bluuebunny/crossref_metadata_2025 huggingface dataset:
Fractional Second-Grade Fluid Flow over a Semi-Infinite Plate by Constructing the Absorbing Boundary Condition
Authors: Yang Jingyu , Liu Lin , Chen Siyu , Feng Libo , Xie Chiyu
Published: May 2024

The modified second-grade fluid flow across a plate of semi-infinite extent, which is initiated by the plate’s movement, is considered herein. The relaxation parameters and fractional parameters are introduced to express the generalized constitutive relation. A convolution-based absorbing boundary condition (ABC) is developed based on the artificial boundary method (ABM), addressing issues related to the semi-infinite boundary. We adopt the finite difference method (FDM) for deriving the numerical solution by employing the L1 scheme to approximate the fractional derivative. To confirm the precision of this method, a source term is added to establish an exact solution for verification purposes. A comparative evaluation of the ABC versus the direct truncated boundary condition (DTBC) is conducted, with their effectiveness and soundness being visually scrutinized and assessed. This study investigates the impact of the motion of plates at different fluid flow velocities, focusing on the effects of dynamic elements influencing flow mechanisms and velocity. This research’s primary conclusion is that a higher fractional parameter correlates with the fluid flow. As relaxation parameters decrease, the delay effect intensifies and the fluid velocity decreases.
Lack of T04C9.1, the Homologue of Mammalian APPL2, Leads to Premature Ageing and Shortens Lifespan in Caenorhabditis elegans
Authors: Li Zirui , Chen Zhiqiang , Zhao Lianghao , Sun Jiaqi , Yin Lin , Jiang Yuwei , Shi Xiaotong , Song Ziye , Zhang Lu
Published: May 2024

Ageing has been identified as an independent risk factor for various diseases; however, the physiological basis and molecular changes related to ageing are still largely unknown. Here, we show that the level of APPL2, an adaptor protein, is significantly reduced in the major organs of aged mice. Knocking down APPL2 causes premature ageing of human umbilical vein endothelial cells (HUVECs). We find that a lack of T04C9.1, the homologue of mammalian APPL2, leads to premature ageing, slow movements, lipid deposition, decreased resistance to stresses, and shortened lifespan in Caenorhabditis elegans (C. elegans), which are associated with decreased autophagy. Activating autophagy by rapamycin or inhibition of let-363 suppresses the age-related alternations, impaired motility, and shortened lifespan of C. elegans, which are reversed by knocking down autophagy-related genes. Our work provides evidence that APPL2 and its C. elegans homologue T04C9.1 decrease with age and reveals that a lack of T04C9.1 bridges autophagy decline and ageing in C. elegans.
Genome-Wide Identification and Characterization of the RWP-RK Proteins in Zanthoxylum armatum
Authors: Zheng Xianzhe , Duan Yanling , Zheng Huifang , Tang Hao , Zheng Liumeng , Yu Xiaobo
Published: May 2024

Apomixis is a common reproductive characteristic of Zanthoxylum plants, and RWP-RKs are plant-specific transcription factors known to regulate embryonic development. However, the genome-wide analysis and function prediction of RWP-RK family genes in Z. armatum are unclear. In this study, 36 ZaRWP-RK transcription factors were identified in the genome of Z. armatum, among which 15 genes belonged to the RKD subfamily and 21 belonged to the NLP subfamily. Duplication events of ZaRWP-RK genes were mainly segmental duplication, and synteny analysis revealed a close phylogenetic relationship between Z. armatum and Arabidopsis. The analysis of cis-elements indicated that ZaRWP-RK genes may be involved in the regulation of the embryonic development of Z. armatum by responding to plant hormones such as abscisic acid, auxin, and gibberellin. Results of a real-time PCR showed that the expression levels of most ZaRWP-RK genes were significantly increased from flowers to young fruits. Protein–protein interaction network analysis further revealed the potential roles of the ZaRWP-RK proteins in apomixis. Collectively, this study is expected to improve our understanding of ZaRWP-RK transcription factors and provide a theoretical basis for future investigations into the ZaRWP-RK genes and their regulatory mechanisms in the apomixis process of Z. armatum.
Identification of ARF Genes and Elucidation of the Regulatory Effects of PsARF16a on the Dormancy of Tree Peony Plantlets
Authors: Fu Zhenzhu , Yuan Xin , Zhao Yinge , Wang Xiaohui , Lu Lin , Wang Huijuan , Li Yanmin , Gao Jie , Wang Limin , Zhang Hechen
Published: May 2024

The low survival rate of transplanted plantlets, which has limited the utility of tissue-culture-based methods for the rapid propagation of tree peonies, is due to plantlet dormancy after rooting. We previously determined that the auxin response factor PsARF may be a key regulator of tree peony dormancy. To clarify the mechanism mediating tree peony plantlet dormancy, PsARF genes were systematically identified and analyzed. Additionally, PsARF16a was transiently expressed in the leaves of tree peony plantlets to examine its regulatory effects on a downstream gene network. Nineteen PsARF genes were identified and divided into four classes. All PsARF genes encoded proteins with conserved B3 and ARF domains. The number of motifs, exons, and introns varied between PsARF genes in different classes. The overexpression of PsARF16a altered the expression of NCED, ZEP, PYL, GA2ox1, GID1, and other key genes in abscisic acid (ABA) and gibberellin (GA) signal transduction pathways, thereby promoting ABA synthesis and decreasing GA synthesis. Significant changes to the expression of some key genes contributing to starch and sugar metabolism (e.g., AMY2A, BAM3, BGLU, STP, and SUS2) may be associated with the gradual conversion of sugar into starch. This study provides important insights into PsARF functions in tree peonies.
Association of ADIPOQ Gene Polymorphisms with Type 2 Diabetes and Obesity Risk in the Kazakh Population: A Case–Control and Population-Based Study
Authors: Sikhayeva Nurgul , Bolatov Aidos , Zholdybayeva Elena , Akhmetollayev Ilyas , Iskakova Aisha
Published: May 2024

Type 2 diabetes mellitus (T2DM) is a socially significant disease with increasing prevalence worldwide. It is characterized by heterogeneous metabolic disorders and is associated with various risk factors, including BMI, abnormal lipid levels, hypertension, smoking, dietary preferences, physical inactivity, sedentary lifestyle, family history of diabetes, prediabetes or gestational diabetes, inflammation, intrauterine environment, age, sex, ethnicity, and socioeconomic status. Assessing the genetic risk of developing T2DM in specific populations remains relevant. The ADIPOQ gene, encoding adiponectin, is directly related to the risk of developing T2DM, obesity, and cardiovascular diseases. Our study demonstrated significant associations of ADIPOQ gene polymorphisms with the risk of developing T2DM and obesity, as well as with fasting glucose levels and BMI, in the Kazakh population. Specifically, rs266729 was significantly associated with T2DM and obesity in the Kazakh population, while other studied polymorphisms (rs1501299, rs2241766, and rs17846866) did not show a significant association. These findings suggest that ADIPOQ gene polymorphisms may influence T2DM risk factors and highlight the importance of genetic factors in T2DM development. However, further research in larger cohorts is needed to confirm these associations.
Induced Partial Saturation: From Mechanical Principles to Engineering Design of an Innovative and Eco-Friendly Countermeasure against Earthquake-Induced Soil Liquefaction
Authors: Mele Lucia , Lirer Stefania , Flora Alessandro
Published: May 2024

Earthquake-induced soil liquefaction is a catastrophic phenomenon that can damage existing building foundations and other structures, resulting in significant economic losses. Traditional mitigation techniques against liquefaction present critical aspects, such as high construction costs, impact on surrounding infrastructure and effects on the surrounding environment. Therefore, research is ongoing in order to develop new approaches and technologies suitable to mitigate liquefaction risk. Among the innovative countermeasures against liquefaction, Induced Partial Saturation (IPS) is considered one of the most promising technologies. It consists of introducing gas/air bubbles into the pore water of sandy soils in order to increase the compressibility of the fluid phase and then enhance liquefaction resistance. IPS is economical, eco-friendly and suitable for urbanised areas, where the need to reduce the risk of liquefaction must be addressed, taking into account the integrity of existing buildings. However, IPS is still far from being a routine technology since more aspects should be better understood. The main aim of this review is to raise some important questions and encourage further research and discussions on this topic. The review first analyses and discusses the effects of air/gas bubbles on the cyclic behaviour of sandy soils, focusing on the soil volume element scale and then extending the considerations to the real scale. The use of useful design charts is also described. Moreover, a section will be devoted to the effect of IPS under shallow foundations. The readers will fully understand the research trend of IPS liquefaction mitigation and will be encouraged to further explore new practical aspects to overcome the application difficulties and contribute to spreading the use of this technology.
Community Attachment to AlUla Heritage Site and Tourists’ Green Consumption: The Role of Support for Green Tourism Development
Authors: Elshaer Ibrahim A. , Alyahya Mansour , Azazz Alaa M. S. , Fayyad Sameh
Published: May 2024

This study explores the interrelationship between community attachment in AlUla Heritage City (located in Saudi Arabia) and tourists’ green consumption practices, testing support for green tourism development as a mediator. The old historical city of AlUla, a significant city experiencing ongoing preservation and tourism development, represents an adequate context for exploring the link between community attachment and green tourism practices. This study employs a quantitative approach, including surveys with 328 local residents of AlUla. A structural equation modeling partial least square (PLS-SEM) analysis is conducted to explore the indirect influence of community attachment on tourists’ green consumption through the mediating role of support for green tourism development. The findings indicated a positive path from community attachment in AlUla to tourists’ tendencies toward green consumption behavior. Moreover, the mediating effects of support for green tourism development suggested that a deep sense of community attachment improves tourists’ support for green practices in the tourism sector. This study adds to the extended body of the literature on place attachment and green tourism by emphasizing the significance of community place attachment in stimulating tourists’ green consumption practices. Several practical implications for policymakers seeking to promote green tourism practices in heritage cities like AlUla are explored from the study results.
‘Rootpac R’ for Apricots? Yes!
Authors: Mendelné Pászti Edina , Bujdosó Géza , Ercisli Sezai , Mendel Ákos
Published: May 2024

The rootstock ‘Rootpac R’ is not used for apricots. The aim of this study was to evaluate the characteristics of ‘Rootpac R’ in comparison to the widely used ‘Myrobalan 29C’ rootstock. The evaluation of the rootstocks was conducted in combination with 16 scion cultivars to assess their effects on vegetative traits and mortality. The total height of the trees on ‘Rootpac R’ initially surpassed the ‘Myrobalan 29C’ trees. By the end of the fourth year, both rootstocks showed comparable heights with ‘Rootpac R’ standing at 317 cm and ‘Myrobalan 29C’ standing at 307 cm. Both rootstocks exhibited comparable TCSA values of 5 cm2 initially; ‘Rootpac R’ surpassed 35% compared to ‘Myrobalan 29C’. Canopy space occupancy assessments revealed that ‘Rootpac R’ initially demonstrated superior space utilization, occupying 8% of the designated volume compared to 4% for ‘Myrobalan 29C’. By the fourth year, ‘Rootpac R’ exhibited a higher occupancy rate of 65% compared to 50% for ‘Myrobalan 29C’. For apricot cultivars, such as ‘Bergeron’, ‘C. óriás’, ‘Gönci magyarkajszi’, ‘Lady Cot’, ‘Tardif de Valance’, and ‘Tom Cot’, ‘Rootpac R’ exhibited survival rates beyond the fourth season, highlighting its effectiveness for these varieties. Based on these results, ‘Rootpac R’ rootstock could be useful in apricot growing.
The Ins and Outs of Homeodomain-Leucine Zipper/Hormone Networks in the Regulation of Plant Development
Authors: Sessa Giovanna , Carabelli Monica , Sassi Massimiliano
Published: May 2024

The generation of complex plant architectures depends on the interactions among different molecular regulatory networks that control the growth of cells within tissues, ultimately shaping the final morphological features of each structure. The regulatory networks underlying tissue growth and overall plant shapes are composed of intricate webs of transcriptional regulators which synergize or compete to regulate the expression of downstream targets. Transcriptional regulation is intimately linked to phytohormone networks as transcription factors (TFs) might act as effectors or regulators of hormone signaling pathways, further enhancing the capacity and flexibility of molecular networks in shaping plant architectures. Here, we focus on homeodomain-leucine zipper (HD-ZIP) proteins, a class of plant-specific transcriptional regulators, and review their molecular connections with hormonal networks in different developmental contexts. We discuss how HD-ZIP proteins emerge as key regulators of hormone action in plants and further highlight the fundamental role that HD-ZIP/hormone networks play in the control of the body plan and plant growth.
Mitigating the Blurring Effect of CryoEM Averaging on a Flexible and Highly Symmetric Protein Complex through Sub-Particle Reconstruction
Authors: Suder Diana S. , Gonen Shane
Published: May 2024

Many macromolecules are inherently flexible as a feature of their structure and function. During single-particle CryoEM processing, flexible protein regions can be detrimental to high-resolution reconstruction as signals from thousands of particles are averaged together. This “blurring” effect can be difficult to overcome and is possibly more pronounced when averaging highly symmetric complexes. Approaches to mitigating flexibility during CryoEM processing are becoming increasingly critical as the technique advances and is applied to more dynamic proteins and complexes. Here, we detail the use of sub-particle averaging and signal subtraction techniques to precisely target and resolve flexible DARPin protein attachments on a designed tetrahedrally symmetric protein scaffold called DARP14. Particles are first aligned as full complexes, and then the symmetry is reduced by alignment and focused refinement of the constituent subunits. The final reconstructions we obtained were vastly improved over the fully symmetric reconstructions, with observable secondary structure and side-chain placement. Additionally, we were also able to reconstruct the core region of the scaffold to 2.7 Å. The data processing protocol outlined here is applicable to other dynamic and symmetric protein complexes, and our improved maps could allow for new structure-guided variant designs of DARP14.
miRNA- and Cell Line-Specific Constraints on Precursor miRNA Processing of Stably Transfected Pancreatic Cancer and Other Mammalian Cells
Authors: Allen-Coyle Taylor J. , Roca Berta Capella , Costello Alan , Barron Niall , Keenan Joanne , Clynes Martin , O’Neill Fiona , O’Sullivan Finbarr
Published: May 2024

MicroRNAs (miRNAs) regulate approximately one-third of all human genes. The dysregulation of miRNAs has been implicated in the development of numerous human diseases, including cancers. In our investigation focusing on altering specific miRNA expression in human pancreatic cancer cells, we encountered an interesting finding. While two expression vector designs effectively enhanced miR-708 levels, they were unable to elevate mature forms of miR-29b, -1290, -2467, and -6831 in pancreatic cancer cell lines. This finding was also observed in a panel of other non-pancreatic cancer cell lines, suggesting that miRNA processing efficiency was cell line specific. Using a step-by-step approach in each step of miRNA processing, we ruled out alternative strand selection by the RISC complex and transcriptional interference at the primary miRNA (pri-miRNA) level. DROSHA processing and pri-miRNA export from the nucleus also appeared to be occurring normally. We observed precursor (pre-miRNA) accumulation only in cell lines where mature miRNA expression was not achieved, suggesting that the block was occurring at the pre-miRNA stage. To further confirm this, synthetic pre-miRNA mimics that bypass DICER processing were processed into mature miRNAs in all cases. This study has demonstrated the distinct behaviours of different miRNAs with the same vector in the same cell line, the same miRNA between the two vector designs, and with the same miRNA across different cell lines. We identified a stable vector pre-miRNA processing block. Our findings on the structural and sequence differences between successful and non-successful vector designs could help to inform future chimeric miRNA design strategies and act as a guide to other researchers on the intricate processing dynamics that can impact vector efficiency. Our research confirms the potential of miRNA mimics to surmount some of these complexities.
Glutamate Receptor-like (GLR) Family in Brassica napus: Genome-Wide Identification and Functional Analysis in Resistance to Sclerotinia sclerotiorum
Authors: Gulzar Rana Muhammad Amir , Ren Chun-Xiu , Fang Xi , Xu You-Ping , Saand Mumtaz Ali , Cai Xin-Zhong
Published: May 2024

Plant glutamate receptor-like channels (GLRs) are homologs of animal ionotropic glutamate receptors. GLRs are critical in various plant biological functions, yet their genomic features and functions in disease resistance remain largely unknown in many crop species. Here, we report the results on a thorough genome-wide study of the GLR family in oilseed rape (Brassica napus) and their role in resistance to the fungal pathogen Sclerotinia sclerotiorum. A total of 61 GLRs were identified in oilseed rape. They comprised three groups, as in Arabidopsis thaliana. Detailed computational analyses, including prediction of domain and motifs, cellular localization, cis-acting elements, PTM sites, and amino acid ligands and their binding pockets in BnGLR proteins, unveiled a set of group-specific characteristics of the BnGLR family, which included chromosomal distribution, motif composition, intron number and size, and methylation sites. Functional dissection employing virus-induced gene silencing of BnGLRs in oilseed rape and Arabidopsis mutants of BnGLR homologs demonstrated that BnGLR35/AtGLR2.5 positively, while BnGLR12/AtGLR1.2 and BnGLR53/AtGLR3.2 negatively, regulated plant resistance to S. sclerotiorum, indicating that GLR genes were differentially involved in this resistance. Our findings reveal the complex involvement of GLRs in B. napus resistance to S. sclerotiorum and provide clues for further functional characterization of BnGLRs.
Induction of Human Wharton’s Jelly of Umbilical Cord Derived Mesenchymal Stem Cells to Be Chondrocytes and Transplantation in Guinea Pig Model with Spontaneous Osteoarthritis
Authors: Nadeem Gulrez , Theerakittayakorn Kasem , Somredngan Sirilak , Thi Nguyen Hong , Boonthai Traimat , Samruan Worawalan , Tangkanjanavelukul Ponthep , Parnpai Rangsun
Published: May 2024

Osteoarthritis (OA) is a degenerative joint disease commonly found in elderly people and obese patients. Currently, OA treatments are determined based on their condition severity and a medical professional’s advice. The aim of this study was to differentiate human Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) into chondrocytes for transplantation in OA-suffering guinea pigs. hWJ-MSCs were isolated using the explant culture method, and then, their proliferation, phenotypes, and differentiation ability were evaluated. Subsequently, hWJ-MSCs-derived chondrocytes were induced and characterized based on immunofluorescent staining, qPCR, and immunoblotting techniques. Then, early-OA-suffering guinea pigs were injected with hyaluronic acid (HA) containing either MSCs or 14-day-old hWJ-MSCs-derived chondrocytes. Results showed that hWJ-MSCs-derived chondrocytes expressed specific markers of chondrocytes including Aggrecan, type II collagen, and type X collagen proteins and β-catenin, Sox9, Runx2, Col2a1, Col10a1, and ACAN gene expression markers. Administration of HA plus hWJ-MSCs-derived chondrocytes (HA-CHON) produced a better recovery rate of degenerative cartilages than HA plus MSCs or only HA. Histological assessments demonstrated no significant difference in Mankin’s scores of recovered cartilages between HA-CHON-treated guinea pigs and normal articular cartilage guinea pigs. Transplantation of hWJ-MSCs-derived chondrocytes was more effective than undifferentiated hWJ-MSCs or hyaluronic acid for OA treatment in guinea pigs. This study provides a promising treatment to be used in early OA patients to promote recovery and prevent disease progression to severe osteoarthritis.
Bioinformatic Analysis of Topoisomerase IIα Reveals Interdomain Interdependencies and Critical C-Terminal Domain Residues
Authors: Endsley Clark E. , Moore Kori A. , Townsley Thomas D. , Durston Kirk K. , Deweese Joseph E.
Published: May 2024

DNA Topoisomerase IIα (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential target, but it is an intrinsically disordered domain, which prevents structural analysis. Therefore, we set out to analyze the sequence of Top2A from 105 species using bioinformatic analysis, including the PSICalc algorithm, Shannon entropy analysis, and other approaches. Our results demonstrate that large (10th-order) interdependent clusters are found including non-proximal positions across the major domains of Top2A. Further, CTD-specific clusters of the third, fourth, and fifth order, including positions that had been previously analyzed via mutation and biochemical assays, were identified. Some of these clusters coincided with positions that, when mutated, either increased or decreased relaxation activity. Finally, sites of low Shannon entropy (i.e., low variation in amino acids at a given site) were identified and mapped as key positions in the CTD. Included in the low-entropy sites are phosphorylation sites and charged positions. Together, these results help to build a clearer picture of the critical positions in the CTD and provide potential sites/regions for further analysis.
From Gut to Brain: Uncovering Potential Serum Biomarkers Connecting Inflammatory Bowel Diseases to Neurodegenerative Diseases
Authors: Sarb Oliviu-Florentiu , Sarb Adriana-Daniela , Iacobescu Maria , Vlad Irina-Maria , Milaciu Mircea-Vasile , Ciurmarnean Lorena , Vacaras Vitalie , Tantau Alina-Ioana
Published: May 2024

Inflammatory bowel diseases (IBDs) are characterized by chronic gastrointestinal inflammation due to abnormal immune responses to gut microflora. The gut–brain axis is disrupted in IBDs, leading to neurobiological imbalances and affective symptoms. Systemic inflammation in IBDs affects the brain’s inflammatory response system, hormonal axis, and blood–brain barrier integrity, influencing the gut microbiota. This review aims to explore the association between dysregulations in the gut–brain axis, serum biomarkers, and the development of cognitive disorders. Studies suggest a potential association between IBDs and the development of neurodegeneration. The mechanisms include systemic inflammation, nutritional deficiency, GBA dysfunction, and the effect of genetics and comorbidities. The objective is to identify potential correlations and propose future research directions to understand the impact of altered microbiomes and intestinal barrier functions on neurodegeneration. Serum levels of vitamins, inflammatory and neuronal damage biomarkers, and neuronal growth factors have been investigated for their potential to predict the development of neurodegenerative diseases, but current results are inconclusive and require more studies.
Enhancing Heart Transplantation: Utilizing Gas-Loaded Nanocarriers to Mitigate Cold/Hypoxia Stress
Authors: Rubeo Chiara , Hoti Gjylije , Giordano Magalì , Molinar Chiara , Aragno Manuela , Mantuano Beatrice , Comità Stefano , Femminò Saveria , Cavalli Roberta , Trotta Francesco , Penna Claudia , Pagliaro Pasquale
Published: May 2024

Gas-loaded nanocarriers (G-LN) show promise in improving heart transplantation (HTx) outcomes. Given their success in reducing cell death during normothermic hypoxia/reoxygenation (H/R) in vitro, we tested their integration into cardioplegic solutions and static cold storage (SCS) during simulated HTx. Wistar rat hearts underwent four hours of SCS with four G-LN variants: O2- or N2-cyclic-nigerosyl-nigerose-nanomonomers (CNN), and O2- or N2-cyclic-nigerosyl-nigerose-nanosponges (CNN-NS). We monitored physiological-hemodynamic parameters and molecular markers during reperfusion to assess cell damage/protection. Hearts treated with nanomonomers (N2-CNN or O2-CNN) showed improvements in left ventricular developed pressure (LVDP) and a trend towards faster recovery of the rate pressure product (RPP) compared to controls. However, nanosponges (N2-CNN-NS or O2-CNN-NS) did not show similar improvements. None of the groups exhibited an increase in diastolic left ventricular pressure (contracture index) during reperfusion. Redox markers and apoptosis/autophagy pathways indicated an increase in Beclin 1 for O2-CNN and in p22phox for N2-CNN, suggesting alterations in autophagy and the redox environment during late reperfusion, which might explain the gradual decline in heart performance. The study highlights the potential of nanomonomers to improve early cardiac performance and mitigate cold/H/R-induced stunning in HTx. These early improvements suggest a promising avenue for increasing HTx success. Nevertheless, further research and optimization are needed before clinical application.
Integrating Multiple Database Resources to Elucidate the Gene Flow in Southeast Asian Pig Populations
Authors: Li Guangzhen , Liu Yuqiang , Feng Xueyan , Diao Shuqi , Zhong Zhanming , Li Bolang , Teng Jinyan , Zhang Wenjing , Zeng Haonan , Cai Xiaodian , Gao Yahui , Liu Xiaohong , Yuan Xiaolong , Li Jiaqi , Zhang Zhe
Published: May 2024

The domestic pig (Sus scrofa) and its subfamilies have experienced long-term and extensive gene flow, particularly in Southeast Asia. Here, we analyzed 236 pigs, focusing on Yunnan indigenous, European commercial, East Asian, and Southeast Asian breeds, using the Pig Genomics Reference Panel (PGRP v1) of Pig Genotype-Tissue Expression (PigGTEx) to investigate gene flow and associated complex traits by integrating multiple database resources. In this study, we discovered evidence of admixtures from European pigs into the genome of Yunnan indigenous pigs. Additionally, we hypothesized that a potential conceptual gene flow route that may have contributed to the genetic composition of the Diannan small-ear pig is a gene exchange from the Vietnamese pig. Based on the most stringent gene introgression scan using the fd statistic, we identified three specific loci on chromosome 8, ranging from 51.65 to 52.45 Mb, which exhibited strong signatures of selection and harbored the NAF1, NPY1R, and NPY5R genes. These genes are associated with complex traits, such as fat mass, immunity, and litter weight, in pigs, as supported by multiple bio-functionalization databases. We utilized multiple databases to explore the potential dynamics of genetic exchange in Southeast Asian pig populations and elucidated specific gene functionalities.
Ovarian Cancer Cell-Conditioning Medium Induces Cancer-Associated Fibroblast Phenoconversion through Glucose-Dependent Inhibition of Autophagy
Authors: Ferraresi Alessandra , Girone Carlo , Maheshwari Chinmay , Vallino Letizia , Dhanasekaran Danny N. , Isidoro Ciro
Published: May 2024

One aspect of ovarian tumorigenesis which is still poorly understood is the tumor–stroma interaction, which plays a major role in chemoresistance and tumor progression. Cancer-associated fibroblasts (CAFs), the most abundant stromal cell type in the tumor microenvironment, influence tumor growth, metabolism, metastasis, and response to therapy, making them attractive targets for anti-cancer treatment. Unraveling the mechanisms involved in CAFs activation and maintenance is therefore crucial for the improvement of therapy efficacy. Here, we report that CAFs phenoconversion relies on the glucose-dependent inhibition of autophagy. We show that ovarian cancer cell-conditioning medium induces a metabolic reprogramming towards the CAF-phenotype that requires the autophagy-dependent glycolytic shift. In fact, 2-deoxy-D-glucose (2DG) strongly hampers such phenoconversion and, most importantly, induces the phenoreversion of CAFs into quiescent fibroblasts. Moreover, pharmacological inhibition (by proline) or autophagy gene knockdown (by siBECN1 or siATG7) promotes, while autophagy induction (by either 2DG or rapamycin) counteracts, the metabolic rewiring induced by the ovarian cancer cell secretome. Notably, the nutraceutical resveratrol (RV), known to inhibit glucose metabolism and to induce autophagy, promotes the phenoreversion of CAFs into normal fibroblasts even in the presence of ovarian cancer cell-conditioning medium. Overall, our data support the view of testing autophagy inducers for targeting the tumor-promoting stroma as an adjuvant strategy to improve therapy success rates, especially for tumors with a highly desmoplastic stroma, like ovarian cancer.
Cordycepin Triphosphate as a Potential Modulator of Cellular Plasticity in Cancer via cAMP-Dependent Pathways: An In Silico Approach
Authors: Gonzalez-Llerena Jose Luis , Espinosa-Rodriguez Bryan Alejandro , Treviño-Almaguer Daniela , Mendez-Lopez Luis Fernando , Carranza-Rosales Pilar , Gonzalez-Barranco Patricia , Guzman-Delgado Nancy Elena , Romo-Mancillas Antonio , Balderas-Renteria Isaias
Published: May 2024

Cordycepin, or 3′-deoxyadenosine, is an adenosine analog with a broad spectrum of biological activity. The key structural difference between cordycepin and adenosine lies in the absence of a hydroxyl group at the 3′ position of the ribose ring. Upon administration, cordycepin can undergo an enzymatic transformation in specific tissues, forming cordycepin triphosphate. In this study, we conducted a comprehensive analysis of the structural features of cordycepin and its derivatives, contrasting them with endogenous purine-based metabolites using chemoinformatics and bioinformatics tools in addition to molecular dynamics simulations. We tested the hypothesis that cordycepin triphosphate could bind to the active site of the adenylate cyclase enzyme. The outcomes of our molecular dynamics simulations revealed scores that are comparable to, and superior to, those of adenosine triphosphate (ATP), the endogenous ligand. This interaction could reduce the production of cyclic adenosine monophosphate (cAMP) by acting as a pseudo-ATP that lacks a hydroxyl group at the 3′ position, essential to carry out nucleotide cyclization. We discuss the implications in the context of the plasticity of cancer and other cells within the tumor microenvironment, such as cancer-associated fibroblast, endothelial, and immune cells. This interaction could awaken antitumor immunity by preventing phenotypic changes in the immune cells driven by sustained cAMP signaling. The last could be an unreported molecular mechanism that helps to explain more details about cordycepin’s mechanism of action.
N-Terminal Pro-Brain Natriuretic Peptide Correlates with Ghrelin and Acyl-Ghrelin in Pre-Dialysis Chronic Kidney Disease
Authors: Rusu Crina Claudia , Anton Florin , Valea Ana , Bondor Cosmina Ioana
Published: May 2024

Pro-B amino-terminal natriuretic peptide (NT-proBNP) is a diagnostic marker for heart failure (HF), a severe complication of chronic kidney disease (CKD). However, its significance in CKD is not clear, as other factors, such as renal function, may also have an impact. Recent studies have shown that ghrelin treatment is effective in HF in the general population, but the impact of ghrelin on cardiac function in CKD patients is still unknown. Our study aimed to investigate the factors associated with NT-proBNP in pre-dialysis CKD patients and to evaluate the correlation between NT-proBNP and ghrelin and acyl-ghrelin, molecules determined using ELISA methods. In a cross-sectional observational study, we included 80 patients with pre-dialysis CKD, with a mean age of 68 years and 50% men. The median values for NT-proBNP were 351.8 pg/mL, for acyl ghrelin 16.39 pg/mL, and for ghrelin 543.32 pg/mL. NT-proBNP was correlated with ghrelin (p = 0.034, r = 0.24), acyl-ghrelin (p = 0.033, r = −0.24), estimated glomerular filtration rate (p = 0.027, r = −0.25), serum urea (p = 0.006, r = 0.31), and ferritin (p = 0.041, r = 0.28). In multivariate analysis, ghrelin (p = 0.040) and blood urea (p = 0.040) remained significant predictors for NT-proBNP levels. NT-proBNP was a significant predictor for acyl-ghrelin (p = 0.036). In conclusion, in pre-dialysis CKD patients, a high value of NT-proBNP was associated with a high value of total ghrelin and a low value of acyl-ghrelin.
Reduced Pharmacological Intervention of Prehospital Services for Acute Alcohol Intoxication during the COVID-19 Pandemic in A Large District of Southern Italy
Authors: Giustino Arcangela , Natola Annamaria , Savoia Giovanni , De Salvia Maria Antonietta , Finelli Carmine
Published: May 2024

Background Stress during a pandemic increases the risk of alcohol consumption, which may require pharmacological management. Methods An observational single-center retrospective study was conducted from 1 January 2018 to 31 December 2021, and divided into 2-year periods (2018–2019 and 2020–2021). This study focused on calls to one of the emergency departments (EDs) of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ESs) who were either admitted or not admitted, due to their refusal. Results A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, an inverse association was found between pharmacological treatment and number of calls coded green (non-critical) and yellow (fairly critical) in patients admitted to EDs. An inverse association was also found for calls coded green in patients not admitted to EDs and pharmacological treatment. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. Conclusions ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs.
The Novel Impact of Augmented Reality and 3D Printing in the Diagnosis of Complex Acetabular Fractures: A Comparative Randomized Study in Orthopedic Residents
Authors: Montemagno Marco , Testa Gianluca , Panvini Flora , Puglisi Gianluca , Papotto Giacomo , Marchese Emanuele , Pavone Vito
Published: May 2024

Augmented reality (AR) and 3D printing (3DP) are novel technologies in the orthopedic field. Over the past decade, enthusiasm for these new digital applications has driven new perspectives in improving diagnostic accuracy and sensitivity in the field of traumatology. Currently, however, it is still difficult to quantify their value and impact in the medical–scientific field, especially in the improvement of diagnostics in complex fractures. Acetabular fractures have always been a challenge in orthopedics, due to their volumetric complexity and low diagnostic reliability. Background/Objectives: The goal of this study was to determine whether these methods could improve the learning aspect and diagnostic accuracy of complex acetabular fractures compared to gold-standard CT (computed tomography). Methods: Orthopedic residents of our department were selected and divided into Junior (JUN) and Senior (SEN) groups. Associated fractures of acetabulum were included in the study, and details of these were provided as CT scans, 3DP models, and AR models displayed on a tablet screen. In a double-blind questionnaire, each resident classified every fracture. Diagnostic accuracy (DA), response time (RT), agreement (R), and confidence (C) were measured. Results: Twenty residents (JUN = 10, SEN = 10) classified five fractures. Overall DA was 26% (CT), 18% (3DP), and 29% (AR). AR-DA was superior to 3DP-DA (p = 0.048). DA means (JUN vs. SEN, respectively): CT-DA was 20% vs. 32% (p < 0.05), 3DP-DA was 12% vs. 24% (p = 0.08), and AR-DA was 28% vs. 30% (p = 0.80). Overall RT was 61.2 s (±24.6) for CT, 35.8 s (±20.1) for 3DP, and 46.7 s (±20.8) for AR. R was fairly poor between methods and groups. Overall, 3DPs had superior C (65%). Conclusions: AR had the same overall DA as CT, independent of experience, 3DP had minor differences in DA and R, but it was the fastest method and the one in which there was the most confidence. Intra- and inter-observer R between methods remained very poor in residents.
Effectiveness of Exercise Programs for Alleviation of Upper Body Pain in Patients with Spinal Cord Injury: A Systematic Review
Authors: Park Jiyoung , Kim Jihyun , Eun Seon-Deok , Kang Dongheon
Published: May 2024

(1) Background: Upper body pain, particularly in the limbs and shoulders, is a common symptom among patients with spinal cord injury (SCI) and wheelchair users. Despite the focus on resistance muscle training as a suitable intervention for SCI individuals, findings across different populations and conditions have been inconsistent. (2) Methods: We conducted a systematic review to elucidate the correlations among exercise interventions, muscle strength enhancement, and pain reduction. A comprehensive literature search was performed using the keywords “spinal cord injury,” “pain,” “exercise,” “disability,” “paraplegia,” and “tetraplegia” across the DBpia, EMBASE, PubMed, and Science Direct databases. (3) Results: From 191 identified articles, 13 studies (1 from Korea and 12 from other countries) were selected for analysis. The results indicate that exercise interventions are effective in reducing pain in patients with SCI, with a particular emphasis on alleviating shoulder pain. (4) Conclusion: Exercise is essential for pain reduction in patients with SCI, especially those experiencing shoulder pain. However, there is a notable lack of experimental research focusing primarily on pain. The development of appropriate measurement instruments is crucial for the prevention and relief of pain in this patient population.
A Data-Driven Approach for Cutting Force Prediction in FEM Machining Simulations Using Gradient Boosted Machines
Authors: Reeber Tim , Wolf Jan , Möhring Hans-Christian
Published: May 2024

Cutting simulations via the Finite Element Method (FEM) have recently gained more significance due to ever increasing computational performance and thus better resulting accuracy. However, these simulations are still time consuming and therefore cannot be deployed for an in situ evaluation of the machining processes in an industrial environment. This is due to the high non-linear nature of FEM simulations of machining processes, which require considerable computational resources. On the other hand, machine learning methods are known to capture complex non-linear behaviors. One of the most widely applied material models in cutting simulations is the Johnson–Cook material model, which has a great influence on the output of the cutting simulations and contributes to the non-linear behavior of the models, but its influence on cutting forces is sometimes difficult to assess beforehand. Therefore, this research aims to capture the highly non-linear behavior of the material model by using a dataset of multiple short-duration cutting simulations from Abaqus to learn the relationship of the Johnson–Cook material model parameters and the resulting cutting forces for a constant set of cutting conditions. The goal is to shorten the time to simulate cutting forces by encapsulating complex cutting conditions in dependence of material parameters in a single model. A total of five different models are trained and the performance is evaluated. The results show that Gradient Boosted Machines capture the influence of varying material model parameters the best and enable good predictions of cutting forces as well as deliver insights into the relevance of the material parameters for the cutting and thrust forces in orthogonal cutting.
Tool Wear Monitoring in Micro-Milling Based on Digital Twin Technology with an Extended Kalman Filter
Authors: Christiand Christiand , Kiswanto Gandjar , Baskoro Ario Sunar , Hasymi Zulhendri , Ko Tae Jo
Published: May 2024

In order to avoid catastrophic events that degrade the quality of machined products, such as tool breakage, it is vital to have a prognostic system for monitoring tool wear during the micro-milling process. Despite the long history of the tool wear monitoring field, creating such a system to track, monitor, and foresee the rapid progression of tool wear still needs to be improved in the application of micro-milling. On the other hand, digital twin technology has recently become widely recognized as significant in manufacturing and, notably, within the Industry 4.0 ecosystem. Digital twin technology is considered a potential breakthrough in developing a prognostic tool wear monitoring system, as it enables the tracking, monitoring, and prediction of the dynamics of a twinned object, e.g., a CNC machine tool. However, few works have explored the digital twin technology for tool wear monitoring, particularly in the micro-milling field. This paper presents a novel tool wear monitoring system for micro-milling machining based on digital twin technology and an extended Kalman filter framework. The proposed system provides wear progression notifications to assist the user in making decisions related to the machining process. In an evaluation using four machining datasets of slot micro-milling, the proposed system achieved a maximum error mean of 0.038 mm from the actual wear value. The proposed system brings a promising opportunity to widen the utilization of digital twin technology with the extended Kalman filter framework for seamless data integration for wear monitoring service.
biSAMNet: A Novel Approach in Maritime Data Completion Using Deep Learning and NLP Techniques
Authors: Li Yong , Wang Zhishan
Published: May 2024

In the extensive monitoring of maritime traffic, maritime management frequently encounters incomplete automatic identification system (AIS) data. This deficiency poses significant challenges to safety management, requiring effective methods to infer corresponding ship information. We tackle this issue using a classification approach. Due to the absence of a fixed road network at sea unlike on land, raw trajectories are difficult to convert and cannot be directly fed into neural networks. We devised a latitude–longitude gridding encoding strategy capable of transforming continuous latitude–longitude data into discrete grid points. Simultaneously, we employed a compression algorithm to further extract significant grid points, thereby shortening the encoding sequence. Utilizing natural language processing techniques, we integrate the Word2vec word embedding approach with our novel biLSTM self-attention chunk-max pooling net (biSAMNet) model, enhancing the classification of vessel trajectories. This method classifies targets into ship types and ship lengths within static information. Employing the Taiwan Strait as a case study and benchmarking against CNN, RNN, and methods based on the attention mechanism, our findings underscore our model’s superiority. The biSAMNet achieves an impressive trajectory classification F1 score of 0.94 in the ship category dataset using only five-dimensional word embeddings. Additionally, through ablation experiments, the effectiveness of the Word2vec pre-trained embedding layer is highlighted. This study introduces a novel method for handling ship trajectory data, addressing the challenge of obtaining ship static information when AIS data are unreliable.
Exploring Inflammatory Parameters in Lung Cancer Patients: A Retrospective Analysis
Authors: Feier Catalin Vladut Ionut , Muntean Calin , Faur Alaviana Monique , Gaborean Vasile , Petrache Ioan Adrian , Cozma Gabriel Veniamin
Published: May 2024

Inflammation-related parameters serve as pivotal indicators in the prognosis and management of lung cancer. This retrospective investigation aimed to explore the relationship between inflammatory markers and diverse clinical variables in non-small-cell lung cancer patients. A cohort of 187 individuals undergoing elective lobectomy for lung cancer was retrospectively analyzed, spanning an 11-year data collection period. Six inflammation ratios derived from complete peripheral blood counts were assessed. Significantly elevated levels of neutrophil-to-lymphocyte ratio (NLR) (p = 0.005), platelet-to-lymphocyte ratio (PLR) (p = 0.001), Aggregate Index of Systemic Inflammation (AISI) (p = 0.015), Systemic Inflammation Response Index (SIRI) (p = 0.004), and Systemic Immune Inflammation Index (SII) (p = 0.004) were observed in patients with advanced T stages. Significantly, elevated values (p < 0.05) of these parameters were observed in the study’s smoker patients compared to non-smokers. A statistically significant correlation was identified between the NLR parameter and tumor size (p = 0.07, r = 0.204), alongside a significant elevation in SIRI (p = 0.041) among patients experiencing postoperative complications. Inflammatory biomarkers emerge as invaluable prognostic indicators for patients with non-small-cell lung cancer, offering potential utility in forecasting their prognosis.