bluuebunny/crossref_metadata_2025 huggingface dataset:
Red-Skin Extracts of Lotus Seeds Alleviate High-Fat-Diet Induced Obesity via Regulating Lipoprotein Lipase Activity
Authors: Xu Hong , Gao Hang , Liu Feiyue , Gong Lingxiao
Published: July 2022

In recent years, obesity has become an epidemic and an important public health concern. This study was designed to explore the anti-obesity effects of red-skin extracts (RSE) from lotus seeds on high-fat-diet (HFD)-fed mice. In this study, a total of 55 phenolic compounds from the RSE were tentatively characterized using a UPLC-Q/TOF-MS system, including 9 phenolic acids and derivatives, 40 flavonoids, 2 proanthocyanidin, and 4 coumarins and derivatives. Our data demonstrated that RSE could significantly ameliorate obesity characteristics of HFD-fed mice by regulating tissue specific lipoprotein lipase (LPL) activities. In detailed, the activity and expression of LPL in adipose tissue was inhibited, and the activity and expression of LPL in skeletal muscle tissue was enhanced. Overall, these findings suggested that RSE from the red skin of lotus seeds could serve as a great candidate for a value-added, functional ingredient due to its anti-obesity effects via the regulation of LPL activity.
Phosphorylated Curdlan Gel/Polyvinyl Alcohol Electrospun Nanofibres Loaded with Clove Oil with Antibacterial Activity
Authors: Suflet Dana M. , Popescu Irina , Pelin Irina M. , David Geta , Serbezeanu Diana , Rîmbu Cristina M. , Daraba Oana M. , Enache Alin A. , Bercea Maria
Published: July 2022

Fibrous membranes based on natural polymers obtained by the electrospinning technique are a great choice for wound dressings. In order to promote an efficient wound repair, and to avoid antibiotics, antibacterial plant extracts can be incorporated. In the present work, the new electrospun nanofibre membranes based on monobasic phosphate curdlan (PCurd) and polyvinyl alcohol (PVA) were obtained for the first time. To establish the adequate mixing ratio for electrospinning, the behaviour of the PCurd and PVA mixture was studied by viscometry and rheology. In order to confer antimicrobial activity with the nanofibre membrane, clove essential oil (CEO) was incorporated into the electrospun solution. Well-defined and drop-free nanofibres with a diameter between 157 nm and 110 nm were obtained. The presence of CEO in the obtained nanofibres was confirmed by ATR–FTIR spectroscopy, by the phenolic and flavonoid contents, and by the antioxidant activity of the membranes. In physiological conditions, CEO was released from the membrane after 24 h. The in vivo antimicrobial tests showed a good inhibitory activity against E. coli and higher activity against S. aureus. Furthermore, the viability cell test showed the lack of cytotoxicity of the nanofibre membrane with and without CEO, confirming its potential use in wound treatment.
Association of TNF–α rs1800629 with Adult Acute B-Cell Lymphoblastic Leukemia
Authors: Abdalhabib Ezeldine K. , Algarni Abdulrahman , Saboor Muhammad , Alanazi Fehaid , Ibrahim Ibrahim K. , Alfeel Ayman H. , Alanazi Abdullah M. , Alanazi Abdulmajeed M. , Alruwaili Abdulaziz M. , Alanazi Muath H. , Alshaikh Nahla A.
Published: July 2022

TNF–α influences lymphomagenesis by upregulating proinflammatory and antiapoptotic pathways. In this study, we evaluated the frequency of TNF–α rs1800629 (–308 G>A) polymorphism in newly diagnosed adult patients with acute lymphoblastic leukemia (ALL) and its correlation with age at diagnosis, gender and subtype of ALL. In this case control study, a total of 330 individuals were recruited, including 165 newly diagnosed adult patients with ALL, from the Radiation and Isotope Center in Khartoum (RICK) and 165 healthy normal controls. TNF–α rs1800629 polymorphism was tested through allele-specific polymerase chain reaction (PCR) assay. The frequency of the rs1800629 GA genotype was high (70.9% vs. 60%, OR = 1.84) in the patient group as compared to healthy controls, whereas GG and AA genotypes did not exhibit any statistically significant difference between controls and patients. Based on subtype, GG and GA rs1800629 genotypes showed increased risk of B-ALL (OR 0.46 and 2.12, respectively), whereas rs1800629 GG, GA and AA genotypes did not show any disease association with T-ALL (p > 0.05). Age at diagnosis and gender did not exhibit any association of rs1800629 with ALL in the patient group. In conclusion, rs1800629 is associated with high risk of adult B-ALL, with an insignificant effect of age at diagnosis and gender.
Identifying Genes Related to Acute Myocardial Infarction Based on Network Control Capability
Authors: Wang Yanhui , Xian Huimin
Published: July 2022

Identifying genes significantly related to diseases is a focus in the study of disease mechanisms. In this paper, from the perspective of integrated analysis and dynamic control, a method for identifying genes significantly related to diseases based on logic networks constructed by the LAPP method, referred to as NCCM, is proposed and applied to the study of the mechanism of acute myocardial infarction (AMI). It is found that 82.35% of 17 differential control capability genes (DCCGs) identified by NCCM are significantly correlated with AMI/MI in the literature and DISEASES database. The enrichment analysis of DCCGs shows that AMI is closely related to the positive regulation of vascular-associated smooth muscle cell proliferation and regulation of cytokine production involved in the immune response, in which HBEGF, THBS1, NR4A3, NLRP3, EDN1, and MMP9 play a crucial role. In addition, although the expression levels of CNOT6L and ACYP1 are not significantly different between the control group and the AMI group, NCCM shows that they are significantly associated with AMI. Although this result still needs further verification, it shows that the method can not only identify genes with large differences in expression but also identify genes that are associated with diseases but with small changes in expression.
Addressing the Gap in Data Communication from Home Health Care to Primary Care during Care Transitions: Completeness of an Interoperability Data Standard
Authors: Sockolow Paulina , Chou Edgar Y. , Park Subin
Published: July 2022

In a future where home health care is no longer an information silo, patient information will be communicated along transitions in care to improve care. Evidence-based practice in the United States supports home health care patients to see their primary care team within the first two weeks of hospital discharge to reduce rehospitalization risk. We sought to identify a parsimonious set of home health care data to be communicated to primary care for the post-hospitalization visit. Anticipating electronic dataset communication, we investigated the completeness of the international reference terminology, Logical Observation Identifiers Names and Codes (LOINC), for coverage of the data to be communicated. We conducted deductive qualitative analysis in three steps: (1) identify home health care data available for the visit by mapping home health care to the information needed for the visit; (2) reduce the resulting home health care data set to a parsimonious set clinicians wanted for the post-hospitalization visit by eliciting primary care clinician input; and (3) map the parsimonious dataset to LOINC and assess LOINC completeness. Our study reduced the number of standardized home health care assessment questions by 40% to a parsimonious set of 33 concepts that primary care team physicians wanted for the post-hospitalization visit. Findings indicate all home health care concepts in the parsimonious dataset mapped to the information needed for the post-hospitalization visit, and 84% of the home health care concepts mapped to a LOINC term. The results indicate data flow of parsimonious home health care dataset to primary care for the post-hospitalization visit is possible using existing LOINC codes, and would require adding some codes to LOINC for communication of a complete parsimonious data set.
The Efficacy of Low-Level Laser Therapy Combined with Single Flap Periodontal Surgery in the Management of Intrabony Periodontal Defects: A Randomized Controlled Trial
Authors: Silviya S. , C.M. Anitha , Prakash P.S.G. , Bahammam Sarah Ahmed , Bahammam Maha A. , Almarghlani Ammar , Assaggaf Mohammad , Kamil Mona Awad , Subramanian Sangeetha , Balaji Thodur Madapusi , Patil Shankargouda
Published: July 2022

This study aimed at assessing the clinical outcomes of the Single Flap Approach (SFA) with the additional use of Low-level laser therapy (LLLT). The defects were treated as per the principles of SFA, whereby 20 defects received only SFA (control group) and 20 defects received additional LLLT for bio stimulation/bio modulation (test group). Stable primary closure of the flaps was obtained with vertical internal mattress sutures. Plaque indices (FMPS), clinical attachment levels (CAL), probing pocket depth (PPD), and gingival bleeding scores (FMBS) were calculated at baseline, and at the 3rd and 6th months in both groups. An EHI score of 1 was observed at all sites except for two, where a score of 2 in the control group at week 2 was observed. In the test group, the PPD reduction at 6 months was 3.60 ± 0.95 and in the control group it was 3.75 ± 0.91 mm. CAL gain at 6 months was 2.70 ± 1.36 mm and 3.45 ± 1.2 mm in the test group and showed no statistical significance. These data suggested the positive effect of LLLT over CAL gain; thus, LLLT may be combined with SFA to potentially enhance the early wound healing and higher clinical outcomes in terms of increase in CAL and decrease in PPD.
Changes in Attitudes toward People with Substance Use Disorder: A Comparative Study of the General Population in Mexico
Authors: Bustos-Gamiño Marycarmen , Mora-Ríos Jazmín , Villatoro-Velázquez Jorge , Fleiz-Bautista Clara , Molina-López Alejandro , Medina-Mora María Elena
Published: July 2022

Background: Substance use disorders are among the most stigmatized conditions worldwide. People with substance use disorder (PWSUD) are often considered responsible for their use of drugs. The objectives are to analyze changes in Mexican attitudes toward PWSUD in the general population over the period 2011 to 2016 and to use the latest Mexican household survey to determine which segments of the population are most likely to have negative attitudes. Methods: Two representative national household surveys employing similar methodologies were conducted in Mexico in 2011 and 2016 with persons aged 12–65 years. Participants were asked about their attitudes toward PWSUD, and changes were compared across GLM. Results: The surveys found a decrease from 2011 to 2016 in the number of respondents who considered PWSUD “sick” or in “need of help” and an increase in the number who believed they were “selfish” or “criminal”. The 2016 survey found that men, people 18 years of age or older, people who do not use drugs and people with lower educational levels were the groups with the most negative attitudes toward PWSUD. Conclusions: These results suggest that it may not be recognized that PWSUD may have a health problem and that this helps to increase stigmatization towards this population.
Big Data, Decision Models, and Public Health
Authors: Chan Chien-Lung , Chang Chi-Chang
Published: July 2022

As the digital era unfolds, the volume and velocity of environmental, population, and public health data are rapidly increasing [...]
Perceived Information Distortion about COVID-19 Vaccination and Addictive Social Media Use among Social Media Users in Hong Kong: The Moderating Roles of Functional Literacy and Critical Literacy
Authors: Xie Luyao , Lee Edmund , Fong Vivian , Hui Kam-Hei , Xin Meiqi , Mo Phoenix
Published: July 2022

During the COVID-19 pandemic, distorted information about the COVID-19 vaccination is widely disseminated through social media. The present study examined the association between perceived information distortion about COVID-19 vaccination on social media, individuals’ functional and critical literacy, and addictive social media use (SMU), as well as the moderating roles of functional and critical literacy in the association between perceived information distortion and addictive SMU among social media users in Hong Kong. A web-based, cross-sectional survey was conducted among 411 Chinese citizens from June to August 2021. Findings showed that after adjusting for significant background variables, including age, gender, marital status, education, occupation, and income, functional literacy was negatively associated with addictive SMU. In addition, significant moderation effects of functional literacy and critical literacy were also observed, such that a positive association between perceived information distortion on social media and addictive SMU was significant among participants with lower functional literacy or higher critical literacy. Findings highlight the importance of improving functional literacy in addictive SMU prevention for social media users. Special attention should also be paid to the potential influence of critical literacy on addictive SMUs.
Exploring the Moderation and Mediation Effects in Addressing the Main Determinants of Income Inequalities in Supporting Quality of Life: Insights from CEE Countries
Authors: Davidescu Adriana AnaMaria , Nae Tamara Maria , Florescu Margareta-Stela
Published: July 2022

Income inequality has become an increasingly pressing economic and social problem in Europe, especially in emerging countries with more significant inequalities than the EU average. The high-level inequality persistence can decrease well-being by accentuating the shortcomings at the household level, increasing poverty and social exclusion, generating political instability, leading to a decline in social cohesion, and, finally, a weakening of the Union as a whole. In this context, the paper aims to identify the main determinants of income inequality across the CEE countries and their significant implications in supporting the quality of life and well-being, highlighting the mediation and moderation effects. The analysis focuses on emerging European countries, using panel-based data analysis for ten EU countries covering 2008–2019. The empirical findings highlighted the importance of the minimum wage, high-tech exports, the degree of economic openness, the quality of institutions, and education spending in reducing income inequality. On the other hand, the proportion of the population with a higher education level and the interaction between official and unofficial economies led to income inequality. Therefore, to increase the quality of life, it is mandatory to decrease inequalities. Thus, fewer people will be at risk of living a less qualitative life. The empirical results also proved that the informal economy and the share of people employed in industry exhibited mediating roles. In contrast, the economic growth, the urbanization degree, and the share of people employed in services exhibited moderating roles. Additionally, we also tested the impact of the income inequality determinants of the quality of life, the empirical results supporting the influence of minimum wage, employment with tertiary education, government effectiveness, the degree of economic openness, and education expenditures.
Marriage Intention among Korean Young Adults: Trends and Influencing Factors
Authors: An Doyeon , Lee Sang-Lim , Woo Hyekyung
Published: July 2022

The recent increase in the tendency of people to marry late or to opt out of marriage entirely is among the key contributors to Korea’s low fertility rate. One possible cause of this tendency may be a change in how marriage is valued among Korea’s youth. The marriage intentions of young adults can be classified into “positive”, “negative”, and “neutral”. Over time, positive marriage intentions have declined across all age groups (2010: 61% → 2020: 39%; ages 25–29), with no significant change in negative marriage intentions. In contrast, neutral marriage intentions have increased significantly (2010: 36% → 2020: 53%; ages 25–29). This phenomenon may be attributable to the increase in the number of young adults who prioritize survival over thinking about the future. However, neutral marriage values can be changed into positive values at any time. A holistic overview of Korean society is necessary to determine how the values of young adults might be influenced to align with a traditional life process.
Identification of Metropolitan Area Boundaries Based on Comprehensive Spatial Linkages of Cities: A Case Study of the Beijing–Tianjin–Hebei Region
Authors: Zhang Xiaoyuan , Wang Hao , Ning Xiaogang , Zhang Xiaoyu , Liu Ruowen , Wang Huibing
Published: July 2022

As a regional management unit to solve "urban diseases,” metropolitan areas are gradually attracting widespread attention. How to objectively and accurately delineate the boundaries of a metropolitan area is the primary prerequisite for carrying out targeted studies and precisely formulating regional planning measures. However, the existing methods for delineating metropolitan area boundaries have problems, such as high data acquisition costs, subjectivity, and a single perspective of urban linkage. To address the above problems, we propose a “bottom-up” approach to metropolitan area boundary delineation based on urban comprehensive spatial linkages. We used only publicly available data to construct a directionally weighted network of urban spatial linkages, and applied community detection algorithms to delineate metropolitan area boundaries. Taking the Beijing–Tianjin–Hebei region as a case study area, the method’s validity was confirmed. The results showed the following: (1) Eight metropolitan areas were delineated within the region, with two types of metropolitan areas: “Inter-municipal” and “single-city”. (2) The overall accuracy of the delineation results reached 83.41%, which is highly consistent with their corresponding isochrone maps. (3) Most metropolitan areas were observed to have an obvious “central–peripheral” structure, with only the JingJinLang metropolitan area being a polycentric mature metropolitan area, whereas the other metropolitan areas remained in the initial stage of development, with Zhangjiakou and Chengde not yet having formed metropolitan areas. This study’s methodology highlights the basic criteria of “inter-city spatial linkage” as the foundation for boundary delineation, avoiding the inaccuracy caused by the subjective selection of boundary thresholds, and can also accurately determine the developmental stage and internal spatial structure of metropolitan areas. Our method can provide new perspectives for regional boundary delineation and spatial planning policy formulation.
Extracting Human Activity Areas from Large-Scale Spatial Data with Varying Densities
Authors: Shen Xiaoqi , Shi Wenzhong , Liu Zhewei , Zhang Anshu , Wang Lukang , Zeng Fanxin
Published: July 2022

Human activity area extraction, a popular research topic, refers to mining meaningful location clusters from raw activity data. However, varying densities of large-scale spatial data create a challenge for existing extraction methods. This research proposes a novel area extraction framework (ELV) aimed at tackling the challenge by using clustering with an adaptive distance parameter and a re-segmentation strategy with noise recovery. Firstly, a distance parameter was adaptively calculated to cluster high-density points, which can reduce the uncertainty introduced by human subjective factors. Secondly, the remaining points were assigned according to the spatial characteristics of the clustered points for a more reasonable judgment of noise points. Then, to face the varying density problem, a re-segmentation strategy was designed to segment the appropriate clusters into low- and high-density clusters. Lastly, the noise points produced in the re-segmentation step were recovered to reduce unnecessary noise. Compared with other algorithms, ELV showed better performance on real-life datasets and reached 0.42 on the Silhouette coefficient (SC) indicator, with an improvement of more than 16.67%. ELV ensures reliable clustering results, especially when the density differences of the activity points are large, and can be valuable in some applications, such as location prediction and recommendation.
Can Modern Molecular Modeling Methods Help Find the Area of Potential Vulnerability of Flaviviruses?
Authors: Shanshin Daniil V. , Borisevich Sophia S. , Bondar Alexander A. , Porozov Yuri B. , Rukhlova Elena A. , Protopopova Elena V. , Ushkalenko Nikita D. , Loktev Valery B. , Chapoval Andrei I. , Ilyichev Alexander A. , Shcherbakov Dmitriy N.
Published: July 2022

Flaviviruses are single-stranded RNA viruses that have emerged in recent decades and infect up to 400 million people annually, causing a variety of potentially severe pathophysiological processes including hepatitis, encephalitis, hemorrhagic fever, tissues and capillaries damage. The Flaviviridae family is represented by four genera comprising 89 known virus species. There are no effective therapies available against many pathogenic flaviviruses. One of the promising strategies for flavivirus infections prevention and therapy is the use of neutralizing antibodies (NAb) that can disable the virus particles from infecting the host cells. The envelope protein (E protein) of flaviviruses is a three-domain structure that mediates the fusion of viral and host membranes delivering the infectious material. We previously developed and characterized 10H10 mAb which interacts with the E protein of the tick-borne encephalitis virus (TBEV) and many other flaviviruses’ E proteins. The aim of this work was to analyze the structure of E protein binding sites recognized by the 10H10 antibody, which is reactive with different flavivirus species. Here, we present experimental data and 3D modeling indicating that the 10H10 antibody recognizes the amino acid sequence between the two cysteines C92-C116 of the fusion loop (FL) region of flaviviruses’ E proteins. Overall, our results indicate that the antibody-antigen complex can form a rigid or dynamic structure that provides antibody cross reactivity and efficient interaction with the fusion loop of E protein.
Efficient Identification of the MYC Regulator with the Use of the CRISPR Library and Context-Matched Database Screenings
Authors: Tanaka Yosuke , Kambayashi Hidetaka , Yamamoto Akiko , Onishi Iichiroh , Sugita Keisuke , Matsumura Miwa , Ishibashi Sachiko , Ikeda Masumi , Yamamoto Kouhei , Kitagawa Masanobu , Kurata Morito
Published: July 2022

MYC is a major oncogene that plays an important role in cell proliferation in human cancers. Therefore, the mechanism behind MYC regulation is a viable therapeutic target for the treatment of cancer. Comprehensive and efficient screening of MYC regulators is needed, and we had previously established a promoter screening system using fluorescent proteins and the CRISPR library. For the efficient identification of candidate genes, a database was used, for which mRNA expression was correlated with MYC using datasets featuring “Similar” and “Not exactly similar” contexts. INTS14 and ERI2 were identified using datasets featuring the “Similar” context group, and INTS14 and ERI2 were capable of enhancing MYC promoter activity. In further database analysis of human cancers, a higher expression of MYC mRNA was observed in the INTS14 mRNA high-expressing prostate and liver cancers. The knockdown of INTS14 in prostate cell lines resulted in decreased MYC mRNA and protein expression and also induced G0/1 arrest. This study confirmed that CRISPR screening combined with context-matched database screening is effective in identifying genes that regulate the MYC promoter. This method can be applied to other genes and is expected to be useful in identifying the regulators of other proto-oncogenes.
The NEL Family of Bacterial E3 Ubiquitin Ligases
Authors: Bullones-Bolaños Andrea , Bernal-Bayard Joaquín , Ramos-Morales Francisco
Published: July 2022

Some pathogenic or symbiotic Gram-negative bacteria can manipulate the ubiquitination system of the eukaryotic host cell using a variety of strategies. Members of the genera Salmonella, Shigella, Sinorhizobium, and Ralstonia, among others, express E3 ubiquitin ligases that belong to the NEL family. These bacteria use type III secretion systems to translocate these proteins into host cells, where they will find their targets. In this review, we first introduce type III secretion systems and the ubiquitination process and consider the various ways bacteria use to alter the ubiquitin ligation machinery. We then focus on the members of the NEL family, their expression, translocation, and subcellular localization in the host cell, and we review what is known about the structure of these proteins, their function in virulence or symbiosis, and their specific targets.
A Quantitative Genetic Study of Sclerotinia Head Rot Resistance Introgressed from the Wild Perennial Helianthus maximiliani into Cultivated Sunflower (Helianthus annuus L.)
Authors: Talukder Zahirul I. , Underwood William , Misar Christopher G. , Seiler Gerald J. , Cai Xiwen , Li Xuehui , Qi Lili
Published: July 2022

Sclerotinia head rot (HR), caused by Sclerotinia sclerotiorum, is an economically important disease of sunflower with known detrimental effects on yield and quality in humid climates worldwide. The objective of this study was to gain insight into the genetic architecture of HR resistance from a sunflower line HR21 harboring HR resistance introgressed from the wild perennial Helianthus maximiliani. An F2 population derived from the cross of HA 234 (susceptible-line)/HR21 (resistant-line) was evaluated for HR resistance at two locations during 2019–2020. Highly significant genetic variations (p < 0.001) were observed for HR disease incidence (DI) and disease severity (DS) in both individual and combined analyses. Broad sense heritability (H2) estimates across environments for DI and DS were 0.51 and 0.62, respectively. A high-density genetic map of 1420.287 cM was constructed with 6315 SNP/InDel markers developed using genotype-by-sequencing technology. A total of 16 genomic regions on eight sunflower chromosomes, 1, 2, 10, 12, 13, 14, 16 and 17 were associated with HR resistance, each explaining between 3.97 to 16.67% of the phenotypic variance for HR resistance. Eleven of these QTL had resistance alleles from the HR21 parent. Molecular markers flanking the QTL will facilitate marker-assisted selection breeding for HR resistance in sunflower.
Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part I)
Authors: Mioc Marius , Milan Andreea , Malița Daniel , Mioc Alexandra , Prodea Alexandra , Racoviceanu Roxana , Ghiulai Roxana , Cristea Andreea , Căruntu Florina , Șoica Codruța
Published: July 2022

Triterpenic acids are phytocompounds with a widespread range of biological activities that have been the subject of numerous in vitro and in vivo studies. However, their underlying mechanisms of action in various pathologies are not completely elucidated. The current review aims to summarize the most recent literature, published in the last five years, regarding the mechanism of action of three triterpenic acids (asiatic acid, oleanolic acid, and ursolic acid), corelated with different biological activities such as anticancer, anti-inflammatory, antidiabetic, cardioprotective, neuroprotective, hepatoprotective, and antimicrobial. All three discussed compounds share several mechanisms of action, such as the targeted modulation of the PI3K/AKT, Nrf2, NF-kB, EMT, and JAK/STAT3 signaling pathways, while other mechanisms that proved to only be specific for a part of the triterpenic acids discussed, such as the modulation of Notch, Hippo, and MALAT1/miR-206/PTGS1 signaling pathway, were highlighted as well. This paper stands as the first part in our literature study on the topic, which will be followed by a second part focusing on other triterpenic acids of therapeutic value.
Targeted Induction of Endogenous VDUP1 by Small Activating RNA Inhibits the Growth of Lung Cancer Cells
Authors: Park Ki Hwan , Yang Jeong-Wook , Kwon Joo-Hee , Lee Hyunju , Yoon Yeo Dae , Choi Byeong Jo , Lee Myeong Youl , Lee Chang Woo , Han Sang-Bae , Kang Jong Soon
Published: July 2022

Recent studies have reported that small double-strand RNAs (dsRNAs) can activate endogenous genes via an RNA-based promoter targeting mechanism termed RNA activation (RNAa). In the present study, we showed that dsVDUP1-834, a novel small activating RNA (saRNA) targeting promoter of vitamin D3 up-regulated protein 1 (VDUP1) gene, up-regulated expression of VDUP1 at both mRNA and protein levels in A549 lung cancer cells. We also demonstrated that dsVDUP1-834 inhibited cell proliferation in A549 lung cancer cells. Further studies showed that dsVDUP1-834 induced cell-cycle arrest by increasing p27 and p53 and decreasing cyclin A and cyclin B1. In addition, knockdown of VDUP1 abrogated dsVDUP1-834-induced up-regulation of VDUP1 gene expression and related effects. The activation of VDUP1 by dsVDUP1-834 was accompanied by an increase in dimethylation of histone 3 at lysine 4 (H3K4me2) and acetylation of histone 3 (H3ac) and a decrease in dimethylation of histone 3 at lysine 9 (H3K9me2) at the target site of VDUP1 promoter. Moreover, the enrichment of Ago2 was detected at the dsVDUP1-834 target site, and Ago2 knockdown significantly suppressed dsVDUP1-834-mediated inhibition of cell proliferation and modulation of cell-cycle regulators. Taken together, the results presented in this report demonstrate that dsVDUP1-834 induces VDUP1 gene expression by epigenetic changes, resulting in cell growth inhibition and cell-cycle arrest. Our results suggest that targeted induction of VDUP1 by dsVDUP1-834 might be a promising therapeutic strategy for the treatment of lung cancer.
PEDF Deletion Induces Senescence and Defects in Phagocytosis in the RPE
Authors: Rebustini Ivan T. , Crawford Susan E. , Becerra S. Patricia
Published: July 2022

The retinal pigment epithelium (RPE) expresses the Serpinf1 gene to produce pigment epithelium-derived factor (PEDF), a retinoprotective protein that is downregulated with cell senescence, aging and retinal degenerations. We determined the expression of senescence-associated genes in the RPE of 3-month-old mice that lack the Serpinf1 gene and found that Serpinf1 deletion induced H2ax for histone H2AX protein, Cdkn1a for p21 protein, and Glb1 gene for β-galactosidase. Senescence-associated β-galactosidase activity increased in the Serpinf1 null RPE when compared with wild-type RPE. We evaluated the subcellular morphology of the RPE and found that ablation of Serpinf1 increased the volume of the nuclei and the nucleoli number of RPE cells, implying chromatin reorganization. Given that the RPE phagocytic function declines with aging, we assessed the expression of the Pnpla2 gene, which is required for the degradation of photoreceptor outer segments by the RPE. We found that both the Pnpla2 gene and its protein PEDF-R declined with the Serpinf1 gene ablation. Moreover, we determined the levels of phagocytosed rhodopsin and lipids in the RPE of the Serpinf1 null mice. The RPE of the Serpinf1 null mice accumulated rhodopsin and lipids compared to littermate controls, implying an association of PEDF deficiency with RPE phagocytosis dysfunction. Our findings establish PEDF loss as a cause of senescence-like changes in the RPE, highlighting PEDF as both a retinoprotective and a regulatory protein of aging-like changes associated with defective degradation of the photoreceptor outer segment in the RPE.
Microsporidia Promote Host Mitochondrial Fragmentation by Modulating DRP1 Phosphorylation
Authors: Luo Jian , Xu Jinzhi , Xie Chaolu , Zhao Zuoming , Guo Junrui , Wen Yuan , Li Tian , Zhou Zeyang
Published: July 2022

Microsporidia are obligate intracellular parasites that infect a wide variety of hosts ranging from invertebrates to vertebrates. These parasites have evolved strategies to directly hijack host mitochondria for manipulating host metabolism and immunity. However, the mechanism of microsporidia interacting with host mitochondria is unclear. In the present study, we show that microsporidian Encephalitozoon greatly induce host mitochondrial fragmentation (HMF) in multiple cells. We then reveal that the parasites promote the phosphorylation of dynamin 1-like protein (DRP1) at the 616th serine (Ser616), and dephosphorylation of the 637th serine (Ser637) by highly activating mitochondrial phosphoglycerate mutase 5 (PGAM5). These phosphorylation modifications result in the translocation of DRP1 from cytosol to the mitochondrial outer membrane, and finally lead to HMF. Furthermore, treatment with mitochondrial division inhibitor 1 (Mdivi1) significantly reduced microsporidian proliferation, indicating that the HMF are crucial for microsporidian replication. In summary, our findings reveal the mechanism that microsporidia manipulate HMF and provide references for further understanding the interactions between these ubiquitous pathogens with host mitochondria.
Maximizing the Performance of Similarity-Based Virtual Screening Methods by Generating Synergy from the Integration of 2D and 3D Approaches
Authors: Fan Ningning , Hirte Steffen , Kirchmair Johannes
Published: July 2022

Methods for the pairwise comparison of 2D and 3D molecular structures are established approaches in virtual screening. In this work, we explored three strategies for maximizing the virtual screening performance of these methods: (i) the merging of hit lists obtained from multi-compound screening using a single screening method, (ii) the merging of the hit lists obtained from 2D and 3D screening by parallel selection, and (iii) the combination of both of these strategies in an integrated approach. We found that any of these strategies led to a boost in virtual screening performance, with the clearest advantages observed for the integrated approach. On test sets for virtual screening, covering 50 pharmaceutically relevant proteins, the integrated approach, using sets of five query molecules, yielded, on average, an area under the receiver operating characteristic curve (AUC) of 0.84, an early enrichment among the top 1% of ranked compounds (EF1%) of 53.82 and a scaffold recovery rate among the top 1% of ranked compounds (SRR1%) of 0.50. In comparison, the 2D and 3D methods on their own (when using a single query molecule) yielded AUC values of 0.68 and 0.54, EF1% values of 19.96 and 17.52, and SRR1% values of 0.20 and 0.17, respectively. In conclusion, based on these results, the integration of 2D and 3D methods, via a (balanced) parallel selection strategy, is recommended, and, in particular, when combined with multi-query screening.
Molecular Effects of Chronic Exposure to Palmitate in Intestinal Organoids: A New Model to Study Obesity and Diabetes
Authors: Filippello Agnese , Di Mauro Stefania , Scamporrino Alessandra , Torrisi Sebastiano Alfio , Leggio Gian Marco , Di Pino Antonino , Scicali Roberto , Di Marco Maurizio , Malaguarnera Roberta , Purrello Francesco , Piro Salvatore
Published: July 2022

Intestinal cell dysfunctions involved in obesity and associated diabetes could be correlated with impaired intestinal cell development. To date, the molecular mechanisms underlying these dysfunctions have been poorly investigated because of the lack of a good model for studying obesity. The main aim of this study was to investigate the effects of lipotoxicity on intestinal cell differentiation in small intestinal organoid platforms, which are used to analyze the regulation of cell differentiation. Mouse intestinal organoids were grown in the presence/absence of high palmitate concentrations (0.5 mM) for 48 h to simulate lipotoxicity. Palmitate treatment altered the expression of markers involved in the differentiation of enterocytes and goblet cells in the early (Hes1) and late (Muc2) phases of their development, respectively, and it modified enterocytes and goblet cell numbers. Furthermore, the expression of enteroendocrine cell progenitors (Ngn3) and I cells (CCK) markers was also impaired, as well as CCK-positive cell numbers and CCK secretion. Our data indicate, for the first time, that lipotoxicity simultaneously influences the differentiation of specific intestinal cell types in the gut: enterocytes, goblet cells and CCK cells. Through this study, we identified novel targets associated with molecular mechanisms affected by lipotoxicity that could be important for obesity and diabetes therapy.
A Virtual Tour for the Promotion of Tourism of the City of Bari
Authors: De Luca Valerio , Marcantonio Giorgia , Barba Maria Cristina , De Paolis Lucio Tommaso
Published: July 2022

The use of information technology in the field of cultural heritage makes it possible to involve more and more people in the promotion of cultural heritage, fostering social, cultural, economic and community growth. This work stems from the interest in using Virtual Reality (VR) in the field of cultural heritage, creating a tour of the city of Bari that tells its evolution over the years. To this end, a low-cost VR360 application has been developed which, by means of a cardboard, allows the user to experience a virtual journey through time. It tells the story of the city, focusing on its urban expansion and the evolution of its architectural styles, influenced by various dominations over the centuries, up to the current state. The virtual environment was created from spherical images of the city, captured through 360° cameras and enriched with various types of information content. The user experience was assessed by means of a questionnaire derived from previous work that was generalised and adapted to the considered scenario: the results showed a very good level of satisfaction, usability, engagement, immersion and sense of presence; the highest score was obtained for the visual quality of the images of the virtual environment.
Chest Tube Placement in Mechanically Ventilated Trauma Patients: Differences between Computed Tomography-Based Indication and Clinical Decision
Authors: Struck Manuel Florian , Kleber Christian , Ewens Sebastian , Ebel Sebastian , Kirsten Holger , Krämer Sebastian , Schob Stefan , Osterhoff Georg , Girrbach Felix , Hilbert-Carius Peter , Ondruschka Benjamin , Hempel Gunther
Published: July 2022

The rate of occult pneumothorax in intubated and mechanically ventilated trauma patients until initial computed tomography (CT) remains undetermined. The primary aims of this study were to analyze initial chest CTs with respect to the thoracic pathology of trauma, the clinical injury severity, and chest tube placement (CTP) before and after CT. In a single-center retrospective analysis of 616 intubated and mechanically ventilated adult patients admitted directly from the scene to the emergency department (ED), 224 underwent CTP (36%). Of these, 142 patients (62%) underwent CTP before CT, of which, 125 (88%) had significant chest injury on CT. Seventeen patients had minor or absent chest injuries, most of which were associated with transient or unrecognized tracheal tube malposition. After CT, CTP was performed in another 82 patients, of which, 56 (68.3%) had relevant pneumothorax and 26 had minor findings on CT. Sixty patients who had already undergone CTP before CT received another CTP after CT, of which, 15 (25%) had relevant pneumothorax and 45 (75%) had functionality issues or malposition requiring replacement. Nine patients showed small pneumothorax on CT, and did not undergo CTP (including four patients with CTP before CT). The physiological variables were unspecific, and the trauma scores were dependent on the CT findings for identifying patients at risk for CTP. In conclusion, the clinical decisions for CTP before CT are associated with relevant false-negative and false-positive cases. Clinical assessment and CT imaging, together, are important indicators for CTP decisions that cannot be achieved by using clinical assessment or CT alone.
Clinical and Histological Effects of Partial Blood Flow Impairment in Vascularized Lymph Node Transfer
Authors: Akita Shinsuke , Ikehara Yuzuru , Arai Minami , Tokumoto Hideki , Yamaji Yoshihisa , Azuma Kazuhiko , Kubota Yoshitaka , Haneishi Hideaki , Kimura Motoko Y. , Mitsukawa Nobuyuki
Published: July 2022

Regarding vascularized lymph node transfer (VLNT) for lymphedema, partial blood flow impairment in transferred lymph node (LN) flaps may adversely affect the therapeutic results. We investigated the clinical and histological effects of partial blood flow impairment in LN flaps. In upper extremity lymphedema cases, based on ultrasonographic examination at 2 weeks after VLNT, we compared the treatment results depending on whether the postoperative blood flow in transferred LNs was good (Group G) or poor (Group P). Novel partial ischemia and congestion of LN flap mouse models were developed to determine their histological features. In 42 cases, significant differences were observed between Group G (n = 37) and Group P (n = 5) based on the amount of volume reduction (136.7 ± 91.7 mL and 55.4 ± 60.4 mL, respectively; p = 0.04) and lymph flow recanalization rate in indocyanine green fluorescent lymphography (67.6% and 0%, respectively; p = 0.0007). In mouse models, thrombi formation in the marginal sinus and numerous Myl9/12-positive immunocompetent cells in follicles were observed in congested LNs. Blood flow maintenance in the transferred LNs is an essential factor influencing the therapeutic effect of VLNT. Postoperatively, surgeons should closely monitor blood flow in the transferred LNs, particularly in cases of congestion.
Effect of Bariatric Surgery on Flow-Mediated Vasodilation as a Measure of Endothelial Function: A Systematic Review and Meta-Analysis
Authors: Jamialahmadi Tannaz , Alidadi Mona , Atkin Stephen L. , Kroh Matthew , Almahmeed Wael , Moallem Seyed Adel , Al-Rasadi Khalid , Rodriguez John H. , Santos Raul D. , Ruscica Massimiliano , Sahebkar Amirhossein
Published: July 2022

Objectives. Flow mediated vasodilation (FMD) is a marker of endothelial function and its decline is related to increased cardiovascular risk. This systematic review and meta-analysis evaluated the impact of bariatric surgery on FMD. Materials and methods. A systematic literature search in PubMed, Scopus, Embase, and Web of Science was performed to 1 May 2021. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. All types of bariatric surgery were considered, with the inclusion that FMD had to have been tested before and after the surgical procedure. Meta-analysis was carried out using a random-effects model and the generic inverse variance approach. The leave-one-out approach was used for sensitivity analysis. To assess metabolic parameter confounders, a weighted random-effects meta-regression was used. Results. A meta-analysis and a systematic review of 23 studies (n = 891 individuals) demonstrated improvement in FMD following bariatric surgery (weighted mean difference (WMD): 5.867, 95% CI: 4.481, 7.252, p < 0.001; I2: 96.70). Iteratively removing each item in the meta-analysis did not result in a significant alteration in the pooled estimate of effect size. There was an improvement in FMD for up to 6 months following bariatric surgery in a meta-analysis from 7 trials that included 356 subjects (WMD: 5.248, 95% CI: 2.361, 8.135, p < 0.001; I2: 98.18). The meta-analysis from 9 trials (n = 414 subjects) showed an improvement in FMD 6 to 12 months after bariatric surgery (WMD: 5.451, 95% CI: 3.316, 7.587, p < 0.001; I2: 94.18). The meta-analysis from 10 trials (n = 414 subjects) demonstrated an improvement in FMD 12 months after bariatric surgery (WMD: 2.401, 95% CI: 0.944, 3.859, p = 0.001; I2: 88.35). Random-effects meta-regression did not show any association between the alteration in FMD and percent body mass index (BMI) change (slope: 0.0258; 95% CI: −0.323, 0.375; p = 0.884), or changes in blood pressure; however, there was an association between the changes in FMD and the duration of follow-up (slope: −0.106; 95% CI: −0.205, −0.008; p = 0.033) with greater changes in FMD after 12 months. Conclusions. Bariatric surgery significantly improved FMD that increased with time, and the resultant improvement in endothelial function was independent of weight loss or a reduction in blood pressure.
Comparative Appraisal of Intravascular Ultrasound and Optical Coherence Tomography in Invasive Coronary Imaging: 2022 Update
Authors: Baruś Piotr , Modrzewski Jakub , Gumiężna Karolina , Dunaj Piotr , Głód Marcin , Bednarek Adrian , Wańha Wojciech , Roleder Tomasz , Kochman Janusz , Tomaniak Mariusz
Published: July 2022

Although coronary angiography has been well established as a standard modality for percutaneous coronary intervention guidance, recent developments in intravascular imaging techniques, such as intravascular ultrasound and optical coherence tomography, have become increasingly adopted, enabling direct detailed lesion visualization, including lesions beyond the scope of assessment using exclusively angiography. Intravascular imaging modalities have been reported to potentially improve both short- and long-term percutaneous intervention outcomes. This review aims to provide a comparative summary of recent advancements in research regarding the clinical applications and outcomes of intravascular ultrasound and optical coherence tomography.
Use of Black-and-White Digital Filters to Optimize Visualization in Cataract Surgery
Authors: Sandali Otman , Tahiri Joutei Hassani Rachid , Armia Balamoun Ashraf , Duliere Cedric , El Sanharawi Mohamed , Borderie Vincent
Published: July 2022

Purpose: To evaluate the effect of a black-and-white (BW) filter on the optimization of visualization at each stage of cataract surgery. Methods: Prospective, single-center, single-surgeon, consecutive case series of 40 patients undergoing cataract surgery with BW filter. Surgical images and videos were recorded with and without the BW filter at each stage of cataract surgery. Contrast measurements of surgical images and subjective analysis of video sequences were performed. Results: The surgeons assessed the BW filter to optimize the tissue visibility of capsulorhexis contours, hydrodissection fluid wave perception, the contrast of instruments through a nucleus during phaco-chop, and subincisional cortex contrast through the corneal edema. Despite the higher contrasts’ value obtained with BW filter images during nucleus removal, posterior capsular polishing and viscous removal, the surgeons subjectively reported no significant advantage of using a BW filter. Standard color images were found to be better for localizing the limbal area during incision and for nucleus sculpture to assess groove depth. Conclusions: In conclusion, we describe here the potential indications for BW filter use at particular stages in cataract surgery. A BW filter could be used, with caution, in cases of poor visualization.