA slowed tumor progression and promoted regression compared to treatment with ionizing radiation alone. The standard fractionated RT protocol of 60 Gy in 30 fractions with oral administration of 120 and 240 mg/kg 5-ALA, the human equivalent dose of photodynamic diagnosis, revealed no significant increase in toxicity to normal skin or brain tissue compared to ionizing radiation alone. Thus, RDT is expected to enhance RT treatment of glioblastoma without severe toxicity under clinically feasible conditions.
Arginine Methylation of hnRNPK Inhibits the DDX3-hnRNPK Interaction to Play an Anti-Apoptosis Role in Osteosarcoma Cells
Authors: Chen Chiao-Che , Yang Jen-Hao , Fu Shu-Ling , Lin Wey-Jinq , Lin Chao-Hsiung
Published: September 2021

Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA/DNA binding protein involved in diverse cell processes; it is also a p53 coregulator that initiates apoptosis under DNA damage conditions. However, the upregulation of hnRNPK is correlated with cancer transformation, progression, and migration, whereas the regulatory role of hnRNPK in cancer malignancy remains unclear. We previously showed that arginine methylation of hnRNPK attenuated the apoptosis of U2OS osteosarcoma cells under DNA damage conditions, whereas the replacement of endogenous hnRNPK with a methylation-defective mutant inversely enhanced apoptosis. The present study further revealed that an RNA helicase, DDX3, whose C-terminus preferentially binds to the unmethylated hnRNPK and could promote such apoptotic enhancement. Moreover, C-terminus-truncated DDX3 induced significantly less apoptosis than full-length DDX3. Notably, we also identified a small molecule that docks at the ATP-binding site of DDX3, promotes the DDX3-hnRNPK interaction, and induces further apoptosis. Overall, we have shown that the arginine methylation of hnRNPK suppresses the apoptosis of U2OS cells via interfering with DDX3–hnRNPK interaction. On the other hand, DDX3–hnRNPK interaction with a proapoptotic role may serve as a target for promoting apoptosis in osteosarcoma cells.
AMPK–mTOR Signaling and Cellular Adaptations in Hypoxia
Authors: Chun Yoomi , Kim Joungmok
Published: September 2021

Cellular energy is primarily provided by the oxidative degradation of nutrients coupled with mitochondrial respiration, in which oxygen participates in the mitochondrial electron transport chain to enable electron flow through the chain complex (I–IV), leading to ATP production. Therefore, oxygen supply is an indispensable chapter in intracellular bioenergetics. In mammals, oxygen is delivered by the bloodstream. Accordingly, the decrease in cellular oxygen level (hypoxia) is accompanied by nutrient starvation, thereby integrating hypoxic signaling and nutrient signaling at the cellular level. Importantly, hypoxia profoundly affects cellular metabolism and many relevant physiological reactions induce cellular adaptations of hypoxia-inducible gene expression, metabolism, reactive oxygen species, and autophagy. Here, we introduce the current knowledge of hypoxia signaling with two-well known cellular energy and nutrient sensing pathways, AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1). Additionally, the molecular crosstalk between hypoxic signaling and AMPK/mTOR pathways in various hypoxic cellular adaptions is discussed.
Jasmonic Acid-Dependent MYC Transcription Factors Bind to a Tandem G-Box Motif in the YUCCA8 and YUCCA9 Promoters to Regulate Biotic Stress Responses
Authors: Pérez-Alonso Marta-Marina , Sánchez-Parra Beatriz , Ortiz-García Paloma , Santamaría Maria Estrella , Díaz Isabel , Pollmann Stephan
Published: September 2021

The indole-3-pyruvic acid pathway is the main route for auxin biosynthesis in higher plants. Tryptophan aminotransferases (TAA1/TAR) and members of the YUCCA family of flavin-containing monooxygenases catalyze the conversion of l-tryptophan via indole-3-pyruvic acid to indole-3-acetic acid (IAA). It has been described that jasmonic acid (JA) locally produced in response to mechanical wounding triggers the de novo formation of IAA through the induction of two YUCCA genes, YUC8 and YUC9. Here, we report the direct involvement of a small number of basic helix-loop-helix transcription factors of the MYC family in this process. We show that the JA-mediated regulation of the expression of the YUC8 and YUC9 genes depends on the abundance of MYC2, MYC3, and MYC4. In support of this observation, seedlings of myc knockout mutants displayed a strongly reduced response to JA-mediated IAA formation. Furthermore, transactivation assays provided experimental evidence for the binding of MYC transcription factors to a particular tandem G-box motif abundant in the promoter regions of YUC8 and YUC9, but not in the promoters of the other YUCCA isogenes. Moreover, we demonstrate that plants that constitutively overexpress YUC8 and YUC9 show less damage after spider mite infestation, thereby underlining the role of auxin in plant responses to biotic stress signals.
Bone Tissue Response to Different Grown Crystal Batches of Octacalcium Phosphate in Rat Long Bone Intramedullary Canal Area
Authors: Shiwaku Yukari , Hamai Ryo , Sato Shinichi , Sakai Susumu , Tsuchiya Kaori , Baba Kazuyoshi , Takahashi Tetsu , Suzuki Osamu
Published: September 2021

The microstructure of biomaterials influences the cellular and biological responses in the bone. Octacalcium phosphate (OCP) exhibits higher biodegradability and osteoconductivity than hydroxyapatite (HA) during the conversion process from OCP to HA. However, the effect of the microstructure of OCP crystals on long tubular bones has not been clarified. In this study, two types of OCPs with different microstructures, fine-OCP (F-OCP) and coarse-OCP (C-OCP), were implanted in rat tibia for 4 weeks. F-OCP promoted cortical bone regeneration compared with C-OCP. The osteoclasts appearance was significantly higher in the C-OCP group than in the control group (defect only) at 1-week post-implantation. To investigate whether the solubility equilibrium depends on the different particle sizes of OCPs, Nano-OCP, which consisted of nanometer-sized OCPs, was prepared. The degree of supersaturation (DS) tended to decrease modestly in the order of C-OCP, F-OCP, and Nano-OCP with respect to HA and OCP in Tris-HCl buffer. F-OCP showed a higher phosphate ion concentration and lower calcium ion concentration after immersion in the buffer than C-OCP. The crystal structures of both OCPs tended to be converted to HA by rat abdominal implantation. These results suggest that differences in the microstructure of OCPs may affect osteoclastogenesis and result in osteoconductivity of this material in long tubular bone by altering dissolution behavior.
Benefit of Atrial Overdrive Pacing in Patients with Sleep Apnea: A Meta-Analysis
Authors: Tokavanich Nithi , Leelapatana Pattranee , Prechawat Somchai , Rungpradubvong Voravut , Mongkonsritrakoon Wimwipa , Vallabhajosyula Saraschandra , Prasitlumkum Narut , Thongprayoon Charat , Cheungpasitporn Wisit , Chokesuwattanaskul Ronpichai
Published: September 2021

Background: Sleep apnea is one of the most common conditions around the world. This disorder can significantly impact cardiovascular morbidity and mortality. Atrial overdrive pacing (AOP) is a treatment modality that can potentially decrease respiratory events. There is currently a lack of evidence to confirm the benefits of AOP. We aimed to assess the impact of AOP in patients with obstructive sleep apnea (OSA), central sleep apnea (CSA), and mixed type. Methods: A literature search for studies that reported the impact on apnea–hypopnea index (AHI) by cardiac implantable electronic devices with different pacing modes was conducted using MEDLINE, Embase, and Cochrane Database from inception through July 2020. Pooled standard mean difference with 95%CI was calculated using a random-effects model. Results: Fifteen studies, including thirteen randomized studies and two observational studies containing 440 patients, were identified. The standard mean difference in apnea–hypopnea index of atrial overdrive pacing demonstrated less duration of apnea/hypopnea in patients with atrial overdrive pacing (AOP) (SMD −0.29, 95%CI: −0.48, −0.10, I2 = 57%). Additional analysis was performed to assess the effect of atrial overdrive pacing in patients with or without severe sleep apnea syndrome (mean AHI < 30 defined as non-severe). There was no statistically significant difference in standardized mean in AHI in both subgroups between AOP and control groups (SMD −0.25, severe sleep apnea syndrome SMD −0.03, I2 = 0.00%). Conclusions: AOP was associated with a statistically significant reduction in AHI, but the magnitude of reduction was small. AOP may potentially be used as an adjunctive treatment with other modalities in treating patients with sleep apnea.
A Pilot Study: Hypertension, Endothelial Dysfunction and Retinal Microvasculature in Rheumatic Autoimmune Diseases
Authors: Mahdy Ahmed , Stradner Martin , Roessler Andreas , Brix Bianca , Lackner Angelika , Salon Adam , Goswami Nandu
Published: September 2021

Background: The etiology of autoimmune rheumatic diseases is unknown. Endothelial dysfunction and premature atherosclerosis are commonly seen in these patients. Atherosclerosis is considered one of the main causes of cardiovascular diseases. Hypertension is considered the most important traditional cardiovascular risk. This case-control study aimed to investigate the relationship between autoimmune diseases and cardiovascular risk. Methods: This study was carried out in patients with rheumatoid arthritis, RA (n = 10), primary Sjögren syndrome, PSS (n = 10), and healthy controls (n = 10). Mean blood pressure (MBP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse wave velocity (PWV, an indicator of arterial stiffness) were assessed via a Vicorder device. Asymmetric dimethylarginine (ADMA) was measured via ELISA. Retinal photos were taken via a CR-2 retinal camera, and retinal microvasculature analysis was carried out. T-tests were conducted to compare the disease and control groups. ANOVA and ANOVA—ANCOVA were also used for the correction of covariates. Results: A high prevalence of hypertension was seen in RA (80% of cases) and PSS (40% of cases) compared to controls (only 20% of cases). Significant changes were seen in MBP (RA 101 ± 11 mmHg; PSS 93 ± 10 mm Hg vs. controls 88 ± 7 mmHg, p = 0.010), SBP (148 ± 16 mmHg in RA vs. 135 ± 16 mmHg in PSS vs. 128 ± 11 mmHg in control group; p = 0.007), DBP (77 ± 8 mmHg in RA, 72 ± 8 mmHg in PSS vs. 67 ± 6 mmHg in control; p = 0.010 in RA compared to the controls). Patients with PSS showed no significant difference as compared to controls (MBP: p = 0.240, SBP: p = 0.340, DBP: p = 0.190). Increased plasma ADMA was seen in RA (0.45 ± 0.069 ng/mL) and PSS (0.43 ± 0.060 ng/mL) patients as compared to controls (0.38 ± 0.059 ng/mL). ADMA in RA vs. control was statistically significant (p = 0.022). However, no differences were seen in ADMA in PSS vs. controls. PWV and retinal microvasculature did not differ across the three groups. Conclusions: The prevalence of hypertension in our cohort was very high. Similarly, signs of endothelial dysfunction were seen in autoimmune rheumatic diseases. As hypertension and endothelial dysfunction are important contributing risk factors for cardiovascular diseases, the association of hypertension and endothelial dysfunction should be monitored closely in autoimmune diseases.
Genetic Polymorphisms of GGH and ABCC2 Are Associated with Methotrexate Intolerance in Patients with Rheumatoid Arthritis
Authors: Escudero-Contreras Alejandro , López-Medina Clementina , Collantes-Estévez Eduardo , Ortega-Castro Rafaela , Calvo-Gutiérrez Jerusalem , Mena-Vázquez Natalia , Panero-Lamothe Blanca , Manzanares-Martín Bárbara , Cáliz-Cáliz Rafael , Jiménez-Morales Alberto , Ruiz-Jiménez Mayte , Font-Ugalde Pilar
Published: September 2021

Objective: to identify new single-nucleotide polymorphisms (SNPs) in genes encoding proteins involved in methotrexate (MTX) metabolism and to evaluate the associations of these SNPs with MTX toxicity or intolerance in a southern Spanish cohort of patients with rheumatoid arthritis (RA). Methods: An observational, retrospective, and multicenter study was conducted at three participating hospitals in southern Spain. The main variable was intolerance to MTX (i.e., bDMARD monotherapy), defined as an interruption of treatment due to adverse events or toxicity. Patients being treated with MTX and bDMARDs (combined treatment) at the time of the study visit were considered “tolerant” of MTX. Ten polymorphisms were selected for sequencing in our patients according to a literature review. Each polymorphism was classified according to three possible genotypes (e.g., two homozygous (AA or GG) and one heterozygous (AG)), and the association of these combinations with MTX intolerance was evaluated. Results: A total of 227 patients were included in the final analysis (107 intolerant of MTX and 120 tolerant). A significant association was observed between MTX intolerance and the GGH-T401C AA/AG genotype (OR 2.13, 95% CI 1.06–4.29) in comparison with the GG genotype. On the other hand, an inverse association was observed between the ABCC2-C24T TT/TC genotype and intolerance to MTX (OR 0.59, 95% CI 0.35–1.00) in comparison with the CC genotype. Conclusion: This study provides new data on the association between genetic polymorphisms and MTX intolerance, which may contribute to the development of new biomarkers and personalized medicine in patients with RA.
Expression and Clinical Utility of Transcription Factors Involved in Epithelial–Mesenchymal Transition during Thyroid Cancer Progression
Authors: Baldini Enke , Tuccilli Chiara , Pironi Daniele , Catania Antonio , Tartaglia Francesco , Di Matteo Filippo Maria , Palumbo Piergaspare , Arcieri Stefano , Mascagni Domenico , Palazzini Giorgio , Tripodi Domenico , Maturo Alessandro , Vergine Massimo , Tarroni Danilo , Lori Eleonora , Ferent Iulia Catalina , De Vito Corrado , Fallahi Poupak , Antonelli Alessandro , Censi Simona , D’Armiento Matteo , Barollo Susy , Mian Caterina , Morrone Aldo , D’Andrea Vito , Sorrenti Salvatore , Ulisse Salvatore
Published: September 2021

The transcription factors involved in epithelial–mesenchymal transition (EMT-TFs) silence the genes expressed in epithelial cells (e.g., E-cadherin) while inducing those typical of mesenchymal cells (e.g., vimentin). The core set of EMT-TFs comprises Zeb1, Zeb2, Snail1, Snail2, and Twist1. To date, information concerning their expression profile and clinical utility during thyroid cancer (TC) progression is still incomplete. We evaluated the EMT-TF, E-cadherin, and vimentin mRNA levels in 95 papillary TC (PTC) and 12 anaplastic TC (ATC) tissues and correlated them with patients’ clinicopathological parameters. Afterwards, we corroborated our findings by analyzing the data provided by a case study of the TGCA network. Compared with normal tissues, the expression of E-cadherin was found reduced in PTC and more strongly in ATC, while the vimentin expression did not vary. Among the EMT-TFs analyzed, Twist1 seems to exert a prominent role in EMT, being significantly associated with a number of PTC high-risk clinicopathological features and upregulated in ATC. Nonetheless, in the multivariate analysis, none of the EMT-TFs displayed a prognostic value. These data suggest that TC progression is characterized by an incomplete EMT and that Twist1 may represent a valuable therapeutic target warranting further investigation for the treatment of more aggressive thyroid cancers.
The Efficacy of Transarterial Embolization for Postpartum Hemorrhage Complicated with Disseminated Intravascular Coagulation: A Single-Center Experience
Authors: Ochiai Daigo , Nakatsuka Seishi , Abe Yushi , Ikenoue Satoru , Kasuga Yoshifumi , Inoue Masanori , Jinzaki Masahiro , Tanaka Mamoru
Published: September 2021

Indications for the use of transarterial embolization (TAE) for postpartum hemorrhage (PPH) have been established. However, the efficacy of TAE for PPH complicated by disseminated intravascular coagulation (DIC) remains controversial. In this study, we investigated the efficacy of TAE for PPH complicated by DIC. A database review was conducted to identify patients who were treated with TAE for PPH at our hospital. TAE was performed in 41 patients during the study period. Effective hemostasis was achieved in all cases, but additional procedures, such as re-embolization or hysterectomy, were required in five patients (12.2%). The typical causes of PPH included uterine atony (18 cases), placenta previa (15 cases), amniotic fluid embolism (DIC-type) (11 cases), and placenta accreta spectrum (10 cases). The mean blood loss was 3836 mL. The mean obstetrical DIC and the International Society on Thrombosis and Hemostasis DIC scores were 7.9 and 2.6, respectively. The efficacy of hemostasis was comparable between patients with and without DIC. However, the complete success rate of TAE was lower in patients with DIC as the condition worsened than that in non-DIC patients. Overall, TAE is effective as a minimally invasive treatment for PPH complicated by DIC.
Beyond Sea Turtles: Fusarium keratoplasticum in Eggshells of Podocnemis unifilis, a Threatened Amazonian Freshwater Turtle
Authors: García-Martín Joaquina M. , Sarmiento-Ramírez Jullie M. , Diéguez-Uribeondo Javier
Published: September 2021

The endangered yellow-spotted river turtle (Podocnemis unifilis) has experienced a dramatic population decline in the Ecuadorian Amazonia, mainly due to overexploitation of its eggs. To reverse this trend, the Wildlife Conservation Society has developed a head-start program in Yasuní National Park since 2008, but the potential risk that microbes associated with its eggs might represent for hatching success has not been evaluated yet. Members of the Fusarium solani species complex (FSSC) are involved in egg failure in sea turtles under natural and hatchery conditions, but their role in infecting the eggs of P. unifilis is unknown. In this study, we collected eggshells of P. unifilis and obtained 50 fungal and bacterial isolates. Some potentially pathogenic fungi of the genera Fusarium, Penicillium and Rhizopus were identified based on molecular data. Most importantly, the sea turtle pathogenic species F. keratoplasticum not only was present, but it was the most frequently found. Conversely, we have also isolated other microorganisms, such as Pseudomonas or Phoma-like species, producing a wide spectrum of antifungal compounds that may have a protective role against fungal diseases. Our survey provides useful information on potential pathogens found in P. unifilis eggshells, upon which the success of conservation programs may depend.
Genomic Analyses of Penicillium Species Have Revealed Patulin and Citrinin Gene Clusters and Novel Loci Involved in Oxylipin Production
Authors: Yin Guohua , Zhao Hui , Pennerman Kayla K. , Jurick Wayne M. , Fu Maojie , Bu Lijing , Guo Anping , Bennett Joan W.
Published: September 2021

Blue mold of apple is caused by several different Penicillium species, among which P. expansum and P. solitum are the most frequently isolated. P. expansum is the most aggressive species, and P. solitum is very weak when infecting apple fruit during storage. In this study, we report complete genomic analyses of three different Penicillium species: P. expansum R21 and P. crustosum NJ1, isolated from stored apple fruit; and P. maximae 113, isolated in 2013 from a flooded home in New Jersey, USA, in the aftermath of Hurricane Sandy. Patulin and citrinin gene cluster analyses explained the lack of patulin production in NJ1 compared to R21 and lack of citrinin production in all three strains. A Drosophila bioassay demonstrated that volatiles emitted by P. solitum SA and P. polonicum RS1 were more toxic than those from P. expansum and P. crustosum strains (R27, R11, R21, G10, and R19). The toxicity was hypothesized to be related to production of eight-carbon oxylipins. Putative lipoxygenase genes were identified in P. expansum and P. maximae strains, but not in P. crustosum. Our data will provide a better understanding of Penicillium spp. complex secondary metabolic capabilities, especially concerning the genetic bases of mycotoxins and toxic VOCs.
Lower Ratio of Liver Volume and Body Weight Is a Negative Predictor of Survival after Transjugular Intrahepatic Portosystemic Shunt
Authors: Schindler Philipp , Riegel Arne , Görlich Dennis , Köppe Jeanette , Seifert Leon Louis , Masthoff Max , Maschmeier Miriam , Wilms Christian , Seidensticker Max , Köhler Michael , Trebicka Jonel , Heinzow Hauke , Wildgruber Moritz
Published: September 2021

Transjugular intrahepatic portosystemic shunt (TIPS) is the most effective measure to treat complications of portal hypertension. However, liver function may deteriorate after TIPS. Predictors of liver function and outcome after TIPS are therefore important for management of TIPS patients. The study aimed to evaluate the impact of liver volume on transplant-free survival (TFS) after TIPS, as well as the evolution of liver volume and its relationship with liver function after TIPS. A retrospective analysis of all consecutive patients who underwent TIPS in a tertiary care university liver center between 2012 and 2017 (n = 216) was performed; n = 72 patients with complete prior and follow-up (FU) computed tomography (CT) imaging studies were included in the study. Volumetry of the liver was performed by a semi-automatic 9-lobe image segmentation algorithm at baseline and FU (FU 1: 90–180 d; FU 2: 180–365 d; FU 3: 365–545 d; FU 4: 545–730 d; FU 5: >730 d). Output variables were total liver volume (TLV, cm3), left liver volume (LLV, cm3), right liver volume (RLV, cm3) and TLV/body weight ratio. CT derived liver volumes were correlated with liver function tests, portosystemic pressure gradient (PPG) measurements and survival. To assess predictors of liver volume change over time we fitted linear mixed models. Kaplan–Meier analysis was performed and validated by matched pair analysis followed by Cox regression to determine independent prognostic factors for survival. The median TLV at baseline was 1507.5 cm3 (773.7–3686.0 cm3). Livers with higher baseline liver volumes and larger TLV/weight ratios retained their volume after an initial loss while smaller livers continuously lost volume after TIPS. At the first follow-up period (90–180 d post-TIPS) lower liver volumes and TLV/weight ratios were associated with higher bilirubin levels. Within the final multivariable model containing time (days since TIPS), baseline INR and baseline TLV, the average loss of liver volume was 0.74 mL per day after TIPS. Twelve-month overall transplant-free survival was 89% and median overall TFS was 33 months. The median TFS for a baseline TLV/body weight ratio > 20 was significantly higher compared with ≤20 (40.0 vs. 27.0 months, p = 0.010) while there were no differences regarding the indication for TIPS or etiology of liver disease in the matched pair analysis. Lower TLV/weight ratios before TIPS were associated with shorter TFS and should therefore be critically considered when selecting patients for TIPS. In addition, this study provides first evidence of an effect of TIPS on subsequent liver volume change and associated liver function.
Time-Varying Risk and the Relation between Idiosyncratic Risk and Stock Return
Authors: Fu Chengbo
Published: September 2021

This paper studies the historical time-varying dynamics of risk for individual stocks in the U.S. market. Total risk of an individual stock is decomposed into two components, systematic risk and idiosyncratic risk, and both components are studied separately. We start from the historical trend in the magnitude of risk and then turn to the relation between idiosyncratic risk and stock returns. The result shows that both components of risk for individual stocks are changing over time. They increased from the 1960s to the 1990s/2000s and then declined until today. This paper also studies the risk-return tradeoff by investigating the relation between idiosyncratic risk and stock return in the long run. Stocks are sorted into portfolios for analysis and the whole sample period is further decomposed into decades for subgroup analysis. Multivariable regressions are used to study this relation as we control for beta, size, book-to-market ratio, momentum and liquidity. From a historical point of view, we show that the relation between idiosyncratic risk and stock return is time-varying, and it did not exist in certain decades. The results indicate that the risk-return tradeoff also varied in history.
Kelly Criterion for Optimal Credit Allocation
Authors: Tran Son , Verhoeven Peter
Published: September 2021

The purpose of this study is to address the critical issue of optimal credit allocation. Predicting a borrower’s probability of default is a key requirement of any credit allocation system but turning it into labeled classes leads to problems in performance measurement. In this paper the connection between the probability of default and optimal credit allocation is established through a conceptual construct called the Kelly criterion. Conflicting performance measures in dichotomous classification are replaced with coherent criteria for judging the performance of credit allocation decisions. Extensive testing on peer-to-peer lending data shows that the Kelly strategy enables consistent outperformance and efficiency in processing information relative to alternative credit allocation approaches.
Political Participation in the Risk Society: The Italian Case
Authors: Bartiromo Marianna , Ivaldi Enrico
Published: September 2021

The risk society has profoundly changed our way of life. Among the social phenomena most affected by its effects is undoubtedly political participation and the degree of trust in institutions. This work aims, through the construction of two different indices, to answer the question “How does the risk society influence conventional participation and trust in institutions?”. The Indagine Multiscopo sulle famiglie and the Benessere Equo Sostenibile surveys provide a complete set of indicators to assess specific aspects of Italian daily life and well-being. This work uses a series of data from these surveys to analyze political participation and trust in institutions in Italy in 2019 at regional level using two composite indices obtained through the application of the MPI method. The result of this paper shows no particular effects of the risk society on conventional forms of political participation. Instead, the effects of the risk society are fully visible on levels of trust in institutions.
Financial Leverage and Debt Maturity Targeting: International Evidence
Authors: Gungoraydinoglu Ali , Öztekin Özde
Published: September 2021

We provide evidence on leverage and debt maturity targeting in a large international setting. There are key differences in the relative importance of institutional factors in explaining actual as opposed to target capital structures. Targets and target deviations are plausibly influenced by the institutional environment. Firms from countries with strong legal institutions target lower leverage and higher long-term debt, whereas better-functioning financial systems result in lower target leverage and long-term debt. Financial crisis has shifted the desired structure of the securities toward shorter maturities and has led to more prevalent target deviations. Better institutions significantly decrease the likelihood of target deviations.
Public Space Layout Optimization in Affordable Housing Based on Social Network Analysis
Authors: Zhao Jie , Peng Zhenghong , Liu Lingbo , Yu Yang , Shang Zhourui
Published: September 2021

The efficient use of public space in affordable housing is of great significance to the physical and mental health of low-income and aging residents. Previous studies have evaluated the layout and quality of public space in residential areas based on residents’ subjective satisfaction, however, there still lack studies exploring residents’ behavior patterns and the use of public spaces based on objective measurement standards. Therefore, this paper selected the public space in the large affordable housing areas in the suburbs as the research object and used social network analysis (SNA) to objectively evaluate the network density, clustering coefficient and small-world value of the public space in affordable housing from the perspective of the physical spatial network of the built public space. Based on the network structure characteristics of existing public spaces, this paper further explores the relationship between the frequency of public space use in and the characteristics of nodes’ social networks and their own attributes, and the influence of public space layout structure on the behavioral patterns of affordable housing residents. This paper puts forward proposals for the renovation and optimization of public space according to the behavioral preferences of affordable housing residents, so as to complete the network of public space, promote the interaction and communication of residents in the residential area, enhance the residents’ experience of using public space and improve the living standard of residents in the residential area.
Protein Sorting in Plasmodium Falciparum
Authors: Mayer D.C. Ghislaine
Published: September 2021

Plasmodium falciparum is a unicellular eukaryote with a very polarized secretory system composed of micronemes rhoptries and dense granules that are required for host cell invasion. P. falciparum, like its relative T. gondii, uses the endolysosomal system to produce the secretory organelles and to ingest host cell proteins. The parasite also has an apicoplast, a secondary endosymbiotic organelle, which depends on vesicular trafficking for appropriate incorporation of nuclear-encoded proteins into the apicoplast. Recently, the central molecules responsible for sorting and trafficking in P. falciparum and T. gondii have been characterized. From these studies, it is now evident that P. falciparum has repurposed the molecules of the endosomal system to the secretory pathway. Additionally, the sorting and vesicular trafficking mechanism seem to be conserved among apicomplexans. This review described the most recent findings on the molecular mechanisms of protein sorting and vesicular trafficking in P. falciparum and revealed that P. falciparum has an amazing secretory machinery that has been cleverly modified to its intracellular lifestyle.
Astrocytes in Neurodegenerative Diseases: A Perspective from Tauopathy and α-Synucleinopathy
Authors: Wang Peng , Ye Yihong
Published: September 2021

Neurodegenerative diseases are aging-associated chronic pathological conditions affecting primarily neurons in humans. Inclusion bodies containing misfolded proteins have emerged as a common pathologic feature for these diseases. In many cases, misfolded proteins produced by a neuron can be transmitted to another neuron or a non-neuronal cell, leading to the propagation of disease-associated pathology. While undergoing intercellular transmission, misfolded proteins released from donor cells can often change the physiological state of recipient cells. Accumulating evidence suggests that astrocytes are highly sensitive to neuron-originated proteotoxic insults, which convert them into an active inflammatory state. Conversely, activated astrocytes can release a plethora of factors to impact neuronal functions. This review summarizes our current understanding of the complex molecular interplays between astrocyte and neuron, emphasizing on Tau and α-synuclein (α-syn), the disease-driving proteins for Alzheimer’s and Parkinson’s diseases, respectively.
Targeting Gut–Liver Axis for Treatment of Liver Fibrosis and Portal Hypertension
Authors: Kalo Eric , Read Scott , Ahlenstiel Golo
Published: September 2021

Antifibrotic therapies for the treatment of liver fibrosis represent an unconquered area of drug development. The significant involvement of the gut microbiota as a driving force in a multitude of liver disease, be it pathogenesis or fibrotic progression, suggest that targeting the gut–liver axis, relevant signaling pathways, and/or manipulation of the gut’s commensal microbial composition and its metabolites may offer opportunities for biomarker discovery, novel therapies and personalized medicine development. Here, we review potential links between bacterial translocation and deficits of host-microbiome compartmentalization and liver fibrosis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies, translated from our current knowledge of the gut–liver axis, targeted at restoring intestinal eubiosis, ameliorating hepatic fibrosis and rising portal hypertension that characterize and define the course of decompensated cirrhosis.
Applicability of Additives for Ground Improvement Utilizing Fine Powder of Waste Glass
Authors: Inazumi Shinya , Hashimoto Ryo , Shinsaka Takashi , Nontananandh Supakij , Chaiprakaikeow Susit
Published: September 2021

As a solidifying material for ground improvement using inorganic waste as a raw material, the authors have been developing an additive mixture of the fine powder of waste glass containing a large amount of silica generated during the production of glass cullet and an alkaline aid (heat-treating type of “Earth-Silica; ES” additive). Furthermore, a solidifying material that solidifies by mixing this additive with the fine powder of blast furnace slag, which is a by-product of steel production, is also being developed. In this study, the authors reviewed the mixing process of the solidified materials, especially the one made with the heat-treating type of ES additive, omitting the heat treatment of the fine powder of waste glass and the alkaline aid and applying only the mixing treatment. As a result, a mixing type of ES additive was manufactured to simplify the manufacturing process, and the difference in the performance of the solidifying material, depending on the presence or absence of the heat-treating process during the additive manufacturing, was verified in terms of the effect on the solidifying action. Specifically, the solidifying materials to which the heat-treating type of ES additive and the mixing type of ES additive were added, respectively, were applied to the high-pressure injection stirring method, one of the ground-improvement methods. Various tests clarified the changes in viscosity of these solidifying materials over time and the acceleration of their solidifying rates when adding ordinary Portland cement separately.
An Automatic on Top Analysis of Single Scan Tracks to Evaluate the Laser Powder Bed Fusion Building Parameters
Authors: Martucci Alessandra , Marinucci Fabrizio , Sivo Antonio , Aversa Alberta , Manfredi Diego , Bondioli Federica , Fino Paolo , Lombardi Mariangela
Published: September 2021

The production of dense samples produced by laser powder bed fusion (LPBF) is mainly determined by the choice of the best combination of construction parameters. Parameter optimization is the first step in the definition of an LPBF process for new alloys or systems. With this goal, much research uses the single scan track (SST) approach for a preliminary parameter screening. This study investigates the definition of a computer-aided method by using an automatic on top analysis for the characterization of SSTs, with the aim of finding ranges of laser power and scan speed values for massive production. An innovative algorithm was implemented to discard non-continuous scans and to measure the SSTs quality using three regularity indexes. Only open source software were used to fine tune this approach. The obtained results on Al4Cu and AlSi10Mg realized with two different commercial systems suggest that it is possible to use this method to easily narrow the process parameter window that allows the production of dense samples.
Shape Prediction of the Sheet in Continuous Roll Forming Based on the Analysis of Exit Velocity
Authors: Gao Jia-Xin , Chen Qing-Min , Sun Li-Rong , Cai Zhong-Yi
Published: September 2021

Continuous roll forming (CRF) is a new technology that combines continuous forming and multi-point forming to produce three-dimensional (3D) curved surfaces. Compared with other methods, the equipment of CRF is very simple, including only a pair of bendable work rolls and the corresponding shape adjustment and support assembly. By controlling the bending shapes of the upper and lower rolls and the size of the roll gap during forming, double curvature surfaces with different shapes can be produced. In this paper, a simplified expression of the exit velocity of the sheet is provided, and the formulas for the calculation of the longitudinal curvature radius are further derived. The reason for the discrepancy between the actual and predicted values of the longitudinal radius is deeply discussed from the perspective of the distribution of the exit velocity. By using the response surface methodology, the effects of the maximum compression ratio, the sheet width, the sheet thickness, and the transverse curvature radius on the longitudinal curvature radius are analyzed. Meanwhile, the correction coefficients of the predicted formulas for the positive and negative Gaussian curvature surfaces are obtained as 1.138 and 0.905, respectively. The validity and practicability of the modified formulas are verified by numerical simulations and forming experiments.
Mechanical and Fracture Properties of Long Fiber Reinforced Geopolymer Composites
Authors: Korniejenko Kinga , Figiela Beata , Miernik Krzysztof , Ziejewska Celina , Marczyk Joanna , Hebda Marek , Cheng An , Lin Wei-Ting
Published: September 2021

The aim of the article is to analyze the structure and mechanical properties in terms of the cracking mechanics of geopolymer composites based on fly ash and river sand, as well as metakaolin and river sand with three types of reinforcement material: glass fiber, carbon fiber, and aramid fiber, in terms of their use in additive manufacturing. Geopolymer composites were reinforced with fibers in a volume ratio of 0.5%, 1.0%, and 2.0%. Subsequently, these samples were subjected to bending strength tests in accordance with the European standard EN 12390-3. The addition of fibers significantly improved the bending strength of all composites made of metakaolin and sand. The reinforcement with aramid fiber in the amount of 2.0% resulted in more than a 3-fold increase in strength compared to the reinforcement-free composites. An analysis of the morphology of the fibers was carried out on the basis of photos taken from an electron microscope. The correct addition of fibers changes the nature of the fracture from brittle to more ductile and reduces the number of cracks in the material.