bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting the Green Growth Effect of Foreign Direct Investment from the Perspective of Environmental Regulation: Evidence from China
Authors: Xiao Deyun , Gao Luyao , Xu Lijia , Wang Zongjun , Wei Wu
Published: February 2023

The inflow of foreign direct investment (FDI) has both advanced China’s economic development process and influenced the ecological quality of China’s regions. Under the deepening of economic globalization and the continuous deterioration in environmental quality, the correlation mechanism between foreign direct investment, environmental regulation, and economic growth is becoming increasingly complex. Therefore, based on the slacks-based measure (SBM) model and the Global Malmquist-Luenberger (GML) index, this study measured the level of green economic growth using data from 30 provinces and cities from 2004–2019 and constructed a panel fixed-effect regression model to study the effect of foreign direct investment on green economic growth in China. The study found that foreign direct investment significantly promoted green economic growth in China, foreign direct investment promoted green economic growth through independent innovation and inhibited green economic growth through imitation innovation, and environmental regulation moderated the impact of foreign direct investment on green economic growth. This paper incorporated foreign direct investment, heterogeneous technological innovation, green economic growth, and environmental regulation into the research framework, and thereby further enriched and improved the research on the theoretical mechanism of green economic growth. The research conclusion clarified the influence mechanism of foreign capital on the quality of China’s economic development, which was conducive to the formulation of more reasonable policies for attracting investments and to the promotion of the formation of a positive interaction mechanism between environmental regulation and foreign direct investment, which is of great practical significance for China’s economy to achieve sustainable development.
The Objective Structured Clinical Examination (OSCE) in Periodontology with Simulated Patient: The Most Realistic Approach to Clinical Practice in Dentistry
Authors: Cidoncha Gema , Muñoz-Corcuera Marta , Sánchez Virginia , Pardo Monedero María Jesús , Antoranz Ana
Published: February 2023

The objective structured clinical examination (OSCE) is becoming an increasingly established assessment test in dental schools. The use of simulated patients in the OSCE makes the stations more similar to clinical practice. Therefore, the student can show their technical and clinical knowledge, and certainly, their ability to manage the patient. These sorts of tests, in which simulated patients can be included, would be used before the student started clinical practice with patients and/or at the end of the degree. The objective of this work was to describe how the periodontology station was developed using a simulated patient for students of a fifth year dentistry degree taking an OSCE test. Furthermore, a questionnaire was created to learn the perception of the students about this station and its characteristics. The fifth year students at the European University of Madrid positively evaluated this station in their examination. In addition, it was recorded that they preferred a simulated patient in their tests, rather than stations with clinical cases, images, X-rays, and presentations. It is essential that once the OSCE has been completed, the student receives a feedback to learn where they have failed and, therefore, be able to improve any of the aspects evaluated in the station.
Implementing a Community-Led Arsenic Mitigation Intervention for Private Well Users in American Indian Communities: A Qualitative Evaluation of the Strong Heart Water Study Program
Authors: Anderson Darcy M. , Bear Annabelle Black , Zacher Tracy , Endres Kelly , Saxton Ronald , Richards Francine , Robe Lisa Bear , Harvey David , Best Lyle G. , Cloud Reno Red , Thomas Elizabeth D. , Gittelsohn Joel , O’Leary Marcia , Navas-Acien Ana , George Christine Marie
Published: February 2023

Arsenic is a naturally occurring toxicant in groundwater, which increases cancer and cardiovascular disease risk. American Indian populations are disproportionately exposed to arsenic in drinking water. The Strong Heart Water Study (SHWS), through a community-centered approach for intervention development and implementation, delivered an arsenic mitigation program for private well users in American Indian communities. The SHWS program comprised community-led water arsenic testing, point-of-use arsenic filter installation, and a mobile health program to promote sustained filter use and maintenance (i.e., changing the filter cartridge). Half of enrolled households received additional in-person behavior change communication and videos. Our objectives for this study were to assess successes, barriers, and facilitators in the implementation, use, and maintenance of the program among implementers and recipients. We conducted 45 semi-structured interviews with implementers and SHWS program recipients. We analyzed barriers and facilitators using the Consolidated Framework for Implementation Research and the Risks, Attitudes, Norms, Abilities, and Self-regulation model. At the implementer level, facilitators included building rapport and trust between implementers and participating households. Barriers included the remoteness of households, coordinating with community plumbers for arsenic filter installation, and difficulty securing a local supplier for replacement filter cartridges. At the recipient level, facilitators included knowledge of the arsenic health risks, perceived effectiveness of the filter, and visual cues to promote habit formation. Barriers included attitudes towards water taste and temperature and inability to procure or install replacement filter cartridges. This study offers insights into the successes and challenges of implementing an arsenic mitigation program tailored to American Indian households, which can inform future programs in partnership with these and potentially similar affected communities. Our study suggests that building credibility and trust between implementers and participants is important for the success of arsenic mitigation programs.
BMSC-Derived Exosomal CircHIPK3 Promotes Osteogenic Differentiation of MC3T3-E1 Cells via Mitophagy
Authors: Ma Shaoyang , Li Sijia , Zhang Yuchen , Nie Jiaming , Cao Jiao , Li Ang , Li Ye , Pei Dandan
Published: February 2023

Exosome-based therapy is emerging as a promising strategy to promote bone regeneration due to exosomal bioactive cargos, among which circular RNA (circRNA) has recently been recognized as the key effector. The role of exosomal circRNA derived from bone marrow mesenchymal stem cells (BMSCs) has not been well-defined. The present study aimed to clarify the regulatory function and molecular mechanism of BMSC-derived exosomal circRNA in osteogenesis. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) were isolated and identified. BMSC-Exos’ pro-osteogenic effect on MC3T3-E1 cells was validated by alkaline phosphatase (ALP) activity and Alizarin Red staining. Through bioinformatic analysis and molecular experiments, circHIPK3 was selected and verified as the key circRNA of BMSC-Exos to promote osteoblast differentiation of MC3T3-E1 cells. Mechanistically, circHIPK3 acted as an miR-29a-5p sponge and functioned in mitophagy via targeting miR-29a-5p and PINK1. Additionally, we showed that the mitophagy level of MC3T3-E1 cells were mediated by BMSC-Exos, which promoted the osteogenic differentiation. Collectively, our results revealed an important role for BMSC-derived exosomal circHIPK3 in osteogenesis. These findings provide a potentially effective therapeutic strategy for bone regeneration.
PEDF Protects Endothelial Barrier Integrity during Acute Myocardial Infarction via 67LR
Authors: Liang Jingtian , Luo Qifeng , Shen Ningning , Qin Xichun , Jia Caili , Chao Zhixiang , Zhang Li , Qin Hao , Liu Xiucheng , Quan Xiaoyu , Yuan Yanliang , Zhang Hao
Published: February 2023

Maintaining the integrity and protecting the stability of tight junctions in endothelial cells is a potential therapeutic strategy against myocardial ischaemia. Laminin receptors (67LR) are highly expressed on endothelial cell membranes and are associated with endothelial barrier function. Herein, we sought to demonstrate the direct effects of pigment epithelial-derived factor (PEDF) on tight junctions between endothelial cells via 67LR during acute myocardial infarction (AMI) and elucidate its underlying mechanisms. We detected that PEDF directly increased the level of the tight junction protein zonula occludens protein 1 (ZO-1) after overexpression in vitro and in vivo using Western blotting. Evans Blue/TTC staining showed that PEDF significantly reduced the size of the infarcted myocardium. Immunofluorescence and the transwell cellular experiments suggested that PEDF significantly upregulated PI3K-AKT permeability and the distribution of ZO-1 between endothelial cells under OGD conditions. Interestingly, PEDF significantly upregulated the phosphorylation levels of PI3K-AKT-mTOR under oxygen and glucose deprivation conditions but had no significant effects on the total protein expression. The protective effect of PEDF on ZO-1 was significantly inhibited following the inhibition of PI3K-AKT-mTOR. The activation of phosphorylation of PI3K-AKT-mTOR by PEDF was blocked after silencing 67LR, as were the protective effects of PEDF on ZO-1. Therefore, we have reason to believe that PEDF increased ZO-1 expression through the 67LR-dependent PI3K-AKT-mTOR signaling pathway, thus maintaining tight junction stability and protecting cardiac function.
Hypoxia Inhibits Cell Cycle Progression and Cell Proliferation in Brain Microvascular Endothelial Cells via the miR-212-3p/MCM2 Axis
Authors: Shi Qixin , Li Shaohua , Lyu Qiang , Zhang Shuai , Bai Yungang , Ma Jin
Published: February 2023

Hypoxia impairs blood–brain barrier (BBB) structure and function, causing pathophysiological changes in the context of stroke and high-altitude brain edema. Brain microvascular endothelial cells (BMECs) are major structural and functional elements of the BBB, and their exact role in hypoxia remains unknown. Here, we first deciphered the molecular events that occur in BMECs under 24 h hypoxia by whole-transcriptome sequencing assay. We found that hypoxia inhibited BMEC cell cycle progression and proliferation and downregulated minichromosome maintenance complex component 2 (Mcm2) expression. Mcm2 overexpression attenuated the inhibition of cell cycle progression and proliferation caused by hypoxia. Then, we predicted the upstream miRNAs of MCM2 through TargetScan and miRanDa and selected miR-212-3p, whose expression was significantly increased under hypoxia. Moreover, the miR-212-3p inhibitor attenuated the inhibition of cell cycle progression and cell proliferation caused by hypoxia by regulating MCM2. Taken together, these results suggest that the miR-212-3p/MCM2 axis plays an important role in BMECs under hypoxia and provide a potential target for the treatment of BBB disorder-related cerebrovascular disease.
Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome after Traumatic Spinal Cord Injury
Authors: Reigada David , Maza Rodrigo M. , Muñoz-Galdeano Teresa , Barreda-Manso María Asunción , Soto Altea , Lindholm Dan , Navarro-Ruíz Rosa , Nieto-Díaz Manuel
Published: February 2023

Mechanical trauma to the spinal cord causes extensive neuronal death, contributing to the loss of sensory-motor and autonomic functions below the injury location. Apoptosis affects neurons after spinal cord injury (SCI) and is associated with increased caspase activity. Cleavage of X-linked inhibitor of apoptosis protein (XIAP) after SCI may contribute to this rise in caspase activity. Accordingly, we have shown that the elevation of XIAP resulted in increased neuronal survival after SCI and improved functional recovery. Therefore, we hypothesise that neuronal overexpression of XIAP can be neuroprotective after SCI with improved functional recovery. In line with this, studies of a transgenic mice with overexpression of XIAP in neurons revealed that higher levels of XIAP after spinal cord trauma favours neuronal survival, tissue preservation, and motor recovery after the spinal cord trauma. Using human SH-SY5Y cells overexpressing XIAP, we further showed that XIAP reduced caspase activity and apoptotic cell death after pro-apoptotic stimuli. In conclusion, this study shows that the levels of XIAP expression are an important factor for the outcome of spinal cord trauma and identifies XIAP as an important therapeutic target for alleviating the deleterious effects of SCI.
LL-37 Triggers Antimicrobial Activity in Human Platelets
Authors: Sánchez-Peña Francisco Javier , Romero-Tlalolini María de los Ángeles , Torres-Aguilar Honorio , Cruz-Hernández Diego Sait , Baltiérrez-Hoyos Rafael , Sánchez-Aparicio Saraí Remedios , Aquino-Domínguez Alba Soledad , Aguilar-Ruiz Sergio Roberto
Published: February 2023

Platelets play a crucial role in hemostasis and the immune response, mainly by recognizing signals associated with vascular damage. However, it has recently been discovered that the antimicrobial peptide LL-37 activates platelets in functions related to thrombus formation and inflammation. Therefore, this work aims to evaluate the effect of LL-37 on the activation of antimicrobial functions of human platelets. Our results show that platelets treated with LL-37 increase the surface expression of receptors (Toll-like receptors (TLRs) 2 and -4, CD32, CD206, Dectin-1, CD35, LOX-1, CD41, CD62P, and αIIbβ3 integrins) for the recognition of microorganisms, and molecules related to antigen presentation to T lymphocytes (CD80, CD86, and HLA-ABC) secrete the antimicrobial molecules: bactericidal/permeability-increasing protein (BPI), azurocidin, human neutrophil peptide (HNP) -1, and myeloperoxidase. They also translate azurocidin, and have enhanced binding to Escherichia coli, Staphylococcus aureus, and Candida albicans. Furthermore, the supernatant of LL-37-treated platelets can inhibit E. coli growth, or platelets can employ their LL-37 to inhibit microbial growth. In conclusion, these findings demonstrate that LL-37 participates in the antimicrobial function of human platelets.
Adjuvant Injections Altered the Ileal and Fecal Microbiota Differently with Changes in Immunoglobulin Isotypes and Antimycobacterial Antibody Responses
Authors: Khadka Sundar , Omura Seiichi , Sato Fumitaka , Tsunoda Ikuo
Published: February 2023

Alterations in the gut microbiota, “dysbiosis,” have been reported in autoimmune diseases, including multiple sclerosis (MS), and their animal models. Although the animal models were induced by injections of autoantigens with adjuvants, including complete Freund’s adjuvant (CFA) and pertussis toxin (PT), the effects of adjuvant injections on the microbiota are largely unknown. We aimed to clarify whether adjuvant injections could affect the microbiota in the ileum and feces. Using 16S rRNA sequencing, we found decreased alpha diversities of the gut microbiota in mice injected with CFA and PT, compared with naïve mice. Overall, microbial profiles visualized by principal component analysis demonstrated dysbiosis in feces, but not in the ileum, of adjuvant-injected mice, where the genera Lachnospiraceae NK4A136 group and Alistipes contributed to dysbiosis. When we compared the relative abundances of individual bacteria, we found changes in 16 bacterial genera in feces and seven genera in the ileum of adjuvant-injected mice, in which increased serum levels of antibody against mycobacteria (a component of CFA) and total IgG2c were correlated with the genus Facklamia. On the other hand, increased IgG1 and IgA concentrations were correlated with the genus Atopostipes. Therefore, adjuvant injections alone could alter the overall microbial profiles (i.e., microbiota) and individual bacterial abundances with altered antibody responses; dysbiosis in animal models could be partly due to adjuvant injections.
Why Are Some People with Lower Urinary Tract Symptoms (LUTS) Depressed? New Evidence That Peripheral Inflammation in the Bladder Causes Central Inflammation and Mood Disorders
Authors: Hughes Francis M. , Odom Michael R. , Cervantes Anissa , Livingston Austin J. , Purves J. Todd
Published: February 2023

Anecdotal evidence has long suggested that patients with lower urinary tract symptoms (LUTS) develop mood disorders, such as depression and anxiety, at a higher rate than the general population and recent prospective studies have confirmed this link. Breakthroughs in our understanding of the diseases underlying LUTS have shown that many have a substantial inflammatory component and great strides have been made recently in our understanding of how this inflammation is triggered. Meanwhile, studies on mood disorders have found that many are associated with central neuroinflammation, most notably in the hippocampus. Excitingly, work on other diseases characterized by peripheral inflammation has shown that they can trigger central neuroinflammation and mood disorders. In this review, we discuss the current evidence tying LUTS to mood disorders, its possible bidirectionally, and inflammation as a common mechanism. We also review modern theories of inflammation and depression. Finally, we discuss exciting new animal studies that directly tie two bladder conditions characterized by extensive bladder inflammation (cyclophosphamide-induced hemorrhagic cystitis and bladder outlet obstruction) to neuroinflammation and depression. We conclude with a discussion of possible mechanisms by which peripheral inflammation is translated into central neuroinflammation with the resulting psychiatric concerns.
Time of Day Influences Concentrations of Total Protein and Albumin in Cerebrospinal Fluid in HIV
Authors: Kakarla Visesha , Letendre Scott L. , Ellis Ronald J.
Published: February 2023

The accumulation of soluble proteins and metabolites during wakefulness and their clearance during sleep via the glymphatic system occurs in healthy adults and is disturbed in some neurological conditions. Such diurnal variations in the cerebrospinal fluid (CSF) proteins produced outside the central nervous system and entering via the blood–brain barrier (BBB) have not been evaluated in people with HIV (PWH). CSF and blood were collected in 165 PWH at six US centers between 2003 and 2007. The time of collection was compared to CSF albumin, globulin, and total protein concentrations using bivariate and multivariate regression. Participants all took antiretroviral therapy (ART) and were mostly middle-aged (median age 44.0 years) men (78.8%), with AIDS (77.0%), plasma HIV RNA ≤ 200 copies/mL (75.8%), and immune recovery (median CD4+ T-cell count 414/µL). CSF was collected at median 1:10 p.m. (range 9:00 a.m. to 5:20 p.m.) and within a median of 15 min of blood collection. A later time of CSF collection was associated with higher total protein (p = 0.0077) and albumin (p = 0.057) in CSF but not in serum, and was additionally associated with higher CSF globulin (p = 0.013). The glymphatic clearance of albumin, globulin, and total protein is preserved in PWH. The analyses of soluble biomarkers in CSF should account for the time of collection.
Sorption of Salts of Various Metals by Polyelectrolyte Microcapsules
Authors: Kim Aleksandr L. , Dubrovskii Alexey V. , Musin Egor V. , Tikhonenko Sergey A.
Published: February 2023

Anthropogenic activity negatively affects the environment by polluting it with the salts of various metals. One of the ways to reduce this influence is to use water purification methods for the salts of various metals. Water purification methods based on nanomaterials are promising. In this regard, we proposed to study polyelectrolyte microcapsules (PMC) as a promising sorption agent for the salts of various metals. It was found that the polystyrene sulfonate-polyallylamine (PSS-PAH) polyelectrolyte complex and polyelectrolyte microcapsules of different compositions are not able to adsorb salts CuSO4, Pb(NO)3, FeCl3, and CuCl2. At the same time, it was found that all types of capsules, except for (PSS/PAH)2/PSS, are capable of sorbing about 420 µg of K3[Fe(CN)6] and about 500 µg of K4[Fe(CN)6] from solution. The adsorption of polyelectrolyte microcapsules has an electrostatic nature which is confirmed by increases in the sorption capacity of PMC of K3[Fe(CN)6] and K4[Fe(CN)6] with decreases in the pH of the solution. Also, It was confirmed that the sorption process of PMC of K3[Fe(CN)6] and K4[Fe(CN)6] is concentration dependent and has the limitation of the number of binding sites.
Toll-like Receptor 2 Mediates VEGF Overexpression and Mesothelial Hyperpermeability in Tuberculous Pleural Effusion
Authors: Chen Wei-Lin , Lee Kai-Ling , Lai Kevin S. , Tsai Jie-Heng , Hsiao Shih-Hsin , Chung Chi-Li
Published: February 2023

Toll-like receptor (TLR) is essential for the immune response to Mycobacterium tuberculosis (MTB) infection. However, the mechanism whereby TLR mediates the MTB-induced pleural mesothelial hyperpermeability in tuberculous pleural effusion (TBPE) remains unclear. Pleural effusion size and pleural fluid levels of vascular endothelial growth factor (VEGF) and soluble TLR2 (sTLR2) in patients with TBPE (n = 36) or transudative pleural effusion (TPE, n = 16) were measured. The effects of MTB H37Ra (MTBRa) on pleural mesothelial permeability and the expression of VEGF and zonula occludens (ZO)-1 in human pleural mesothelial cells (PMCs) were assessed. Levels of VEGF and sTLR2 were significantly elevated in TBPE compared to TPE. Moreover, effusion VEGF levels correlated positively, while sTLR2 values correlated negatively, with pleural effusion size in TBPE. In human PMCs, MTBRa substantially activated JNK/AP-1 signaling and upregulated VEGF expression, whereas knockdown of TLR2 remarkably inhibited MTBRa-induced JNK phosphorylation and VEGF overexpression. Additionally, both MTBRa and VEGF markedly reduced ZO-1 expression and induced pleural mesothelial permeability, while TLR2 silencing or pretreatment with anti-VEGF antibody significantly attenuated the MTBRa-triggered effects. Collectively, TLR2 mediates VEGF overproduction and downregulates ZO-1 expression in human PMCs, leading to mesothelial hyperpermeability in TBPE. Targeting TLR2/VEGF pathway may confer a potential treatment strategy for TBPE.
Functional Characterization of a Familial ALS-Associated Missense TBK1 (p-Arg573Gly) Mutation in Patient-Derived Lymphoblasts
Authors: Porras Gracia , Ruiz Silvana , Maestro Inés , Borrego-Hernández Daniel , Redondo Alberto G. , Martínez Ana , Martín-Requero Ángeles
Published: February 2023

The goal of this work was to elucidate the pathogenic mechanism of an ALS-associated missense mutation, p.Arg573Gly (R573G), in the TBK1 gene. In particular, we seek to analyze the influence of this variant on the cellular levels and the function of TBK1 in immortalized cells from an ALS patient. The patient (Code# E7) belonged to a Spanish family with autosomal dominant disease manifesting in the sixth decade as either dementia or ALS. Four control individuals without signs of neurological disease were also included in this study. Our results indicate that the R375G TBK1 mutation did not affect the levels of mRNA nor the total TBK1 content; however, we observed a significant decrease in the levels of TBK1 phosphorylation, which is essential for TBK1 activity, as well as a significant reduction in the phosphorylation of p62 and RIPK1, known substrates for TBK1. Lymphoblasts from the R573G TBK1 mutation carrier patient display pathological TDP-43 homeostasis, showing elevated levels of phosphorylated TDP-43 and accumulation of the protein in the cytosolic compartment. In addition, the functional decrease in TBK1 activity observed in the E7 patient did not alter the autophagy flux, but it seems to be enough to increase ROS levels as well as the expression of pro-inflammatory cytokine IL-6.
The Regulation of Cyclins and Cyclin-Dependent Kinases in the Development of Gastric Cancer
Authors: Javed Aadil , Yarmohammadi Mahdieh , Korkmaz Kemal Sami , Rubio-Tomás Teresa
Published: February 2023

Gastric cancer predominantly occurs in adenocarcinoma form and is characterized by uncontrolled growth and metastases of gastric epithelial cells. The growth of gastric cells is regulated by the action of several major cell cycle regulators including Cyclins and Cyclin-dependent kinases (CDKs), which act sequentially to modulate the life cycle of a living cell. It has been reported that inadequate or over-activity of these molecules leads to disturbances in cell cycle dynamics, which consequently results in gastric cancer development. Manny studies have reported the key roles of Cyclins and CDKs in the development and progression of the disease in either in vitro cell culture studies or in vivo models. We aimed to compile the evidence of molecules acting as regulators of both Cyclins and CDKs, i.e., upstream regulators either activating or inhibiting Cyclins and CDKs. The review entails an introduction to gastric cancer, along with an overview of the involvement of cell cycle regulation and focused on the regulation of various Cyclins and CDKs in gastric cancer. It can act as an extensive resource for developing new hypotheses for future studies.
Assessment of Inflammation in 3D Reconstructed Human Skin Exposed to Combined Exposure to Ultraviolet and Wi-Fi Radiation
Authors: Szilágyi Zsófia , Németh Zsuzsanna , Bakos József , Kubinyi Györgyi , Necz Péter Pál , Szabó Erika , Thuróczy György , Pinto Rosanna , Selmaoui Brahim
Published: February 2023

In the human environment, the increasing exposure to radiofrequency (RF) radiation, especially that emitted by wireless devices, could be absorbed in the body. Recently, mobile and emerging wireless technologies (UMTS, DECT, LTE, and Wi-Fi) have been using higher frequencies than 2G GSM systems (900/1800 MHz), which means that most of the circulating RF currents are absorbed into the skin and the superficial soft tissue. The harmful genotoxic, cytotoxic, and mutagenic effects of solar ultraviolet (UV) radiation on the skin are well-known. This study aimed at investigating whether 2422 MHz (Wi-Fi) RF exposure combined with UV radiation in different sequences has any effect on the inflammation process in the skin. In vitro experiments examined the inflammation process by cytokines (IL-1α, IL-6, IL-8) and MMP-1 enzyme secretion in a 3D full-thickness human skin model. In the first study, UV exposure was immediately followed by RF exposure to measure the potential additive effects, while in the second study, the possible protective phenomenon (i.e., adaptive response) was investigated when adaptive RF exposure was challenged by UV radiation. Our results suggest that 2422 MHz Wi-Fi exposure slightly, not significantly increased cytokine concentrations of the prior UV exposure. We could not detect the adaptive response phenomenon.
Mechanisms of Interaction between Enhancers and Promoters in Three Drosophila Model Systems
Authors: Kyrchanova Olga , Sokolov Vladimir , Georgiev Pavel
Published: February 2023

In higher eukaryotes, the regulation of developmental gene expression is determined by enhancers, which are often located at a large distance from the promoters they regulate. Therefore, the architecture of chromosomes and the mechanisms that determine the functional interaction between enhancers and promoters are of decisive importance in the development of organisms. Mammals and the model animal Drosophila have homologous key architectural proteins and similar mechanisms in the organization of chromosome architecture. This review describes the current progress in understanding the mechanisms of the formation and regulation of long-range interactions between enhancers and promoters at three well-studied key regulatory loci in Drosophila.
Mechanisms Contributing to the Comorbidity of COPD and Lung Cancer
Authors: Forder Aisling , Zhuang Rebecca , Souza Vanessa G. P. , Brockley Liam J. , Pewarchuk Michelle E. , Telkar Nikita , Stewart Greg L. , Benard Katya , Marshall Erin A. , Reis Patricia P. , Lam Wan L.
Published: February 2023

Lung cancer and chronic obstructive pulmonary disease (COPD) often co-occur, and individuals with COPD are at a higher risk of developing lung cancer. While the underlying mechanism for this risk is not well understood, its major contributing factors have been proposed to include genomic, immune, and microenvironment dysregulation. Here, we review the evidence and significant studies that explore the mechanisms underlying the heightened lung cancer risk in people with COPD. Genetic and epigenetic changes, as well as the aberrant expression of non-coding RNAs, predispose the lung epithelium to carcinogenesis by altering the expression of cancer- and immune-related genes. Oxidative stress generated by tobacco smoking plays a role in reducing genomic integrity, promoting epithelial-mesenchymal-transition, and generating a chronic inflammatory environment. This leads to abnormal immune responses that promote cancer development, though not all smokers develop lung cancer. Sex differences in the metabolism of tobacco smoke predispose females to developing COPD and accumulating damage from oxidative stress that poses a risk for the development of lung cancer. Dysregulation of the lung microenvironment and microbiome contributes to chronic inflammation, which is observed in COPD and known to facilitate cancer initiation in various tumor types. Further, there is a need to better characterize and identify the proportion of individuals with COPD who are at a high risk for developing lung cancer. We evaluate possible novel and individualized screening strategies, including biomarkers identified in genetic studies and exhaled breath condensate analysis. We also discuss the use of corticosteroids and statins as chemopreventive agents to prevent lung cancer. It is crucial that we optimize the current methods for the early detection and management of lung cancer and COPD in order to improve the health outcomes for a large affected population.
Identification of Anoikis-Related Subgroups and Prognosis Model in Liver Hepatocellular Carcinoma
Authors: Chen Yutong , Huang Weiran , Ouyang Jian , Wang Jingxiang , Xie Zhengwei
Published: February 2023

Resistance to anoikis is a key characteristic of many cancer cells, promoting cell survival. However, the mechanism of anoikis in hepatocellular carcinoma (HCC) remains unknown. In this study, we applied differentially expressed overlapping anoikis-related genes to classify The Cancer Genome Atlas (TCGA) samples using an unsupervised cluster algorithm. Then, we employed weighted gene coexpression network analysis (WGCNA) to identify highly correlated genes and constructed a prognostic risk model based on univariate Cox proportional hazards regression. This model was validated using external datasets from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). Finally, we used a CIBERSORT algorithm to investigate the correlation between risk score and immune infiltration. Our results showed that the TCGA cohorts could be divided into two subgroups, with subgroup A having a lower survival probability. Five genes (BAK1, SPP1, BSG, PBK and DAP3) were identified as anoikis-related prognostic genes. Moreover, the prognostic risk model effectively predicted overall survival, which was validated using ICGC and GEO datasets. In addition, there was a strong correlation between infiltrating immune cells and prognostic genes and risk score. In conclusion, we identified anoikis-related subgroups and prognostic genes in HCC, which could be significant for understanding the molecular mechanisms and treatment of HCC.
Correlations between H2 Permeation and Physical/Mechanical Properties in Ethylene Propylene Diene Monomer Polymers Blended with Carbon Black and Silica Fillers
Authors: Jung Jae K. , Lee Ji H. , Jeon Sang K. , Tak Nae H. , Chung Nak K. , Baek Un B. , Lee Si H. , Lee Chang H. , Choi Myung C. , Kang Hyun M. , Bae Jong W. , Moon Won J.
Published: February 2023

H2 permeation in peroxide-crosslinked EPDM blended with carbon black (CB) and silica fillers was studied at pressures ranging from 1.2 MPa to 90 MPa via the volumetric analysis technique. H2 uptake in the CB-filled EPDM revealed dual-sorption behaviors via Henry’s law and the Langmuir model, which were attributed to H2 absorption by the polymer chains and H2 adsorption at the filler interfaces, respectively. Additionally, single-sorption mechanisms were observed for neat EPDM and silica-blended EPDM according to Henry’s law, indicating H2 absorption by the polymer chain. The linear decreases in the diffusivity with filler content for the silica-blended EPDMs were attributed to increases in the diffusion paths caused by the filler. Exponential decreases in the diffusivity with increasing filler content and in the permeation with the physical/mechanical properties for CB-filled EPDMs were caused by decreases in the fractional free volume due to increased densities for the EPDM composites. Moreover, good filler-dependent correlations between permeability and density, hardness, and tensile strength were demonstrated for EPDMs used as sealing materials for O-rings. From the resulting equation, we predicted the permeation value without further measurements. Thus, we can select EPDM candidates satisfying the permeation guidelines used in hydrogen infrastructure for the future hydrogen economy.
Cellular Senescence as a Brake or Accelerator for Oncogenic Transformation and Role in Lymphatic Metastasis
Authors: Banerjee Priyanka , Gaddam Niyanshi , Pandita Tej K. , Chakraborty Sanjukta
Published: February 2023

Cellular senescence—the irreversible cell cycle arrest driven by a variety of mechanisms and, more specifically, the senescence-associated secretory phenotype (SASP)—is an important area of research in the context of different age-related diseases, such as cardiovascular disease and cancer. SASP factors play both beneficial and detrimental roles in age-related disease progression depending on the source of the SASPs, the target cells, and the microenvironment. The impact of senescence and the SASP on different cell types, the immune system, and the vascular system has been widely discussed. However, the impact of replicative or stress-induced senescence on lymphatic biology and pathological lymphangiogenesis remains underexplored. The lymphatic system plays a crucial role in the maintenance of body fluid homeostasis and immune surveillance. The perturbation of lymphatic function can hamper normal physiological function. Natural aging or stress-induced premature aging influences the lymphatic vessel structure and function, which significantly affect the role of lymphatics in tumor dissemination and metastasis. In this review, we focus on the role of senescence on lymphatic pathobiology, its impact on cancer, and potential therapeutic interventions to manipulate the aged or senescent lymphatic system for disease management.
Cytoprotective Effects of Human Platelet Lysate during the Xeno-Free Culture of Human Donor Corneas
Authors: Talpan Delia , Salla Sabine , Meusel Linus , Walter Peter , Kuo Chao-Chung , Franzen Julia , Fuest Matthias
Published: February 2023

We evaluated the suitability of 2% human platelet lysate medium (2%HPL) as a replacement for 2% fetal bovine serum medium (2%FBS) for the xeno-free organ culture of human donor corneas. A total of 32 corneas from 16 human donors were cultured in 2%FBS for 3 days (TP1), then evaluated using phase contrast microscopy (endothelial cell density (ECD) and cell morphology). Following an additional 25-day culture period (TP2) in either 2%FBS or 2%HPL, the pairs were again compared using microscopy; then stroma and Descemet membrane/endothelium (DmE) were processed for next generation sequencing (NGS). At TP2 the ECD was higher in the 2%HPL group (2179 ± 288 cells/mm2) compared to 2%FBS (2113 ± 331 cells/mm2; p = 0.03), and endothelial cell loss was lower (ECL HPL = −0.7% vs. FBS = −3.8%; p = 0.01). There were no significant differences in cell morphology between TP1 and 2, or between 2%HPL and 2%FBS. NGS showed the differential expression of 1644 genes in endothelial cells and 217 genes in stromal cells. It was found that 2%HPL led to the upregulation of cytoprotective, anti-inflammatory and anti-fibrotic genes (HMOX1, SERPINE1, ANGPTL4, LEFTY2, GADD45B, PLIN2, PTX3, GFRA1/2), and the downregulation of pro-inflammatory/apoptotic genes (e.g., CXCL14, SIK1B, PLK5, PPP2R3B, FABP5, MAL, GATA3). 2%HPL is a suitable xeno-free substitution for 2%FBS in human cornea organ culture, inducing less ECL and producing potentially beneficial alterations in gene expression.
Dysregulation of Iron Metabolism-Linked Genes at Myocardial Tissue and Cell Levels in Dilated Cardiomyopathy
Authors: Massaiu Ilaria , Campodonico Jeness , Mapelli Massimo , Salvioni Elisabetta , Valerio Vincenza , Moschetta Donato , Myasoedova Veronika A. , Cappellini Maria Domenica , Pompilio Giulio , Poggio Paolo , Agostoni Piergiuseppe
Published: February 2023

In heart failure, the biological and clinical connection between abnormal iron homeostasis, myocardial function, and prognosis is known; however, the expression profiles of iron-linked genes both at myocardial tissue and single-cell level are not well defined. Through publicly available bulk and single-nucleus RNA sequencing (RNA-seq) datasets of left ventricle samples from adult non-failed (NF) and dilated cardiomyopathy (DCM) subjects, we aim to evaluate the altered iron metabolism in a diseased condition, at the whole cardiac tissue and single-cell level. From the bulk RNA-seq data, we found 223 iron-linked genes expressed at the myocardial tissue level and 44 differentially expressed between DCM and NF subjects. At the single-cell level, at least 18 iron-linked expressed genes were significantly regulated in DCM when compared to NF subjects. Specifically, the iron metabolism in DCM cardiomyocytes is altered at several levels, including: (1) imbalance of Fe3+ internalization (SCARA5 down-regulation) and reduction of internal conversion from Fe3+ to Fe2+ (STEAP3 down-regulation), (2) increase of iron consumption to produce hemoglobin (HBA1/2 up-regulation), (3) higher heme synthesis and externalization (ALAS2 and ABCG2 up-regulation), (4) lower cleavage of heme to Fe2+, biliverdin and carbon monoxide (HMOX2 down-regulation), and (5) positive regulation of hepcidin (BMP6 up-regulation).
The Impact of Permethrin and Cypermethrin on Plants, Soil Enzyme Activity, and Microbial Communities
Authors: Borowik Agata , Wyszkowska Jadwiga , Zaborowska Magdalena , Kucharski Jan
Published: February 2023

Pyrethroids are insecticides most commonly used for insect control to boost agricultural production. The aim of the present research was to determine the effect of permethrin and cypermethrin on cultured and non-cultivated bacteria and fungi and on the activity of soil enzymes, as well as to determine the usefulness of Zea mays in mitigating the adverse effects of the tested pyrethroids on the soil microbiome. The analyses were carried out in the samples of both soil not sown with any plant and soil sown with Zea mays. Permethrin and cypermethrin were found to stimulate the multiplication of cultured organotrophic bacteria (on average by 38.3%) and actinomycetes (on average by 80.2%), and to inhibit fungi growth (on average by 31.7%) and the enzymatic activity of the soil, reducing the soil biochemical fertility index (BA) by 27.7%. They also modified the number of operational taxonomic units (OTUs) of the Actinobacteria and Proteobacteria phyla and the Ascomycota and Basidiomycota phyla. The pressure of permethrin and cypermethrin was tolerated well by the bacteria Sphingomonas (clone 3214512, 1052559, 237613, 1048605) and Bacillus (clone New.ReferenceOTU111, 593219, 578257), and by the fungi Penicillium (SH1533734.08FU, SH1692798.08FU) and Trichocladium (SH1615601.08FU). Both insecticides disturbed the growth and yielding of Zea mays, as a result of which its yield and leaf greenness index decreased. The cultivation of Zea mays had a positive effect on both soil enzymes and soil microorganisms and mitigated the anomalies caused by the tested insecticides in the microbiome and activity of soil enzymes. Permethrin decreased the yield of its aerial parts by 37.9% and its roots by 33.9%, whereas respective decreases caused by cypermethrin reached 16.8% and 4.3%.
Efficacy and Mechanisms of Action of Essential Oils’ Vapours against Blue Mould on Apples Caused by Penicillium expansum
Authors: Buonsenso Fabio , Schiavon Giada , Spadaro Davide
Published: February 2023

Biofumigation with slow-release diffusers of essential oils (EOs) of basil, oregano, savoury, thyme, lemon, and fennel was assessed for the control of blue mould of apples, caused by Penicillium expansum. In vitro, the ability of the six EOs to inhibit the mycelial growth was evaluated at concentrations of 1.0, 0.5, and 0.1%. EOs of thyme, savoury, and oregano, at all three concentrations, and basil, at 1.0 and 0.5%, were effective in inhibiting the mycelial growth of P. expansum. In vivo, disease incidence and severity were evaluated on ‘Opal’ apples artificially inoculated with the pathogen and treated at concentrations of 1.0% and 0.5% of EOs. The highest efficacy in reducing blue mould was observed with EOs of lemon and oregano at 1.0% after 60 days of storage at 1 ± 1 °C (incidence of rot, 3 and 1%, respectively) and after a further 14 days of shelf-life at 15 ± 1 °C (15 and 17%). Firmness, titratable acidity, and total soluble solids were evaluated at harvest, after cold storage, and after shelf-life. Throughout the storage period, no evident phytotoxic effects were observed. The EOs used were characterised through GC-MS to analyse their compositions. Moreover, the volatile organic compounds (VOCs) present in the cabinets were characterised during storage using the SPME-GC-MS technique. The antifungal effects of EOs were confirmed both in vitro and in vivo and the possible mechanisms of action were hypothesised. High concentrations of antimicrobial and antioxidant compounds in the EOs explain the efficacy of biofumigation in postharvest disease control. These findings provide new insights for the development of sustainable strategies for the management of postharvest diseases and the reduction of fruit losses during storage.
Data-Driven Anomaly Detection Framework for Complex Degradation Monitoring of Aero-Engine
Authors: Yan Zichen , Sun Jianzhong , Yi Yang , Yang Caiqiong , Sun Jingbo
Published: February 2023

Data analysis is an important part of aero engine health management. In order to complete accurate condition monitoring, it is necessary to establish more effective analysis tools. Therefore, an integrated algorithm library dedicated for engine anomaly detection is established, which is PyPEFD (Python Package for Engine Fault Detection). Different algorithms for baseline modeling, anomaly detection and trend analysis are presented and compared. In this paper, the simulation data are used to verify the function of the anomaly detection algorithms, successfully completing the detection of multiple faults and comparing the accuracy algorithm under different conditions.
Biologics for Reducing Cardiovascular Risk in Psoriasis Patients
Authors: Terui Hitoshi , Asano Yoshihide
Published: February 2023

Psoriasis is a chronic inflammatory skin disease with a high prevalence of cardiovascular disease (CVD), obesity, dyslipidemia, hypertension, diabetes mellitus, and metabolic syndrome. Among them, CVD is the most common cause of morbidity and mortality in psoriasis patients. Since CVD is associated with considerable morbidity and mortality, primary care clinicians are increasingly committed to reducing the risk of CVD in patients with psoriasis. Biologics targeting TNF-α, IL-12/23, and IL-17 are systemic therapies that can dramatically improve the condition of psoriasis. Recent studies have reported that these inflammatory cytokine signals may promote atherosclerosis, suggesting that biologics might be effective for improving psoriasis as well as reducing the risk of CVD. Here, we reviewed cardiovascular risk in psoriasis patients, the association between psoriatic inflammation and atherosclerosis, and the efficacy of biologics for reducing the risk of cardiovascular diseases.
Comparison of Percutaneous Screw Fixation to Open Reduction and Internal Fixation in Acetabular Fractures: A Matched Pair Study Regarding the Short-Term Rate of Conversion to Total Hip Arthroplasty and Functional Outcomes
Authors: Einhorn Stephanie , Höch Andreas , Osterhoff Georg , Josten Christoph , Kleber Christian , Pieroh Philipp
Published: February 2023

Closed reduction and percutaneous internal fixation (CRPIF) for acetabular fractures was introduced as a less invasive alternative to open reduction and internal fixation (ORIF) for moderately displaced fractures. Currently, comparisons of ORIF and CRPIF outcomes are rare. Twenty-three patients treated with CRPIF were matched with patients treated with ORIF based on sex, age, and fracture classification. Surgery-dependent and -independent factors of the in-hospital stay, the conversion rate to total hip arthroplasty (THA), and quality of life were assessed. The ORIF group had a higher preoperative fracture step (p = 0.04) and gull wing sign (p = 0.003) compared with the CRPIF group. Postoperatively, the gap and step size were not significantly different between the groups (p > 0.05). CRPIF required less time (p < 0.0001) and transfusions (p = 0.009) and showed fewer complications (p = 0.0287). Four patients were converted to THA (CRPIF, n = 1; ORIF, n = 3; p = 0.155) because of posttraumatic osteoarthritis. Functional outcomes and pain were similar in both groups (p > 0.05). The present study revealed less blood loss and a lesser extent of reduction in patients treated with CRPIF than in those treated with ORIF. The rates of conversion to THA and functional outcomes did not differ between CRPIF and ORIF. CRPIF appeared to be a valuable treatment option for selected patients.
Electric Cardioversion vs. Pharmacological with or without Electric Cardioversion for Stable New-Onset Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Prasai Paritosh , Shrestha Dhan Bahadur , Saad Eltaib , Trongtorsak Angkawipa , Adhikari Aarya , Gaire Suman , Oli Prakash Raj , Shtembari Jurgen , Adhikari Pabitra , Sedhai Yub Raj , Akbar Muhammad Sikander , Elgendy Islam Y. , Shantha Ghanshyam
Published: February 2023

Background: There is no clear consensus on the preference for pharmacological cardioversion (PC) in comparison to electric cardioversion (EC) for hemodynamically stable new-onset atrial fibrillation (NOAF) patients presenting to the emergency department (ED). Methods: A systematic review and meta-analysis was conducted to assess PC (whether being followed by EC or not) vs. EC in achieving cardioversion for hemodynamically stable NOAF patients. PubMed, PubMed Central, Embase, Scopus, and Cochrane databases were searched to include relevant studies until 7 March 2022. The primary outcome was the successful restoration of sinus rhythm, and secondary outcomes included emergency department (ED) revisits with atrial fibrillation (AF), hospital readmission rate, length of hospital stay, and cardioversion-associated adverse events. Results: A total of three randomized controlled trials (RCTs) and one observational study were included. There was no difference in the rates of successful restoration to sinus rhythm (88.66% vs. 85.25%; OR 1.14, 95% CI 0.35–3.71; n = 868). There was no statistical difference across the two groups for ED revisits with AF, readmission rates, length of hospital stay, and cardioversion-associated adverse effects, with the exception of hypotension, whose incidence was lower in the EC group (OR 0.11, 95% CI 0.04–0.27: n = 727). Conclusion: This meta-analysis suggests that there is no difference in successful restoration of sinus rhythm with either modality among patients with hemodynamically stable NOAF.