bluuebunny/crossref_metadata_2025 huggingface dataset:
PLOD2 Is a Prognostic Marker in Glioblastoma That Modulates the Immune Microenvironment and Tumor Progression
Authors: Kreße Nina , Schröder Hannah , Stein Klaus-Peter , Wilkens Ludwig , Mawrin Christian , Sandalcioglu Ibrahim Erol , Dumitru Claudia Alexandra
Published: May 2022

This study aimed to investigate the role of Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase 2 (PLOD2) in glioblastoma (GBM) pathophysiology. To this end, PLOD2 protein expression was assessed by immunohistochemistry in two independent cohorts of patients with primary GBM (n1 = 204 and n2 = 203, respectively). Association with the outcome was tested by Kaplan–Meier, log-rank and multivariate Cox regression analysis in patients with confirmed IDH wild-type status. The biological effects and downstream mechanisms of PLOD2 were assessed in stable PLOD2 knock-down GBM cell lines. High levels of PLOD2 significantly associated with (p1 = 0.020; p2< 0.001; log-rank) and predicted (cohort 1: HR = 1.401, CI [95%] = 1.009–1.946, p1 = 0.044; cohort 2: HR = 1.493; CI [95%] = 1.042–2.140, p2 = 0.029; Cox regression) the poor overall survival of GBM patients. PLOD2 knock-down inhibited tumor proliferation, invasion and anchorage-independent growth. MT1-MMP, CD44, CD99, Catenin D1 and MMP2 were downstream of PLOD2 in GBM cells. GBM cells produced soluble factors via PLOD2, which subsequently induced neutrophils to acquire a pro-tumor phenotype characterized by prolonged survival and the release of MMP9. Importantly, GBM patients with synchronous high levels of PLOD2 and neutrophil infiltration had significantly worse overall survival (p < 0.001; log-rank) compared to the other groups of GBM patients. These findings indicate that PLOD2 promotes GBM progression and might be a useful therapeutic target in this type of cancer.
Altered Brain Arginine Metabolism and Polyamine System in a P301S Tauopathy Mouse Model: A Time-Course Study
Authors: Mein Hannah , Jing Yu , Ahmad Faraz , Zhang Hu , Liu Ping
Published: May 2022

Altered arginine metabolism (including the polyamine system) has recently been implicated in the pathogenesis of tauopathies, characterised by hyperphosphorylated and aggregated microtubule-associated protein tau (MAPT) accumulation in the brain. The present study, for the first time, systematically determined the time-course of arginine metabolism changes in the MAPT P301S (PS19) mouse brain at 2, 4, 6, 8 and 12 months of age. The polyamines putrescine, spermidine and spermine are critically involved in microtubule assembly and stabilization. This study, therefore, further investigated how polyamine biosynthetic and catabolic enzymes changed in PS19 mice. There were general age-dependent increases of L-arginine, L-ornithine, putrescine and spermidine in the PS19 brain (particularly in the hippocampus and parahippocampal region). While this profile change clearly indicates a shift of arginine metabolism to favor polyamine production (a polyamine stress response), spermine levels were decreased or unchanged due to the upregulation of polyamine retro-conversion pathways. Our results further implicate altered arginine metabolism (particularly the polyamine system) in the pathogenesis of tauopathies. Given the role of the polyamines in microtubule assembly and stabilization, future research is required to understand the functional significance of the polyamine stress response and explore the preventive and/or therapeutic opportunities for tauopathies by targeting the polyamine system.
The Use of Pro-Angiogenic and/or Pro-Hypoxic miRNAs as Tools to Monitor Patients with Diffuse Gliomas
Authors: Levallet Guénaëlle , Dubois Fatéméh , Leclerc Arthur , Petit Edwige , Bekaert Lien , Faisant Maxime , Creveuil Christian , Emery Evelyne , Zalcman Gérard , Lechapt-Zalcman Emmanuèle
Published: May 2022

IDH (isocitrate dehydrogenase) mutation, hypoxia, and neo-angiogenesis, three hallmarks of diffuse gliomas, modulate the expression of small non-coding RNAs (miRNA). In this paper, we tested whether pro-angiogenic and/or pro-hypoxic miRNAs could be used to monitor patients with glioma. The miRNAs were extracted from tumoral surgical specimens embedded in the paraffin of 97 patients with diffuse gliomas and, for 7 patients, from a blood sample too. The expression of 10 pro-angiogenic and/or pro-hypoxic miRNAs was assayed by qRT-PCR and normalized to the miRNA expression of non-tumoral brain tissues. We confirmed in vitro that IDH in hypoxia (1% O2, 24 h) alters pro-angiogenic and/or pro-hypoxic miRNA expression in HBT-14 (U-87 MG) cells. Then, we reported that the expression of these miRNAs is (i) strongly affected in patients with glioma compared to that in a non-tumoral brain; (ii) correlated with the histology/grade of glioma according to the 2016 WHO classification; and (iii) predicts the overall and/or progression-free survival of patients with glioma in univariate but not in a multivariate analysis after adjusting for sex, age at diagnosis, and WHO classification. Finally, the expression of miRNAs was found to be the same between the plasma and glial tumor of the same patient. This study highlights a panel of seven pro-angiogenic and/or pro-hypoxic miRNAs as a potential tool for monitoring patients with glioma.
Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis
Authors: Katafuchi Takeshi , Makishima Makoto
Published: May 2022

Bile acids (BAs) are a group of amphiphilic molecules consisting of a rigid steroid core attached to a hydroxyl group with a varying number, position, and orientation, and a hydrophilic side chain. While BAs act as detergents to solubilize lipophilic nutrients in the small intestine during digestion and absorption, they also act as hormones. Farnesoid X receptor (FXR) is a nuclear receptor that forms a heterodimer with retinoid X receptor α (RXRα), is activated by BAs in the enterohepatic circulation reabsorbed via transporters in the ileum and the colon, and plays a critical role in regulating gene expression involved in cholesterol, BA, and lipid metabolism in the liver. The FXR/RXRα heterodimer also exists in the distal ileum and regulates production of fibroblast growth factor (FGF) 15/FGF19, a hormone traveling via the enterohepatic circulation that activates hepatic FGF receptor 4 (FGFR4)-β-klotho receptor complex and regulates gene expression involved in cholesterol, BA, and lipid metabolism, as well as those regulating cell proliferation. Agonists for FXR and analogs for FGF15/19 are currently recognized as a promising therapeutic target for metabolic syndrome and cholestatic diseases.
Angiotensin II Inhibits Insulin Receptor Signaling in Adipose Cells
Authors: Gutierrez-Rodelo Citlaly , Arellano-Plancarte Araceli , Hernandez-Aranda Judith , Landa-Galvan Huguet V. , Parra-Mercado G. Karina , Moreno-Licona Nicole J. , Hernandez-Gonzalez Karla D. , Catt Kevin J. , Villalobos-Molina Rafael , Olivares-Reyes J. Alberto
Published: May 2022

Angiotensin II (Ang II) is a critical regulator of insulin signaling in the cardiovascular system and metabolic tissues. However, in adipose cells, the regulatory role of Ang II on insulin actions remains to be elucidated. The effect of Ang II on insulin-induced insulin receptor (IR) phosphorylation, Akt activation, and glucose uptake was examined in 3T3-L1 adipocytes. In these cells, Ang II specifically inhibited insulin-stimulated IR and insulin receptor substrate-1 (IRS-1) tyrosine-phosphorylation, Akt activation, and glucose uptake in a time-dependent manner. These inhibitory actions were associated with increased phosphorylation of the IR at serine residues. Interestingly, Ang II-induced serine-phosphorylation of IRS was not detected, suggesting that Ang II-induced desensitization begins from IR regulation itself. PKC inhibition by BIM I restored the inhibitory effect of Ang II on insulin actions. We also found that Ang II promoted activation of several PKC isoforms, including PKCα/βI/βII/δ, and its association with the IR, particularly PKCβII, showed the highest interaction. Finally, we also found a similar regulatory effect of Ang II in isolated adipocytes, where insulin-induced Akt phosphorylation was inhibited by Ang II, an effect that was prevented by PKC inhibitors. These results suggest that Ang II may lead to insulin resistance through PKC activation in adipocytes.
Challenges and Future of Drug-Induced Liver Injury Research—Laboratory Tests
Authors: Weber Sabine , Gerbes Alexander L.
Published: May 2022

Drug-induced liver injury (DILI) is a rare but potentially severe adverse drug event, which is also a major cause of study cessation and market withdrawal during drug development. Since no acknowledged diagnostic tests are available, DILI diagnosis poses a major challenge both in clinical practice as well as in pharmacovigilance. Differentiation from other liver diseases and the identification of the causative agent in the case of polymedication are the main issues that clinicians and drug developers face in this regard. Thus, efforts have been made to establish diagnostic testing methods and biomarkers in order to safely diagnose DILI and ensure a distinguishment from alternative liver pathologies. This review provides an overview of the diagnostic methods used in differential diagnosis, especially with regards to autoimmune hepatitis (AIH) and drug-induced autoimmune hepatitis (DI-AIH), in vitro causality methods using individual blood samples, biomarkers for diagnosis and severity prediction, as well as experimental predictive models utilized in pre-clinical settings during drug development regimes.
Determination of IgG1 and IgG3 SARS-CoV-2 Spike Protein and Nucleocapsid Binding—Who Is Binding Who and Why?
Authors: Iles Jason K. , Zmuidinaite Raminta , Sadee Christoph , Gardiner Anna , Lacey Jonathan , Harding Stephen , Wallis Gregg , Patel Roshani , Roblett Debra , Heeney Jonathan , Baxendale Helen , Iles Ray Kruse
Published: May 2022

The involvement of immunoglobulin (Ig) G3 in the humoral immune response to SARS-CoV-2 infection has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) in COVID-19. The exact molecular mechanism is unknown, but it is thought to involve this IgG subtype’s differential ability to fix, complement and stimulate cytokine release. We examined the binding of convalescent patient antibodies to immobilized nucleocapsids and spike proteins by matrix-assisted laser desorption/ionization–time of flight (MALDI-ToF) mass spectrometry. IgG3 was a major immunoglobulin found in all samples. Differential analysis of the spectral signatures found for the nucleocapsid versus the spike protein demonstrated that the predominant humoral immune response to the nucleocapsid was IgG3, whilst for the spike protein it was IgG1. However, the spike protein displayed a strong affinity for IgG3 itself, as it would bind from control plasma samples, as well as from those previously infected with SARS-CoV-2, similar to the way protein G binds IgG1. Furthermore, detailed spectral analysis indicated that a mass shift consistent with hyper-glycosylation or glycation was a characteristic of the IgG3 captured by the spike protein.
Next-Generation Diagnostic with CRISPR/Cas: Beyond Nucleic Acid Detection
Authors: Bhardwaj Pooja , Kant Rajni , Behera Sthita Pragnya , Dwivedi Gaurav Raj , Singh Rajeev
Published: May 2022

The early management, diagnosis, and treatment of emerging and re-emerging infections and the rising burden of non-communicable diseases (NCDs) are necessary. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas system has recently acquired popularity as a diagnostic tool due to its ability to target specific genes. It uses Cas enzymes and a guide RNA (gRNA) to cleave target DNA or RNA. The discovery of collateral cleavage in CRISPR-Cas effectors such as Cas12a and Cas13a was intensively repurposed for the development of instrument-free, sensitive, precise and rapid point-of-care diagnostics. CRISPR/Cas demonstrated proficiency in detecting non-nucleic acid targets including protein, analyte, and hormones other than nucleic acid. CRISPR/Cas effectors can provide multiple detections simultaneously. The present review highlights the technical challenges of integrating CRISPR/Cas technology into the onsite assessment of clinical and other specimens, along with current improvements in CRISPR bio-sensing for nucleic acid and non-nucleic acid targets. It also highlights the current applications of CRISPR/Cas technologies.
Mitochondrial rRNA Methylation by Mettl15 Contributes to the Exercise and Learning Capability in Mice
Authors: Averina Olga A. , Laptev Ivan G. , Emelianova Mariia A. , Permyakov Oleg A. , Mariasina Sofia S. , Nikiforova Alyona I. , Manskikh Vasily N. , Grigorieva Olga O. , Bolikhova Anastasia K. , Kalabin Gennady A. , Dontsova Olga A. , Sergiev Petr V.
Published: May 2022

Mitochondrial translation is a unique relic of the symbiotic origin of the organelle. Alterations of its components cause a number of severe human diseases. Hereby we report a study of mice devoid of Mettl15 mitochondrial 12S rRNA methyltransferase, responsible for the formation of m4C839 residue (human numbering). Homozygous Mettl15−/− mice appeared to be viable in contrast to other mitochondrial rRNA methyltransferase knockouts reported earlier. The phenotype of Mettl15−/− mice is much milder than that of other mutants of mitochondrial translation apparatus. In agreement with the results obtained earlier for cell cultures with an inactivated Mettl15 gene, we observed accumulation of the RbfA factor, normally associated with the precursor of the 28S subunit, in the 55S mitochondrial ribosome fraction of knockout mice. A lack of Mettl15 leads to a lower blood glucose level after physical exercise relative to that of the wild-type mice. Mettl15−/− mice demonstrated suboptimal muscle performance and lower levels of Cox3 protein synthesized by mitoribosomes in the oxidative soleus muscles. Additionally, we detected decreased learning capabilities in the Mettl15−/− knockout mice in the tests with both positive and negative reinforcement. Such properties make Mettl15−/− knockout mice a suitable model for mild mitochondriopathies.
Navigating around the Current Options to Preserve and Regenerate Meniscus: A Long Journey Still to Be Pursued
Authors: Di Matteo Berardo , Anzillotti Giuseppe , Kon Elizaveta
Published: May 2022

The beginning of meniscal surgery was attributed to Annadale at the end of the 19th century: interestingly, he performed the first documented surgical repair of the meniscus [...]
A Micro-Immunotherapy Sequential Medicine MIM-seq Displays Immunomodulatory Effects on Human Macrophages and Anti-Tumor Properties towards In Vitro 2D and 3D Models of Colon Carcinoma and in an In Vivo Subcutaneous Xenograft Colon Carcinoma Model
Authors: Jacques Camille , Marchesi Irene , Fiorentino Francesco Paolo , Chatelais Mathias , Lilli Nicoletta Libera , Appel Kurt , Lejeune Beatrice , Floris Ilaria
Published: May 2022

In this study, the immunomodulatory effects of a sequential micro-immunotherapy medicine, referred as MIM-seq, were appraised in human primary M1 and M2 macrophages, in which the secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-12, IL-23, and tumor necrosis factor (TNF)-alpha, was inhibited. In addition, the potential anti-proliferative effects of MIM-seq on tumor cells was assessed in three models of colorectal cancer (CRC): an in vitro two-dimensions (2D) model of HCT-116 cells, an in vitro tri-dimensional (3D) model of spheroids, and an in vivo model of subcutaneous xenografted mice. In these models, MIM-seq displayed anti-proliferative effects when compared with the vehicle. In vivo, the tumor growth was slightly reduced in MIM-seq-treated animals. Moreover, MIM-seq could slightly reduce the growth of our spheroid models, especially under serum-deprivation. When MIM-seq was combined with two well-known anti-cancerogenic agents, either resveratrol or etoposide, MIM-seq could even further reduce the spheroid’s volume, pointing up the need to further assess whether MIM-seq could be beneficial for CRC patients as an adjuvant therapy. Altogether, these data suggest that MIM-seq could have anti-tumor properties against CRC and an immunomodulatory effect towards the mediators of inflammation, whose systemic dysregulation is considered to be a poor prognosis for patients.
Circulating Growth Differentiation Factor 15 Is Associated with Diabetic Neuropathy
Authors: Weng Shao-Wen , Chen Wen-Chieh , Shen Feng-Chih , Wang Pei-Wen , Chen Jung-Fu , Liou Chia-Wei
Published: May 2022

Background: Growth differentiation factor (GDF15) is a superfamily of transforming growth factor-beta which has been suggested to be correlated with various pathological conditions. The current study aimed to investigate the predicted role of circulating GDF15 in diabetic metabolism characteristics and diabetic neuropathy. Methods: 241 diabetic patients and 42 non-diabetic subjects were included to participate in the study. The plasma GDF15 levels were measured using ELISA. Chronic kidney disease and albuminuria were defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline. The nerve conductive study (NCS) was performed with measurement of distal latency, amplitude, nerve conduction velocity (NCV), H-reflex, and F-wave studies. Results: The diabetic group had a significantly higher prevalence of chronic kidney disease and higher plasma GDF15 level. After adjusting for age and BMI, GDF15 was significantly positively correlated with waist circumference (r = 0.332, p = <0.001), hip circumference (r = 0.339, p < 0.001), HbA1c (r = 0.302, p < 0.001), serum creatine (r = 0.146, p = 0.017), urine albumin/creatinine ratio (r = 0.126, p = 0.040), and HOMA-IR (r = 0.166, p = 0.007). As to NCS, GDF15 was significantly correlated with all latency and amplitude of sensory and motor nerves, as well as F-wave and H-reflex latencies. The area under the curve (AUC) in predicting tibial motor nerve neuropathy (MNCV) in all subjects and in the diabetic group for GDF15 was 0.646 (p = 0.001) and 0.610 (p = 0.012), respectively; for HbA1c was 0.639 (p = 0.001) and 0.604 (p = 0.018), respectively. Predicting ulnar sensory nerve neuropathy for GDF15 was 0.639 (p = 0.001) and 0.658 (p = 0.001), respectively; for HbA1c was 0.545 (p = 0.307) and 0.545 (p = 0.335), respectively. Predicting median sensory nerve neuropathy for GDF15 was 0.633 (p = 0.007) and 0.611 (p = 0.032), respectively; for HbA1c was 0.631 (p = 0.008) and 0.607 (p = 0.038), respectively. Predicting CKD for GDF15 was 0.709 (95% CI, 0.648–0.771), p < 0.001) and 0.676 (95% CI, 0.605–0.746), p < 0.001), respectively; for HbA1c was 0.560 (95% CI, 0.493–0.627); p = 0.080) and 0.515 (95% CI, 0.441–0.588); p = 0.697), respectively. Conclusions: We suggest that there is a significant association between the increased serum GDF-15 level and metabolic parameters and diabetic neuropathy. Plasma GDF15 may be an independent predictor of diabetic neuropathy.
Quality of Life in Older Patients after a Heart Failure Hospitalization: Results from the SENECOR Study
Authors: Luiso Daniele , Herrero-Torrus Marta , Badosa Neus , Roqueta Cristina , Ruiz-Bustillo Sonia , Belarte-Tornero Laia C. , Valdivielso-Moré Sandra , Morales Ronald O. , Vázquez Olga , Farré Núria
Published: May 2022

Background: Information about health-related quality of life (HRQoL) in heart failure (HF) in older adults is scarce. Methods: We aimed to describe the HRQoL of the SENECOR study cohort, a single-center, randomized trial comparing the effects of multidisciplinary intervention by a geriatrician and a cardiologist (intervention group) to that of a cardiologist alone (control group) in older patients with a recent HF hospitalization. Results: HRQoL was assessed by the short version of the disease-specific Kansas Cardiomyopathy Questionnaire (KCCQ-12) in 141 patients at baseline and was impaired (KCCQ-12 < 75) in almost half of the cohort. Women comprised 50% of the population, the mean age was 82.2 years, and two-thirds of patients had preserved ejection fraction. Comorbidities were highly prevalent. Patients with impaired HRQoL had a worse NYHA functional class, a lower NT-proBNP, a lower Barthel index, and a higher Clinical Frailty Scale. One-year all-cause mortality was 22.7%, significantly lower in the group with good-to-excellent HRQoL (14.5% vs. 30.6%; hazard ratio 0.28; 95% confidence interval 0.10–0.78; p = 0.014). In the group with better HRQoL, all-cause hospitalization was lower, and there was a trend towards lower HF hospitalization. Conclusions: The KCCQ-12 questionnaire can provide inexpensive prognostic information even in older patients with HF. (Funded by grant Primitivo de la Vega, Fundación MAPFRE. ClinicalTrials number, NCT03555318).
Reinforcement of the Standard Therapy with Two Infusions of Convalescent Plasma for Patients with COVID-19: A Randomized Clinical Trial
Authors: Bargay-Lleonart Joan , Sarubbo Fiorella , Arrizabalaga Maria , Guerra José Maria , Borràs Josep , El Haji Khaoulah , Flexas Magdalena , Perales Jorge , Fernández-Baca Victoria , Gallegos Carmen , Cruz Manuel Raya , Velasco Sonia , López Víctor , Cruz Ana , Bautista-Gili Antonia , Jimenez-Marco Teresa , Girona-Llobera Enric , Vilaplana Laia , Calonge Laura , Tena Juan , Galán Maria Pilar , Payeras Antoni
Published: May 2022

Background: The aim was to evaluate the reinforcement of the standard therapy with hyperimmune plasma (HP) in Coronavirus-19 disease (COVID-19) patients. Methods: Open-label, multicenter, randomized clinical trial performed in three hospitals in the Balearic Islands. Non-severe COVID-19 hospitalized patients with clinical time evolution equal to/less than 7 days were included, and randomized in: plasma group (PG) (n = 37), receiving 600 mL divided into two doses from convalescent plasma donor, administered on days 1 and 2 after the enrollment; and control group (CG) (n = 17). Primary outcome was the time for clinical improvement within 21 days, defined as patient achievement of categories 8, 7, and 6 in the Adaptive COVID-19 Treatment Trial scale (ACTT). The trial was terminated early due to the impossibility of recruitment due to the pandemic. Results: PG presented better scores on the ACTT scale at 7 days after HP infusion, whereas CG was needed 14 days to achieve similar results. The plasma infusion was safe. Conclusions: Despite the tendency observed in the plasma group to achieve slightly earlier better physical condition compared with the standard treatment alone. The administration of HP has been shown to be a safe therapy. No robust evidence was found to affirm a therapeutic effect of the early administration of two infusions of HP for non-severe COVID-19 infected patients. The interpretation is limited by the early termination of the trial, which resulted in a small sample size.
The State of Ethereum Smart Contracts Security: Vulnerabilities, Countermeasures, and Tool Support
Authors: Zhou Haozhe , Milani Fard Amin , Makanju Adetokunbo
Published: May 2022

Smart contracts are self-executing programs that run on the blockchain and make it possible for peers to enforce agreements without a third-party guarantee. The smart contract on Ethereum is the fundamental element of decentralized finance with billions of US dollars in value. Smart contracts cannot be changed after deployment and hence the code needs to be verified for potential vulnerabilities. However, smart contracts are far from being secure and attacks exploiting vulnerabilities that have led to losses valued in the millions. In this work, we explore the current state of smart contracts security, prevalent vulnerabilities, and security-analysis tool support, through reviewing the latest advancement and research published in the past five years. We study 13 vulnerabilities in Ethereum smart contracts and their countermeasures, and investigate nine security-analysis tools. Our findings indicate that a uniform set of smart contract vulnerability definitions does not exist in research work and bugs pertaining to the same mechanisms sometimes appear with different names. This inconsistency makes it difficult to identify, categorize, and analyze vulnerabilities. We explain some safeguarding approaches and best practices. However, as technology improves new vulnerabilities may emerge. Regarding tool support, SmartCheck, DefectChecker, contractWard, and sFuzz tools are better choices in terms of more coverage of vulnerabilities; however, tools such as NPChecker, MadMax, Osiris, and Sereum target some specific categories of vulnerabilities if required. While contractWard is relatively fast and more accurate, it can only detect pre-defined vulnerabilities. The NPChecker is slower, however, can find new vulnerability patterns.
Opportunities and Challenges to Develop Digital Twins for Subsea Pipelines
Authors: Chen Bai-Qiao , Videiro Paulo M. , Guedes Soares C.
Published: May 2022

A vision of the digital twins of the subsea pipelines is provided in this paper, with a coverage of the current applications and the challenges of the digital twins in the design, construction, service life, and assessments of life extension. Digital twins are described as a paradigm combining multi-physics modelling with data-driven analytics, which are used to mirror the life of its corresponding twin. Realistic virtual models of structural systems are shown to bridge the gap between design and construction and to mirror the real and virtual worlds. Challenges in properly using the new tools and how to create accurate digital twins considering data acquired during the construction phase are discussed. The key opportunities for improved integrity management using the digital twin are data contextualization, standardization, automated anomaly detection, and learning through sharing. The collection, interpretation and sharing of data, and cyber-security are identified as some of the main challenges.
Three New Species of Microdochium (Sordariomycetes, Amphisphaeriales) on Miscanthus sinensis and Phragmites australis from Hainan, China
Authors: Liu Shubin , Liu Xiaoyong , Zhang Zhaoxue , Xia Jiwen , Zhang Xiuguo , Meng Zhe
Published: May 2022

Species in Microdochium, potential agents of biocontrol, have often been reported as plant pathogens, occasionally as endophytes and fungicolous fungi. Combining multiple molecular markers (ITS rDNA, LSU rDNA, TUB2 and RPB2) with morphological characteristics, this study proposes three new species in the genus Microdochium represented by seven strains from the plant hosts Miscanthus sinensis and Phragmites australis in Hainan Island, China. These three species, Microdochium miscanthi sp. Nov., M. sinense sp. Nov. and M. hainanense sp. Nov., are described with MycoBank number, etymology, typification, morphological features and illustrations, as well as placement on molecular phylogenetic trees. Their affinity with morphologically allied and molecularly closely related species are also analyzed. For facilitating identification, an updated key to the species of Microdochium is provided herein.
Divergent Response of the Supply Capacity and Turnover of Inorganic Nitrogen to Pitaya Cultivation in the Subtropical Karst Region of Southwest China
Authors: Yang Lin , Zhang Xuebin , Liu Jinxia , Wen Dongni , Meng Lei , Zhu Tongbin
Published: May 2022

Determining the availability and supply capacity of soil inorganic nitrogen (N) can effectively guide the appropriate application of N fertilizers during crop cultivation. However, the mechanism underlying soil inorganic N production remains unknown for cash crops in karst regions. In this study, the rates of organic N mineralization to ammonium (NH4+) and NH4+ nitrification to nitrate (NO3−) were determined using a 15N tracing technique to evaluate the supply capacity of inorganic N in soils from woodland and pitaya plantations with different cultivation years (3, 9, and 15 years) in the subtropical karst region of China. The conversion of woodland to pitaya plantations significantly decreased the content of soil organic carbon (SOC), total N, calcium (Ca), and magnesium (Mg), along with the soil pH and cation-exchange capacity (CEC), but significantly increased the content of available potassium, available phosphorus, iron, and aluminum, in a more pronounced fashion with the increasing length of pitaya cultivation. The conversion of woodland to pitaya plantations has not significantly changed soil NH4+ and NO3− content, but this land use has resulted in divergent effects on mineralization and nitrification rates. Compared to woodland (5.49 mg N kg−1 d−1), pitaya cultivation significantly reduced the mineralization rate to 0.62–2.38 mg N kg−1 d−1. Conversely, the nitrification rate significantly increased from 4.71 mg N kg−1 d−1 in soil under woodland to 9.32 mg N kg−1 d−1 in soil under 3-year pitaya cultivation, but this rate decreased to 1.74 mg N kg−1 d−1 under 15-year cultivation. Furthermore, the mean residence time of inorganic N was significantly higher in long-term than in short-term pitaya plantations, indicating the decline in inorganic N turnover with the increasing length of pitaya cultivation. Taken together, long-term pitaya cultivation could significantly decrease the supply capacity and turnover of inorganic N in soil. The Ca, Mg, SOC, and total N content, as well as CEC, were significantly and positively related to the mineralization rate, but negatively related to the mean residence time of NH4+ and NO3−, suggesting that the incorporation of organic matter can accelerate the soil inorganic N supply and turnover for long-term pitaya plantation in subtropical regions.
Land Management Change as Adaptation to Climate and Other Stressors: A Systematic Review of Decision Contexts Using Values-Rules-Knowledge
Authors: Kirk Nicholas A. , Cradock-Henry Nicholas A.
Published: May 2022

Agricultural producers are already experiencing the adverse effects of climate change, highlighting the urgent need for adaptation. While incremental changes to cope with interannual variability are widely applied, there is limited understanding of the social contexts that inform, enable, or constrain more transformational adaptations in response to anticipated or actual climate change and other stressors. Systematic review methods are used to identify 31 empirical examples of land management change as an adaptation response by agricultural producers in developed countries. We then applied the values-rules-knowledge (vrk) framework to analyse interactions between societal values, institutional rules, and scientific and experiential knowledge. The vrk is a heuristic to help decision makers analyze how the social system shapes their decision context. Three propositions highlighting the relative influence of different values–rules, values–knowledge, and rules–knowledge relationships on agri-food and forestry land-management decisions are presented and discussed. We suggest that further testing of these propositions will provide evidence for decision makers about how decision contexts can be shifted to enable anticipatory transformative adaptation in the primary industries and support sustainable transitions towards more resilient futures.
Exploring the Effects of Transportation Supply on Mixed Land-Use at the Parcel Level
Authors: Almansoub Yunes , Zhong Ming , Raza Asif , Safdar Muhammad , Dahou Abdelghani , Al-qaness Mohammed A. A.
Published: May 2022

The interactive relationship between transportation and land use has become more difficult to understand and predict, due to the economic boom and corresponding fast-paced proliferation of private transportation and land-development activities. A lack of coordination between transportation and land-use planning has created an imbalanced provision of transportation infrastructure and land-use patterns; this is indicated by places where a high-density land-development pattern is supported by a low-capacity transport system or vice versa. With this, literature suggests that Mixed Land-Use (MLU) developments have the potential to provide relevant solutions for urban sustainability, smart growth, inclusive public transit use, and efficient land-use. Therefore, this study employed deep neural network models—Long Short-Term Memory (LSTM), and Multilayer Perceptron (MLP)—for forecasting the effect of transportation supply on the MLU pattern at the parcel level in the Jiang’an District, Wuhan, China. The findings revealed a strong relationship between the supply of public transportation and MLU. Moreover, the study results indicated that MLU is widely available in areas with high accessibility, high density, and proximity to the city center. The forecasting results from the MLP and LSTM models showed an average error of 5.55–7.36% and 3.62–4.28% for mixed use, respectively, while most of their 90th percentile errors were less than 13.73% and 10.46% for mixed use, respectively. The proposed models and the findings from this study should be useful for stakeholders and policy makers for more precise forecasting of MLU at the urban level.
Unsafe from Any Angle: Vulnerability-Generation on the US–Canada Border
Authors: Frenyo Edit
Published: May 2022

This article provides a review of the functioning and legality of the Safe Third Country Agreement between Canada and the United States, placing it in the broader context of systemic factors that generate and exacerbate the vulnerability of protection seekers. It offers a critical evaluation of what the legal challenges against the STCA reveal about the promises and limitations of safe-country-related litigation and the future of the Agreement.
YAP Inhibition by Verteporfin Causes Downregulation of Desmosomal Genes and Proteins Leading to the Disintegration of Intercellular Junctions
Authors: Huang Yunying , Ahmad Usama , Rehman Ambreen , Uttagomol Jutamas , Wan Hong
Published: May 2022

The Hippo-YAP pathway serves as a central signalling hub in epithelial tissue generation and homeostasis. Yes-associated protein (YAP) is an essential downstream transcription cofactor of this pathway, with its activity being negatively regulated by Hippo kinase-mediated phosphorylation, leading to its cytoplasmic translocation or degradation. Our recent study showed phospho-YAP complexes with Desmoglein-3 (Dsg3), the desmosomal cadherin known to be required for junction assembly and cell–cell adhesion. In this study, we show that YAP inhibition by Verteporfin (VP) caused a significant downregulation of desmosomal genes and a remarkable reduction in desmosomal proteins, including the Dsg3/phospho-YAP complex, resulting in attenuation of cell cohesion. We also found the desmosomal genes, along with E-cadherin, were the YAP-TEAD transcriptional targets and Dsg3 regulated key Hippo components, including WWTR1/TAZ, LATS2 and the key desmosomal molecules. Furthermore, Dsg3 and phospho-YAP exhibited coordinated regulation in response to varied cell densities and culture durations. Overexpression of Dsg3 could compensate for VP mediated loss of adhesion components and proper architecture of cell junctions. Thus, our findings suggest that Dsg3 plays a crucial role in the Hippo network and regulates junction configuration via complexing with phospho-YAP.
Delayed Maturation of Oligodendrocyte Progenitors by Microgravity: Implications for Multiple Sclerosis and Space Flight
Authors: Tran Victoria , Carpo Nicholas , Shaka Sophia , Zamudio Joile , Choi Sungshin , Cepeda Carlos , Espinosa-Jeffrey Araceli
Published: May 2022

In previous studies, we examined the effects of space microgravity on human neural stem cells. To date, there are no studies on a different type of cell that is critical for myelination and electrical signals transmission, oligodendrocyte progenitors (OLPs). The purpose of the present study was to examine the behavior of space-flown OLPs (SPC-OLPs) as they were adapting to Earth’s gravity. We found that SPC-OLPs survived, and most of them proliferated normally. Nonetheless, some of them displayed incomplete cytokinesis. Both morphological and ontogenetic analyses showed that they remained healthy and expressed the immature OLP markers Sox2, PDGFR-α, and transferrin (Tf) after space flight, which confirmed that SPC-OLPs displayed a more immature phenotype than their ground control (GC) counterparts. In contrast, GC OLPs expressed markers that usually appear later (GPDH, O4, and ferritin), indicating a delay in SPC-OLPs’ development. These cells remained immature even after treatment with culture media designed to support oligodendrocyte (OL) maturation. The most remarkable and surprising finding was that the iron carrier glycoprotein Tf, previously described as an early marker for OLPs, was expressed ectopically in the nucleus of all SPC-OLPs. In contrast, their GC counterparts expressed it exclusively in the cytoplasm, as previously described. In addition, analysis of the secretome demonstrated that SPC-OLPs contained 3.5 times more Tf than that of GC cells, indicating that Tf is gravitationally regulated, opening two main fields of study to understand the upregulation of the Tf gene and secretion of the protein that keep OLPs at a progenitor stage rather than moving forward to more mature phenotypes. Alternatively, because Tf is an autocrine and paracrine factor in the central nervous system (CNS), in the absence of neurons, it accumulated in the secretome collected after space flight. We conclude that microgravity is becoming a novel platform to study why in some myelin disorders OLPs are present but do not mature.
Upcycling of Pharmaceutical Glass into Highly Porous Ceramics: From Foams to Membranes
Authors: Mehta Akansha , Karbouche Khaoula , Kraxner Jozef , Elsayed Hamada , Galusek Dušan , Bernardo Enrico
Published: May 2022

The present COVID-19 emergency has dramatically increased the demand for pharmaceutical containers, especially vials. End-of-life containers, however, cannot be easily recycled in the manufacturing of new articles. This paper presents some strategies for upcycling of pharmaceutical glass into various porous ceramics. Suspensions of a fine glass powder (70 vol%) are used as a starting material. Highly uniform cellular structures may be easily prepared by vigorous mechanical stirring of partially gelified suspensions with added surfactant, followed by drying and firing at 550–650 °C. Stabilization of the cellular structures at temperatures as low as the glass transition temperature (Tg) of the used glass is facilitated by thermal decomposition of the gel phase, instead of viscous flow sintering of glass. This finding enabled the preparation of glass membranes (∼78 vol% open porosity), by direct firing of hardened suspensions, avoiding any surfactant addition and mechanical stirring. The powders obtained by crushing of hardened suspensions, even in unfired state, may be used as a low-cost sorbent for dye removal.
NSF-Based Analysis of the Structural Stressing State of Trussed Steel and a Concrete Box Girder
Authors: Yuan Jian , Lai Jie , Xu Feng , Wu Zhengfa , Yu Suhui , Sun Guorui
Published: May 2022

This paper analyses the characteristics of the mechanical behavior of a trussed steel and concrete box beam under bending conditions based on the structural stressing state theory and the numerical shape function method. Firstly, the parametric generalized strain energy density was introduced to characterize the structural stressing state of trussed steel stud concrete box girders, and the strain energy density sum was plotted. Then the Mann-Kendall criterion was used to discriminate the leap point of the curve change and to redefine the structural failure load. By analyzing the strain and displacement, the existence of a sudden change in the structural response during the load-bearing process was again demonstrated. Afterwards, the numerical shape function method was used to extend the strain data, and further in-depth analyses of strain/stress fields and internal forces were carried out to show in detail the working characteristics of each under load. Through an in-depth analysis from different angles, the rationality of updating the failure load was verified. Finally, the effects of different structure parameters on the evolution of the structural stresses of the members were analyzed in a transversal comparison. The analysis results of the stress state of a steel-concrete truss structure reveal the working behavior characteristics of a steel-concrete truss structure from a new angle, which provides a reference for the design of a steel-concrete truss structure in the future.
Two-Dimensional ZnS/SnS2 Heterojunction as a Direct Z-Scheme Photocatalyst for Overall Water Splitting: A DFT Study
Authors: Chen Xing , Zhao Cuihua , Wu Hao , Shi Yong , Chen Cuiting , Zhou Xi
Published: May 2022

Direct Z-scheme photocatalysts have attracted extensive attention due to their strong redox ability and efficient separation of photogenerated electron-hole pairs. In this study, we constructed two types of ZnS/SnS2 heterojunctions with different stacking models of ZnS and SnS2 layers, and investigated their structures, stabilities, and electronic and optical properties. Both types of heterojunctions are stable and are direct Z-scheme photocatalysts with band gaps of 1.87 eV and 1.79 eV, respectively. Furthermore, their oxidation and reduction potentials straddle the redox potentials of water, which makes them suitable as photocatalysts for water splitting. The built-in electric field at the heterojunction interface improves the separation of photogenerated electron-hole pairs, thus enhancing their photocatalytic efficiency. In addition, ZnS/SnS2 heterojunctions have higher carrier mobilities and light absorption intensities than ZnS and SnS2 monolayers. Therefore, the ZnS/SnS2 heterojunction has a broad application prospect as a direct Z-scheme visible-light-driven photocatalyst for overall water splitting.
The Influence of Ce, La, and SiC Particles Addition on the Formability of an Al-Si-Cu-Mg-Fe SiCp-MMC
Authors: Du Andong , Lattanzi Lucia , Jarfors Anders E. W. , Zhou Jie , Zheng Jinchuan , Wang Kaikun , Yu Gegang
Published: May 2022

Road transport and the associated fuel consumption plays a primary role in emissions. Weight reduction is critical to reaching the targeted reduction of 34% in 2025. Weight reduction in moving parts, such as pistons and brake disc rotors, provide a high-impact route to achieve this goal. The current study aims to investigate the formability of Al–Si alloys reinforced with different fractions and different sizes of SiCp to create an efficient and lightweight Al-MMC brake disk. Lanthanum (La) and cerium (Ce) were added to strengthen the aluminium matrix alloy and to improve the capability of the Al-MMC brake discs to withstand elevated temperature conditions, such as more extended braking periods. La and Ce formed intermetallic phases that further strengthened the composite. The analysis showed the processability and thermal stability of the different material’s combinations: increased particle sizes and broader size range mixture supported the formation of the SiCp particle interactions, acting as an internal scaffolding. In conclusion, the additions of Ce and La strengthened the softer matrix regions and resulted in a doubled compression peak strength of the material without affecting the formability, as demonstrated by the processing maps.
Experimental and Theoretical Study of Plastic Deformation of Epoxy Coatings on Metal Substrates Using the Acoustic Emission Method
Authors: Louda Petr , Sharko Aleksandr , Stepanchikov Dmitry , Sharko Artem
Published: May 2022

Propagation of acoustic emission signals in continuous conjugated media under real-time loading was explored. The results of explored plastic deformation polymer coatings on a metal base using the acoustic emission method with synchronization of deformations and the moments of occurrence of acoustic emission signals are presented. Using the principal component method, the acoustic emission spectra, which make it possible to trace the evolution of deformation transformation processes, were analyzed. Presented the results of theoretical and experimental studies on the separate propagation of acoustic emission vibrations in a polymer coating, a metal base, and their joint combination in the form of multilayer structures. Boundary problems of propagation of acoustic emission signals in the conjugation of continuous media are considered from the standpoint of an elastic continuum and wave representations. The main variables are the force that initiates the appearance of acoustic emission signals and the displacement that determines the propagation of elastic waves. Based on the local rearrangement of the internal structure of conjugated media under conditions of development of deformation processes in the material, the verification of the main theoretical models of energy spectrum acoustic signals in continuous media at the micro-, meso-, and macro-levels was carried out. In this work, we present experimental data on a set of basic acoustic emission characteristics for four-point bending. It is shown that the principal components method reduces the dimension of data while maintaining the least amount of new information. Using the method of principal components to determine the stages of plastic deformation of polymer coatings on a metal base using the acoustic emission method. With the digitalization of acoustic emission signals and noise filtering, new possibilities for isolating a weak signal at the noise level appear even when its amplitude is significantly lower than the noise level. The study results can be used to predict the degree of destruction of two-layer materials under loading.
pH and Redox-Dual Sensitive Chitosan Nanoparticles Having Methyl Ester and Disulfide Linkages for Drug Targeting against Cholangiocarcinoma Cells
Authors: Yang Ju-Il , Lee Hye Lim , Yun Je-Jung , Kim Jungsoo , So Kyoung-Ha , Jeong Young-IL , Kang Dae-Hwan
Published: May 2022

The aim of this study is to prepare pH- and redox-sensitive nanoparticles for doxorubicin (DOX) delivery against DOX-resistant HuCC-T1 human cholangiocarcinoma (CCA) cells. For this purpose, L-histidine methyl ester (HIS) was attached to chitosan oligosaccharide (COS) via dithiodipropionic acid (abbreviated as ChitoHISss). DOX-incorporated nanoparticles of ChitoHISss conjugates were fabricated by a dialysis procedure. DOX-resistant HuCC-T1 cells were prepared by repetitive exposure of HuCC-T1 cells to DOX. ChitoHISss nanoparticles showed spherical morphology with a small diameter of less than 200 nm. The acid pH and glutathione (GSH) addition induced changes in the size distribution pattern of ChitoHISss nanoparticles from a narrow/monomodal distribution pattern to a wide/multimodal pattern and increased the fluorescence intensity of the nanoparticle solution. These results indicate that a physicochemical transition of nanoparticles can occur in an acidic pH or redox state. The more acidic the pH or the higher the GSH concentration the higher the drug release rate was, indicating that an acidic environment or higher redox states accelerated drug release from ChitoHISss nanoparticles. Whereas free DOX showed decreased anticancer activity at DOX-resistant HuCC-T1 cells, DOX-incorporated ChitoHISss nanoparticles showed dose-dependent anticancer activity. Intracellular delivery of DOX-incorporated ChitoHISss nanoparticles was relatively increased at an acidic pH and in the presence of GSH, indicating that DOX-incorporated ChitoHISss nanoparticles have superior acidic pH- and redox-sensitive behavior. In an in vivo tumor xenograft model, DOX-incorporated ChitoHISss nanoparticles were specifically delivered to tumor tissues and then efficiently inhibited tumor growth. We suggest that ChitoHISss nanoparticles are a promising candidate for treatment of CCA.