bluuebunny/crossref_metadata_2025 huggingface dataset:
Coastal Water Quality Modelling Using E. coli, Meteorological Parameters and Machine Learning Algorithms
Authors: Tselemponis Athanasios , Stefanis Christos , Giorgi Elpida , Kalmpourtzi Aikaterini , Olmpasalis Ioannis , Tselemponis Antonios , Adam Maria , Kontogiorgis Christos , Dokas Ioannis M. , Bezirtzoglou Eugenia , Constantinidis Theodoros C.
Published: June 2023

In this study, machine learning models were implemented to predict the classification of coastal waters in the region of Eastern Macedonia and Thrace (EMT) concerning Escherichia coli (E. coli) concentration and weather variables in the framework of the Directive 2006/7/EC. Six sampling stations of EMT, located on beaches of the regional units of Kavala, Xanthi, Rhodopi, Evros, Thasos and Samothraki, were selected. All 1039 samples were collected from May to September within a 14-year follow-up period (2009–2021). The weather parameters were acquired from nearby meteorological stations. The samples were analysed according to the ISO 9308-1 for the detection and the enumeration of E. coli. The vast majority of the samples fall into category 1 (Excellent), which is a mark of the high quality of the coastal waters of EMT. The experimental results disclose, additionally, that two-class classifiers, namely Decision Forest, Decision Jungle and Boosted Decision Tree, achieved high Accuracy scores over 99%. In addition, comparing our performance metrics with those of other researchers, diversity is observed in using algorithms for water quality prediction, with algorithms such as Decision Tree, Artificial Neural Networks and Bayesian Belief Networks demonstrating satisfactory results. Machine learning approaches can provide critical information about the dynamic of E. coli contamination and, concurrently, consider the meteorological parameters for coastal waters classification.
The Effects of COVID-19 Lockdown on Social Connectedness and Psychological Distress in U.S. Adults with Chronic Diseases
Authors: King Ben , Adepoju Omolola E. , Woodard LeChauncy , Oluyomi Abiodun O. , Zhang Xiaotao , Amos Christopher I. , Badr Hoda
Published: June 2023

Lockdown measures enacted in 2020 to control the spread of COVID-19 led to increases in the prevalence of mental health problems. Due to their high-risk status, individuals with chronic diseases may be at increased risk and disproportionately adversely affected by the COVID-19 pandemic. The investigators examined associations between having a high-risk chronic condition, social connectedness, and general distress and COVID-19-specific distress among U.S. adults during the COVID-19 lockdown. Baseline measures of a longitudinal survey collected at the beginning of the pandemic (April to June 2020) were analyzed to identify factors associated with loss of social connectedness from pre- to post-lockdown. The associations between social connectedness and both general and COVID-19-specific psychological distress were adjusted for certain high-risk chronic illnesses and interaction effects. The sample available for analysis included 1354 subjects (262 high-risk chronic diseases and 1092 without chronic illness). Those reporting the loss of social connectedness were younger (median = 39 vs. 42) and more likely to be unemployed because of the pandemic (19.4% vs. 11.0%). Adjustment for interaction demonstrated a stronger negative association between social connectedness change and the psychosocial impact of COVID-19 for those with high-risk illness(es) (change in connectedness*chronic illness OR = 0.88, 95%CI: 0.79–0.98, p = 0.020). These findings inform our understanding of the distribution and intersection of responses to public health lockdown orders in the U.S. and build further evidence of the importance of social connectedness on psychological distress.
Occupational Safety and Health Equity Impacts of Artificial Intelligence: A Scoping Review
Authors: Fisher Elizabeth , Flynn Michael A. , Pratap Preethi , Vietas Jay A.
Published: June 2023

Artificial intelligence (AI) has the potential to either reduce or exacerbate occupational safety and health (OSH) inequities in the workplace, and its impact will be mediated by numerous factors. This paper anticipates challenges to ensuring that the OSH benefits of technological advances are equitably distributed among social groups, industries, job arrangements, and geographical regions. A scoping review was completed to summarize the recent literature on AI’s role in promoting OSH equity. The scoping review was designed around three concepts: artificial intelligence, OSH, and health equity. Scoping results revealed 113 articles relevant for inclusion. The ways in which AI presents barriers and facilitators to OSH equity are outlined along with priority focus areas and best practices in reducing OSH disparities and knowledge gaps. The scoping review uncovered priority focus areas. In conclusion, AI’s role in OSH equity is vastly understudied. An urgent need exists for multidisciplinary research that addresses where and how AI is being adopted and evaluated and how its use is affecting OSH across industries, wage categories, and sociodemographic groups. OSH professionals can play a significant role in identifying strategies that ensure the benefits of AI in promoting workforce health and wellbeing are equitably distributed.
Social Capital in Relation to Mental Health—The Voices of Adolescents in Sweden
Authors: Ahlborg Mikael G. , Nygren Jens M. , Svedberg Petra
Published: June 2023

The social environment that adolescents interact in has undoubtedly changed over the past decades. The latent constructs of social capital that have been described in theory may be universal, but it is necessary to reveal sociocultural specific pathways and manifestation in order to validly operationalize social capital for adolescents. There is a call for qualitative data to enhance our understanding of social capital for adolescents today and the specific sociocultural context they live in. The aim of this study was to explore social capital from the perspective of adolescents in relation to mental health. Twenty-three semi-structured interviews were conducted in a school setting with a sample of adolescents aged 11 and 15 years. Qualitative content analysis was applied, and analysis remained on a manifest level. From having adolescents describe their social relations and networks in relation to mental health, three main categories were formed: accessing a safe space, with sub-categories of trusting enough to share, having someone close to you, and being part of an inclusive and honest environment; feeling connected to others, with sub-categories of hanging out and having things in common; and maintaining control, with sub-categories of deciding for yourself, dealing with change, and having social skills. Having access to a safe space is vital for adolescents’ mental health, by providing resources such as mutual trust, honesty, and unconditional access. Feeling connected to others is important in close relationships and reveals the glue that holds networks together, but also links to sociability in a wider sense. Predictability in adolescents’ social relationships and networks, influenced by internal and external factors, may be a resource of increasing importance in todays’ society and an interesting subject for intervention and future research on social capital and adolescent mental health.
Meaning in Life, Social Axioms, and Emotional Outcomes during the First Outbreak of COVID-19 in Hong Kong
Authors: Sun Rong-Wei , Lau Esther Yuet Ying , Cheung Sing-Hang , Chan Chi-Keung
Published: June 2023

Social unrest, coupled with the outbreak of COVID-19, was a double-hit for Hong Kong in early 2020. Those stressful societal situations not only trigger negative emotions, such as anxiety and/or depression, but also consolidate a person’s belief towards oneself (i.e., meaning in life) and society (i.e., social axioms). The study included 2031 participants from the Formation and Transformation of Beliefs in Chinese (FTBC) project dataset. The data were collected in Hong Kong from February 2020 to March 2020 (double-hit). Path analysis and multiple regression were used to examine the mediating and moderating effects of the presence subscale (P) of the Meaning in Life Questionnaire (MLQ) on the relations between social axioms and negative emotions. Results showed that low MLQ-P mediated the associations between cynicism and negative emotions and between low religiosity and negative emotions and moderated the relation between social cynicism and emotional outcomes. Exploratory analyses showed that MLQ-Search (S) mediated the relations between reward for application and negative emotions, between social complexity and negative emotions, and between fate control and negative emotions, and moderated the relation between religiosity and stress. As far as we know, this study reported the first evidence of the role of meaning in life in explaining and modifying the associations between social axioms and mood states. The presence of and search for meaning in life seem to work differently with respect to the relations between social axioms and negative emotions, with important implications for understanding the dynamics of social and personal beliefs in affecting mental health in times of large-scale public crisis.
Effects of Physical Activity on Physical and Mental Health of Older Adults Living in Care Settings: A Systematic Review of Meta-Analyses
Authors: Agbangla Nounagnon Frutueux , Séba Marie-Philippine , Bunlon Frédérique , Toulotte Claire , Fraser Sarah Anne
Published: June 2023

Previous studies included in meta-analyses have highlighted the effects of physical activity on the physical and psychological health of older adults living in care settings. We conducted a systematic review of meta-analyses, of institutionalized older adults, to evaluate and conduct a narrative synthesis of the results of these meta-analyses. A literature search was conducted in three databases (PubMed, Web of Science, and Cochrane Library) until 22 March 2023. After screening the identified articles with the PRISMA criteria filters, we included 11 meta-analyses in this systematic review. Higgins’ (2013) assessment tool of the meta-analyses demonstrates that the studies were of good quality although future meta-analyses need to provide more information on the treatment of missing data. A summary of the results of these meta-analyses shows that physical activity reduces the rate of falls, mobility issues, functional dependence, and depression, and improves health status. Future studies need to focus on new ways to promote and adapt physical activities to increase the participation of older adults in care settings.
RNA Sequencing Reveals Unique Transcriptomic Signatures of the Thyroid in a Murine Lung Cancer Model Treated with PD-1 and PD-L1 Antibodies
Authors: Pollack Rena , Stokar Joshua , Lishinsky Natan , Gurt Irina , Kaisar-Iluz Naomi , Shaul Merav E. , Fridlender Zvi G. , Dresner-Pollak Rivka
Published: June 2023

Immune checkpoint inhibitors (ICI) are commonly associated with thyroid immune-related adverse events, yet the mechanism has not been fully elucidated. We aimed to further explore the mechanism of ICI-induced thyroid dysfunction by assessing changes induced in the thyroid transcriptome by ICI treatment (αPD-1/αPD-L1) in a lung cancer murine model. RNA-sequencing of thyroid tissues revealed 952 differentially expressed genes (DEGs) with αPD-1 treatment (|fold-change| ≥1.8, FDR < 0.05). Only 35 DEG were identified with αPD-L1, and we therefore focused on the αPD-1 group alone. Ingenuity Pathway Analysis revealed that of 952 DEGs with αPD-1 treatment, 362 were associated with functions of cell death and survival, with predicated activation of pathways for apoptosis and necrosis (Z = 2.89 and Z = 3.21, respectively) and negative activation of pathways for cell viability and cell survival (Z = −6.22 and Z = −6.45, respectively). Compared to previously published datasets of interleukin-1β and interferon γ-treated human thyroid cells, apoptosis pathways were similarly activated. However, unique changes related to organ inflammation and upstream regulation by cytokines were observed. Our data suggest that there are unique changes in gene expression in the thyroid associated with αPD-1 therapy. ICI-induced thyroid dysfunction may be mediated by increased tissue apoptosis resulting in destructive thyroiditis.
Microcystin-LR-Induced Interaction between M2 Tumor-Associated Macrophage and Colorectal Cancer Cell Promotes Colorectal Cancer Cell Migration through Regulating the Expression of TGF-β1 and CST3
Authors: Jiang Xinying , Zhang Hailing , Zhang Hengshuo , Wang Fan , Wang Xiaochang , Ding Tong , Zhang Xuxiang , Wang Ting
Published: June 2023

Microcystin-LR (MC-LR) is a toxic secondary metabolite produced by cyanobacteria that has been demonstrated to promote colorectal cancer (CRC). However, the mechanism by which MC-LR enhances CRC in the tumor microenvironment (TME) is poorly understood. To elucidate its role in TME, a co-culture system was established using CRC cells and M2 macrophages in a Transwell chamber. The study found that MC-LR promotes CRC cell migration by upregulating TGF-β1 expression and secretion in M2 macrophages and downregulating CST3 in CRC cells. Neutralizing TGF-β1 increased CST3 expression in CRC cells, while overexpressing CST3 in CRC cells suppressed TGF-β1 expression in M2 macrophages, both of which weakened MC-LR-induced cellular motility in the co-culture system. In vivo, the mice in the MC-LR/AOM/DSS group had more tumor nodules, deeper tumor invasion, and higher M2 macrophage infiltration compared to the AOM/DSS group, and the expression of TGF-β1 and CST3 in tumors was consistent with the cellular level. Overall, this study provides insights into the regulatory mechanism of MC-LR on TME, revealing that MC-LR upregulates the expression and secretion of TGF-β1 in M2 macrophages, which in turn inhibits the expression of CST3 in CRC cells to promote migration.
Rapid and Cost-Efficient Detection of RET Rearrangements in a Large Consecutive Series of Lung Carcinomas
Authors: Tiurin Vladislav I. , Preobrazhenskaya Elena V. , Mitiushkina Natalia V. , Romanko Aleksandr A. , Anuskina Aleksandra A. , Mulkidjan Rimma S. , Saitova Evgeniya S. , Krivosheyeva Elena A. , Kharitonova Elena D. , Shevyakov Mikhail P. , Tryakin Ilya A. , Aleksakhina Svetlana N. , Venina Aigul R. , Sokolova Tatiana N. , Martianov Aleksandr S. , Shestakova Anna D. , Ivantsov Alexandr O. , Iyevleva Aglaya G. , Imyanitov Evgeny N.
Published: June 2023

RET-kinase-activating gene rearrangements occur in approximately 1–2% of non-small-cell lung carcinomas (NSCLCs). Their reliable detection requires next-generation sequencing (NGS), while conventional methods, such as immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) or variant-specific PCR, have significant limitations. We developed an assay that compares the level of RNA transcripts corresponding to 5′- and 3′-end portions of the RET gene; this test relies on the fact that RET translocations result in the upregulation of the kinase domain of the gene and, therefore, the 5′/3′-end expression imbalance. The present study included 16,106 consecutive NSCLC patients, 14,449 (89.7%) of whom passed cDNA quality control. The 5′/3′-end unbalanced RET expression was observed in 184 (1.3%) tumors, 169 of which had a sufficient amount of material for the identification of translocation variants. Variant-specific PCR revealed RET rearrangements in 155/169 (91.7%) tumors. RNA quality was sufficient for RNA-based NGS in 10 cases, 8 of which carried exceptionally rare or novel (HOOK1::RET and ZC3H7A::RET) RET translocations. We also applied variant-specific PCR for eight common RET rearrangements in 4680 tumors, which emerged negative upon the 5′/3′-end unbalanced expression test; 33 (0.7%) of these NSCLCs showed RET fusion. While the combination of the analysis of 5′/3′-end RET expression imbalance and variant-specific PCR allowed identification of RET translocations in approximately 2% of consecutive NSCLCs, this estimate approached 120/2361 (5.1%) in EGFR/KRAS/ALK/ROS1/BRAF/MET-negative carcinomas. RET-rearranged tumors obtained from females, but not males, had a decreased level of expression of thymidylate synthase (p < 0.00001), which is a known predictive marker of the efficacy of pemetrexed. The results of our study provide a viable alternative for RET testing in facilities that do not have access to NGS due to cost or technical limitations.
Enhanced ZBTB16 Levels by Progestin-Only Contraceptives Induces Decidualization and Inflammation
Authors: Arlier Sefa , Kayisli Umit A. , Semerci Nihan , Ozmen Asli , Larsen Kellie , Schatz Frederick , Lockwood Charles J. , Guzeloglu-Kayisli Ozlem
Published: June 2023

Progestin-only long-acting reversible-contraceptive (pLARC)-exposed endometria displays decidualized human endometrial stromal cells (HESCs) and hyperdilated thin-walled fragile microvessels. The combination of fragile microvessels and enhanced tissue factor levels in decidualized HESCs generates excess thrombin, which contributes to abnormal uterine bleeding (AUB) by inducing inflammation, aberrant angiogenesis, and proteolysis. The- zinc finger and BTB domain containing 16 (ZBTB16) has been reported as an essential regulator of decidualization. Microarray studies have demonstrated that ZBTB16 levels are induced by medroxyprogesterone acetate (MPA) and etonogestrel (ETO) in cultured HESCs. We hypothesized that pLARC-induced ZBTB16 expression contributes to HESC decidualization, whereas prolonged enhancement of ZBTB16 levels triggers an inflammatory milieu by inducing pro-inflammatory gene expression and tissue-factor-mediated thrombin generation in decidualized HESCs. Thus, ZBTB16 immunostaining was performed in paired endometria from pre- and post-depo-MPA (DMPA)-administrated women and oophorectomized guinea pigs exposed to the vehicle, estradiol (E2), MPA, or E2 + MPA. The effect of progestins including MPA, ETO, and levonorgestrel (LNG) and estradiol + MPA + cyclic-AMP (E2 + MPA + cAMP) on ZBTB16 levels were measured in HESC cultures by qPCR and immunoblotting. The regulation of ZBTB16 levels by MPA was evaluated in glucocorticoid-receptor-silenced HESC cultures. ZBTB16 was overexpressed in cultured HESCs for 72 h followed by a ± 1 IU/mL thrombin treatment for 6 h. DMPA administration in women and MPA treatment in guinea pigs enhanced ZBTB16 immunostaining in endometrial stromal and glandular epithelial cells. The in vitro findings indicated that: (1) ZBTB16 levels were significantly elevated by all progestin treatments; (2) MPA exerted the greatest effect on ZBTB16 levels; (3) MPA-induced ZBTB16 expression was inhibited in glucocorticoid-receptor-silenced HESCs. Moreover, ZBTB16 overexpression in HESCs significantly enhanced prolactin (PRL), insulin-like growth factor binding protein 1 (IGFBP1), and tissue factor (F3) levels. Thrombin-induced interleukin 8 (IL-8) and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA levels in control-vector-transfected HESCs were further increased by ZBTB16 overexpression. In conclusion, these results supported that ZBTB16 is enhanced during decidualization, and long-term induction of ZBTB16 expression by pLARCs contributes to thrombin generation through enhancing tissue factor expression and inflammation by enhancing IL-8 and PTGS2 levels in decidualized HESCs.
Overexpression of the Purple Perilla (Perilla frutescens (L.)) FAD3a Gene Enhances Salt Tolerance in Soybean
Authors: Li Zhan , Wang Ying , Yu Lili , Gu Yongzhe , Zhang Lijuan , Wang Jun , Qiu Lijuan
Published: June 2023

The increasingly serious trend of soil salinization inhibits the normal growth and development of soybeans, leading to reduced yields and a serious threat to global crop production. Microsomal ω-3 fatty acid desaturase encoded by the FAD3 gene is a plant enzyme that plays a significant role in α-linolenic acid synthesis via regulating the membrane fluidity to better accommodate various abiotic stresses. In this study, PfFAD3a was isolated from perilla and overexpressed in soybeans driven by CaMV P35S, and the salt tolerance of transgenic plants was then evaluated. The results showed that overexpression of PfFAD3a increased the expression of PfFAD3a in both the leaves and seeds of transgenic soybean plants, and α-linolenic acid content also significantly increased; hence, it was shown to significantly enhance the salt tolerance of transgenic plants. Physiological and biochemical analysis showed that overexpression of PfFAD3a increased the relative chlorophyll content and PSII maximum photochemical efficiency of transgenic soybean plants under salt stress; meanwhile, a decreased accumulation of MDA, H2O2, and O2•−, increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbic acid peroxidase (APX), as well as the production of proline and soluble sugar. In summary, the overexpression of PfFAD3a may enhance the salt tolerance in transgenic soybean plants through enhanced membrane fluidity and through the antioxidant capacity induced by C18:3.
Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options
Authors: Zhou Yang , Zhou Zuying , Zheng Lin , Gong Zipeng , Li Yueting , Jin Yang , Huang Yong , Chi Mingyan
Published: June 2023

Urinary tract infections (UTIs) are common bacterial infections that represent a severe public health problem. They are often caused by Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumonia), Proteus mirabilis (P. mirabilis), Enterococcus faecalis (E. faecalis), and Staphylococcus saprophyticus (S. saprophyticus). Among these, uropathogenic E. coli (UPEC) are the most common causative agent in both uncomplicated and complicated UTIs. The adaptive evolution of UPEC has been observed in several ways, including changes in colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. While antibiotic therapy has historically been very successful in controlling UTIs, high recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly reduce the efficacy of these treatments. Furthermore, the gradual global emergence of multidrug-resistant UPEC has highlighted the need to further explore its pathogenesis and seek alternative therapeutic and preventative strategies. Therefore, a thorough understanding of the clinical status and pathogenesis of UTIs and the advantages and disadvantages of antibiotics as a conventional treatment option could spark a surge in the search for alternative treatment options, especially vaccines and medicinal plants. Such options targeting multiple pathogenic mechanisms of UPEC are expected to be a focus of UTI management in the future to help combat antibiotic resistance.
Generation of a Well-Characterized Homozygous Chromodomain-Helicase-DNA-Binding Protein 4G1003D Mutant hESC Line Using CRISPR/eCas9 (ULIEGEe001-A-1)
Authors: Chohra Ilyas , Giri Subhajit , Malgrange Brigitte
Published: June 2023

The chromatin remodeler Chromodomain-helicase-DNA-binding protein 4 (CHD4) is crucial for the development of multiple organ systems. Functional mutations of CHD4 have recently been described in a developmental disorder, namely Siffrim-Hitz-Weiss syndrome (SIHIWES). Herein, we have generated a homozygous CHD4G1003D hESC line (WAe025-A-1) using CRISPR/eCas9-based gene editing in the WA-25 hESC line. The edited hESC line maintains normal karyotype, pluripotency, and ability to differentiate into three germ layers. This cell line will be a valuable resource for studying the functional role of CHD4 during the development and disease modeling of SIHIWES in vitro.
Discovery of Novel Pentacyclic Triterpene Acid Amide Derivatives as Excellent Antimicrobial Agents Dependent on Generation of Reactive Oxygen Species
Authors: Yang Yihong , Chen Kunlun , Wang Guangdi , Liu Hongwu , Shao Lihui , Zhou Xiang , Liu Liwei , Yang Song
Published: June 2023

Developing new agricultural bactericides is a feasible strategy for stopping the increase in the resistance of plant pathogenic bacteria. Some pentacyclic triterpene acid derivatives were elaborately designed and synthesized. In particular, compound A22 exhibited the best antimicrobial activity against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac) with EC50 values of 3.34 and 3.30 mg L−1, respectively. The antimicrobial mechanism showed that the compound A22 induced excessive production and accumulation of reactive oxygen species (ROS) in Xoo cells, leading to a decrease in superoxide dismutase and catalase enzyme activities and an increase in malondialdehyde content. A22 also produced increases in Xoo cell membrane permeability and eventual cell death. In addition, in vivo experiments showed that A22 at 200 mg L−1 exhibited protective activity against rice bacterial blight (50.44%) and citrus canker disease (84.37%). Therefore, this study provides a paradigm for the agricultural application of pentacyclic triterpene acid.
Molecular Dynamics Simulations of Matrix Metalloproteinase 13 and the Analysis of the Specificity Loop and the S1′−Site
Authors: Choi Jun Yong , Chung Eugene
Published: June 2023

The specificity loop of Matrix Metalloproteinases (MMPs) is known to regulate recognition of their substrates, and the S1′−site surrounded by the loop is a unique place to address the selectivity of ligands toward each MMP. Molecular dynamics (MD) simulations of apo−MMP−13 and its complex forms with various ligands were conducted to identify the role of the specificity loop for the ligand binding to MMP−13. The MD simulations showed the dual role of T247 as a hydrogen bond donor to the ligand, as well as a contributor to the formation of the van der Waal surface area, with T245 and K249 on the S1′−site. The hydrophobic surface area mediated by T247 blocks the access of water molecules to the S1′−site of MMP−13 and stabilizes the ligand in the site. The F252 residue is flexible in order to search for the optimum location in the S1′−site of the apo−MMP−13, but once a ligand binds to the S1′−site, it can form offset π−π or edge−to−π stacking interactions with the ligand. Lastly, H222 and Y244 provide the offset π−π and π−CH(Cβ) interactions on each side of the phenyl ring of the ligand, and this sandwiched interaction could be critical for the ligand binding to MMP−13.
Label-Free Electrochemical Aptasensor for Sensitive Detection of Malachite Green Based on AuNPs/MWCNTs@TiO2 Nanocomposites
Authors: Chen Zanlin , Li Haiming , Xie Miaojia , Zhao Fengguang , Han Shuangyan
Published: June 2023

This study proposes a label-free aptamer biosensor for the sensitive detection of malachite green(MG) using gold nanoparticles/multi-walled carbon nanotubes @ titanium dioxide(AuNPs/MWCNTs@TiO2). The nanocomposite provides a large surface area and good electrical conductivity, improving current transfer and acting as a platform for aptamer immobilization. The aptamer and the complementary chain(cDNA) are paired by base complementary to form the recognition element and fixed on the AuNPs by sulfhydryl group, which was modified on the cDNA. Since DNA is negatively charged, the redox probe in the electrolyte is less exposed to the electrode surface under the repulsion of the negative charge, resulting in a low-electrical signal level. When MG is present, the aptamer is detached from the cDNA and binds to MG, the DNA on the electrode surface is reduced, and the rejection of the redox probe is weakened, which leads to an enhanced electrical signal and enables the detection of MG concentration by measuring the change in the electrical signal. Under the best experimental conditions, the sensor demonstrates a good linear relationship for the detection of MG from 0.01 to 1000 ng/mL, the limit of detection (LOD)is 8.68 pg/mL. This sensor is stable, specific, and reproducible, allowing for the detection of various small-molecule pollutants by changing the aptamer, providing an effective method for detecting small-molecule pollutants.
Systemic Review of Clot Retraction Modulators
Authors: Guilbeau Alaina , Majumder Rinku
Published: June 2023

Through a process termed clot retraction, platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from Cudrania trucuspidata, Arctium lappa, and Panax ginseng that diminish clot retraction and have numerous other health benefits. Caffeic acid and diindolylmethane, both common in plants and vegetables, likewise reduce clot retraction, as do all-trans retinoic acid (a vitamin A derivative), two MAP4K inhibitors, and the chemotherapeutic drug Dasatinib. Conversely, the endogenous anticoagulant Protein S (PS) and the matricellular protein secreted modular calcium-binding protein 1 (SMOC1) both enhance clot retraction. Most studies aiming to identify mechanisms of clot retraction modulators have focused on the increased phosphorylation of vasodilator-stimulated phosphoprotein and inositol 1,4,5-triphosphate receptor I and the decreased phosphorylation of various phospholipases (e.g., phospholipase A2 (PLA2) and phosphatidylinositol-specific phospholipase Cγ2 (PLCγ2), c-Jun N-terminal kinase, and (PI3Ks). One study focused on the decreased phosphorylation of Sarcoma Family Kinases (SFK), and others have focused on increased cAMP levels and the downregulation of inflammatory markers such as thromboxanes, including thromboxane A2 (TXA2) and thromboxane B2 (TXB2); prostaglandin A2 (PGE2); reactive oxygen species (ROS); and cyclooxygenase (COX) enzyme activity. Additionally, pregnancy, fibrinolysis, and the autoimmune condition systemic lupus erythematosus all seem to affect, or at least have some relation with, clot retraction. All the clot retraction modulators need in-depth study to explain these effects.
KDM6B Negatively Regulates the Neurogenesis Potential of Apical Papilla Stem Cells via HES1
Authors: Zhang Chen , Ye Weilong , Zhao Mengyao , Long Lujue , Xia Dengsheng , Fan Zhipeng
Published: June 2023

Stem cells from the apical papilla (SCAPs) are used to regulate the microenvironment of nerve defects. KDM6B, which functions as an H3K27me3 demethylase, is known to play a crucial role in neurogenesis. However, the mechanism by which KDM6B influences the neurogenesis potential of SCAPs remains unclear. We evaluated the expression of neural markers in SCAPs by using real-time RT-PCR and immunofluorescence staining. To assess the effectiveness of SCAP transplantation in the SCI model, we used the BBB scale to evaluate motor function. Additionally, toluidine blue staining and Immunofluorescence staining of NCAM, NEFM, β-III-tubulin, and Nestin were used to assess nerve tissue remodeling. Further analysis was conducted through Microarray analysis and ChIP assay to study the molecular mechanisms. Our results show that KDM6B inhibits the expression of NeuroD, TH, β-III tubulin, and Nestin. In vivo studies indicate that the SCAP-KDM6Bsh group is highly effective in restoring spinal cord structure and motor function in rats suffering from SCI. Our findings suggest that KDM6B directly binds to the HES1 promoter via regulating H3K27me3 and HES1 expression. In conclusion, our study can help understand the regulatory role of KDM6B in neurogenesis and provide more effective treatments for nerve injury.
Comprehensive Metabolite Profile Uncovers the Bioactive Components, Antioxidant and Antibacterial Activities in Wild Tree Peony Leaves
Authors: Xin Ziwei , Yang Weizong , Niu Lixin , Zhang Yanlong
Published: June 2023

Tree peonies (Paeonia Section Moutan)—including nine wild species, which belong to subsections Vaginatae and Delavayanae—are economically important plants with ornamental, nutritional, and medicinal applications. In this study, for the first time, we determined the bioactive components and antioxidant activities and antibacterial activities of the newly grown leaves of nine wild tree peony species (WTPS). A total of 276 bioactive components were identified through non-targeted metabolomics; more than 80% of the 276 metabolites identified are terpenoids and flavonoids. A total of 42 differential metabolites were quantitatively determined. The main differential metabolites were Paeoniflorin, Luteoloside, Hyperin, Apigenin-7-glucoside, Rhoifolin, and Cantharidin. Such a high terpenoid and flavonoid content of the leaf extracts renders them as species with strong antibacterial capacities, and most of the bacteria tested showed greater sensitivity derived from the members of subsection Vaginatae than those of subsection Delavayanae. All WTPS have significant antioxidant activity; this activity is attributed to high levels of the total phenolic content (TPC) and total flavonoid content (TFC), of which, among the nine WTPS, P. lutea has the strongest antioxidant capacity. Our results provided a theoretical basis for the in-deep application of tree peony leaves for food, medical, and pharmaceutical industries.
Immune Cell-Related Genes in Juvenile Idiopathic Arthritis Identified Using Transcriptomic and Single-Cell Sequencing Data
Authors: Zhang Wenbo , Cai Zhe , Liang Dandan , Han Jiaochan , Wu Ping , Shan Jiayi , Meng Guangxun , Zeng Huasong
Published: June 2023

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. The heterogeneity of the disease can be investigated via single-cell RNA sequencing (scRNA-seq) for its gap in the literature. Firstly, five types of immune cells (plasma cells, naive CD4 T cells, memory-activated CD4 T cells, eosinophils, and neutrophils) were significantly different between normal control (NC) and JIA samples. WGCNA was performed to identify genes that exhibited the highest correlation to differential immune cells. Then, 168 differentially expressed immune cell-related genes (DE-ICRGs) were identified by overlapping 13,706 genes identified by WGCNA and 286 differentially expressed genes (DEGs) between JIA and NC specimens. Next, four key genes, namely SOCS3, JUN, CLEC4C, and NFKBIA, were identified by a protein–protein interaction (PPI) network and three machine learning algorithms. The results of functional enrichment revealed that SOCS3, JUN, and NFKBIA were all associated with hallmark TNF-α signaling via NF-κB. In addition, cells in JIA samples were clustered into four groups (B cell, monocyte, NK cell, and T cell groups) by single-cell data analysis. CLEC4C and JUN exhibited the highest level of expression in B cells; NFKBIA and SOCS3 exhibited the highest level of expression in monocytes. Finally, real-time quantitative PCR (RT-qPCR) revealed that the expression of three key genes was consistent with that determined by differential analysis. Our study revealed four key genes with prognostic value for JIA. Our findings could have potential implications for JIA treatment and investigation.
3D Cell Models in Radiobiology: Improving the Predictive Value of In Vitro Research
Authors: Antonelli Francesca
Published: June 2023

Cancer is intrinsically complex, comprising both heterogeneous cellular composition and extracellular matrix. In vitro cancer research models have been widely used in the past to model and study cancer. Although two-dimensional (2D) cell culture models have traditionally been used for cancer research, they have many limitations, such as the disturbance of interactions between cellular and extracellular environments and changes in cell morphology, polarity, division mechanism, differentiation and cell motion. Moreover, 2D cell models are usually monotypic. This implies that 2D tumor models are ineffective at accurately recapitulating complex aspects of tumor cell growth, as well as their radiation responses. Over the past decade there has been significant uptake of three-dimensional (3D) in vitro models by cancer researchers, highlighting a complementary model for studies of radiation effects on tumors, especially in conjunction with chemotherapy. The introduction of 3D cell culture approaches aims to model in vivo tissue interactions with radiation by positioning itself halfway between 2D cell and animal models, and thus opening up new possibilities in the study of radiation response mechanisms of healthy and tumor tissues.
Thymoquinone Ameliorates Carfilzomib-Induced Renal Impairment by Modulating Oxidative Stress Markers, Inflammatory/Apoptotic Mediators, and Augmenting Nrf2 in Rats
Authors: Qadri Marwa M. , Alam Mohammad Firoz , Khired Zenat A. , Alaqi Reem O. , Khardali Amani A. , Alasmari Moudi M. , Alrashah Ahmad S. S. , Muzafar Hisham M. A. , Qahl Abdullah M.
Published: June 2023

Chemotherapy-induced kidney damage is an emerging problem that restricts cancer treatment effectiveness. The proteasome inhibitor carfilzomib (CFZ) is primarily used to treat multiple myeloma and has been associated with severe renal injury in humans. CFZ-induced nephrotoxicity remains an unmet medical need, and there is an urgent need to find and develop a nephroprotective and antioxidant therapy for this condition. Thymoquinone (TQ) is a bioactive compound that has been isolated from Nigella sativa seeds. It has a wide range of pharmacological properties. Therefore, this experimental design aimed to study the effectiveness of TQ against CFZ-induced renal toxicity in rats. The first group of rats was a normal control (CNT); the second group received CFZ (4 mg/kg b.w.); the third and fourth groups received TQ (10 and 20 mg/kg b.w.) 2 h before receiving CFZ; the fifth group received only TQ (20 mg/kg b.w.). This experiment was conducted for 16 days, and at the end of the experiment, blood samples and kidney tissue were collected for biochemical assays. The results indicated that administration of CFZ significantly enhanced serum marker levels such as BUN, creatinine, and uric acid in the CFZ group. Similarly, it was also noticed that CFZ administration induced oxidative stress by reducing antioxidants (GSH) and antioxidant enzymes (CAT and SOD) and increasing lipid peroxidation. CFZ treatment also enhanced the expression of IL-1β, IL-6, and TNF-α production. Moreover, CFZ increased caspase-3 concentrations and reduced Nrf2 expression in the CFZ-administered group. However, treatment with 10 and 20 mg/kg TQ significantly decreased serum markers and increased antioxidant enzymes. TQ treatment considerably reduced IL-1β, IL-6, TNF-α, and caspase-3 concentrations. Overall, this biochemical estimation was also supported by histopathological outcomes. This study revealed that TQ administration significantly mitigated the negative effects of CFZ treatment on Nrf2 expression. Thus, it indicates that TQ may have utility as a potential drug to prevent CFZ-induced nephrotoxicity in the future.
The Nature of the Enthalpy–Entropy Compensation and “Exotic” Arrhenius Parameters in the Denaturation Kinetics of Proteins
Authors: Baklanov Alexey V. , Kiselev Vitaly G.
Published: June 2023

Protein unfolding is a ubiquitous process responsible for the loss of protein functionality (denaturation), which, in turn, can be accompanied by the death of cells and organisms. The nature of enthalpy–entropy compensation (EEC) in the kinetics of protein unfolding is a subject of debate. In order to investigate the nature of EEC, the “completely loose” transition state (TS) model has been applied to calculate the Arrhenius parameters for the unfolding of polyglycine dimers as a model process. The calculated Arrhenius parameters increase with increasing dimer length and demonstrate enthalpy–entropy compensation. It is shown that EEC results from the linear correlations of enthalpy and entropy of activation with dimer length, which are derived directly from the properties of the transition state. It is shown that EEC in solvated (hydrated, etc.) proteins is a direct consequence of EEC in proteins themselves. The suggested model allows us also to reproduce and explain “exotic” very high values of the pre-exponential factor measured for the proteins unfolding, which are drastically higher than those known for unimolecular reactions of organic molecules. A similar approach can be applied to analyzing the nature of EEC phenomena observed in other areas of chemistry.
ECM Composition Differentially Regulates Intracellular and Extracellular pH in Normal and Cancer Pancreatic Duct Epithelial Cells
Authors: Di Molfetta Daria , Cannone Stefania , Greco Maria Raffaella , Caroppo Rosa , Piccapane Francesca , Carvalho Tiago Miguel Amaral , Altamura Concetta , Saltarella Ilaria , Tavares Valente Diana , Desaphy Jean Francois , Reshkin Stephan J. , Cardone Rosa Angela
Published: June 2023

Intracellular pH (pHi) regulation is a challenge for the exocrine pancreas, where the luminal secretion of bicarbonate-rich fluid is accompanied by interstitial flows of acid. This acid–base transport requires a plethora of ion transporters, including bicarbonate transporters and the Na+/H+ exchanger isoform 1 (NHE1), which are dysregulated in Pancreatic Ductal Adenocarcinoma (PDAC). PDAC progression is favored by a Collagen-I rich extracellular matrix (ECM) which exacerbates the physiological interstitial acidosis. In organotypic cultures of normal human pancreatic cells (HPDE), parenchymal cancer cells (CPCs) and cancer stem cells (CSCs) growing on matrices reproducing ECM changes during progression, we studied resting pHi, the pHi response to fluxes of NaHCO3 and acidosis and the role of NHE1 in pHi regulation. Our findings show that: (i) on the physiological ECM, HPDE cells have the most alkaline pHi, followed by CSCs and CPCs, while a Collagen I-rich ECM reverses the acid–base balance in cancer cells compared to normal cells; (ii) both resting pHi and pHi recovery from an acid load are reduced by extracellular NaHCO3, especially in HPDE cells on a normal ECM; (iii) cancer cell NHE1 activity is less affected by NaHCO3. We conclude that ECM composition and the fluctuations of pHe cooperate to predispose pHi homeostasis towards the presence of NaHCO3 gradients similar to that expected in the tumor.
3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1β, and Inflammatory Cell Accumulation in the Retina
Authors: Weinberger Yehonatan , Budnik Ivan , Nisgav Yael , Palevski Dahlia , Ben-David Gil , Fernández José A. , Margalit Shany Nivinsky , Levy-Mendelovich Sarina , Kenet Gili , Weinberger Dov , Griffin John H. , Livnat Tami
Published: June 2023

3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with cytoprotective properties and reduced bleeding risks. We studied the potential use of 3K3A-APC as a multi-target therapeutic option for choroidal neovascularization (CNV), a common cause of vision loss in age-related macular degeneration. CNV was induced by laser photocoagulation in a murine model, and 3K3A-APC was intravitreally injected. The impact of 3K3A-APC treatment on myeloid and microglia cell activation and recruitment and on NLRP3 inflammasome, IL-1β, and VEGF levels was assessed using cryosection, retinal flat-mount immunohistochemistry and vascular imaging. Additionally, we evaluated the use of fluorescein angiography as a surrogate marker for in vivo evaluation of the efficacy of 3K3A-APC treatment against leaking CNV lesions. Our results demonstrated that 3K3A-APC treatment significantly reduced the accumulation and activation of myeloid cells and microglia in the CNV area and decreased the NLRP3 and IL-1β levels at the CNV site and the surrounding retina. Furthermore, 3K3A-APC treatment resulted in leakage regression and CNV growth suppression. These findings indicate that the anti-inflammatory activities of 3K3A-APC contribute to CNV inhibition. Our study suggests the potential use of 3K3A-APC as a novel multi-target treatment for CNV.
INSUS: Indoor Navigation System Using Unity and Smartphone for User Ambulation Assistance
Authors: Fajrianti Evianita Dewi , Funabiki Nobuo , Sukaridhoto Sritrusta , Panduman Yohanes Yohanie Fridelin , Dezheng Kong , Shihao Fang , Surya Pradhana Anak Agung
Published: June 2023

Currently, outdoor navigation systems have widely been used around the world on smartphones. They rely on GPS (Global Positioning System). However, indoor navigation systems are still under development due to the complex structure of indoor environments, including multiple floors, many rooms, steps, and elevators. In this paper, we present the design and implementation of the Indoor Navigation System using Unity and Smartphone (INSUS). INSUS shows the arrow of the moving direction on the camera view based on a smartphone’s augmented reality (AR) technology. To trace the user location, it utilizes the Simultaneous Localization and Mapping (SLAM) technique with a gyroscope and a camera in a smartphone to track users’ movements inside a building after initializing the current location by the QR code. Unity is introduced to obtain the 3D information of the target indoor environment for Visual SLAM. The data are stored in the IoT application server called SEMAR for visualizations. We implement a prototype system of INSUS inside buildings in two universities. We found that scanning QR codes with the smartphone perpendicular in angle between 60∘ and 100∘ achieves the highest QR code detection accuracy. We also found that the phone’s tilt angles influence the navigation success rate, with 90∘ to 100∘ tilt angles giving better navigation success compared to lower tilt angles. INSUS also proved to be a robust navigation system, evidenced by near identical navigation success rate results in navigation scenarios with or without disturbance. Furthermore, based on the questionnaire responses from the respondents, it was generally found that INSUS received positive feedback and there is support to improve the system.
Effect of Sintering Temperature on the Magnetic Properties of Fe3Mn3Co60.66Si33.34
Authors: Zou Jiang , Zhao Zehang , Zhou Xiongyu , Xie Quan
Published: June 2023

With the rapid development of society, the demand for information storage is increasing. Hence, research involving magnetic storage materials is gaining importance. In this study, Fe3Mn3Co60.66Si33.34 powders were prepared via mechanical alloying and sintering. The effect of the sintering temperature on the crystal structure was analyzed by X-ray diffraction, and the results showed that doped Co2Si powder was successfully prepared. Vibrating sample magnetometry was used to investigate the magnetic properties of Fe3Mn3Co60.66Si33.34, and showed that the coercivity of the samples decreased with increasing sintering temperature. Fe3Mn3Co60.66Si33.34 sintered at 950 °C yielded a magnetic saturation strength of 36.42 emu/g, coercivity of 135.92 Oe, and remanent magnetization of 4.97 emu/g. Electron microscopy analyses showed that the prepared particles were spherical, and the average grain size increased with increasing sintering temperature. The electromagnetic loss was analyzed by simulating electromagnetic parameters, which revealed that the electromagnetic loss tangent decreased with increasing sintering temperature. Hence, it is inferred that Fe3Mn3Co60.66Si33.34 powder materials sintered at high temperatures are expected to have suitable properties for magnetic storage applications.