bluuebunny/crossref_metadata_2025 huggingface dataset:
Leveraging Structural Health Monitoring Data Through Avatars to Extend the Service Life of Mass Timber Buildings
Authors: Riggio Mariapaola , Mrissa Michael , Krész Miklós , Včelák Jan , Sandak Jakub , Sandak Anna
Published: June 2022

Mass timber construction systems, incorporating engineered wood products as structural elements, are gaining acceptance as a sustainable alternative to multi-story concrete or steel-frame structures. The relative novelty of these systems brings uncertainties on whether these buildings perform long-term as expected. Consequently, several structural health monitoring (SHM) projects have recently emerged to document their behavior. A wide and systematic use of this data by the mass timber industry is currently hindered by limitations of SHM programs. These limitations include scalability, difficulty of data integration, diverse strategies for data collection, scarcity of relevant data, complexity of data analysis, and limited usability of predictive tools. This perspective paper envisions the use of avatars as a Web-based layer on top of sensing devices to support SHM data and protocol interoperability, analysis, and reasoning capability and to improve life cycle management of mass timber buildings. The proposed approach supports robustness, high level and large-scale interoperability and data processing by leveraging the Web protocol stack, overcoming many limitations of conventional centralized SHM systems. The design of avatars is applied in an exemplary scenario of hygrothermal data reconstruction, and use of this data to compare different mold growth prediction models. The proposed approach demonstrates the ability of avatars to efficiently filter and enrich data from heterogeneous sensors, thus overcoming problems due to data gaps or insufficient spatial distribution of sensors. In addition, the designed avatars can provide prediction or reasoning capability about the building, thus acting as a digital twin solution to support building lifecycle management.
VAP Proteins – From Organelle Tethers to Pathogenic Host Interactors and Their Role in Neuronal Disease
Authors: Kors Suzan , Costello Joseph L. , Schrader Michael
Published: June 2022

Vesicle-associated membrane protein (VAMP)-associated proteins (VAPs) are ubiquitous ER-resident tail-anchored membrane proteins in eukaryotic cells. Their N-terminal major sperm protein (MSP) domain faces the cytosol and allows them to interact with a wide variety of cellular proteins. Therefore, VAP proteins are vital to many cellular processes, including organelle membrane tethering, lipid transfer, autophagy, ion homeostasis and viral defence. Here, we provide a timely overview of the increasing number of VAPA/B binding partners and discuss the role of VAPA/B in maintaining organelle-ER interactions and cooperation. Furthermore, we address how viruses and intracellular bacteria hijack VAPs and their binding partners to induce interactions between the host ER and pathogen-containing compartments and support pathogen replication. Finally, we focus on the role of VAP in human disease and discuss how mutated VAPB leads to the disruption of cellular homeostasis and causes amyotrophic lateral sclerosis.
Epigenetic Regulation of Inflammatory Signaling and Inflammation-Induced Cancer
Authors: Tan Shawn Ying Xuan , Zhang Jieqiong , Tee Wee-Wei
Published: June 2022

Epigenetics comprise a diverse array of reversible and dynamic modifications to the cell’s genome without implicating any DNA sequence alterations. Both the external environment surrounding the organism, as well as the internal microenvironment of cells and tissues, contribute to these epigenetic processes that play critical roles in cell fate specification and organismal development. On the other hand, dysregulation of epigenetic activities can initiate and sustain carcinogenesis, which is often augmented by inflammation. Chronic inflammation, one of the major hallmarks of cancer, stems from proinflammatory cytokines that are secreted by tumor and tumor-associated cells in the tumor microenvironment. At the same time, inflammatory signaling can establish positive and negative feedback circuits with chromatin to modulate changes in the global epigenetic landscape. In this review, we provide an in-depth discussion of the interconnected crosstalk between epigenetics and inflammation, specifically how epigenetic mechanisms at different hierarchical levels of the genome control inflammatory gene transcription, which in turn enact changes within the cell’s epigenomic profile, especially in the context of inflammation-induced cancer.
Design and Synthesis of Novel PRMT1 Inhibitors and Investigation of Their Effects on the Migration of Cancer Cell
Authors: Wang Caijiao , Dong Luyao , Zhao Ziqi , Zhang Zeqing , Sun Yutong , Li Chonglong , Li Guoqing , You Xuefu , Yang Xinyi , Wang Hao , Hong Wei
Published: June 2022

Protein arginine methyltransferase 1 (PRMT1) can catalyze the protein arginine methylation by transferring the methyl group from S-adenosyl-L-methionine (SAM) to the guanidyl nitrogen atom of protein arginine, which influences a variety of biological processes including epithelial–mesenchymal transition (EMT) and EMT-mediated mobility of cancer cells. The upregulation of PRMT1 is involved in a diverse range of cancer, such as lung cancer, and there is an urgent need to develop novel and potent PRMT1 inhibitors. In this article, a series of 2,5-substituted furan derivatives and 2,4-substituted thiazole derivatives were designed and synthesized by targeting at the substrate arginine-binding site on PRMT1, and 10 compounds demonstrated significant inhibitory effects against PRMT1. Among them, the most potent inhibitor, compound 1r (WCJ-394), significantly affected the expression of PRMT1-related proteins in A549 cells and downregulated the expression of mesenchymal markers, by which WCJ-394 inhibited the TGF-β1-induced EMT in A549 cells and prevented the cancer cell migration. The current study demonstrated that WCJ-394 was a potent PRMT1 inhibitor, which could be used as the leading compound for further drug discovery.
Seed Treatment with Diamide and Neonicotinoid Mixtures for Controlling Fall Armyworm on Corn: Toxicity Evaluation, Effects on Plant Growth and Residuality
Authors: Li Hongbo , Feng Lei , Fu Junhong , Zhang Ying , Huang Wenyuan , Duan Tingting , Hu Yang , Xing Jichun
Published: June 2022

The diamides, chlorantraniliprole (CHL) and cyantraniliprole (CYA), have been used as seed treatment agents against the fall armyworm (FAW), Spodoptera frugiperda in China. However, large-scale application of these two insecticides is prohibited because of their high cost. The neonicotinoid insecticides, clothianidin (CLO) and thiamethoxam (THI), are cheaper and widely used. In this study, we tested the efficacy of CHL + CLO and CYA + THI as seed treatment agents against FAW larvae both in laboratory and field conditions. Laboratory experiments showed that the two binary mixtures (both 240 g.a.i.100 kg−1 corn seeds) caused FAW mortality exceeded 84.00% at 14 days after seedling emergence (DAE). The mortality of the binary mixtures were similar to either CHL (300 g.a.i.100 kg−1corn seeds) or CYA (144 g a.i.100 kg−1corn seeds), but higher than CLO (120 g.a.i.100 Kg−1corn seeds) or THI (180 g a.i.100 kg−1corn seeds). Two independent field experiments showed that both binary mixtures resulted in above 68.00% control efficacy at 14 DAE, suggesting that these insecticidal combinations could effectively control FAW over a relative long period. In addition, both binary mixtures showed no negative effects on the growth and development of corn seedlings. The residues of binary mixtures in corn leave were also lower at 28 DAE as compared to residues in CHL or CYA alone. Most importantly, the costs of CHL + CLO were reduced up to 50% and CYA + THI up to 20% when compared to singly used chemical. Totally, our results indicated that CHL + CLO and CYA + THI had the same control efficacy as CHL or CYA alone, but with much lower cost.
Unveiling the Pathogenic Bacteria Causing Descending Necrotizing Mediastinitis
Authors: Sun Qiang , Li Zixuan , Wang Panpan , Zhao Junfang , Chen Shuai , Sun Minglei
Published: June 2022

The combination of maxillofacial infections (MI) with descending necrotizing mediastinitis (DNM) is a complex disease characterized by rapid development and high mortality. Here, we performed metagenomic next-generation sequencing (mNGS) using samples from 21 patients with MI and eight patients with DNM. In this study, we found that the species richness of the DNM group was higher than that of the MI group, and the species diversity of the DNM group was higher than that of the MI group, with no statistically significant differences between groups (P > 0.05). LefSE analysis revealed that the main species differing between groups were Bacillus, Lactobacillus, Streptococcaceae, and Streptococcus (S. constellatus and S. anginosus). In addition, the PLS-DA analysis revealed that the dominant groups in the DNM group at the species level were S. constellatus, S. anginosus, Streptococcus intermedius, Prevotella oris, Mogibacterium timidum, and Eubacterium nodatum. Next, we correlated the clinical characteristics of the patients with the relative abundance of the pathogens identified in the LefSe and PLS-DA analyses. The relative abundance of S. anginosus was positively correlated with C-reactive protein (CRP) and calcitoninogen (PCT) but negatively correlated with the percentage of lymphocytes (Lymph%) (P < 0.05). On the other hand, M. timidum was positively correlated with the percentage of neutrophils (Neut%) and glycated hemoglobin (GLU) (P < 0.05), and Parvimonas micra was positively correlated with CRP (P < 0.05).
Infections and Pregnancy: Effects on Maternal and Child Health
Authors: Kumar Manoj , Saadaoui Marwa , Al Khodor Souhaila
Published: June 2022

Pregnancy causes physiological and immunological adaptations that allow the mother and fetus to communicate with precision in order to promote a healthy pregnancy. At the same time, these adaptations may make pregnant women more susceptible to infections, resulting in a variety of pregnancy complications; those pathogens may also be vertically transmitted to the fetus, resulting in adverse pregnancy outcomes. Even though the placenta has developed a robust microbial defense to restrict vertical microbial transmission, certain microbial pathogens have evolved mechanisms to avoid the placental barrier and cause congenital diseases. Recent mechanistic studies have begun to uncover the striking role of the maternal microbiota in pregnancy outcomes. In this review, we discuss how microbial pathogens overcome the placental barrier to cause congenital diseases. A better understanding of the placental control of fetal infection should provide new insights into future translational research.
10-Year Impact of Transcatheter Aortic Valve Replacement Leaflet Design (Intra- Versus Supra-Annular) in Mortality and Hemodynamic Performance
Authors: Scotti Andrea , Fovino Luca Nai , Coisne Augustin , Fabris Tommaso , Cardaioli Francesco , Massussi Mauro , Rodinò Giulio , Barolo Alberto , Boiago Mauro , Continisio Saverio , Montonati Carolina , Sciarretta Tommaso , Zuccarelli Vittorio , Bernardini Valentina , Masiero Giulia , Napodano Massimo , Fraccaro Chiara , Marchese Alfredo , Esposito Giovanni , Granada Juan F. , Latib Azeem , Iliceto Sabino , Tarantini Giuseppe
Published: June 2022

Background

The impact of transcatheter aortic valve replacement (TAVR) leaflet design on long-term device performance is still unknown. This study sought to compare the clinical and hemodynamic outcomes of intra- (IA) versus supra-annular (SA) TAVR designs up-to 10-years following implantation.

Methods

Consecutive patients with at least 5-years follow-up following TAVR for severe symptomatic aortic stenosis from June 2007 to December 2016 were included. Bioprosthetic valve failure (BVF) and hemodynamic valve deterioration (HVD) were defined according to VARC-3 updated definitions and estimated using cumulative incidence function to account for the competing risk of death.

Results

A total of 604 patients (82 years; 53% female) were analyzed and divided into IA (482) and SA (122) groups. Overall survival rates at 10-years were similar (IA 15%, 95%CI: 10–22; SA 11%, 95%CI: 6–20; p = 0.21). Compared to the SA TAVR, mean transaortic gradients were significantly higher and increased over time in the IA group. IA TAVRs showed higher 10-year cumulative incidences of BVF (IA 8% vs. SA 1%, p = 0.02) and severe HVD (IA 5% vs. SA 1%, p = 0.05). The occurrence of BVF and HVD in the IA group occurred primarily in the smallest TAVR devices (20–23-mm). After excluding these sizes, the cumulative incidences of BVF (IA 5% vs. SA 1%, p = 0.40) and severe HVD (IA 2% vs. SA 1%, p = 0.11) were similar.

Conclusion

In this study, TAVR leaflet design had no impact on survival at 10-years. IA devices showed higher transaortic gradients and cumulative incidences of HVD and BVF predominantly occurring in the smallest valve sizes.
A New Data Processing Method for High-Precision Mining Subsidence Measurement Using Airborne LiDAR
Authors: Dong Yue , Wang Dong , Liu Fengying , Wang Junjie
Published: June 2022

Coal resources are the principal energy in China, and the surface subsidence caused by coal mining has a serious impact on the safe production and life of human beings. The traditional observation method of rock movement is slow and laborious, while the accuracy of airborne LiDAR, InSAR and other methods is relatively low. In this paper, aiming at the problem of the low accuracy of deformation monitoring of airborne LiDAR, the data registration of LiDAR point cloud is analyzed by combining theoretical analysis with field experiment. An advanced distribution mode of control points is discussed, and a current method of multi-period point cloud registration using seven-parameter transformation is proposed to obtain a surface subsidence model for mining area with high precision. The results show that the RMSE of airborne LiDAR is decreased from 0.013 m to 0.008 m by using the new method for data registration, and the maximum error value is reduced from 0.022 m to 0.014 m, which effectively enhances the deformation monitoring capability of airborne LiDAR.
Subseasonal to Annual Long-Term Trends in Climate Extremes Over East Asia, 1981–2021
Authors: Moon Ja-Yeon , Choi Youngeun , Kim Yujin , Min Sookjoo
Published: June 2022

This study examines the up-to-date observed trends of subseasonal to annual range climate extremes over the East Asia region using the high-resolution global unified gauge-based analysis of the NOAA Climate Prediction Center for 1981–2021. The spatial extent of extreme events is identified using the Expert Team on Climate Change Detection and Indices (ETCCDI)-based modified climate extreme index (EmCEI) with five subcomponents (maximum temperature, minimum temperature. total rainfall, heavy rainfall, and wet and dry days). By combining the spatiotemporal fields into a simple index, trends in climate extremes are systematically obtained in various time ranges. Annual and semi-annual long-term trends in East Asia showed a statistically significant increase in the percentage of area affected by the upper-extreme climate (warm days, warm nights, wet extreme) and concurrently by the decrease of lower-extreme climate (cool days, cool nights, dry extreme). As the time range becomes higher, the tendency is consistent but extremeness depends on seasons and calendar months. The total EmCEI shows an increasing trend greater in the warm (summer) season than in the cold (winter) season. The temperature extreme components (C1 and C2) are dominated in spring and summer. In the subseasonal months, March has the highest trend among the calendar months both in C1 and C2. The increasing trend is consistently distinct in the 2010s for all time ranges and all components. The long-term trend in winter exhibits distinctive features of the smallest increase than in other seasons and months caused by robust interannual to multidecadal variability in the 1990s–2000s. The area affected by heavy rainfall is mainly dominated in summer while the total rainfall and wet day extreme extend in summer and fall, respectively. The EmCEI suggests that the change in the spatial extent of climate extremes is mainly caused by a shift in temperature and rainfall distributions toward warm and wet extremes over East Asia.
Fracture Characteristics of Sliding Crack in Brittle Rock: Analysis Based on an Improved Equivalent Crack Model
Authors: Zhang Yin , Cui Shenghua , Yu Zhibing , Cheng Jianlong
Published: June 2022

Under low confinement axial compression, the failure of brittle rock is mainly caused by tensile fracture. Many scholars adopt the sliding crack as an idealized model to present the intrinsic mechanism of the tensile failure but due to the complex configuration of sliding crack, its stress intensity factor (SIF) calculation has always been a difficult problem. In this study, an improved model of sliding crack is proposed; in the context of linear elastic fracture mechanics (LEFM) and weight function method, the expression of stress intensity factor (SIF) has been derived. The propagation manners of sliding crack under axial loading and lateral unloading conditions have been further analyzed. The extended finite element method (XFEM) is employed to verify the correctness of the theoretical SIF formulation and its inferences. The formula of SIF shows that a sliding crack is highly sensitive to the change of the lateral stress, which theoretically explains compressive failure characteristics of brittle rock as follows: 1) under the condition of axial compression, increasing the lateral stress has a very strong no-linear impact on the strength of brittle rock; 2) under the condition of lateral unloading, the destruction of rock is more abrupt and ferocious than that of the loading case. In order to confirm that micro-fractures in rocks are notably influenced by confining pressure, as the former theoretical fracture analysis predicted, the tri-axial compression test combined with the acoustic emission monitoring technique has been conducted on basalt samples. According to the acoustic waveform parameter method, it shows that increasing the confining pressure will greatly reduce the proportion of tension-type fractures, which indirectly proves the correctness of the sliding crack hypothesis and fracture analysis.
Effects of Long-Term Exposure to PM2.5 on Oxidative Stress Injury and Expression of Inflammatory Factors, NF-κB p65 and Cx43 in Bone Marrow of Mice
Authors: Liu Li-Li , Yang Jing , Ye Zhong-Lv , Tian Chuan , Huang Xiu-Lan , Zhang Hui-Qin , Mo Xiao-Huan
Published: June 2022

Objective: This study aims to explore the toxic effect of PM2.5 on the hematopoietic microenvironment of the bone marrow, and investigate the effect of PM2.5 on oxidative stress injury, the secretion of inflammatory cytokines and the expression of NF-κB p65 and C x 43 in the bone marrow of mice.

Methods: A total of 615 mice were treated with normal saline, low dose (0.1 mg/ml) PM2.5 suspension, and high dose (0.2 mg/ml) PM2.5 suspension by intratracheal instillation, respectively. The ROS content, activity of total SOD (T-SOD), DNA injury, and the protein expression levels of IL-1 β, IL-6, TNF-α, NF-κB p65 and Cx43 in bone marrow cells (BMCs) of mice were detected in these three groups.

Results: Compared with the normal saline control group, the expression level of reactive oxygen species (ROS) significantly increased in BMCs, while the activity of SOD enzymes significantly decreased in PM2.5 exposed mice. Furthermore, DNA injury significantly increased in PM2.5 exposed mice, and the expression of IL-1 β, IL-6, TNF-α and NF-κB p65 significantly increased, while the protein expression of Cx43 significantly decreased in the PM2.5 exposed mice. The differences were statistically significant (p < 0.05). There were significant differences in ROS content, T-SOD activity, DNA injury (TL, TD and TM), protein expression of IL-1β, IL-6, TNF-α and Cx43 between the high-dose PM2.5 exposure group and low-dose PM2.5 exposure group (p < 0.05), but there was no significant difference in the expression of NF-κB p65 between the high-dose and low-dose PM2.5 exposure groups (p > 0.05).

Conclusion: PM2.5 has toxic effects on the bone marrow of mice. Oxidative stress injury, inflammatory reaction and abnormal intercellular communication may be the underlying mechanism.
Towards Sustainable Environment in G7 Nations: The Role of Renewable Energy Consumption, Eco-innovation and Trade Openness
Authors: Olanrewaju Victoria Olushola , Irfan Muhammad , Altuntaş Mehmet , Agyekum Ephraim Bonah , Kamel Salah , El-Naggar Mohamed F.
Published: June 2022

Some of the globe’s most economically advanced nations make up the G7 (Canada, Japan, France, Germany, Italy, United States and United Kingdom). Nevertheless, in tandem with such strong economic growth, the environmental conditions in these nations have deteriorated, raising serious issues among stakeholders. Therefore, we examine the effect of eco-innovation and trade openness on CO2 emissions in G7 nations. We also take into account the role of renewable energy, economic growth and nonrenewable energy use using a dataset covering the period from 1990–2019. We employed recent econometric techniques such as slope heterogeneity (SH) and cross-sectional dependence (CSD), Westerlund cointegration, fully modified ordinary least square (FMOLS), dynamic ordinary least square (DOLS), panel quantile regression and panel causality tests to assess these associations. The outcomes of the CSD and SH tests disclosed that using a first-generation unit root test will produce biase outcomes. Furthermore, the outcomes of the Westerlund cointegration disclosed support long-run association between CO2 and its drivers. In addition, the results of the long-run estimators (FMOLS and DOLS) unveiled that nonrenewable energy and trade openness contribute to the damage to the environment while economic expansion, renewable energy and eco-innovation enhance the quality of the environment. Furthermore, the outcomes of GDP, REC and ECO curb CO2 while NREC energy and TO surge CO2. Finally, the outcomes of the panel causality test unveiled that CO2 emissions can be predicted by all the exogenous variables.
How Does Green Finance Affect CO2 Emissions? Heterogeneous and Mediation Effects Analysis
Authors: Wang Jianda , Ma Ying
Published: June 2022

The original intention of green finance advocacy is to provide financing support for energy conservation and emission-reduction activities. In this context, the carbon dioxide (CO2) emission-reduction effect is worth further discussion. To this end, by gauging the green finance index, we apply the econometric method to evaluate the impact of green finance on CO2 emissions. We also discuss geographical heterogeneity and the impact mechanism. The main findings imply that: 1) China’s implementation of green finance is an effective measure to mitigate greenhouse gas emissions; in other words, green finance in China can effectively reduce CO2 emissions; 2) both green finance and CO2 emissions show significant geographical heterogeneity and asymmetry; only in the eastern and central regions, can green finance help alleviate the greenhouse effect; and 3) besides the total effect, green finance can affect the greenhouse effect by promoting the rapid growth of the provincial economy, restraining the improvement of energy efficiency, and accelerating the optimization of the current industrial structure. Following the above three findings, we propose some policy suggestions related to green finance evolution and CO2 emissions reduction.
Historic and Contemporary Land Use Shape Plant-Pollinator Networks and Community Composition
Authors: Cortina Camila A. , Neff John L. , Jha Shalene
Published: June 2022

Globally, grasslands represent a critical but shrinking habitat for native plants and pollinators, with declines driven by alterations to landscape-scale habitat cover and local-scale disturbance regimes, among other factors. Specifically, as cities expand in size, an increasing proportion of regional pasture and grassland habitat is being replaced by urban development, and fewer periodic grazing and burning regimes are being supported locally, despite evidence that such regimes promote plant species richness and facilitate their interaction with native pollinators. The quantification of these plant-pollinator networks—through indices such as network connectance, specialization, nestedness, and robustness—can provide a unique opportunity to characterize key structural properties of species interactions and their response to human management and seasonal phenology. While urbanization and local disturbance regimes likely influence plant and pollinator communities and their interactions, past research in this area has primarily been conducted at limited spatial and temporal scales and has not typically quantified the impacts of both local and landscape forces on network properties. In this study, we investigate the effects of contemporary (past 10 years) and historic (prior 90 years) disturbance regimes on plant-pollinator community composition and network structure across more than 200 km of grassland in Central Texas. Our analyses indicate that for plant and pollinator communities, both contemporary and historic land management practices have led to significantly dissimilar community composition. Plant and pollinator richness and network nestedness are negatively correlated with phenological period, while pollinator richness is positively correlated with landscape-scale (2 km) urbanized land cover and is higher in historically grazed land, likely due to greater food and nesting resource availability. In contrast, we show that network connectance is positively correlated with phenological period and negatively correlated with landscape-scale urban cover. Finally, we show that pollinator robustness, a measure of resilience to plant species loss, is positively correlated with landscape-scale urbanization, likely due to greater redundancy provided by common weedy plant species. Overall, our results demonstrate that historic grazing regimes, current urbanization levels, and distinct phenological periods can simultaneously drive plant-pollinator community composition and network dynamics in shrinking but critical grassland ecosystems.
The Novel lncRNA ENST00000530525 Affects ANO1, Contributing to Blood–Brain Barrier Injury in Cultured hCMEC/D3 Cells Under OGD/R Conditions
Authors: Jiang Wen , Li Jie , Cai Yuefang , Liu Wenchen , Chen Mei , Xu Xiaoying , Deng Minzhen , Sun Jingbo , Zhou Lihua , Huang Yan , Wu Shuang , Cheng Xiao
Published: June 2022

Ischemic stroke (IS) is a major neurological disease with high fatality and residual disability burdens. Long noncoding RNAs (lncRNAs) have been found to play an important role in IS. However, the roles and significance of most lncRNAs in IS are still unknown. This study was performed to identify differentially expressed (DE) lncRNAs using a lncRNA microarray in whole blood samples of patients suffering from acute cerebral ischemia. Bioinformatics analyses, including GO, KEGG pathway enrichment analysis, and proximity to putative stroke risk location analysis were performed. The novel lncRNA, ENST00000530525, significantly decreased after IS. Furthermore, we evaluated lncRNA ENST00000530525 expression in cultured hCMEC/D3 cells under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions using fluorescent in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (RT–qPCR) analysis. To investigate the function of lncRNA ENST00000530525, its over-expression (OE) and negative control (NC) plasmids were transfected into hCMEC/D3 cells, and cell viability was detected by a cell counting kit-8 (CCK-8) assay after OGD/R. LncRNA ENST00000530525 and ANO1 expression were investigated using RT–qPCR and immunofluorescence. For blood–brain barrier (BBB) permeability, FITC-dextran transendothelial permeability assay and tight junction (TJ) protein immunofluorescence assays were performed. There were 3352 DE lncRNAs in the blood samples of acute IS patients. The validation results were consistent with the gene chip data. The GO and KEGG results showed that these lncRNAs were mainly related to oxygen and glucose metabolism, leukocyte transendothelial migration, mitophagy and cellular senescence. Among these, lncRNA ENST00000530525 was the most highly downregulated lncRNA and it was mapped within the IS-associated gene anoctamin-1 (ANO1). We further found that lncRNA ENST00000530525 was downregulated in hCMEC/D3 cells under 4 h OGD and 20 h reoxygenation (OGD4/R20) conditions. Upregulating lncRNA ENST00000530525 by plasmid transfection decreased cell viability while increasing ANO1 expression and it contributed to BBB injury in hCMEC/D3 cells after OGD4/R20. The lncRNA ENST00000530525 might play deleterious roles in post-stroke pathogenesis. These results show that some DE lncRNAs in humans participate through characteristic roles in post-stroke pathogenesis; thus, the roles and significance of some novel lncRNAs in IS warrant further study.
Identification and Validation of Necroptosis-Related LncRNA Signature in Hepatocellular Carcinoma for Prognosis Estimation and Microenvironment Status
Authors: Chen Cong , Wu Yumeng , Chen Kang , Xia Zicong , Liu Xiaokan , Zhang Chaojie , Zhao Hui , Shen Aiguo
Published: June 2022

Background: Hepatocellular carcinoma (HCC) is among malignancies with the highest fatality toll globally and minimal therapeutic options. Necroptosis is a programmed form of necrosis or inflammatory cell death, which can affect prognosis and microenvironmental status of HCC. Therefore, we aimed to explore the prognostic value of necroptosis-related lncRNAs (NRLs) in HCC and the role of the tumor microenvironment (TME) in immunotherapy.

Methods: The RNA-sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). NRLs were identified by Pearson correlation analysis. The signature was constructed using the LASSO–Cox regression analysis and evaluated using the receiver operating characteristic curve (ROC) and the area under the Kaplan–Meier curve. The nomogram was built based on clinical information and risk score. Gene set enrichment analysis (GSEA), immunoassay, half-maximum inhibitory concentration (IC50) analysis of the risk group, and the HCC subtype identification based on NRLs were also carried out. Finally, we detected the expression of lncRNAs in HCC tissues and cell lines in vitro.

Results: A total of 508 NRLs were screened out, and seven NRLs were constructed as a risk stratification system to classify patients into distinct low- and high-risk groups. Patients in the high-risk group had a significantly lower overall survival (OS) than those in the low-risk group. Using multivariate Cox regression analysis, we found that the risk score was an independent predictor of OS. Functional analysis showed that the immune status of different patients was different. The IC50 analysis of chemotherapy demonstrated that patients in the high-risk group were more sensitive to commonly prescribed drugs. qRT-PCR showed that three high-risk lncRNAs were upregulated in drug-resistant cells, and the expression in HCC tissues was higher than that in adjacent tissues.

Conclusion: The prediction signature developed in this study can be used to assess the prognosis and microenvironment of HCC patients, and serve as a new benchmark for HCC treatment selection.
Prognostic Implication and Immunological Role of PSMD2 in Lung Adenocarcinoma
Authors: Zhao Huihui , Lu Guojun
Published: June 2022

Background: Although previous studies reported that 26S proteasome non-ATPase regulatory subunit 2 (PSMD2) is involved in many human cancers. However, its clinical significance and function in lung adenocarcinoma remain unclear. Here, we examined the prognostic and immunological role of PSMD2 in lung adenocarcinoma.

Methods: The Cancer Genome Atlas (TCGA) was conducted to analyze PSMD2 expression and verified using UALCAN. PrognoScan and Kaplan-Meier curves were utilized to assess the effect of PSMD2 on survival. cBioPortal database was conducted to identify the mutation characteristics of PSMD2. Functional enrichment was performed to determine PSMD2-related function. Cancer Single-cell State Atlas (CancerSEA) was used to explore the cancer functional status of PSMD2 at single-cell resolution. PSMD2-related immune infiltration analysis was conducted. Tumor-Immune system interaction database (TISIDB) was performed to verify the correlation between PSMD2 expression and tumor-infiltrating lymphocytes (TILs).

Results: Both mRNA and protein expression of PSMD2 were significantly elevated in lung adenocarcinoma. High expression of PSMD2 was significantly correlated with high T stage (p = 0.014), lymph node metastases (p < 0.001), and TNM stage p = 0.005). Kaplan-Meier curves indicated that high expression of PSMD2 was correlated with poor overall survival (38.2 vs. 59.7 months, p < 0.001) and disease-specific survival (59.9 months vs. not available, p = 0.004). Multivariate analysis suggested that PSMD2 was an independent biomarker for poor overall survival (HR 1.471, 95%CI, 1.024–2.114, p = 0.037). PSMD2 had a high mutation frequency of 14% in lung adenocarcinoma. The genetic mutation of PSMD2 was also correlated with poor overall survival, disease-specific survival, and progression-free survival in lung adenocarcinoma. Functional enrichment suggested PSMD2 expression was involved in the cell cycle, RNA transport, and cellular senescence. CancerSEA analysis indicated PSMD2 expression was positively correlated with cell cycle, DNA damage, and DNA repair. Immune infiltration analysis suggested that PSMD2 expression was correlated with immune cell infiltration levels and abundance of TILs.

Conclusion: The upregulation of PSMD2 is significantly correlated with poor prognosis and immune infiltration levels in lung adenocarcinoma. Our findings suggest that PSMD2 is a potential biomarker for poor prognosis and immune therapeutic target in lung adenocarcinoma.
Correlation Between Immune-Related Genes and Tumor-Infiltrating Immune Cells With the Efficacy of Neoadjuvant Chemotherapy for Breast Cancer
Authors: Zhou Yan , Tian Qi , Gao Huan , Zhu Lizhe , Yang Jiao , Zhang Juan , Yang Jin
Published: June 2022

Background: In the absence of targeted therapy or clear clinically relevant biomarkers, neoadjuvant chemotherapy (NAC) is still the standard neoadjuvant systemic therapy for breast cancer. Among the many biomarkers predicting the efficacy of NAC, immune-related biomarkers, such as immune-related genes and tumor-infiltrating lymphocytes (TILs), play a key role.

Methods: We analyzed gene expression from several datasets in the Gene Expression Omnibus (GEO) database and evaluated the relative proportion of immune cells using the CIBERSORT method. In addition, mIHC/IF detection was performed on clinical surgical specimens of triple-negative breast cancer patients after NAC.

Results: We obtained seven immune-related genes, namely, CXCL1, CXCL9, CXCL10, CXCL11, IDO1, IFNG, and ORM1 with higher expression in the pathological complete response (pCR) group than in the non-pCR group. In the pCR group, the levels of M1 and γδT macrophages were higher, while those of the M2 macrophages and mast cells were lower. After NAC, the proportions of M1, γδT cells, and resting CD4 memory T cells were increased, while the proportions of natural killer cells and dendritic cells were decreased with downregulated immune-related genes. The results of mIHC/IF detection and the prognostic information of corresponding clinical surgical specimens showed the correlation of proportions of natural killer cells, CD8-positive T cells, and macrophages with different disease-free survival outcomes.

Conclusion: The immune-related genes and immune cells of different subtypes in the tumor microenvironment are correlated with the response to NAC in breast cancer, and the interaction between TILs and NAC highlights the significance of combining NAC with immunotherapy to achieve better clinical benefits.
Whole-Exome Sequencing Identified Genes Responsible for Thoracic Aortic Aneurysms and Dissections in three Chinese Families
Authors: Guo Renle , Du Pengcheng , Pei Yifei , Yang Jin , Li Shuangshuang , Chang Sheng , Sun Huiying , He Xiaomin , Dong Jian , Zhou Jian , Jing Zaiping
Published: June 2022

Thoracic aortic aneurysms and dissections are precarious conditions that often cannot be diagnosed with fatal outcomes. Over the last few years, pathogenic variants in numerous genes have been identified that predispose to heritable presentations of TAAD. An evidence-based strategy for the selection of genes to test in familial TAAD helps inform family screening and intervention to prevent life-threatening events. Using whole-exome sequencing, four members of three unrelated families clinically diagnosed with TAAD were used to identify the genetic origin of the disorder. Variant evaluation was carried out to detect the pathogenic mutation. Our studies suggest that mutations of COL3A1 and ACTA2 are responsible for familial TAAD. In addition, we highlight FBLN5, FBN1, SLC2A10, FBN2, and NOTCH1 as candidate genes. Future studies of crosstalk among the pathways may provide us a step toward understanding the pathogenic mechanism. This finding indicates the necessity of obtaining family medical history and screening of extended relatives of patients with TAAD for the early identification and treatment of TAAD.
Multi-Technique Approach to Enhance the Properties of Fine Recycled Aggregate Concrete
Authors: Amadi I. G. , Beushausen H. , Alexander M.G.
Published: June 2022

This study investigated the properties of fine recycled aggregates (FRA), with a view to enhancing their properties for structural concrete applications. The study explored several approaches including mixing; curing; systematic screening of FRA particles below 1.18 mm to reduce the adhered cement paste (ACP) content; and the use of fly ash as 30% cement replacement to modify the microstructure of FRA concrete. To test these approaches, two series of concrete mixes were prepared at 0.45 and 0.55 w/b ratio, with FRA replacing natural sand at 0, 25, and 50% by mass, and tests were carried out after 3, 28, and 180 days of curing. Results show that the combination of ACP reduction and fly ash treatment significantly enhanced the compressive strength and elastic modulus of FRA concrete, especially at 180 days, through microstructure modification and pozzolanic reactions.
Nano-Sonosensitized Sonodynamic Nanomedicine Augments Tumor-Selective Catalytic Tumor Eradication
Authors: Zhang Haixian , Li Yiming , Liu Junying , Chang Cai
Published: June 2022

Inspired by the distinct metabolic pathway of tumor cells, here a new anti-cancer therapy (i.e., Cu-TCPP(Fe) metal-organic frameworks (MOFs) with sonosensitizer for sonodynamic therapy (SDT) and tumor microenvironment (TME)-specific release of copper/iron for chemical catalysis) is introduced and verified. Upon exposure to ultrasound, the porphyrin structure in the MOFs yields reactive oxygen species (ROS), and the copper/iron induces the Fenton reaction in the TME existing H2O2 and acid. Thus, highly toxic ROS are generated through these TME-specific reactions to trigger the apoptosis and death of tumor cells. The current work paves a new avenue to design SDT with catalytic nanomedicine for the selective and effective treatment of tumors.
Impact of BNT162b2 mRNA Vaccination on the Development of Short and Long-Term Vaccine-Related Adverse Events in Inflammatory Bowel Disease: A Multi-Center Prospective Study
Authors: Shehab Mohammad , Alrashed Fatema , Abdullah Israa , Alfadhli Ahmad , Ali Hamad , Abu-Farha Mohamed , Channanath Arshad Mohamed , Abubaker Jehad Ahmed , Al-Mulla Fahd
Published: June 2022

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has been effective in protecting against severe COVID-19 infections and related mortality. It is recommended for all individuals including patients with inflammatory bowel disease (IBD). However, safety data are lacking in this group of patients. Therefore, we aim to evaluate the short- and long-term vaccine related adverse events (AEs) in patients with IBD.

Methods

This is a prospective, observational cohort study investigating short- and long-term AEs related to the BNT162b2 vaccine in patients with IBD (study group) after the first and second dose compared to healthy participants (control group). Patients were recruited at the time of attendance to the clinic or infusion rooms. Short term (<3 weeks) localized and systemic AEs were assessed via questionnaire. Follow-up phone-based survey was made to collect data on long term (up to 24 weeks) AEs.

Results

A total of 408 patients answered the questionnaires, 204 patients in each group, the study and control group. No serious adverse events were reported in either the study or the control group after the first or the second dose. Participants in the control group reported more frequent pain at the injection site than those in the study group after the first dose [58 (57%) vs. 38 (37%) respectively, P = 0.005]. After the second dose, tiredness was reported more frequently in the control group [49 (48%)] compared to the study group [25 (24%) (P < 0.001)]. At 20–24 weeks post vaccination, 386 out of 408 (94.6%) patients were willing to participate in the follow-up phone based questionnaire [196 (96.1%) in the study group vs. 190 (93.1%) in the control group]. In both groups, none of the patients reported local, systemic, or severe adverse events (0 out of 386) at week 20–24 post second dose.

Conclusion

The BNT162b2 vaccine is safe in patients with IBD. No severe or long-term adverse events were reported in our study. The frequency of local and systemic adverse events after the second dose was generally higher among healthy participants compared to patients with IBD. Further studies including a larger cohort with a longer follow-up duration are needed to assess for possible rare adverse events.
Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective
Authors: Ahmad Katya , Rizzi Andrea , Capelli Riccardo , Mandelli Davide , Lyu Wenping , Carloni Paolo
Published: June 2022

The dissociation rate (koff) associated with ligand unbinding events from proteins is a parameter of fundamental importance in drug design. Here we review recent major advancements in molecular simulation methodologies for the prediction ofkoff. Next, we discuss the impact of the potential energy function models on the accuracy of calculatedkoffvalues. Finally, we provide a perspective from high-performance computing and machine learning which might help improve such predictions.
Tracing New Landscapes in the Arena of Nanoparticle-Based Cancer Immunotherapy
Authors: Nadukkandy Aisha Shigna , Ganjoo Eshani , Singh Ankit , Dinesh Kumar Lekha
Published: June 2022

Over the past two decades, unique and comprehensive cancer treatment has ushered new hope in the holistic management of the disease. Cancer immunotherapy, which harnesses the immune system of the patient to attack the cancer cells in a targeted manner, scores over others by being less debilitating compared to the existing treatment strategies. Significant advancements in the knowledge of immune surveillance in the last few decades have led to the development of several types of immune therapy like monoclonal antibodies, cancer vaccines, immune checkpoint inhibitors, T-cell transfer therapy or adoptive cell therapy (ACT) and immune system modulators. Intensive research has established cancer immunotherapy to be a safe and effective method for improving survival and the quality of a patient’s life. However, numerous issues with respect to site-specific delivery, resistance to immunotherapy, and escape of cancer cells from immune responses, need to be addressed for expanding and utilizing this therapy as a regular mode in the clinical treatment. Development in the field of nanotechnology has augmented the therapeutic efficiency of treatment modalities of immunotherapy. Nanocarriers could be used as vehicles because of their advantages such as increased surface areas, targeted delivery, controlled surface and release chemistry, enhanced permeation and retention effect, etc. They could enhance the function of immune cells by incorporating immunomodulatory agents that influence the tumor microenvironment, thus enabling antitumor immunity. Robust validation of the combined effect of nanotechnology and immunotherapy techniques in the clinics has paved the way for a better treatment option for cancer than the already existing procedures such as chemotherapy and radiotherapy. In this review, we discuss the current applications of nanoparticles in the development of ‘smart’ cancer immunotherapeutic agents like ACT, cancer vaccines, monoclonal antibodies, their site-specific delivery, and modulation of other endogenous immune cells. We also highlight the immense possibilities of using nanotechnology to accomplish leveraging the coordinated and adaptive immune system of a patient to tackle the complexity of treating unique disease conditions and provide future prospects in the field of cancer immunotherapy.
Relationship Between the Ability to Detect Frequency Changes or Temporal Gaps and Speech Perception Performance in Post-lingual Cochlear Implant Users
Authors: Xie Dianzhao , Luo Jianfen , Chao Xiuhua , Li Jinming , Liu Xianqi , Fan Zhaomin , Wang Haibo , Xu Lei
Published: June 2022

Previous studies, using modulation stimuli, on the relative effects of frequency resolution and time resolution on CI users’ speech perception failed to reach a consistent conclusion. In this study, frequency change detection and temporal gap detection were used to investigate the frequency resolution and time resolution of CI users, respectively. Psychophysical and neurophysiological methods were used to simultaneously investigate the effects of frequency and time resolution on speech perception in post-lingual cochlear implant (CI) users. We investigated the effects of psychophysical results [frequency change detection threshold (FCDT), gap detection threshold (GDT)], and acoustic change complex (ACC) responses (evoked threshold, latency, or amplitude of ACC induced by frequency change or temporal gap) on speech perception [recognition rate of monosyllabic words, disyllabic words, sentences in quiet, and sentence recognition threshold (SRT) in noise]. Thirty-one adult post-lingual CI users of Mandarin Chinese were enrolled in the study. The stimuli used to induce ACCs to frequency changes were 800-ms pure tones (fundamental frequency was 1,000 Hz); the frequency change occurred at the midpoint of the tones, with six percentages of frequency changes (0, 2, 5, 10, 20, and 50%). Temporal silences with different durations (0, 5, 10, 20, 50, and 100 ms) were inserted in the middle of the 800-ms white noise to induce ACCs evoked by temporal gaps. The FCDT and GDT were obtained by two 2-alternative forced-choice procedures. The results showed no significant correlation between the CI hearing threshold and speech perception in the study participants. In the multiple regression analysis of the influence of simultaneous psychophysical measures and ACC responses on speech perception, GDT significantly predicted every speech perception index, and the ACC amplitude evoked by the temporal gap significantly predicted the recognition of disyllabic words in quiet and SRT in noise. We conclude that when the ability to detect frequency changes and the temporal gap is considered simultaneously, the ability to detect frequency changes may have no significant effect on speech perception, but the ability to detect temporal gaps could significantly predict speech perception.