bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated H3K4me3 Through MLL2-WDR82 upon Hyperglycemia Causes Jagged Ligand Dependent Notch Activation to Interplay with Differentiation State of Endothelial Cells
Authors: Pandya Thakkar Niyati , Pereira Beatriz Maria Veloso , Katakia Yash T. , Ramakrishnan Shyam Kumar , Thakar Sumukh , Sakhuja Ashima , Rajeev Gayathry , Soorya S. , Thieme Karina , Majumder Syamantak
Published: March 2022

Endothelial-to-mesenchymal transition (EndMT) is a hallmark of diabetes-associated vascular complications. Epigenetic mechanisms emerged as one of the key pathways to regulate diabetes-associated complications. In the current study, we aimed to determine how abrupt changes in histone 3 lysine 4 tri-methylation (H3K4me3) upon hyperglycemia exposure reprograms endothelial cells to undergo EndMT. Through in vitro studies, we first establish that intermittent high-glucose exposure to EC most potently induced partial mesenchyme-like characteristics compared with transient or constant high-glucose-challenged endothelial cells. In addition, glomerular endothelial cells of BTBR Ob/Ob mice also exhibited mesenchymal-like characteristics. Intermittent hyperglycemia-dependent induction of partial mesenchyme-like phenotype of endothelial cells coincided with an increase in H3K4me3 level in both macro- and micro-vascular EC due to selective increase in MLL2 and WDR82 protein of SET1/COMPASS complex. Such an endothelial-specific heightened H3K4me3 level was also detected in intermittent high-glucose-exposed rat aorta and in kidney glomeruli of Ob/Ob mice. Elevated H3K4me3 enriched in the promoter regions of Notch ligands Jagged1 and Jagged2, thus causing abrupt expression of these ligands and concomitant activation of Notch signaling upon intermittent hyperglycemia challenge. Pharmacological inhibition and/or knockdown of MLL2 in cells in vitro or in tissues ex vivo normalized intermittent high-glucose-mediated increase in H3K4me3 level and further reversed Jagged1 and Jagged2 expression, Notch activation and further attenuated acquisition of partial mesenchyme-like phenotype of endothelial cells. In summary, the present study identifies a crucial role of histone methylation in hyperglycemia-dependent reprograming of endothelial cells to undergo mesenchymal transition and indicated that epigenetic pathways contribute to diabetes-associated vascular complications.
A Self-Reference Interference Sensor Based on Coherence Multiplexing
Authors: Shen Ying , Huang Zeyu , Huang Feng , He Yonghong , Ye Ziling , Zhang Hongjian , Guo Cuixia
Published: March 2022

Interferometry has been widely used in biosensing due to its ability to acquire molecular affinity and kinetics in real-time. However, interferometric-based sensors are susceptible to environmental disturbances, including temperature and non-specific binding of target molecules, which reduces their detection robustness. To address this shortcoming, this paper proposes a self-referencing interference sensor based on coherence multiplexing to resist environmental disturbances. The proposed sensor can address temperature and non-specific binding, but it is not limited only to these types of disturbances. In the proposed sensor design, each sensor signal is encoded using a specific optical path difference determined by the optical thickness of a sensor chip. In addition, two sensor signals for disturbances tracking and biomolecule detection are detected simultaneously without additional cost to the second spectrometer and then differenced to achieve real-time self-reference. The temperature fluctuations experiments and specific binding experiments of protein A to IgG are performed to verify the performance of the proposed sensor. The results demonstrate that the proposed sensor can eliminate non-specific binding and temperature disturbances in real-time during biomolecule detection, achieving higher detection robustness. The proposed sensor is suitable for applications that require large-scale testing of biomolecular interactions, such as drug screening.
Evaluation of the Speed, Accuracy and Precision of the QuickMIC Rapid Antibiotic Susceptibility Testing Assay With Gram-Negative Bacteria in a Clinical Setting
Authors: Malmberg Christer , Torpner Jessie , Fernberg Jenny , Öhrn Håkan , Ångström Jonas , Johansson Cecilia , Tängdén Thomas , Kreuger Johan
Published: March 2022

The rapidly changing landscape of antimicrobial resistance poses a challenge for empirical antibiotic therapy in severely ill patients and highlights the need for fast antibiotic susceptibility diagnostics to guide treatment. Traditional methods for antibiotic susceptibility testing (AST) of bacteria such as broth microdilution (BMD) or the disc diffusion method (DDM) are comparatively slow and show high variability. Rapid AST methods under development often trade speed for resolution, sometimes only measuring responses at a single antibiotic concentration. QuickMIC is a recently developed lab-on-a-chip system for rapid AST. Here we evaluate the performance of the QuickMIC method with regard to speed, precision and accuracy in comparison to traditional diagnostic methods. 151 blood cultures of clinical Gram-negative isolates with a high frequency of drug resistance were tested using the QuickMIC system and compared with BMD for 12 antibiotics. To investigate sample turnaround time and method functionality in a clinical setting, another 41 clinical blood culture samples were acquired from the Uppsala University Hospital and analyzed on site in the clinical laboratory with the QuickMIC system, and compared with DDM for 8 antibiotics routinely used in the clinical laboratory. The overall essential agreement between MIC values obtained by QuickMIC and BMD was 83.4%, with an average time to result of 3 h 2 min (SD: 24.8 min) for the QuickMIC method. For the clinical dataset, the categorical agreement between QuickMIC and DDM was 96.8%, whereas essential and categorical agreement against BMD was 91.0% and 96.7%, respectively, and the total turnaround time as compared to routine diagnostics was shown to be reduced by 40% (33 h vs. 55 h). Interexperiment variability was low (average SD: 44.6% from target MIC) compared to the acceptable standard of ±1 log2 unit (i.e. -50% to +100% deviation from target MIC) in BMD. We conclude that the QuickMIC method can provide rapid and accurate AST, and may be especially valuable in settings with high resistance rates, and for antibiotics where wildtype and antibiotic-resistant bacteria have MIC distributions that are close or overlapping.
Toxoplasma gondii Genotyping: A Closer Look Into Europe
Authors: Fernández-Escobar Mercedes , Schares Gereon , Maksimov Pavlo , Joeres Maike , Ortega-Mora Luis Miguel , Calero-Bernal Rafael
Published: March 2022

Toxoplasma gondii is a major zoonotic agent which may cause harmful effects mainly in pregnant and immunocompromised hosts. Despite many efforts on its genetic characterization, an entirely clear picture of the population structure in Europe has not been achieved yet. The present study aimed to summarize the available genotyping information and to map the distribution of circulating strains. There is consensus on type II T. gondii genotypes prevailing in Europe, but the absence of harmonization in the use of typing methods limits detailed knowledge. Standardized, high-end typing tools and integrative strategies are needed to fill the gaps and complete an accurate image of the T. gondii genetic population in Europe.
A Predicted Model for Refractory/Recurrent Cytomegalovirus Infection in Acute Leukemia Patients After Haploidentical Hematopoietic Stem Cell Transplantation
Authors: Shen Meng-Zhu , Hong Shen-Da , Wang Jie , Zhang Xiao-Hui , Xu Lan-Ping , Wang Yu , Yan Chen-Hua , Chen Huan , Chen Yu-Hong , Han Wei , Wang Feng-Rong , Wang Jing-Zhi , Liu Kai-Yan , Huang Xiao-Jun , Mo Xiao-Dong
Published: March 2022

Objective

We aimed to establish a model that can predict refractory/recurrent cytomegalovirus (CMV) infection after haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT).

Methods

Consecutive acute leukemia patients receiving HID HSCT were enrolled (n = 289). We randomly selected 60% of the entire population (n = 170) as the training cohort, and the remaining 40% comprised the validation cohort (n = 119). Patients were treated according to the protocol registered at https://clinicaltrials.gov (NCT03756675).

Results

The model was as follows: Y = 0.0322 × (age) – 0.0696 × (gender) + 0.5492 × (underlying disease) + 0.0963 × (the cumulative dose of prednisone during pre-engraftment phase) – 0.0771 × (CD34+ cell counts in graft) – 1.2926. The threshold of probability was 0.5243, which helped to separate patients into high- and low-risk groups. In the low- and high-risk groups, the 100-day cumulative incidence of refractory/recurrent CMV was 42.0% [95% confidence interval (CI), 34.7%–49.4%] vs. 63.7% (95% CI, 54.8%–72.6%) (P < 0.001) for total patients and was 50.5% (95% confidence interval (CI), 40.9%–60.1%) vs. 71.0% (95% CI, 59.5%–82.4%) (P = 0.024) for those with acute graft-versus-host disease. It could also predict posttransplant mortality and survival.

Conclusion

We established a comprehensive model that could predict the refractory/recurrent CMV infection after HID HSCT.

Clinical Trial Registration

https://clinicaltrials.gov, identifier NCT03756675.
Outer Product-Based Fusion of Smartwatch Sensor Data for Human Activity Recognition
Authors: Mallol-Ragolta Adria , Semertzidou Anastasia , Pateraki Maria , Schuller Björn
Published: March 2022

The advent of IoT devices in combination with Human Activity Recognition (HAR) technologies can contribute to battle with sedentariness by continuously monitoring the users' daily activities. With this information, autonomous systems could detect users' physical weaknesses and plan personalized training routines to improve them. This work investigates the multimodal fusion of smartwatch sensor data for HAR. Specifically, we exploit pedometer, heart rate, and accelerometer information to train unimodal and multimodal models for the task at hand. The models are trained end-to-end, and we compare the performance of dedicated Recurrent Neural Network-based (RNN) and Convolutional Neural Network-based (CNN) architectures to extract deep learnt representations from the input modalities. To fuse the embedded representations when training the multimodal models, we investigate a concatenation-based and an outer product-based approach. This work explores the harAGE dataset, a new dataset for HAR collected using a Garmin Vivoactive 3 device with more than 17 h of data. Our best models obtain an Unweighted Average Recall (UAR) of 95.6, 69.5, and 60.8% when tackling the task as a 2-class, 7-class, and 10-class classification problem, respectively. These performances are obtained using multimodal models that fuse the embedded representations extracted with dedicated CNN-based architectures from the pedometer, heart rate, and accelerometer modalities. The concatenation-based fusion scores the highest UAR in the 2-class classification problem, while the outer product-based fusion obtains the best performances in the 7-class and the 10-class classification problems.
Will Smartphone Applications Replace the Insertable Cardiac Monitor in the Detection of Atrial Fibrillation? The First Comparison in a Case Report of a Cryptogenic Stroke Patient
Authors: Wouters Femke , Gruwez Henri , Vranken Julie , Ernon Ludovic , Mesotten Dieter , Vandervoort Pieter , Verhaert David
Published: March 2022

Background and Case

This case report exemplifies the clinical application of non-invasive photoplethysmography (PPG)-based rhythm monitoring in the awakening mobile health (mHealth) era to detect symptomatic and asymptomatic paroxysmal atrial fibrillation (AF) in a cryptogenic stroke patient. Despite extensive diagnostic workup, the etiology remains unknown in one out of three ischemic strokes (i.e., cryptogenic stroke). Prolonged cardiac monitoring can reveal asymptomatic atrial fibrillation in up to one-third of this population. This case report describes a cryptogenic stroke patient who received prolonged cardiac monitoring with an insertable cardiac monitor (ICM) as standard of care. In the context of a clinical study, the patient simultaneously monitored his heart rhythm with a PPG-based smartphone application. AF was detected simultaneously on both the ICM and smartphone application after three days of monitoring. Similar AF burden was detected during follow-up (five episodes, median duration of 28 and 34 h on ICM and mHealth, respectively, p = 0.5). The detection prompted the initiation of oral anticoagulation and AF catheter ablation procedure.

Conclusion

This is the first report of the cryptogenic stroke patient in whom PPG-based mHealth was able to detect occurrence and burden of the symptomatic and asymptomatic paroxysmal AF episodes with similar precision as ICM. It accentuates the potential role of PPG-based mHealth in prolonged cardiac rhythm monitoring in cryptogenic stroke patients.
Interpretation of Magnetic Anomalies by Simple Geometrical Structures Using the Manta-Ray Foraging Optimization
Authors: Ben Ubong C. , Ekwok Stephen E. , Akpan Anthony E. , Mbonu Charles C. , Eldosouky Ahmed M. , Abdelrahman Kamal , Gómez-Ortiz David
Published: March 2022

In this paper, a geophysical strategy based on the recently proposed Manta-Ray Foraging (MRF) Optimization algorithm is adapted and presented for the blind computation of depth/shape defining parameters from magnetic anomalies due to buried geo-bodies. The model parameters deciphered are the coefficient of amplitude (K), buried structure’s origin (x0), the depth (z), magnetization angle (α), and a shape factor (q). After detailed and piecewise design, the new inversion tool is originally trial-tested on anomaly data generated synthetically. The uncorrupted version of the test data is first analyzed, then - it is corrupted with noise varied at 5, 10, 15, and 20% corruption levels. Thereafter, it is experimented with magnetic profiles taken from exploration fields in the United States, Peru, and Egypt. From the evaluation of results obtained, the new procedure is observed as exhibiting outstanding stability and flexibility especially with noisy dataset and notable efficiency in the quantitative resolution of magnetic inversion problems. The results obtained for the field cases are also mostly consistent especially when compared with background results from similar studies conducted with other methods; further affirming the new tool as reliable for the geophysical investigation of buried minerals.
Three-Dimensional Distribution of Platinum Group Minerals in Natural MSS-ISS Ores From the Norilsk One Deposit, Russia
Authors: Sittner J. , Brovchenko V. , Siddique A. , Buyse F. , Boone M. , Renno A.D. , Cnudde V. , Merkulova M. , Sluzhenikin S.F.
Published: March 2022

The Mt. Rudnaya MSS-ISS (monosulfide and intermediate solid solution) fine-grained ores from a NE termination of Norilsk 1 deposit were analyzed using a combination of X-ray computed micro tomography, spectral X-ray computed micro tomography and scanning electron microscopy to achieve both, 2D and 3D data. The ores consist of ISS composed of tiny lamellar intergrowths of cubanite and chalcopyrite solid solutions, which form up to 4-mm distinct globules surrounded by an ISS-MSS matrix. Our X-ray computed micro tomography results may provide 3D textural evidence of a possible natural sulfide-sulfide liquid immiscibility between Cu-rich and Cu-poor sulfide liquids that occurred before MSS and ISS were crystallized. The platinum group minerals (PGM) distribution shows that 20.6 vol% of all PGM occur in the ISS-MSS matrix and 79.4 vol% in the ISS globules. We suggest that this distributional behavior is due to the fact that the platinum group elements (PGE) cannot be dissolved in ISS, which led to the formation of the large PGM grains, which are up to 120 μm on their longest axis. The initial enrichment of ISS in PGE was controlled by differences in the partition coefficients of platinum and palladium between Cu-poor and Cu-rich liquids.
Multi-Decadal Glacier Area and Mass Balance Change in the Southern Peruvian Andes
Authors: Taylor Liam S. , Quincey Duncan J. , Smith Mark W. , Potter Emily R. , Castro Joshua , Fyffe Catriona L.
Published: March 2022

Around 70% of the world’s tropical glaciers are located in Peru, and they are melting rapidly in response to climate change. The glaciers of the data-sparse Southern Peruvian Andes, comprising the Cordilleras Vilcanota, Vilcabamba, and Urubamba, are a primary water source for thousands of people living in the rural foothills, and support people throughout the wider Cusco region. Here, we calculate geodetic mass balance for the Cordillera Vilcanota (−0.48 ± 0.07 m w.e. yr−1) using the ASTER satellite archive and derive a total loss of 3.18 ± 0.44 Gt ice between 2000 and 2020. Glacierised area has shrunk rapidly since the 1970s (losses of 54, 56, and 64% for the Cordilleras Vilcanota, Vilcabamba, and Urubamba respectively) as a consequence of changing climatic patterns, with low-lying glaciers receding the most across all regions. We calculate a rise in the median elevation of glaciers ranging from 15.9 m per decade over the Quelccaya ice cap in the Cordillera Vilcanota, to 32.8 m per decade in the Cordillera Vilcabamba, over the period 1975 to 2020. This change implies an increased hazard potential as the mountain regions become destabilised, and will lead to increasing pressure on fresh water supply as meltwater streamflow decreases and river discharge becomes increasingly, and irreversibly, variable.
Cybervictimization in Chilean Schools: An Intersectional Multilevel Study
Authors: Jensen Matías , Yañez Cristóbal , Rojas Javiera , López Verónica , González Luis , Urbina Carolina , San Juan Madeleine , Squicciarini Ana María , Sánchez Paola
Published: March 2022

Even though research has established the prevalence and predicting factors of cybervictimization in the school context, studies have not considered their nested nature, which might lead to differences within and between schools. Research has only just begun to recognize the intersectionality of various cultural labels and marginalized identities, but most studies have been qualitative. Using a quantitative approach that considers the nested nature of the data and inspired by an intersectional theoretical framework, we performed a multilevel analysis of cybervictimization in a sample of 34,959 students enrolled in fifth to eighth grade in 410 Chilean schools with low socioeconomic status. Findings showed that 14.3% of students reported some type of cybervictimization during the last month. Level 1 (individual) findings showed that being male, over age, of an ethnic origin, and reporting a negative perception of school climate significantly contributed to self-reported cybervictimization. Discrimination due to sexual orientation was the most critical variable at both the individual (b= 1.39,p< 0.001) and school (b= 1.26,p< 0.001) levels. Likewise, this factor interacted significantly with all variables at the individual level. We discuss the implications of this study, among them that school-related cybervictimization seems to be strongly associated with homophobia and homophobic school environments in which gender-non-conforming students feel discriminated. This calls for the incorporation of an intersectional and inclusive approach to policies and practices for preventing and diminishing cyberbullying and its different expressions, promoting heterogeneity as a virtue in schools.
Rethinking Quality Science Education for Climate Action: Transdisciplinary Education for Transformative Learning and Engagement
Authors: Kubisch Susanne , Krimm Hanna , Liebhaber Nina , Oberauer Karin , Deisenrieder Veronika , Parth Sandra , Frick Melanie , Stötter Johann , Keller Lars
Published: March 2022

Latest findings of the IPCC highlight the fact that there is an urgent need for climate action on both individual and societal levels, because political regulations and technical advances just would not be enough to counter climate change. Acknowledging young people’s role as present and future decision-makers, their engagement is absolutely imperative in order to achieve Sustainable Development Goal 13, “Climate Action.” Therefore, new methods of teaching and learning are necessary, and they need to encourage transformative learning, which, it is assumed, will lay foundations for transformative engagement. Research in the field of science education credits scientific literacy vision III as fostering transformative learning and engagement. In this study, transdisciplinary education is analyzed as a promising concept that enables exchange of knowledge, experiences, and perspectives between students and scientific partners while they jointly complete research on real-world issues. A quantitative analysis capturing scientific literacy and transformative engagement for climate action of Austrian and German secondary school students (N= 162) is carried out alongside a literature review. This study reveals that the didactical concept of transdisciplinary education notably contributes to the implementation of scientific literacy vision III as well as vision II. According to the results, the three visions of scientific literacy are predictors for transformative engagement for climate action, assuming to be preceded by a transformative learning process. These encouraging findings need to be replicated by further scholars in other contexts.
Associations of Sperm mtDNA Copy Number, DNA Fragmentation Index, and Reactive Oxygen Species With Clinical Outcomes in ART Treatments
Authors: Shi Wei-Hui , Ye Mu-Jin , Qin Ning-Xin , Zhou Zhi-Yang , Zhou Xuan-You , Xu Nai-Xin , Chen Song-Chang , Li Shu-Yuan , Xu Chen-Ming
Published: March 2022

Recent studies have suggested that sperm mitochondrial DNA copy number (mtDNA-CN), DNA fragmentation index (DFI), and reactive oxygen species (ROS) content are crucial to sperm function. However, the associations between these measurements and embryo development and pregnancy outcomes in assisted reproductive technology (ART) remain unclear. Semen samples were collected from 401 participants, and seminal quality, parameters of sperm concentration, motility, and morphology were analyzed by a computer-assisted sperm analysis system. DFI, mtDNA-CN, and ROS levels were measured using sperm chromatin structure assay, real-time quantitative polymerase chain reaction, and ROS assay, respectively. Among the participants, 126 couples underwent ART treatments, including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and 79 of the couples had embryos transferred. In 401 semen samples, elevated mtDNA-CN and DFI were associated with poor seminal quality. In 126 ART couples, only mtDNA-CN was negatively correlated with the fertilization rate, but this correlation was not significant after adjusting for male age, female age, seminal quality, ART strategy, number of retrieved oocytes, controlled stimulation protocols, and cycle rank. Regarding pregnancy outcomes, sperm mtDNA-CN, ROS, and DFI were not associated with the clinical pregnancy rate or live birth rate in 79 transferred cases. In conclusion, increased mtDNA-CN and DFI in sperm jointly contributed to poor seminal quality, but sperm mtDNA-CN, ROS, and DFI were not associated with clinical outcomes in ART.
Innovative Activities in the Sphere of Mining Process Management
Authors: Bazaluk Oleg , Ashcheulova Oleksandra , Mamaikin Oleksandr , Khorolskyi Andrii , Lozynskyi Vasyl , Saik Pavlo
Published: March 2022

The purpose of this paper is to propose a new methodological approach to complex assessment of coal-mining enterprises basing on the evaluation of technological schemes from the viewpoint of their susceptibility to innovations. To solve the specified problems, a complex method has been used. The method involves geometrical interpretation of a task of determining boundary parameters of technological schemes, application of criteria-based estimations for determining a level of production efficiency, and use of complex index of economic re liability. For the first time, optimality criteria for innovation management in coal industry have been proposed; they take into consideration a level of organization of innovations, organization of innovative production system, and organization of innovative production process. A complex index “internal potential of technological networks” has been developed, being one of the essential parameters for evaluating coal mine conditions. It has been identified that its formation is the result of the influence of certain factors determining the underground mining efficiency and, first of all, the coal mine property—spatial development. According to the represented concept, a policy of optimal control for maintaining the operating mine capacities is based on the evaluation of remained reserves, substantiated planning of a stoping line, and correspondence of extraction equipment to the operating conditions. It is possible to increase the concentration of production by redistributing the remained reserves and integration of mines by mining operations; that makes it possible to concentrate resources within those parts of a mine field where the effect will show its maximum. Modelling of such problems is based on a system of constraints without any requirements for providing the planned mine loading, obligatory in the past. Analysis of the indices of efficiency of coal-mining technological schemes and accounting of the developed factual system of indices have helped elaborate recommendations concerning the use of optimality criteria in the organizational tasks of assessment of the potential of technological scheme of mines. Further application of graphs and network models will allow optimizing the mining production parameters. Consequently, the carried out research has resulted in a new system as for innovation management in a mining complex.
Human Impacts on Insect Chemical Communication in the Anthropocene
Authors: Knaden Markus , Anderson Peter , Andersson Martin N. , Hill Sharon R. , Sachse Silke , Sandgren Mats , Stensmyr Marcus C. , Löfstedt Christer , Ignell Rickard , Hansson Bill S.
Published: March 2022

The planet is presently undergoing dramatic changes caused by human activities. We are living in the era of the Anthropocene, where our activities directly affect all living organisms on Earth. Insects constitute a major part of the world’s biodiversity and currently, we see dwindling insect biomass but also outbreaks of certain populations. Most insects rely on chemical communication to locate food, mates, and suitable oviposition sites, but also to avoid enemies and detrimental microbes. Emissions of, e.g., CO2, NOx, and ozone can all affect the chemical communication channel, as can a rising temperature. Here, we present a review of the present state of the art in the context of anthropogenic impact on insect chemical communication. We concentrate on present knowledge regarding fruit flies, mosquitoes, moths, and bark beetles, as well as presenting our views on future developments and needs in this emerging field of research. We include insights from chemical, physiological, ethological, and ecological directions and we briefly present a new international research project, the Max Planck Centre for Next Generation Insect Chemical Ecology (nGICE), launched to further increase our understanding of the impact of human activities on insect olfaction and chemical communication.
Basidiomycota Fungi and ROS: Genomic Perspective on Key Enzymes Involved in Generation and Mitigation of Reactive Oxygen Species
Authors: Mattila Hans , Österman-Udd Janina , Mali Tuulia , Lundell Taina
Published: March 2022

Our review includes a genomic survey of a multitude of reactive oxygen species (ROS) related intra- and extracellular enzymes and proteins among fungi of Basidiomycota, following their taxonomic classification within the systematic classes and orders, and focusing on different fungal lifestyles (saprobic, symbiotic, pathogenic). Intra- and extracellular ROS metabolism-involved enzymes (49 different protein families, summing 4170 protein models) were searched as protein encoding genes among 63 genomes selected according to current taxonomy. Extracellular and intracellular ROS metabolism and mechanisms in Basidiomycota are illustrated in detail. In brief, it may be concluded that differences between the set of extracellular enzymes activated by ROS, especially by H2O2, and involved in generation of H2O2, follow the differences in fungal lifestyles. The wood and plant biomass degrading white-rot fungi and the litter-decomposing species of Agaricomycetes contain the highest counts for genes encoding various extracellular peroxidases, mono- and peroxygenases, and oxidases. These findings further confirm the necessity of the multigene families of various extracellular oxidoreductases for efficient and complete degradation of wood lignocelluloses by fungi. High variations in the sizes of the extracellular ROS-involved gene families were found, however, among species with mycorrhizal symbiotic lifestyle. In addition, there are some differences among the sets of intracellular thiol-mediation involving proteins, and existence of enzyme mechanisms for quenching of intracellular H2O2 and ROS. In animal- and plant-pathogenic species, extracellular ROS enzymes are absent or rare. In these fungi, intracellular peroxidases are seemingly in minor role than in the independent saprobic, filamentous species of Basidiomycota. Noteworthy is that our genomic survey and review of the literature point to that there are differences both in generation of extracellular ROS as well as in mechanisms of response to oxidative stress and mitigation of ROS between fungi of Basidiomycota and Ascomycota.
DOT1L Mediated Gene Repression in Extensively Self-Renewing Erythroblasts
Authors: Borosha Shaon , Ratri Anamika , Ghosh Subhra , Malcom Carrie A. , Chakravarthi V. Praveen , Vivian Jay L. , Fields Timothy A. , Rumi M. A. Karim , Fields Patrick E.
Published: March 2022

DOT1L is essential for embryonic hematopoiesis but the precise mechanisms of its action remain unclear. The only recognized function of DOT1L is histone H3 lysine 79 (H3K79) methylation, which has been implicated in both transcriptional activation and repression. We observed that deletion of the mouse Dot1L gene (Dot1L-KO) or selective mutation of its methyltransferase domain (Dot1L-MM) can differentially affect early embryonic erythropoiesis. However, both mutations result in embryonic lethality by mid-gestation and growth of hematopoietic progenitor cells (HPCs) is similarly affected in extensively self-renewing erythroblast (ESRE) cultures established from yolk sac cells. To understand DOT1L-mediated gene regulation and to clarify the role of H3K79 methylation, we analyzed whole transcriptomes of wildtype and Dot1L-mutant ESRE cells. We observed that more than 80% of the differentially expressed genes (DEGs) were upregulated in the mutant ESRE cells either lacking the DOT1L protein or the DOT1L methyltransferase activity. However, approximately 45% of the DEGs were unique to either mutant group, indicating that DOT1L possesses both methyltransferase-dependent and -independent gene regulatory functions. Analyses of Gene Ontology and signaling pathways for the DEGs were consistent, with DEGs that were found to be common or unique to either mutant group. Genes related to proliferation of HPCs were primarily impacted in Dot1L-KO cells, while genes related to HPC development were affected in the Dot1L-MM cells. A subset of genes related to differentiation of HPCs were affected in both mutant groups of ESREs. Our findings suggest that DOT1L primarily acts to repress gene expression in HPCs, and this function can be independent of its methyltransferase activity.
Comprehensive Analysis of RNA-Seq in Endometriosis Reveals Competing Endogenous RNA Network Composed of circRNA, lncRNA and mRNA
Authors: Yin Meichen , Zhai Lingyun , Wang Jianzhang , Yu Qin , Li Tiantian , Xu Xinxin , Guo Xinyue , Mao Xinqi , Zhou Jianwei , Zhang Xinmei
Published: March 2022

Although long non coding RNAs (lncRNAs) and circular RNAs (circRNAs) play important roles in the pathogenesis of diseases, endometriosis related lncRNAs and circRNAs are still rarely reported. This study focused on the potential molecular mechanism of endometriosis related competitive endogenous RNA (ceRNA) composed of lncRNAs and circRNAs. We performed high-throughout sequencing of six normal endometria, six eutopic endometria and six ectopic endometria for the first time to describe and analyze the expression profile of lncRNA, circRNA and mRNA. Our results showed that 140 lncRNAs, 107 circRNAs and 1,206 mRNAs were differentially expressed in the ectopic group, compared with the normal and eutopic groups. We established an lncRNA/circRNA-mRNA co-expression network using pearson correlation test. Meanwhile, the results of Gene set enrichment analysis analysis showed that the 569 up-regulated differentially expressed mRNA (DEmRNA) were mainly related to the epithelial-mesenchymal transition, regulation of immune system process and immune effector process. Subsequently, we established a DElncRNA-miRNA and DEcircRNA-miRNA network using the starbase database, identified the common miRNAs and constructed DElncRNA/DEcircRNA-miRNA pairs. miRDB, Targetscan, miRwalk and circRNA/lncRNA-mRNA pairs jointly determined the miRNA-mRNA portion of the circRNA/lncRNA-miRNA-mRNA co-expression network. RT-qPCR results of 15 control samples and 25 ectopic samples confirmed that circGLIS2, circFN1, LINC02381, IGFL2-AS1, CD84, LYPD1 and FAM163A were significantly overexpressed in ectopic tissues. In conclusion, this is the first study to illustrate ceRNA composed of differentially expressed circRNA, lncRNA and mRNA in endometriosis. We also found that lncRNA and circRNA exerted a pivotal function on the pathogenesis of endometriosis, which can provide new insights for further exploring the pathogenesis of endometriosis and identifying new targets.
Polycyclic Aromatic Hydrocarbons Affect Rheumatoid Arthritis Pathogenesis via Aryl Hydrocarbon Receptor
Authors: Xi Xiaoyu , Ye Qinbin , Fan Danping , Cao Xiaoxue , Wang Qiong , Wang Xing , Zhang Mengxiao , Xu Yuan , Xiao Cheng
Published: March 2022

Rheumatoid arthritis (RA), the most common autoimmune disease, is characterized by symmetrical synovial inflammation of multiple joints with the infiltration of pro-inflammatory immune cells and increased cytokines (CKs) levels. In the past few years, numerous studies have indicated that several factors could affect RA, such as mutations in susceptibility genes, epigenetic modifications, age, and race. Recently, environmental factors, particularly polycyclic aromatic hydrocarbons (PAHs), have attracted increasing attention in RA pathogenesis. Therefore, exploring the specific mechanisms of PAHs in RA is vitally critical. In this review, we summarize the recent progress in understanding the mechanisms of PAHs and aryl hydrocarbon receptors (AHRs) in RA. Additionally, the development of therapeutic drugs that target AHR is also reviewed. Finally, we discuss the challenges and perspectives on AHR application in the future.
Nanoparticles for Inducing Antigen-Specific T Cell Tolerance in Autoimmune Diseases
Authors: Benne Naomi , ter Braake Daniëlle , Stoppelenburg Arie Jan , Broere Femke
Published: March 2022

Autoimmune diseases affect many people worldwide. Current treatment modalities focus on the reduction of disease symptoms using anti-inflammatory drugs which can lead to side effects due to systemic immune suppression. Restoration of immune tolerance by down-regulating auto-reactive cells in an antigen-specific manner is currently the “holy grail” for the treatment of autoimmune diseases. A promising strategy is the use of nanoparticles that can deliver antigens to antigen-presenting cells which in turn can enhance antigen-specific regulatory T cells. In this review, we highlight some promising cell targets (e.g. liver sinusoidal endothelial cells and splenic marginal zone macrophages) for exploiting natural immune tolerance processes, and several strategies by which antigen-carrying nanoparticles can target these cells. We also discuss how nanoparticles carrying immunomodulators may be able to activate tolerance in other antigen-presenting cell types. Finally, we discuss some important aspects that must be taken into account when translating data from animal studies to patients.
Cardiovascular Dysfunction in COVID-19: Association Between Endothelial Cell Injury and Lactate
Authors: Yang Kun , Holt Matthew , Fan Min , Lam Victor , Yang Yong , Ha Tuanzhu , Williams David L. , Li Chuanfu , Wang Xiaohui
Published: March 2022

Coronavirus disease 2019 (COVID-19), an infectious respiratory disease propagated by a new virus known as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has resulted in global healthcare crises. Emerging evidence from patients with COVID-19 suggests that endothelial cell damage plays a central role in COVID-19 pathogenesis and could be a major contributor to the severity and mortality of COVID-19. Like other infectious diseases, the pathogenesis of COVID-19 is closely associated with metabolic processes. Lactate, a potential biomarker in COVID-19, has recently been shown to mediate endothelial barrier dysfunction. In this review, we provide an overview of cardiovascular injuries and metabolic alterations caused by SARS-CoV-2 infection. We also propose that lactate plays a potential role in COVID-19-driven endothelial cell injury.
The Risk of Multiple Anthropogenic and Climate Change Threats Must Be Considered for Continental Scale Conservation and Management of Seagrass Habitat
Authors: McMahon Kathryn , Kilminster Kieryn , Canto Robert , Roelfsema Chris , Lyons Mitchell , Kendrick Gary A. , Waycott Michelle , Udy James
Published: March 2022

Globally marine-terrestrial interfaces are highly impacted due to a range of human pressures. Seagrass habitats exist in the shallow marine waters of this interface, have significant values and are impacted by a range of pressures. Cumulative risk analysis is widely used to identify risk from multiple threats and assist in prioritizing management actions. This study conducted a cumulative risk analysis of seagrass habitat associated with the Australian continent to support management actions. We developed a spatially explicit risk model based on a database of threats to coastal aquatic habitat in Australia, spanning 35,000 km of coastline. Risk hotspots were identified using the model and reducing the risk of nutrient and sediment pollution for seagrass habitat was assessed. Incorporating future threats greatly altered the spatial-distribution of risk. High risk from multiple current threats was identified throughout all bioregions, but high risk from climate change alone manifested in only two. Improving management of nutrient and sediment loads, a common approach to conserve seagrass habitat did reduce risk, but only in temperate regions, highlighting the danger of focusing management on a single strategy. Monitoring, management and conservation actions from a national and regional perspective can be guided by these outputs.
Research on the Bonding Performance of UHPC–NC Interfaces With Different Sizes of Grooves
Authors: Yang Jun , Xia Junrun , Cheng Chongsheng , Wang Jieyun , Zhang Jie , Wang Gang
Published: March 2022

The interfacial treatment between normal concrete (NC) and ultra-high–performance concrete (UHPC) is crucial to ensure bonding strength. Grooving is an effective method to treat the UHPC–NC interface, but the shear properties and failure modes at the composite interface remain under-investigated. This study focuses on the bonding performance of different groove designs (width, spacing, and angle) at the UHPC–NC interface, and push-off tests with 15 specimens were carried out to evaluate the strength and stiffness. Furthermore, a finite element model (FEM) and calculation methods were validated with the experimental study to reveal the bonding strength, and a parametric study on the groove depth was also carried out. The interface treated by grooves increases 3.32 and 2.48 times in strength and stiffness compared with specimens bonded by epoxy resin adhesive. The results also show that failing at the interface and NC matrix made up a majority of the failure modes. The shear strength of the UHPC–NC interface increased with the width and decreased with the space between the grooves. Grooves with 10 mm width, 100 mm space, 25 mm depth, and right angle were recommended. This paper will lay a foundation for the surface preparation of UHPC strengthening NC bridges.
Novel Method for the Growth of Two-Dimensional Layered InSe Thin Films on Amorphous Substrate by Molecular Beam Epitaxy
Authors: Hsiao Sheng-Wei , Yang Chu-Shou , Yang Hao-Ning , Wu Chia-Hsing , Wu Ssu-Kuan , Chang Li-Yun , Ho Yen-Teng , Chang Shu-Jui , Chou Wu-Ching
Published: March 2022

A two-dimensional (2D) material known as indium selenide (InSe) is widely considered a promising layered semiconductor with potential applications in electronics and optoelectronics. However, the single phase of InSe is still a challenge due to the close formation energy of InSe and In2Se3. In this study, we demonstrate a novel growth method for 2D InSe with an indium precursor layer by molecular beam epitaxy. Indium pre-deposited on substrate at room temperature followed by growth of InSe at 550°C can overcome the problem of stoichiometry control and can be applied on amorphous substrate with high quality. According to Raman scattering spectra, X-ray diffraction, and high-resolution transmission electron microscopy results, we find that 2D InSe phase can be facile formed under both indium-rich and -poor conditions. The pre-deposited indium precursor effectively induces replacement with subsequent Se and In atoms to form the InSe phase while suppressing the In2Se3 phase. Additionally, this single phase InSe is stable in the atmosphere, exhibiting superior electronic properties even after over 100 days exposure. Recently, this method has been successfully applied to a flexible substrate, such as aluminum foil, resulting in reliable InSe quality. Our results demonstrate an innovative and forward-looking approach to developing 2D InSe material.
Triple Therapy in COPD: Can We Welcome the Reduction in Cardiovascular Risk and Mortality?
Authors: Solidoro Paolo , Albera Carlo , Ribolla Fulvia , Bellocchia Michela , Brussino Luisa , Patrucco Filippo
Published: March 2022

Chronic obstructive pulmonary disease (COPD) is a complex disease which consists in the reduction of the airflow and leads to the disruption of the pulmonary tissue due to a chronic inflammation. The progression of the disease is characterized by an exacerbation of the symptoms and the presence of life-threatening systemic complications, such as stroke and ischemic heart disease, with a progressive decline in lung function which can deeply impact the quality of life. Mortality represents the most important COPD outcome, with an increased risk in patients with cardiovascular comorbidities. The efficacy and safety of triple inhaled therapy were demonstrated by numerous controlled trials. Above all, many robust data are now available on the effectiveness of the triple therapy to reduce mortality in COPD patients.
Pinpointing Cancer Sub-Type Specific Metabolic Tasks Facilitates Identification of Anti-cancer Targets
Authors: Gao Shuaishi , Dai Ziwei , Xu Hanyu , Lai Luhua
Published: March 2022

Metabolic reprogramming is one of the hallmarks of tumorigenesis. Understanding the metabolic changes in cancer cells may provide attractive therapeutic targets and new strategies for cancer therapy. The metabolic states are not the same in different cancer types or subtypes, even within the same sample of solid tumors. In order to understand the heterogeneity of cancer cells, we used the Pareto tasks inference method to analyze the metabolic tasks of different cancers, including breast cancer, lung cancer, digestive organ cancer, digestive tract cancer, and reproductive cancer. We found that cancer subtypes haves different propensities toward metabolic tasks, and the biological significance of these metabolic tasks also varies greatly. Normal cells treat metabolic tasks uniformly, while different cancer cells focus on different pathways. We then integrated the metabolic tasks into the multi-objective genome-scale metabolic network model, which shows higher accuracy in the in silico prediction of cell states after gene knockout than the conventional biomass maximization model. The predicted potential single drug targets could potentially turn into biomarkers or drug design targets. We further implemented the multi-objective genome-scale metabolic network model to predict synthetic lethal target pairs of the Basal and Luminal B subtypes of breast cancer. By analyzing the predicted synthetic lethal targets, we found that mitochondrial enzymes are potential targets for drug combinations. Our study quantitatively analyzes the metabolic tasks of cancer and establishes cancer type-specific metabolic models, which opens a new window for the development of specific anti-cancer drugs and provides promising treatment plans for specific cancer subtypes.
The Combined Use of Orf Virus and PAK4 Inhibitor Exerts Anti-tumor Effect in Breast Cancer
Authors: Deng Hao , Xiao Bin , Huang Yinger , Weng Kongyan , Chen Jialing , Li Kun , Wu Hongfeng , Luo Shuhong , Hao Wenbo
Published: March 2022

The parapoxvirus Orf virus (ORFV) has long been recognized as one of the valuable vectors in researches of oncolytic virus. In order to develop a potential therapeutic strategy for breast cancer based on the oncolytic virotherapy via ORFV, firstly we explore the oncolytic effects of ORFV. Our research showed that ORFV exerts anti-tumor effects in vitro by inducing breast cancer cell G2/M phase arrest and cell apoptosis. In vivo experiments were carried out, in which we treated 4T1 tumor-bearing BALB/C mice via intratumoral injection of ORFV. ORFV can exert anti-tumor activity by regulating tumor microenvironment (TME) and inducing a host immune response plus directly oncolytic effect. The CRISPR-Cas9 knockout library targeting 507 kinases was used to screen out PAK4, which is beneficial to the anti-tumor effect of ORFV on breast cancer cells. PF-3758309 is a potent PAK4-targeted inhibitor. Co-using of ORFV and PF-3758309 as a combination treatment produces its anti-tumor effects through inhibition of cell viability, induction of apoptosis and suppression of cell migration and invasion in vitro. The results of in vivo experiments showed that the tumor growth of mice in the combination treatment group was significantly inhibited, which proved that the combination treatment exerts an effective anti-tumor effect in vivo. In summary, we have clarified the oncolytic effect of ORFV on breast cancer, and found that the combination of ORFV and PAK4 inhibitor can effectively improve the oncolytic effect of ORFV. We hope our research could provide a new idea for the development of new treatment strategies for breast cancer.