bluuebunny/crossref_metadata_2025 huggingface dataset:
Anxiety and Depression and Health-Related Quality of Life in Adults with Gastroesophageal Reflux Disease: A Population-Based Study
Authors: Alwhaibi Monira
Published: September 2023

Background: Adults with gastroesophageal reflux disease (GERD) are susceptible to mental disorders that might significantly affect their health-related quality of life (HRQoL). Therefore, the purpose of this study was to evaluate how HRQoL in individuals with GERD is related to coexisting anxiety and depression. Methods: A cross sectional study was conducted among 3068 adult patients 22 years of age and older with GERD diagnoses have been identified using the data from the Medical Expenditure Panel Survey from 2017 to 2020 for United States adults. Data are gathered by MEPS using an overlapping panel design over a period of two and a half years. HRQoL was established using the Physical and Mental Component Summary (PCS & MCS) values from the SF-12. Multivariate forward linear regression analysis was used to assess the relationship between anxiety, depression, and HRQoL in people with GERD after accounting for various factors. Results: Of the 3068 people with GERD who had been identified, 56.4% were women, 59.4% were in their 50s or 60s and 64.8% were employed. Thirteen per cent of people with GERD had depression, thirteen per cent had anxiety, and ten per cent had both. Adults with concurrent anxiety and depression had the lowest mean PCS and MCS scores compared to those with GERD. After adjusting for all independent factors, GERD patients with anxiety (MCS = −10.819, p-value < 0.0001), depression (MCS = −6.395, p-value < 0.0001), and both (MCS= −42.869, p-value < 0.0001) had substantially worse HRQoL than those without these comorbidities. Notably, better HRQoL scores were positively associated with marital status, employment, perceived overall health, and physical activity. Conclusions: The results from this nationally representative sample shed insight into the relationships between low HRQoL and anxiety and depression among individuals with GERD. It also demonstrated the detrimental impacts of co-occurring chronic illnesses, low socioeconomic status, and the positive benefits of employment and exercise on HRQoL. This study emphasizes the clinical, policy, and public health implications for better healthcare, allocation of resources, and promotion of lifestyle modifications to improve the HRQoL in patients with GERD.
Personalized Technological Support for Informal Caregivers of Older People with Dementia: A Co-Design Approach Involving Potential End Users and Healthcare Professionals in Three Focus Groups in Italy
Authors: Gris Francesca , D’Amen Barbara , Lamura Giovanni , Paciaroni Lucia , Socci Marco , Melchiorre Maria Gabriella
Published: September 2023

Informal/family caregivers (ICs) of older people with dementia (PwD) can suffer from depression and burnout. However, digital solutions can potentially provide innovative ways to facilitate care provision. The aim of this study was to analyze the opinions of end users (EUs), i.e., PwD aged 65 years and over and their ICs and healthcare professionals (HPs), on the use of digital technology to support care activities. Qualitative data were collected during the co-design phase of the European project “DemiCare—Personalized support for informal caregivers of people with dementia”. This study focused on the Italian context and included two PwD, three ICs, and seven HPs. Three focus groups were held in April–June 2022. Qualitative data were analyzed using MaxQDA 2020 software. Seven thematic areas were identified: daily activities, care tasks, information needs, support received, relationship with and expectations from technology, functionality of the DemiCare integrated system, and ethical issues. Smart devices seemed to be received positively by ICs and HPs, although older PwD seemed to have difficulty accepting the technology. Overall, despite the low number of participants, it seems important and potentially effective to consider the needs and preferences of PwD during exploratory co-design to allow social interactions with them. This study was not registered.
Understanding Women’s Knowledge, Awareness, and Perceptions of STIs/STDs in Asia: A Scoping Review
Authors: Kaur Wandeep , Balakrishnan Vimala , Zhi Wei Ian Ng , Chen Annabel Yeo Yung , Ni Zhao
Published: September 2023

Objective: This study aimed to conduct a scoping review to collect current literature on the knowledge, awareness, and perception (KAP) of sexually transmitted infections/diseases (STIs/STDs) among women in Asia. Methodology: The PRISMA-Scoping methodology was used in this study to extract papers from four databases published between 2018 and 2022. Sixty-eight articles were included after screening and elimination. Results: The studies on KAP of STIs/STDs among women were largely undertaken in Southeast Asia (Indonesia, Malaysia, and Vietnam) and South Asia (India, Pakistan, and Bangladesh). Regardless of the specific cohort of women studied, research indicates consistently low levels of knowledge and awareness across Asia. This trend seems to be more prevalent among female commercial sex workers, women with lower educational levels, and those in poorer socioeconomic positions. In South Asia, cultural, sociological, economic, and gender inequalities, particularly male domination, all have a significant impact on KAP levels. Conclusion: As education is a major factor that influences health behaviour, this review underscores the need to allocate more resources to educational initiatives, particularly targeting vulnerable groups such as sex workers, transgender women, pregnant women, and rural housewives. This strategic focus may contribute significantly to preventing STIs/STDs, particularly in less developed regions/countries.
Active Lifestyle and Mobility of Adults with Vision Impairment: A Multiphase Mixed-Methods Study
Authors: Barasche-Berdah Deborah , Paltiel Ora , Raz Raanan
Published: September 2023

Individuals with vision impairment (VI) are less physically active than their sighted peers, heightening their risk of chronic illness. This study aimed to explore real and perceived barriers and promoters of an active lifestyle among adults with VI. We used mixed-methods, including a quantitative analysis of spatial data and a qualitative analysis of input from focus groups. The data were analyzed using descriptive statistics, graphical and thematic analysis. The spatial analysis highlighted frequent impediments, including high proportions of inaccessible crosswalks and stairs, a high density of obstacles (12/km) and almost inexistent guidance markings (0.1/km). Factors influencing active lifestyle of individuals with VI reported in the focus groups included: VI severity and self-confidence; accessibility of the physical environment as well as support and consideration of the society; use of behavioral strategies, striving for good health and willpower. Combined psychosocial, behavioral and infrastructural modifications could enhance active lifestyles among adults with VI. Consideration of the needs of individuals with VI is critical among environmental planners. Sustainable solutions for improving accessibility and mobility in the city for individuals with VI will influence not only their social integration but will enable them to adopt an active lifestyle and reduce their risk of chronic illness.
Bridge Healing: A Pilot Project of a New Model to Prevent Repeat “Social Admit” Visits to the Emergency Department and Help Break the Cycle of Homelessness in Canada
Authors: Robrigado Matthew , Zorić Igor , Sleet David A. , Francescutti Louis Hugo
Published: September 2023

Homelessness continues to be a pervasive public health problem throughout Canada. Hospital Emergency Departments (EDs) and inpatient wards have become a source of temporary care and shelter for homeless patients. Upon leaving the hospital, homeless patients are not more equipped than before to find permanent housing. The Bridge Healing program in Edmonton, Alberta, has emerged as a novel approach to addressing homelessness by providing transitional housing for those relying on repeated visits to the ED. This paper describes the three essential components to the Bridge Healing model: partnership between the ED and a Housing First community organization; facility design based on The Eden Alternative™ principles; and grassroots community funding. This paper, in conjunction with the current pilot project of the Bridge Healing facilities, serves as a proof of concept for the model and can inform transitional housing approaches in other communities.
Exploring the Mediating Role of Parental Anxiety in the Link between Children’s Mental Health and Glycemic Control in Type 1 Diabetes
Authors: Silina Evija , Taube Maris , Zolovs Maksims
Published: September 2023

Pediatric diabetes type 1 diabetes mellitus (T1D), as a chronic, incurable disease, is associated with psychoemotional and socioeconomic burden for the whole family. Disease outcomes are determined by the metabolic compensation of diabetes, characterized by the level of glycated hemoglobin (HbA1c). The caregivers play a critical role in the metabolic control of children with T1D. The aim of this study was to investigate which environmental factors may explain the relationship between diabetes compensation and anxiety and depression of a child. The cross-sectional interdisciplinary study recruited dyads from adolescents and their parents (N = 251). Adolescent and parent groups were screened for anxiety and depression. General linear model (GLM) mediation analysis was performed to determine the potential mediating effect of surrounding factors on the relationship between dependent variables (glycated hemoglobin) and independent variables (the child’s anxiety and depression symptoms). The study revealed that the relationship between HbA1c and the child’s anxiety and depression is fully mediated (B = 0.366, z = 4.31, p < 0.001) by parental anxiety. Diabetes metabolic control in adolescents with T1D is related to adolescents’ mental health via parents’ anxiety. This means that parents’ anxiety plays a more significant role in the level of HbA1c than the anxiety and depression of the adolescent.
A Heuristic Approach for Resolving Spatial Conflicts of Buildings in Urban Villages
Authors: Li Wende , Yan Haowen , Lu Xiaomin , Shen Yilang
Published: September 2023

Building displacement is a common operation to resolve the spatial conflicts between map features, and it has important theoretical value and practical application significance for multi-scale mapping. The prerequisite for a successful displacement operation is that there is extra space around the conflicting buildings into which they can be displaced. Otherwise, additional generalization operators need to be combined to resolve spatial conflicts. Based on this idea, this study proposes a new heuristic spatial conflict resolution framework that mainly resolves the spatial conflicts between buildings and other features in urban villages by combining three cartographic generalization operators: selection, displacement, and aggregation. This method first reduces the density of buildings in the block through selection operation, then resolves the spatial conflicts between buildings and other features through displacement operation, and finally, the aggregation operation is performed to eliminate any remaining conflicts and newly generated conflicts. Experiments were carried out using real urban village data, and visual inspection and quantitative analysis were used to evaluate the experimental results. The evaluation results show that the proposed framework can not only resolve spatial conflicts well, but also maintain the spatial distribution and area balance of the buildings in urban villages.
An Intelligent UAV Path-Planning Method Based on the Theory of the Three-Dimensional Subdivision of Earth Space
Authors: Sun Guoyi , Xu Qian , Zhang Guangyuan , Qu Tengteng , Cheng Chengqi , Deng Haojiang
Published: September 2023

With the rapid development of the big data era, Unmanned Aerial Vehicles (UAVs) are being increasingly adopted for various complex environments. This has imposed new requirements for UAV path planning. How to efficiently organize, manage, and express all kinds of data in complex scenes and intelligently carry out fast and efficient path planning for UAVs are new challenges brought about by UAV application requirements. However, traditional path-planning methods lack the ability to effectively integrate and organize multivariate data in dynamic and complicated airspace environments. To address these challenges, this paper leverages the theory of the three-dimensional subdivision of earth space and proposes a novel environment-modeling approach based on airspace grids. In this approach, we carried out the grid-based modeling and storage of the UAV flight airspace environment and built a stable and intelligent deep-reinforcement-learning grid model to solve the problem of the passage cost of UAV path planning in the real world. Finally, we designed multiple sets of experiments to verify the efficiency of the global subdivision coding system as an environmental organization framework for path planning compared to a longitude–latitude system and to demonstrate the superiority of the improved deep-reinforcement-learning model in specific scenarios.
Genome-Wide DNA Methylation Profiles in Whole-Blood and Buccal Samples—Cross-Sectional, Longitudinal, and across Platforms
Authors: Van Asselt Austin J. , Beck Jeffrey J. , Finnicum Casey T. , Johnson Brandon N. , Kallsen Noah , Hottenga Jouke Jan , de Geus Eco J. C. ,   BIOS Consortium, Boomsma Dorret I. , Ehli Erik A. , van Dongen Jenny
Published: September 2023

The field of DNA methylation research is rapidly evolving, focusing on disease and phenotype changes over time using methylation measurements from diverse tissue sources and multiple array platforms. Consequently, identifying the extent of longitudinal, inter-tissue, and inter-platform variation in DNA methylation is crucial for future advancement. DNA methylation was measured in 375 individuals, with 197 of those having 2 blood sample measurements ~10 years apart. Whole-blood samples were measured on Illumina Infinium 450K and EPIC methylation arrays, and buccal samples from a subset of 58 participants were measured on EPIC array. The data were analyzed with the aims to examine the correlation between methylation levels in longitudinal blood samples in 197 individuals, examine the correlation between methylation levels in the blood and buccal samples in 58 individuals, and examine the correlation between blood methylation profiles assessed on the EPIC and 450K arrays in 83 individuals. We identified 136,833, 7674, and 96,891 CpGs significantly and strongly correlated (>0.50) longitudinally, across blood and buccal samples as well as array platforms, respectively. A total of 3674 of these CpGs were shared across all three sets. Analysis of these shared CpGs identified previously found associations with aging, ancestry, and 7016 mQTLs as well.
Clusterin Expression in Colorectal Carcinomas
Authors: Téllez Teresa , Martin-García Desirée , Redondo Maximino , García-Aranda Marilina
Published: September 2023

Colorectal cancer is the third most diagnosed cancer, behind only breast and lung cancer. In terms of overall mortality, it ranks second due to, among other factors, problems with screening programs, which means that one of the factors that directly impacts survival and treatment success is early detection of the disease. Clusterin (CLU) is a molecular chaperone that has been linked to tumorigenesis, cancer progression and resistance to anticancer treatments, which has made it a promising drug target. However, it is still necessary to continue this line of research and to adjust the situations in which its use is more favorable. The aim of this paper is to review the current genetic knowledge on the role of CLU in tumorigenesis and cancer progression in general, and discuss its possible use as a therapeutic target in colorectal cancer.
Halogen Bond-Involving Self-Assembly of Iodonium Carboxylates: Adding a Dimension to Supramolecular Architecture
Authors: Radzhabov Amirbek D. , Ledneva Alyona I. , Soldatova Natalia S. , Fedorova Irina I. , Ivanov Daniil M. , Ivanov Alexey A. , Yusubov Mekhman S. , Kukushkin Vadim Yu. , Postnikov Pavel S.
Published: September 2023

We designed 0D, 1D, and 2D supramolecular assemblies made of diaryliodonium salts (functioning as double σ-hole donors) and carboxylates (as σ-hole acceptors). The association was based on two charge-supported halogen bonds (XB), which occurred between IIII sites of the iodonium cations and the carboxylate anions. The sequential introduction of the carboxylic groups in the aryl ring of the benzoic acid added a dimension to the 0D supramolecular organization of the benzoate, which furnished 1D-chained and 2D-layered structures when terephthalate and trimesate anions, correspondingly, were applied as XB acceptors. The structure-directing XB were studied using DFT calculations under periodic boundary conditions and were followed by the one-electron-potential analysis and the Bader atoms-in-molecules topological analysis of electron density. These theoretical methods confirmed the existence of the XB and verified the philicities of the interaction partners in the designed solid-state structures.
Unusual Trisomy X Phenotype Associated with a Concurrent Heterozygous 16p11.2 Deletion: Importance of an Integral Approach for Proper Diagnosis
Authors: González-del Angel Ariadna , Alcántara-Ortigoza Miguel Angel , Ramos Sandra , Algara-Ramírez Carolina , Hernández-Hernández Marco Antonio , Saenger-Rivas Lorenza
Published: September 2023

Trisomy X is the most frequent sex chromosome anomaly in women, but it is often underdiagnosed postnatally because most patients do not show any clinical manifestation. It is estimated that only 10% of patients with trisomy X are diagnosed by clinical findings. Thus, it has been proposed that the clinical spectrum is not yet fully delimited, and additional uncommon or atypical clinical manifestations could be related to this entity. The present report describes a female carrying trisomy X but presenting atypical manifestations, including severe intellectual disability, short stature, thymus hypoplasia, and congenital hypothyroidism (CH). These clinical findings were initially attributed to trisomy X. However, chromosome microarray analysis (CMA) subsequently revealed that the patient also bears a heterozygous 304-kb deletion at 16p11.2. This pathogenic copy-number variant (CNV) encompasses 13 genes, including TUFM. Some authors recommend that when a phenotype differs from that described for an identified microdeletion, the presence of pathogenic variants in the non-deleted allele should be considered to assess for an autosomal recessive disorder; thus, we used a panel of 697 genes to rule out a pathogenic variant in the non-deleted TUFM allele. We discuss the possible phenotypic modifications that might be related to an additional CNV in individuals with sex chromosome aneuploidy (SCA), as seen in our patient. The presence of karyotype-demonstrated trisomy X and CMA-identified 16p11.2 deletion highlights the importance of always correlating a patient’s clinical phenotype with the results of genetic studies. When the phenotype includes unusual manifestations and/or exhibits discrepancies with that described in the literature, as exemplified by our patient, a more extensive analysis should be undertaken to enable a correct diagnosis that will support proper management, genetic counseling, and medical follow-up.
β-Sitosterol Suppresses Lipopolysaccharide-Induced Inflammation and Lipogenesis Disorder in Bovine Mammary Epithelial Cells
Authors: Fan Yating , Shen Jinglin , Liu Xinlu , Cui Junhao , Liu Jiayi , Peng Dongqiao , Jin Yongcheng
Published: September 2023

β-sitosterol, a natural plant steroid, has been shown to promote anti-inflammatory and antioxidant activities in the body. In this study, β-sitosterol was used to protect against lipopolysaccharide (LPS)-induced cell damage in bovine mammary epithelial cells, which are commonly studied as a cell model of mammary inflammatory response and lipogenesis. Results showed that treatment with a combination of LPS and β-sitosterol significantly reduced oxidative stress and inflammation, while increasing the expression of anti-apoptotic proteins and activating the hypoxia-inducible factor-1(HIF-1α)/mammalian target of rapamycin(mTOR) signaling pathway to inhibit apoptosis and improve lipid synthesis-related gene expression. Our finding suggests that β-sitosterol has the potential to alleviate inflammation in the mammary gland.
Bortezomib Is Effective in the Treatment of T Lymphoblastic Leukaemia by Inducing DNA Damage, WEE1 Downregulation, and Mitotic Catastrophe
Authors: Din Rahman Ud , Jiao Anan , Qiu Yinxia , Mohan Aarmann Anil Mohinani , Yuen Kei-Ching , Wong Hoi-Tung , Wan Timothy Ming-Hun , Wong Phoebe On-Yi , Sin Chun-Fung
Published: September 2023

T lymphoblastic leukemia (T-ALL) is an aggressive haematolymphoid malignancy comprising 15% of acute lymphoblastic leukemia (ALL). Although its prognosis has improved with intensive chemotherapy, the relapse/refractory disease still carries a dismal prognosis. Thus, there is an urgent need to develop novel therapy for T-ALL. Bortezomib, a 26S proteasome inhibitor, is licensed to treat plasma cell myeloma and mantle cell lymphoma. Due to its favorable side effect profile, it is a novel agent of research interest in the treatment of ALL. Despite an increasing number of clinical trials of bortezomib in T-ALL, its detailed mechanistic study in terms of DNA damage, cell cycle, and mitotic catastrophe remains elusive. Moreover, WEE1, a protein kinase overexpressed in ALL and involved in cell-cycle regulation, has been known to be a novel therapeutic target in many cancers. But the role of bortezomib in modulating WEE1 expression in ALL still remains elusive. In this study, we demonstrate the therapeutic efficacy of bortezomib on T-ALL primary samples and cell lines. Our findings reveal that bortezomib treatment induces DNA damage and downregulates WEE1, leading to G2-M cell-cycle progression with damaged DNA. This abnormal mitotic entry induced by bortezomib leads to mitotic catastrophe in T-ALL. In conclusion, our findings dissect the mechanism of action of bortezomib and provide further insights into the use of bortezomib to treat T-ALL. Our findings suggest the possibility of novel combination therapy using proteasome inhibitors together with DNA-damaging agents in the future, which may fill the research gaps and unmet clinical needs in treating ALL.
Gibbs Energy and Gene Expression Combined as a New Technique for Selecting Drug Targets for Inhibiting Specific Protein–Protein Interactions
Authors: Rietman Edward A. , Siegelmann Hava T. , Klement Giannoula Lakka , Tuszynski Jack A.
Published: September 2023

One of the most important aspects of successful cancer therapy is the identification of a target protein for inhibition interaction. Conventionally, this consists of screening a panel of genes to assess which is mutated and then developing a small molecule to inhibit the interaction of two proteins or to simply inhibit a specific protein from all interactions. In previous work, we have proposed computational methods that analyze protein–protein networks using both topological approaches and thermodynamic quantification provided by Gibbs free energy. In order to make these approaches both easier to implement and free of arbitrary topological filtration criteria, in the present paper, we propose a modification of the topological–thermodynamic analysis, which focuses on the selection of the most thermodynamically stable proteins and their subnetwork interaction partners with the highest expression levels. We illustrate the implementation of the new approach with two specific cases, glioblastoma (glioma brain tumors) and chronic lymphatic leukoma (CLL), based on the publicly available patient-derived datasets. We also discuss how this can be used in clinical practice in connection with the availability of approved and investigational drugs.
Iron Oxide Nanoparticles with Supramolecular Ureido-Pyrimidinone Coating for Antimicrobial Peptide Delivery
Authors: Turrina Chiara , Cookman Jennifer , Bellan Riccardo , Song Jiankang , Paar Margret , Dankers Patricia Y. W. , Berensmeier Sonja , Schwaminger Sebastian P.
Published: September 2023

Antimicrobial peptides (AMPs) can kill bacteria by disrupting their cytoplasmic membrane, which reduces the tendency of antibacterial resistance compared to conventional antibiotics. Their possible toxicity to human cells, however, limits their applicability. The combination of magnetically controlled drug delivery and supramolecular engineering can help to reduce the dosage of AMPs, control the delivery, and improve their cytocompatibility. Lasioglossin III (LL) is a natural AMP form bee venom that is highly antimicrobial. Here, superparamagnetic iron oxide nanoparticles (IONs) with a supramolecular ureido-pyrimidinone (UPy) coating were investigated as a drug carrier for LL for a controlled delivery to a specific target. Binding to IONs can improve the antimicrobial activity of the peptide. Different transmission electron microscopy (TEM) techniques showed that the particles have a crystalline iron oxide core with a UPy shell and UPy fibers. Cytocompatibility and internalization experiments were carried out with two different cell types, phagocytic and nonphagocytic cells. The drug carrier system showed good cytocompatibility (>70%) with human kidney cells (HK-2) and concentration-dependent toxicity to macrophagic cells (THP-1). The particles were internalized by both cell types, giving them the potential for effective delivery of AMPs into mammalian cells. By self-assembly, the UPy-coated nanoparticles can bind UPy-functionalized LL (UPy-LL) highly efficiently (99%), leading to a drug loading of 0.68 g g−1. The binding of UPy-LL on the supramolecular nanoparticle system increased its antimicrobial activity against E. coli (MIC 3.53 µM to 1.77 µM) and improved its cytocompatible dosage for HK-2 cells from 5.40 µM to 10.6 µM. The system showed higher cytotoxicity (5.4 µM) to the macrophages. The high drug loading, efficient binding, enhanced antimicrobial behavior, and reduced cytotoxicity makes ION@UPy-NH2 an interesting drug carrier for AMPs. The combination with superparamagnetic IONs allows potential magnetically controlled drug delivery and reduced drug amount of the system to address intracellular infections or improve cancer treatment.
bFGF-like Activity Supported Tissue Regeneration, Modulated Neuroinflammation, and Rebalanced Ca2+ Homeostasis following Spinal Cord Injury
Authors: Ardizzone Alessio , Bova Valentina , Casili Giovanna , Filippone Alessia , Lanza Marika , Repici Alberto , Esposito Emanuela , Paterniti Irene
Published: September 2023

A spinal cord injury (SCI) is a well-defined debilitating traumatic event to the spinal cord that usually triggers permanent changes in motor, sensory, and autonomic functions. Injured tissue becomes susceptible to secondary mechanisms caused by SCIs, which include pro-inflammatory cytokine release, the activation of astrocytes and microglia, and increased neuronal sensibility. As a consequence, the production of factors such as GFAP, IBA-1, TNF-α, IL-1β, IFN-γ, and S100-β slow down or inhibit central nervous system (CNS) regeneration. In this regard, a thorough understanding of the mechanisms regulating the CNS, and specifically SCI, is essential for the development of new therapeutic strategies. It has been demonstrated that basic fibroblast growth factor (bFGF) was successful in the modulation of neurotrophic activity, also promoting neurite survival and tissue repair, thus resulting in the valuable care of CNS disorders. However, bFGF therapeutic use is limited due to the undesirable effects developed following its administration. Therefore, the synthetic compound mimetic of bFGF, SUN11602 (with chemical name 4-[[4-[[2-[(4-Amino-2,3,5,6-tetramethylphenyl)amino]acetyl]methylamino]-1-piperidinyl]methyl]benzamide), has been reported to show neuroprotective activities similar to those of bFGF, also demonstrating a good pharmacokinetic profile. Here, we aimed to investigate the neuroprotective activity of this bFGF-like compound in modulating tissue regeneration, neuroinflammation, and Ca2+ overload by using a subacute mouse model of SCI. SUN11602 (1, 2.5, and 5 mg/kg) was administered orally to mice for 72 h daily following the in vivo model of SCI, which was generated by the extradural compression of the spinal cord. The data obtained demonstrated that SUN11602 treatment considerably decreased motor alteration and diminished the neuroinflammatory state through the regulation of glial activation, the NF-κB pathway, and kinases. Additionally, by controlling Ca2+-binding proteins and restoring neurotrophin expression, we showed that SUN11602 therapy restored the equilibrium of the neuronal circuit. Because of these findings, bFGF-like compounds may be an effective tool for reducing inflammation in SCI patients while enhancing their quality of life.
The miRNA-mRNA Regulatory Modules of Pinus massoniana Lamb. in Response to Drought Stress
Authors: Chen Xinhua , Chen Hu , Shen Tengfei , Luo Qunfeng , Xu Meng , Yang Zhangqi
Published: September 2023

Masson pine (Pinus massoniana Lamb.) is a major fast-growing woody tree species and pioneer species for afforestation in barren sites in southern China. However, the regulatory mechanism of gene expression in P. massoniana under drought remains unclear. To uncover candidate microRNAs, their expression profiles, and microRNA-mRNA interactions, small RNA-seq was used to investigate the transcriptome from seedling roots under drought and rewatering in P. massoniana. A total of 421 plant microRNAs were identified. Pairwise differential expression analysis between treatment and control groups unveiled 134, 156, and 96 differential expressed microRNAs at three stages. These constitute 248 unique microRNAs, which were subsequently categorized into six clusters based on their expression profiles. Degradome sequencing revealed that these 248 differentially expressed microRNAs targeted 2069 genes. Gene Ontology enrichment analysis suggested that these target genes were related to translational and posttranslational regulation, cell wall modification, and reactive oxygen species scavenging. miRNAs such as miR482, miR398, miR11571, miR396, miR166, miRN88, and miRN74, along with their target genes annotated as F-box/kelch-repeat protein, 60S ribosomal protein, copper-zinc superoxide dismutase, luminal-binding protein, S-adenosylmethionine synthase, and Early Responsive to Dehydration Stress may play critical roles in drought response. This study provides insights into microRNA responsive to drought and rewatering in Masson pine and advances the understanding of drought tolerance mechanisms in Pinus.
Paclitaxel and Caffeine–Taurine, New Colchicine Alternatives for Chromosomes Doubling in Maize Haploid Breeding
Authors: Arshad Saeed , Wei Mengli , Ali Qurban , Mustafa Ghulam , Ma Zhengqiang , Yan Yuanxin
Published: September 2023

The doubled haploid (DH) technology is employed worldwide in various crop-breeding programs, especially maize. Still, restoring tassel fertility is measured as one of the major restrictive factors in producing DH lines. Colchicine, nitrous oxide, oryzalin, and amiprophosmethyl are common chromosome-doubling agents that aid in developing viable diploids (2n) from sterile haploids (n). Although colchicine is the most widely used polyploidy-inducing agent, it is highly toxic to mammals and plants. Therefore, there is a dire need to explore natural, non-toxic, or low-toxic cheaper and accessible substitutes with a higher survival and fertility rate. To the best of our knowledge, the advanced usage of human anticancer drugs “Paclitaxel (PTX)” and “Caffeine–Taurine (CAF–T)” for in vivo maize haploids doubling is being disclosed for the first time. These two antimitotic and antimicrotubular agents (PTX and CAF–T) were assessed under various treatment conditions compared to colchicine. As a result, the maximum actual doubling rates (ADR) for PTX versus colchicine in maize haploid seedlings were 42.1% (400 M, 16 h treatment) versus 31.9% (0.5 mM, 24 h treatment), respectively. In addition, the ADR in maize haploid seeds were CAF–T 20.0% (caffeine 2 g/L + taurine 12 g/L, 16 h), PTX 19.9% (100 μM, 24 h treatment), and colchicine 26.0% (2.0 mM, 8 h treatment). Moreover, the morphological and physiological by-effects in haploid plants by PTX were significantly lower than colchicine. Hence, PTX and CAF–T are better alternatives than the widely used traditional colchicine to improve chromosome-doubling in maize crop.
BIRC5 Inhibition Is Associated with Pyroptotic Cell Death via Caspase3-GSDME Pathway in Lung Adenocarcinoma Cells
Authors: Zhang Qingwei , Chen Ximing , Hu Yingying , Zhou Tong , Du Menghan , Xu Run , Chen Yongchao , Tang Pingping , Chen Zhouxiu , Li Jiamin
Published: September 2023

Lung adenocarcinoma (LUAD) is a prevalent type of thoracic cancer with a poor prognosis and high mortality rate. However, the exact pathogenesis of this cancer is still not fully understood. One potential factor that can contribute to the development of lung adenocarcinoma is DNA methylation, which can cause changes in chromosome structure and potentially lead to the formation of tumors. The baculoviral IAP repeat containing the 5 (BIRC5) gene encodes the Survivin protein, which is a multifunctional gene involved in cell proliferation, migration, and invasion of tumor cells. This gene is elevated in various solid tumors, but its specific role and mechanism in lung adenocarcinoma are not well-known. To identify the potential biomarkers associated with lung adenocarcinoma, we screened the methylation-regulated differentially expressed genes (MeDEGs) of LUAD via bioinformatics analysis. Gene ontology (GO) process and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to investigate the biological function and pathway of MeDEGs. A protein–protein interaction (PPI) network was employed to explore the key module and screen hub genes. We screened out eight hub genes whose products are aberrantly expressed, and whose DNA methylation modification level is significantly changed in lung adenocarcinoma. BIRC5 is a bona fide marker which was remarkably up-regulated in tumor tissues. Flow cytometry analysis, lactate dehydrogenase release (LDH) assay and Micro-PET imaging were performed in A549 cells and a mouse xenograft tumor to explore the function of BIRC5 in cell death of lung adenocarcinoma. We found that BIRC5 was up-regulated and related to a high mortality rate in lung adenocarcinoma patients. Mechanically, the knockdown of BIRC5 inhibited the proliferation of A549 cells and induced pyroptosis via caspase3/GSDME signaling. Our findings have unraveled that BIRC5 holds promise as a novel biomarker and therapeutic target for lung adenocarcinoma. Additionally, we have discovered a novel pathway in which BIRC5 inhibition can induce pyroptosis through the caspase3-GSDME pathway in lung adenocarcinoma cells.
Structure-Function Characterisation of Eop1 Effectors from the Erwinia-Pantoea Clade Reveals They May Acetylate Their Defence Target through a Catalytic Dyad
Authors: Tomar Vishant , Rikkerink Erik H. A. , Song Janghoon , Sofkova-Bobcheva Svetla , Bus Vincent G. M.
Published: September 2023

The YopJ group of acetylating effectors from phytopathogens of the genera Pseudomonas and Ralstonia have been widely studied to understand how they modify and suppress their host defence targets. In contrast, studies on a related group of effectors, the Eop1 group, lag far behind. Members of the Eop1 group are widely present in the Erwinia-Pantoea clade of Gram-negative bacteria, which contains phytopathogens, non-pathogens and potential biocontrol agents, implying that they may play an important role in agroecological or pathological adaptations. The lack of research in this group of YopJ effectors has left a significant knowledge gap in their functioning and role. For the first time, we perform a comparative analysis combining AlphaFold modelling, in planta transient expressions and targeted mutational analyses of the Eop1 group effectors from the Erwinia-Pantoea clade, to help elucidate their likely activity and mechanism(s). This integrated study revealed several new findings, including putative binding sites for inositol hexakisphosphate and acetyl coenzyme A and newly postulated target-binding domains, and raises questions about whether these effectors function through a catalytic triad mechanism. The results imply that some Eop1s may use a catalytic dyad acetylation mechanism that we found could be promoted by the electronegative environment around the active site.
Sigma Receptors: Novel Regulators of Iron/Heme Homeostasis and Ferroptosis
Authors: Nguyen Nhi T. , Jaramillo-Martinez Valeria , Mathew Marilyn , Suresh Varshini V. , Sivaprakasam Sathish , Bhutia Yangzom D. , Ganapathy Vadivel
Published: September 2023

Sigma receptors are non-opiate/non-phencyclidine receptors that bind progesterone and/or heme and also several unrelated xenobiotics/chemicals. They reside in the plasma membrane and in the membranes of the endoplasmic reticulum, mitochondria, and nucleus. Until recently, the biology/pharmacology of these proteins focused primarily on their role in neuronal functions in the brain/retina. However, there have been recent developments in the field with the discovery of unexpected roles for these proteins in iron/heme homeostasis. Sigma receptor 1 (S1R) regulates the oxidative stress-related transcription factor NRF2 and protects against ferroptosis, an iron-induced cell death process. Sigma receptor 2 (S2R), which is structurally unrelated to S1R, complexes with progesterone receptor membrane components PGRMC1 and PGRMC2. S2R, PGRMC1, and PGRMC2, either independently or as protein–protein complexes, elicit a multitude of effects with a profound influence on iron/heme homeostasis. This includes the regulation of the secretion of the iron-regulatory hormone hepcidin, the modulation of the activity of mitochondrial ferrochelatase, which catalyzes iron incorporation into protoporphyrin IX to form heme, chaperoning heme to specific hemoproteins thereby influencing their biological activity and stability, and protection against ferroptosis. Consequently, S1R, S2R, PGRMC1, and PGRMC2 potentiate disease progression in hemochromatosis and cancer. These new discoveries usher this intriguing group of non-traditional progesterone receptors into an unchartered territory in biology and medicine.
Excessive Pregestational Weight and Maternal Obstetric Complications: The Role of Adipokines
Authors: Valencia-Ortega Jorge , Solis-Paredes Juan Mario , Saucedo Renata , Estrada-Gutierrez Guadalupe , Camacho-Arroyo Ignacio
Published: September 2023

There is a high frequency of overweight and obesity in women of reproductive age. Women who start pregnancy with overweight or obesity have an increased risk of developing maternal obstetric complications such as gestational hypertension, pre-eclampsia, gestational diabetes mellitus, postpartum hemorrhage, and requiring C-section to resolve the pregnancy with a higher risk of C-section surgical site infection. Excessive weight in pregnancy is characterized by dysregulation of adipokines, the functions of which partly explain the predisposition of pregnant women with overweight or obesity to these maternal obstetric complications. This review compiles, organizes, and analyzes the most recent studies on adipokines in pregnant women with excess weight and the potential pathophysiological mechanisms favoring the development of maternal pregnancy complications.
Innovative Integration of Arrayan (Luma apiculata) Extracts in Chitosan Coating for Fresh Strawberry Preservation
Authors: Benavides Sergio , Franco Wendy
Published: September 2023

Strawberries are a rich source of vitamins and antioxidants, among other nutrients, but they are highly susceptible to mechanical injuries, dehydration, and microbial spoilage, and thus have a limited post-harvest shelf-life. Bioactive edible coatings have been studied to decrease or prevent these damages. In this study, ethanolic extracts of Arrayan (Luma apiculata), a traditional berry from the south of Chile, were used to enrich a chitosan-based edible film and coat fresh strawberries. A long-term storage (10 °C) study was conducted to determine the strawberries’ weight loss, microbial stability, fruit firmness impact, and antioxidant activity. Later, a sensory panel was conducted to determine overall consumer acceptance. Our results show that the bioactive coating inhibited the growth of different pathogenic bacteria and spoilage yeast. In the stored strawberries, the weight loss was significantly lower when the bioactive coating was applied, and the samples’ firmness did not change significantly over time. Microbial growth in the treated strawberries was also lower than in the control ones. As expected, the antioxidant activity in the coated strawberries was higher because of the Arrayan extract, which has high antioxidant activity. Regarding sensory qualities, the covered strawberries did not show significant differences from the uncoated samples, with an overall acceptance of 7.64 on a 9-point scale. To our knowledge, this is the first time an edible coating enriched with Arrayan extracts has been reported as able to prevent strawberries’ decay and spoilage.
miRNA Studies in Glaucoma: A Comprehensive Review of Current Knowledge and Future Perspectives
Authors: Dobrzycka Margarita , Sulewska Anetta , Biecek Przemyslaw , Charkiewicz Radoslaw , Karabowicz Piotr , Charkiewicz Angelika , Golaszewska Kinga , Milewska Patrycja , Michalska-Falkowska Anna , Nowak Karolina , Niklinski Jacek , Konopińska Joanna
Published: September 2023

Glaucoma, a neurodegenerative disorder that leads to irreversible blindness, remains a challenge because of its complex nature. MicroRNAs (miRNAs) are crucial regulators of gene expression and are associated with glaucoma and other diseases. We aimed to review and discuss the advantages and disadvantages of miRNA-focused molecular studies in glaucoma through discussing their potential as biomarkers for early detection and diagnosis; offering insights into molecular pathways and mechanisms; and discussing their potential utility with respect to personalized medicine, their therapeutic potential, and non-invasive monitoring. Limitations, such as variability, small sample sizes, sample specificity, and limited accessibility to ocular tissues, are also addressed, underscoring the need for robust protocols and collaboration. Reproducibility and validation are crucial to establish the credibility of miRNA research findings, and the integration of bioinformatics tools for miRNA database creation is a valuable component of a comprehensive approach to investigate miRNA aberrations in patients with glaucoma. Overall, miRNA research in glaucoma has provided significant insights into the molecular mechanisms of the disease, offering potential biomarkers, diagnostic tools, and therapeutic targets. However, addressing challenges such as variability and limited tissue accessibility is essential, and further investigations and validation will contribute to a deeper understanding of the functional significance of miRNAs in glaucoma.
CRISPR-Cas9 Direct Fusions for Improved Genome Editing via Enhanced Homologous Recombination
Authors: Tabassum Tahmina , Pietrogrande Giovanni , Healy Michael , Wolvetang Ernst J.
Published: September 2023

DNA repair in mammalian cells involves the coordinated action of a range of complex cellular repair machinery. Our understanding of these DNA repair processes has advanced to the extent that they can be leveraged to improve the efficacy and precision of Cas9-assisted genome editing tools. Here, we review how the fusion of CRISPR-Cas9 to functional domains of proteins that directly or indirectly impact the DNA repair process can enhance genome editing. Such studies have allowed the development of diverse technologies that promote efficient gene knock-in for safer genome engineering practices.
Repellency of Carvacrol, Thymol, and Their Acetates against Imported Fire Ants
Authors: Paudel Pradeep , Shah Farhan Mahmood , Guddeti Dileep Kumar , Ali Abbas , Chen Jian , Khan Ikhlas A. , Li Xing-Cong
Published: September 2023

In the United States, imported fire ants are commonly referred to as red imported fire ants (Solenopsis invicta Buren), black imported fire ants (S. richteri Forel), and hybrid imported fire ants (S. invicta × S. richteri). They are significant pests, and their control heavily relies on synthetic insecticides. The extensive use of insecticides has led to public concern about their potential negative effects on human health and the well-being of wildlife and the environment. As an alternative, plant-derived natural compounds, particularly essential oils (EOs) and their main constituents, show promise as safe and environmentally friendly products for controlling fire ants. Repellants are useful in managing fire ants, and plant-derived natural repellants may serve as a safer and more environmentally friendly option. This study investigates the repellency of EO-derived compounds carvacrol, thymol, and their acetates against imported fire ant workers. The results revealed that carvacrol, a GRAS compound (Generally Recognized As Safe), was the most potent repellent against S. invicta, S. richteri, and their hybrid, with minimum repellent effective doses (MREDs) of 0.98 µg/g, 7.80 µg/g, and 0.98 µg/g, respectively. Thymol also exhibited strong repellency, with MREDs of 31.25 µg/g, 31.25 µg/g, and 7.8 µg/g, respectively. Furthermore, thyme-red essential oil, characterized by a thymol chemotype containing 48.8% thymol and 5.1% carvacrol, was found to effectively repel the hybrid ants with an MRED of 15.6 µg/g. In contrast, thyme essential oil, characterized by a linalool chemotype lacking thymol and carvacrol, did not exhibit any repellent effect, even at the highest tested dose of 125 µg/g. This study provides the first evidence of the potent repellency of carvacrol and thymol against imported fire ant workers, indicating their potential as promising repellents for fire ant control.
A Multi-Color Flow Cytometric Assay for Quantifying Dinutuximab Binding to Neuroblastoma Cells in Tumor, Bone Marrow, and Blood
Authors: Keyel Michelle E. , Furr Kathryn L. , Kang Min H. , Reynolds C. Patrick
Published: September 2023

GD2, a disialoganglioside, is present on the surface of most neuroblastomas, as well as on some other cancers, such as melanoma and osteogenic sarcoma. The anti-GD2 antibody ch14.18 (dinutuximab) has an FDA-registered indication for use as maintenance therapy for high-risk neuroblastoma with cytokines and 13-cis-retinoic acid after myeloablative therapy. Recent studies using immunohistochemistry of tumor or tumor cells in marrow have shown that some neuroblastomas are negative for GD2. Dinutuximab and other anti-GD2 antibodies are increasingly used in combination with cytotoxic chemotherapy for treating relapsed neuroblastoma, so it is important to be able to identify patients with tumor cells with low GD2 expression, as such patients may experience toxicity but not benefit from the antibody therapy. As the most common clinical samples available for relapsed neuroblastoma are bone marrow aspirates, we developed a method to quantify dinutuximab binding density and the frequency of neuroblastoma cells positive for the antibody in bone marrow aspirates. Here, we describe a multi-color flow cytometry assay that employs non-GD2 antibodies to identify neuroblastoma cells in a mixed population (tumor, bone marrow, or blood) and an anti-GD2 antibody to quantify both the frequency and density of GD2 expression on neuroblastoma cells.