bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative Regulation of Autophagy during Macrophage Infection by Mycobacterium bovis BCG via Protein Kinase C Activation
Authors: Maldonado-Bravo Rafael , Villaseñor Tomás , Pedraza-Escalona Martha , Pérez-Martínez Leonor , Hernández-Pando Rogelio , Pedraza-Alva Gustavo
Published: March 2024

Mycobacterium tuberculosis (Mtb) employs various strategies to manipulate the host’s cellular machinery, overriding critical molecular mechanisms such as phagosome-lysosome fusion, which are crucial for its destruction. The Protein Kinase C (PKC) signaling pathways play a key role in regulating phagocytosis. Recent research in Interferon-activated macrophages has unveiled that PKC phosphorylates Coronin-1, leading to a shift from phagocytosis to micropinocytosis, ultimately resulting in Mtb destruction. Therefore, this study aims to identify additional PKC targets that may facilitate Mycobacterium bovis (M. bovis) infection in macrophages. Protein extracts were obtained from THP-1 cells, both unstimulated and mycobacterial-stimulated, in the presence or absence of a general PKC inhibitor. We conducted an enrichment of phosphorylated peptides, followed by their identification through mass spectrometry (LC-MS/MS). Our analysis revealed 736 phosphorylated proteins, among which 153 exhibited alterations in their phosphorylation profiles in response to infection in a PKC-dependent manner. Among these 153 proteins, 55 are involved in various cellular processes, including endocytosis, vesicular traffic, autophagy, and programmed cell death. Importantly, our findings suggest that PKC may negatively regulate autophagy by phosphorylating proteins within the mTORC1 pathway (mTOR2/PKC/Raf-1/Tsc2/Raptor/Sequestosome-1) in response to M. bovis BCG infection, thereby promoting macrophage infection.
Integration of iPSC-Derived Microglia into Brain Organoids for Neurological Research
Authors: Mrza Muhammad Asif , He Jitian , Wang Youwei
Published: March 2024

The advent of Induced Pluripotent Stem Cells (iPSCs) has revolutionized neuroscience research. This groundbreaking innovation has facilitated the development of three-dimensional (3D) neural organoids, which closely mimicked the intricate structure and diverse functions of the human brain, providing an unprecedented platform for the in-depth study and understanding of neurological phenomena. However, these organoids lack key components of the neural microenvironment, particularly immune cells like microglia, thereby limiting their applicability in neuroinflammation research. Recent advancements focused on addressing this gap by integrating iPSC-derived microglia into neural organoids, thereby creating an immunized microenvironment that more accurately reflects human central neural tissue. This review explores the latest developments in this field, emphasizing the interaction between microglia and neurons within immunized neural organoids and highlights how this integrated approach not only enhances our understanding of neuroinflammatory processes but also opens new avenues in regenerative medicine.
Changes in the Serum Metabolome in an Inflammatory Model of Osteoarthritis in Rats
Authors: Berenguer Neus I. , Canet Vicente J. Sifre , Soler Canet Carme , Segarra Sergi , García de Carellán Alejandra , Serra Aguado C. Iván
Published: March 2024

Osteoarthritis (OA) is a pathology of great impact worldwide. Its physiopathology is not completely known, and it is usually diagnosed by imaging techniques performed at advanced stages of the disease. The aim of this study was to evaluate early serum metabolome changes and identify the main metabolites involved in an inflammatory OA animal model. This study was performed on thirty rats. OA was induced in all animals by intra-articular injection of monoiodoacetate into the knee joint. Blood samples were taken from all animals and analyzed by mass spectrometry before OA induction and 28, 56, and 84 days following induction. Histological evaluation confirmed OA in all samples. The results of this study allow the identification of several changes in 18 metabolites over time, including organic acids, benzenoids, heterocyclic compounds, and lipids after 28 days, organic acids after 56 days, and lipid classes after 84 days. We conclude that OA induces serological changes in the serum metabolome, which could serve as potential biomarkers. However, it was not possible to establish a relationship between the identified metabolites and the time at which the samples were taken. Therefore, these findings should be confirmed in future OA studies.
Regulation of STAT1 and STAT4 Expression by Growth Factor and Interferon Supplementation in Sjögren’s Syndrome Cell Culture Models
Authors: Mougeot Jean-Luc C. , Thornburg Thomas E. , Noll Braxton D. , Brennan Michael T. , Mougeot Farah Bahrani
Published: March 2024

Our goal was to investigate the effects of epidermal growth factor (EGF) and interferons (IFNs) on signal transducer and activator of transcription STAT1 and STAT4 mRNA and active phosphorylated protein expression in Sjögren’s syndrome cell culture models. iSGECs (immortalized salivary gland epithelial cells) and A253 cells were treated with EGF, IFN-alpha, -beta, -gamma, or mitogen-activated protein kinase p38 alpha (p38-MAPK) inhibitor for 0–24–48–72 h. STAT1 and STAT4 mRNA expression was quantified by qRT-PCR. Untreated and treated cells were compared using the delta-delta-CT method based on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) normalized relative fold changes. phospho-tyrosine-701-STAT1 and phospho-serine-721-STAT4 were detected by Western blot analysis. STAT4 mRNA expression decreased 48 h after EGF treatment in A253 cells, immortalized salivary gland epithelial cells iSGECs nSS2 (sicca patient origin), and iSGECs pSS1 (anti-SSA negative Sjögren’s Syndrome patient origin). EGF and p38-MAPK inhibitor decreased A253 STAT4 mRNA levels. EGF combined with IFN-gamma increased phospho-STAT4 and phospho-STAT1 after 72 h in all cell lines, suggesting additive effects for phospho-STAT4 and a major effect from IFN-gamma for phospho-STAT1. pSS1 and nSS2 cells responded differently to type I and type II interferons, confirming unique functional characteristics between iSGEC cell lines. EGF/Interferon related pathways might be targeted to regulate STAT1 and STAT4 expression in salivary gland epithelial cells. Further investigation is required learn how to better target the Janus kinases/signal transducer and activator of transcription proteins (JAK/STAT) pathway-mediated inflammatory response in Sjögren’s syndrome.
Association between Albumin Alterations and Renal Function in Patients with Type 2 Diabetes Mellitus
Authors: Nugnes Marta , Baldassarre Maurizio , Ribichini Danilo , Tedesco Daniele , Capelli Irene , Vetrano Daniele , Marchignoli Francesca , Brodosi Lucia , Pompili Enrico , Petroni Maria Letizia , La Manna Gaetano , Marchesini Giulio , Naldi Marina , Bartolini Manuela
Published: March 2024

Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether albumin structural alterations correlate with DKD severity and evaluate whether native and reduced albumin concentrations could complement the diagnosis of DKD. To this end, one hundred and seventeen T2DM patients without (n = 42) and with (n = 75) DKD (DKD I-III upon KDIGO classification) were evaluated; the total albumin concentration (tHA) was quantified by a bromocresol green assay, while structural alterations were profiled via liquid chromatography–high-resolution mass spectrometry (LC-HRMS). The concentrations of native albumin (eHA, effective albumin) and reduced albumin (rHA) were subsequently assessed. The HRMS analyses revealed a reduced relative amount of native albumin in DKD patients along with an increased abundance of altered forms, especially those bearing oxidative modifications. Accordingly, both eHA and rHA values varied during the stages of progressive renal failure, and these alterations were dose-dependently correlated with renal dysfunction. A ROC curve analysis revealed a significantly greater sensitivity and specificity of eHA and rHA than of tHA for diagnosing DKD. Importantly, according to the multivariate logistic regression analysis, the eHA was identified as an independent predictor of DKD.
Dig-up Primers: A Pipeline for Identification of Polymorphic Microsatellites Loci within Assemblies of Related Species
Authors: Turudić Ante , Liber Zlatko , Grdiša Martina , Jakše Jernej , Varga Filip , Poljak Igor , Šatović Zlatko
Published: March 2024

Simple sequence repeats (SSRs) have become one of the most popular molecular markers and are used in numerous fields, including conservation genetics, population genetic studies, and genetic mapping. Advances in next-generation sequencing technology and the growing amount of genomic data are driving the development of bioinformatics tools for SSR marker design. These tools work with different combinations of input data, which can be raw reads or assemblies, and with one or more input datasets. We present here a new strategy and implementation of a simple standalone pipeline that utilizes more than one assembly for the in silico design of PCR primers for microsatellite loci in more than one species. Primers are tested in silico to determine if they are polymorphic, eliminating the need to test time-consuming cross-species amplification in the laboratory. The end result is a set of markers that are in silico polymorphic in all analyzed species and have great potential for the identification of interspecies hybrids. The efficiency of the tool is demonstrated using two examples at different taxonomic levels and with different numbers of input assemblies to generate promising, high-quality SSR markers.
ReporType: A Flexible Bioinformatics Tool for Targeted Loci Screening and Typing of Infectious Agents
Authors: Cruz Helena , Pinheiro Miguel , Borges Vítor
Published: March 2024

In response to the pressing need for continuous monitoring of emergence and circulation of pathogens through genomics, it is imperative to keep developing bioinformatics tools that can help in their rapid characterization and classification. Here, we introduce ReporType, a versatile bioinformatics pipeline designed for targeted loci screening and typing of infectious agents. Developed using the snakemake workflow manager, ReporType integrates multiple software for read quality control and de novo assembly, and then applies ABRicate for locus screening, culminating in the production of easily interpretable reports for the identification of pathogen genotypes and/or screening of specific genomic loci. The pipeline accommodates a range of input formats, from Illumina or Oxford Nanopore Technology (ONT) reads (FASTQ) to Sanger sequencing files (AB1), or FASTA files, making it flexible for application in multiple pathogens and with different purposes. ReporType is released with pre-prepared databases for some viruses and bacteria, yet it remains easily configurable to handle custom databases. ReporType performance and functionality were validated through proof-of-concept exercises, encompassing diverse pathogenic species, including viruses such as measles, Newcastle disease virus (NDV), Dengue virus (DENV), influenza, hepatitis C virus (HCV) and Human T-Cell Lymphotropic virus type 1 (HTLV-1), as well as bacteria like Chlamydia trachomatis and Legionella pneumophila. In summary, ReporType emerges as a simple, dynamic and pan-pathogen tool, poised to evolve in tandem with the ever-changing needs of the fields of pathogen genomics, infectious disease epidemiology, and one health bioinformatics. ReporType is freely available at GitHub.
Pyridoxal 5′-Phosphate Biosynthesis by Pyridox-(am)-ine 5′-Phosphate Oxidase: Species-Specific Features
Authors: Rivero Maribel , Novo Nerea , Medina Milagros
Published: March 2024

Enzymes reliant on pyridoxal 5′-phosphate (PLP), the metabolically active form of vitamin B6, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B6 is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells via pyridoxal kinase (PLK) and pyridox-(am)-ine 5′-phosphate oxidase (PNPOx). The flavin mononucleotide-dependent PNPOx enzyme converts pyridoxine 5′-phosphate and pyridoxamine 5′-phosphate into PLP. PNPOx is vital for both biosynthesis and salvage pathways in organisms producing B6 vitamers. However, for those depending on vitamin B6 as a nutrient, PNPOx participates only in the salvage pathway. Transferring the PLP produced via PNPOx to client apo-enzymes is indispensable for their catalytic function, proper folding and targeting of specific organelles. PNPOx activity deficiencies due to inborn errors lead to severe neurological pathologies, particularly neonatal epileptic encephalopathy. PNPOx maintains PLP homeostasis through highly regulated mechanisms, including structural alterations throughout the catalytic cycle and allosteric PLP binding, influencing substrate transformation at the active site. Elucidation at the molecular level of the mechanisms underlying PNPOx activity deficiencies is a requirement to develop personalized approaches to treat related disorders. Finally, despite shared features, the few PNPOx enzymes molecularly and functionally studied show species-specific regulatory properties that open the possibility of targeting it in pathogenic organisms.
MicroRNAs as Prognostic Biomarkers and Therapeutic Targets in Chondrosarcoma
Authors: Skipar Palina , Dey Mritunjoy , Piątkowski Jakub , Sulejczak Dorota , Rutkowski Piotr , Czarnecka Anna M.
Published: March 2024

Chondrosarcoma, the second most common primary malignant bone tumor, originates from cartilaginous tissue and accounts for almost 20% of all primary bone tumors. The management of chondrosarcoma remains challenging due to its diverse clinical course and prognosis, which can range from benign to highly aggressive with a huge risk of metastasis. Emerging research has demonstrated the importance of microRNA (miRNA) dysregulation in the pathogenesis of chondrosarcoma. MiRNAs are small, noncoding RNA molecules that play an essential role in gene expression regulation by targeting specific messenger RNAs (mRNAs) for degradation or translational repression. This article provides an extensive review of current miRNA research in chondrosarcoma, focusing on diagnostic strategies, cell cycle regulation, drug resistance, biomarkers of progression, and stem cell phenotype. We will examine recent studies identifying differentially expressed miRNAs in chondrosarcoma compared to normal cartilage tissue, exploring their potential as diagnostic and prognostic biomarkers. Furthermore, we will discuss the role of miRNAs in regulating cell cycle progression and their potential as therapeutic targets to overcome drug resistance. We will also investigate the prospective utility of miRNAs as biomarkers of progression and their role in modulating the stem cell phenotype of chondrosarcoma cells. This article offers a comprehensive analysis of current miRNA research in chondrosarcoma, focusing on its potential as diagnostic and prognostic biomarkers, therapeutic targets, and regulators of disease progression. By integrating the latest discoveries in this field, we aim to contribute to the development of novel approaches to the prevention, diagnosis, and treatment of chondrosarcoma, ultimately enhancing patient outcomes.
Age- and Sex-Associated Pathogenesis of Cell Culture-Passaged Kemerovo Virus in IFNAR(−/−) Mice
Authors: Migné Camille Victoire , Heckmann Aurélie , Monsion Baptiste , Mohd Jaafar Fauziah , Galon Clémence , Rakotobe Sabine , Bell-Sakyi Lesley , Moutailler Sara , Attoui Houssam
Published: March 2024

Kemerovo virus (KEMV) is a tick-borne orbivirus transmitted by ticks of the genus Ixodes. Previous animal experimentation studies with orbiviruses, in particular the interferon receptor double knock-out (IFNAR(−/−)) mouse model, did not indicate bias that is related to age or sex. We endeavoured to assess the effect of serial and alternated passages of KEMV in mammalian or Ixodes cells on virus replication and potential virulence in male or female IFNAR(−/−) mice, with important age differences: younger males (4–5 months old), older males (14–15 months old), and old females (14–15 months old). After 30 serial passages in mammalian or tick cells, or alternated passages in the two cell types, older female mice which were inoculated with the resulting virus strains were the first to show clinical signs and die. Younger males behaved differently from older males whether they were inoculated with the parental strain of KEMV or with any of the cell culture-passaged strains. The groups of male and female mice inoculated with the mammalian cell culture-adapted KEMV showed the lowest viraemia. While older female and younger male mice died by day 6 post-inoculation, surprisingly, the older males survived until the end of the experiment, which lasted 10 days. RNA extracted from blood and organs of the various mice was tested by probe-based KEMV real-time RT-PCR. Ct values of the RNA extracts were comparable between older females and younger males, while the values for older males were >5 Ct units higher for the various organs, indicating lower levels of replication. It is noteworthy that the hearts of the old males were the only organs that were negative for KEMV RNA. These results suggest, for the first time, an intriguing age- and sex-related bias for an orbivirus in this animal model. Changes in the amino acid sequence of the RNA-dependent RNA polymerase of Kemerovo virus, derived from the first serial passage in Ixodes cells (KEMV Ps.IRE1), were identified in the vicinity of the active polymerase site. This finding suggests that selection of a subpopulation of KEMV with better replication fitness in tick cells occurred.
The Impact of Metabolic Memory on Immune Profile in Young Patients with Uncomplicated Type 1 Diabetes
Authors: Neubauer-Geryk Jolanta , Wielicka Melanie , Myśliwiec Małgorzata , Zorena Katarzyna , Bieniaszewski Leszek
Published: March 2024

Metabolic memory refers to the long-term effects of achieving early glycemic control and the adverse implications of high blood glucose levels, including the development and progression of diabetes complications. Our study aimed to investigate whether the phenomenon of metabolic memory plays a role in the immune profile of young patients with uncomplicated type 1 diabetes (T1D). The study group included 67 patients with uncomplicated type 1 diabetes with a mean age of 15.1 ± 2.3 years and a minimum disease duration of 1.2 years. The control group consisted of 27 healthy children and adolescents with a mean age of 15.1 ± 2.3 years. Patients were divided into three groups according to their HbA1c levels at the onset of T1D, and the average HbA1c levels after one and two years of disease duration. The subgroup A1 had the lowest initial HbA1c values, while the subgroup C had the highest initial HbA1c values. Cytokine levels (including TNF-α, IL-35, IL-4, IL-10, IL-18, and IL-12) were measured in all study participants. Our data analysis showed that subgroup A1 was characterized by significantly higher levels of IL-35 and IL-10 compared to all other groups, and significantly higher levels of IL-4 compared to group B. Additionally, a comparative analysis of cytokine levels between the groups of diabetic patients and healthy controls demonstrated that subgroup A1 had significantly higher levels of anti-inflammatory cytokines. The lipid profile was also significantly better in subgroup A1 compared to all other patient groups. Based on our findings, it appears that an inflammatory process, characterized by an imbalance between the pro- and anti-inflammatory cytokines, is associated with poor glycemic control at the onset of diabetes and during the first year of disease duration. These findings also suggest that both metabolic memory and inflammation contribute to the abnormal lipid profile in patients with type 1 diabetes.
Application of Photodynamic Therapy in Cardiology
Authors: Wańczura Piotr , Aebisher David , Kłosowicz Maksymilian , Myśliwiec Angelika , Dynarowicz Klaudia , Bartusik-Aebisher Dorota
Published: March 2024

The origins of photodynamic therapy (PDT) date back to 1904. Since then, the amount of research proving PDT and, consequently, its applicability to various disease states has steadily increased. Currently, PDT is mainly used in oncology to destroy cancer cells. It is being worked on for possible use in other medical fields as well, including cardiology. It can be used in the prevention of restenosis, often occurring after vascular surgical interventions, for destroying atherosclerotic plaques and as a new ablative method of ectopic centers in the treatment of atrial fibrillation. The purpose of this review is to summarize the knowledge to date regarding the therapeutic potential of using PDT for various pathological conditions in cardiology. The review also focuses on the current limitations associated with the use of PDT and identifies areas where more research is needed to develop better drug regimens. Materials and methods: The study analyzed 189 medical articles. The articles came from PubMed, Frontiers, Google Scholar, Science Direct and Web of Science databases. Through the excitation of light, a photosensitizer (PS) introduced into the body, the destruction of pathological cells occurs. PTD is widely used in oncology of the central nervous system (CNS). This process is made possible by the production of free oxygen radicals (ROS) and singlet oxygen, which generate oxidative stress that destroys sensitive cancer cells. In recent years, photosensitizers have also been discovered to have a strong affinity for macrophages that fill atherosclerotic plaques, making these compounds suitable for treating atherosclerosis. By inducing apoptosis of smooth muscle cells, inactivating basic fibroblast growth factor (FGF-β) and inhibiting endothelial cell hyperplasia, PDT can be used to prevent restenosis after surgical proceduresPDT appears to be a minimally invasive and highly effective therapeutic method, especially when combined with other therapeutic methods. Unfortunately, the small number of animal model studies and human clinical trials greatly limit the applicability of PDT on a wider scale. Current limitations, such as the depth of penetration, delivery of photosensitizer particles to the direct site of the lesion or the appropriate choice of photosensitizer in relation to the nature of the pathology, unfortunately make it impossible to replace current therapeutic approaches.
Role of Civionics in the Civil Structural Health Monitoring System
Authors: Mufti Aftab A. , Thomson Douglas J.
Published: March 2024

Civil structural health monitoring (CSHM) tracks different aspects of an infrastructure system’s service and safety condition by utilizing reliably measured data and physics-based model simulations. Data and physical models are coupled with heuristic experience to proactively represent current and expected future performance. In the past two decades, more bridges and dams have been instrumented and monitored during and after construction to determine their performances and responses to various loading, material, boundary, and environmental conditions. Furthermore, bridge and dam owners increasingly utilize civionics systems to obtain essential data for developing data-driven asset management programs and addressing the state of good repair requirements.
Age Determination of Chrysomya megacephala Pupae through Reflectance and Machine Learning Analysis
Authors: Zhang Xiangyan , Qu Hongke , Zhou Ziqi , Chen Sile , Ngando Fernand Jocelin , Yang Fengqin , Xiao Jiao , Guo Yadong , Cai Jifeng , Zhang Changquan
Published: March 2024

Estimating the age of pupa during the development time of the blow fly Chrysomya megacephala (Diptera: Calliphoridae) is of forensic significance as it assists in determining the time of colonization (TOC), which could help to determine the postmortem interval (PMI). However, establishing an objective, accurate, and efficient method for pupa age inference is still a leading matter of concern among forensic entomologists. In this study, we utilized hyperspectral imaging (HSI) technology to analyze the reflectance changes of pupa development under different temperatures (15 °C, 20 °C, 25 °C, and 30 °C). The spectrograms showed a downtrend under all temperatures. We used PCA to reduce the dimensionality of the spectral data, and then machine learning models (RF, SVR-RBF, SVR-POLY, XGBR, and Lasso) were built. RF, SVR with RBF kernel, and XGBR could show promise in accurate developmental time estimation using accumulated degree days. Among these, the XGBR model consistently exhibited the most minor errors, ranging between 3.9156 and 7.3951 (MAE). This study has identified the value of further refinement of HSI in forensic applications involving entomological specimens, and identified the considerable potential of HSI in forensic practice.
Validation and Evaluation of Reference Genes for Quantitative Real-Time PCR Analysis in Mythimna loreyi (Lepidoptera: Noctuidae)
Authors: Wang Liuyang , Yang Chaoxia , Liu Qingyu , Zhang Xiaofang , Mei Xiangdong , Zhang Tao , Ning Jun
Published: March 2024

Quantitative real-time PCR (qRT-PCR) is a widely applied technique for accurately assessing the expression of target genes. In practice, the evaluation of gene expression requires appropriate reference genes. To screen reliable reference genes for evaluating gene expression via qRT-PCR in Mythimna loreyi, a notorious migratory pest across Asia, Africa, Europe, and Australia, we assessed the expression stability of 13 candidate reference genes in M. loreyi using the ΔCt method, BestKeeper, Normfinder, GeNorm, and the web-based comprehensive platform RefFinder. These reference genes include RPL10, RPL27, RPL32, RPS3, TATA−box, GAPDH, AK, Actin, EF, α−tubulin, SOD, 18S rRNA, and FTZ−F1, which is frequently employed in Lepidoptera insects. Our findings revealed that the performance of the candidate reference gene depended on experimental conditions. Specifically, RPL27 and RPL10 were the most suitable for evaluating expression changes across developmental stages, tissues, and adult ages. The optimal reference genes were recommended in specific experiment conditions, for instance, EF and RPS3 were recommended for mating status, AK and RPL10 were recommended for temperature treatments, RPL27 and FTZ−F1 were recommended for larva diet, and EF and RPL27 were recommended for adult diet treatments. Additionally, expression profiles of pheromone-binding protein 2 (MlorPBP2) and glutathione S-transferase (MlorGST1) were used to validate the reference genes. This study provides reference genes for the accurate normalization of qRT-PCR data, laying the groundwork for studying the expression of target genes in M. loreyi.
Self-Defense Mechanism in Rice to Salinity: Proline
Authors: Koc Yunus Emre , Aycan Murat , Mitsui Toshiaki
Published: March 2024

The increasing global population and climate change threaten food security, with the need for sustenance expected to rise by 85% by 2050. Rice, a crucial staple food for over 50% of the global population, is a major source of calories in underdeveloped and developing countries. However, by the end of the century, over 30% of rice fields will become saline due to soil salinity caused by earthquakes, tsunamis, and rising sea levels. Plants have developed strategies to deal with salt stress, such as ion homeostasis, antioxidant defense mechanisms, and morphological adaptations. Proline, an endogenous osmolyte, is the predominant endogenous osmolyte that accumulates in response to salinity, and its overexpression in rice plants has been observed to increase plant salinity tolerance. Exogenously applied proline has been shown to improve plant salt tolerance by reducing the destructive effect of salinity. Recent research has focused on ionic toxicity, nitrogen fixation, and gene expression related to salt tolerance. Exogenous proline has been shown to improve water potential and leaf content, restoring water usage efficiency. It can also ease growth inhibition in salt-sensitive plants. Exogenously applied proline increases antioxidant activities and enhances plant salinity tolerance. This review examines the role and processes of proline in rice plants under salt stress and its relationship with other tolerance mechanisms.
Enhancing Docking Accuracy with PECAN2, a 3D Atomic Neural Network Trained without Co-Complex Crystal Structures
Authors: Shim Heesung , Allen Jonathan E. , Bennett W. F. Drew
Published: March 2024

Decades of drug development research have explored a vast chemical space for highly active compounds. The exponential growth of virtual libraries enables easy access to billions of synthesizable molecules. Computational modeling, particularly molecular docking, utilizes physics-based calculations to prioritize molecules for synthesis and testing. Nevertheless, the molecular docking process often yields docking poses with favorable scores that prove to be inaccurate with experimental testing. To address these issues, several approaches using machine learning (ML) have been proposed to filter incorrect poses based on the crystal structures. However, most of the methods are limited by the availability of structure data. Here, we propose a new pose classification approach, PECAN2 (Pose Classification with 3D Atomic Network 2), without the need for crystal structures, based on a 3D atomic neural network with Point Cloud Network (PCN). The new approach uses the correlation between docking scores and experimental data to assign labels, instead of relying on the crystal structures. We validate the proposed classifier on multiple datasets including human mu, delta, and kappa opioid receptors and SARS-CoV-2 Mpro. Our results demonstrate that leveraging the correlation between docking scores and experimental data alone enhances molecular docking performance by filtering out false positives and false negatives.
A Review of Cyclic Imines in Shellfish: Worldwide Occurrence, Toxicity and Assessment of the Risk to Consumers
Authors: Finch Sarah C. , Harwood D. Tim , Boundy Michael J. , Selwood Andrew I.
Published: March 2024

Cyclic imines are a class of lipophilic shellfish toxins comprising gymnodimines, spirolides, pinnatoxins, portimines, pteriatoxins, prorocentrolides, spiro-prorocentrimine, symbiomines and kabirimine. They are structurally diverse, but all share an imine moiety as part of a bicyclic ring system. These compounds are produced by marine microalgal species and are characterized by the rapid death that they induce when injected into mice. Cyclic imines have been detected in a range of shellfish species collected from all over the world, which raises the question as to whether they present a food safety risk. The European Food Safety Authority (EFSA) considers them to be an emerging food safety issue, and in this review, the risk posed by these toxins to shellfish consumers is assessed by collating all available occurrence and toxicity data. Except for pinnatoxins, the risk posed to human health by the cyclic imines appears low, although this is based on only a limited dataset. For pinnatoxins, two different health-based guidance values have been proposed at which the concentration should not be exceeded in shellfish (268 and 23 µg PnTX/kg shellfish flesh), with the discrepancy caused by the application of different uncertainty factors. Pinnatoxins have been recorded globally in multiple shellfish species at concentrations of up to 54 times higher than the lower guidance figure. Despite this observation, pinnatoxins have not been associated with recorded human illness, so it appears that the lower guidance value may be conservative. However, there is insufficient data to generate a more robust guidance value, so additional occurrence data and toxicity information are needed.
Antioxidant Activity, Inhibition of Intestinal Cancer Cell Growth and Polyphenolic Compounds of the Seagrass Posidonia oceanica’s Extracts from Living Plants and Beach Casts
Authors: Kevrekidou Alkistis , Assimopoulou Andreana N. , Trachana Varvara , Stagos Dimitrios , Malea Paraskevi
Published: March 2024

The aim of the present study was to investigate the use of Posidonia oceanica for making products beneficial for human health. Firstly, we demonstrated that the antioxidant defense (i.e., SOD and APX activity) of P. oceanica’s living leaves (LP) has low efficacy, as they partly neutralize the produced H2O2. However, high H2O2 levels led LP to produce, as a response to oxidative stress, high phenolic content, including chicoric acid, p-coumaric acid, caftaric acid, trans-cinnamic and rutin hydrate, as shown by UHPLC-DAD analysis. In addition, LP extracts inhibited intestinal cancer cell proliferation. Moreover, P. oceanica’s beach casts consisting of either Wet ‘Necromass’ (WNP) or Dry ‘Necromass’ (DNP) were used for preparing extracts. Both DNP and WNP exhibited antioxidant and antiproliferative activities, although lower as compared to those of LP extracts. Although both P. oceanica’s meadows and beach casts are considered priority habitats in the Mediterranean Sea due to their high ecological value, legislation framework for beach casts forbidding their removal is still missing. Our results suggested that both LP and DNP could be utilized for the production of high-added value products promoting human health, provided that a sustainability management strategy would be applied for P. oceanica’s meadows and beach casts.
Gross Taper Failure and Fracture of the True Neck in Total Hip Arthroplasty: Retrieval Scanning Electron Microscope Analysis
Authors: Ciatti Corrado , Moschella Michelangelo , Bori Edoardo , Doria Carlo , Caggiari Gianfilippo , Innocenti Bernardo , Pisanu Francesco
Published: March 2024

Background and objectives: wear and corrosion can lead to the gross failure of the Morse taper junction with the consequent fracture of the true neck of the prosthetic stem in hip arthroplasty. Materials and Methods: 58-year-old male patient, with a BMI of 38 kg/m2. Because of avascular necrosis, in 2007, a metal-on-metal total hip arthroplasty was implanted in him, with a TMZF stem and a Co-Cr head. In December 2020, he complained of acute left hip pain associated with the deterioration of his left leg and total functional impairment, preceded by the crunching of the hip. X-rays and CT scan showed a fracture of the prosthetic neck that necessitated prosthetic revision surgery. A Scanning Electron Microscope (SEM) analysis of the retrieved prosthetic components was conducted. Results: Macroscopically, the trunnion showed a typical bird beak appearance, due to a massive material loss of about half of its volume. The gross material loss apparently due to abrasion extended beyond the trunnion to the point of failure on the true neck about half a centimeter distal from the taper. SEM analysis demonstrated fatigue rupture modes, and the crack began close to the neck’s surface. On the lateral surface, several scratches were found, suggesting an intense wear that could be due to abrasion. Conclusions: The analysis we conducted on the explanted THA showed a ductile rupture, began close to the upper surface of the prosthetic neck where the presence of many scratches had concentrated stresses and led to a fatigue fracture.
Survival Analysis of Male Patients with Brain Metastases at Initial Breast Cancer Diagnosis over the Last Decade
Authors: Avila Jorge , Leone Julieta , Vallejo Carlos T. , Leone José P.
Published: March 2024

Breast cancer in men represents approximately 1% of all breast cancer diagnoses. Among all patients with breast cancer, approximately 30% will develop brain metastases. Over the past decade, there have been multiple advances in the treatment of metastatic breast cancer; however, long-term outcomes of this presentation in male patients are lacking. We evaluated male patients with de novo stage IV breast cancer using the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2019. Overall survival (OS) was estimated using the Kaplan–Meier method and differences between groups were compared using log rank tests. In total, 22 male patients with brain metastases at initial breast cancer diagnosis were included. Patients with HR-positive/HER2-negative tumors had the longest OS (median 13 months). Factors associated with shorter overall survival were advanced age, unmarried marital status, lower household income, and grade III disease, among others. Brain metastases remains an unmet medical need for patients with breast cancer; the development of new drugs may provide an improvement in overall survival for male patients in the future.
Evaluation of Oil-Absorbing Film for Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging (IDESI-MSI) on Biological Samples
Authors: Li Jiedong , Wei Ruolun , Meng Yifan , Zare Richard N.
Published: March 2024

Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging (IDESI-MSI) has proven to be a robust and reliable tool for chemically imaging biological samples such as fungi, animal tissues, and plants, but the choice of the imprint substrate is crucial. It must effectively transfer maximum amounts of species from the sample while preserving the original spatial distribution of detected molecules. In this study, we explored the potential of utilizing an oil-absorbing film, known for its soft nature and excellent lipophilicity, as an imprint substrate for IDESI-MSI on biological samples. To assess the transfer efficiency of the amounts of molecules and molecular patterns, we conducted experiments using mouse brain tissue. The result shows that more than 90% of the analytes can be transferred to the oil-absorbing film from the original tissue. A comparison of IDESI-MSI results between the oil-absorbing film and the original tissue demonstrates the material’s capability to transfer most molecules from the original tissue and retain images of different analytes with high spatial fidelity. We extended our investigation to plant imaging, where we applied IDESI-MSI to a cross-section of okra. The oil-absorbing film exhibited promise in this context as well. These findings suggest that IDESI-MSI utilizing the oil-absorbing film holds potential across various research fields, including biological metabolism, chemistry, and clinical research, making this technique widely applicable.
An Analytical Mechanics Model for the Rotary Sliding Triboelectric Nanogenerator
Authors: Gong Guangping , Zhang Maoyi , An Dongqi , Li Rui , Su Yewang
Published: March 2024

In recent years, global attention towards new energy has surged due to increasing energy demand and environmental concerns. Researchers have intensified their focus on new energy, leading to advancements in technologies like triboelectrification, which harnesses energy from the environment. The invention of the triboelectric nanogenerator (TENG) has led to new possibilities, with the rotary sliding TENG standing out for its superior performance. However, understanding its mechanical behavior remains a challenge, potentially leading to structural issues. This paper introduces a novel analytical mechanics model to analyze the mechanical performance of the stator of the rotary sliding TENG, offering a new analytical solution. The solution also presents an innovative approach to solving axisymmetric problems in elasticity theory since it challenges a traditional assumption that the stress function depends solely on the radial coordinate, proposing a new stress function to derive a more general solution, supplementing the classical approach in the theory of elasticity. Through the obtained solutions, the mechanical characteristics of the rotary sliding TENG during operation are analyzed. A clearer relationship between mechanical characteristics and electrical output is expected to provide a theoretical basis for the design of the rotary sliding TENG.
Comparison of Methodologies for Microplastic Isolation through Multicriteria Analysis (AHP)
Authors: Phinikettou Valentina , Papamichael Iliana , Voukkali Irene , Zorpas Antonis A.
Published: March 2024

Environmental pollution caused by microplastics has evolved into a global concern; however, limited knowledge exists about microplastics in soils due to the absence of standardized extraction methods. This research aimed to develop an inexpensive, rapid method with user-friendly and environmentally sustainable outcomes for microplastics retrieval. Three salt solutions (Sodium Chloride, Magnesium Sulfate, Sodium Hexametaphosphate) and an oil solution (canola oil) underwent evaluation for microplastics extraction through the flotation process due to the density and oleophilic properties of plastics. Four widely used plastic types, obtained through fragmentation using a grinding mill from clean new plastic containers or membranes, were subjected to analysis. The experimental procedures for microplastics retrieval varied among the evaluated solutions. Through a comprehensive multicriteria analysis, the saturated Sodium Chloride solution emerged as the optimal scenario for microplastics extraction, followed closely by the canola oil scenario. The recovery method utilizing Sodium Chloride demonstrated economic feasibility, safety, and reliability. This study provides valuable insights into an effective and sustainable approach for mitigating microplastic pollution in soil, offering a promising avenue for future environmental conservation efforts.
Efficient Zinc Vanadate Homojunction with Cadmium Nanostructures for Photocatalytic Water Splitting and Hydrogen Evolution
Authors: Hasan Imran , El Marghany Adel , Abduh Naaser A. Y. , Alharthi Fahad A.
Published: March 2024

Construction of a homojunction is an effective strategy for effective charge transfer to suppress charge carrier recombination in augmented photocatalysis. The present work reveals the synthesis of homojunction formation through the reinforcement of Cd nanostructures into a solid lattice of zinc vanadate (Zn3V2O8, ZnV) using the hydrothermal method. The formation of a homojunction between cadmium vanadate (CdV, Cd3V2O8) and ZnV was confirmed by various spectroscopic and electron microscopic techniques such as Fourier-transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) associated with energy-dispersive X-ray (EDX) mapping, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and ultraviolet–visible spectrophotometry (UV–Vis). The synthesized material was explored for photocatalytic hydrogen (PC H2) production using the water splitting process under visible-light illumination. The spectroscopic and experimental results revealed that the formation of a CdV/ZnV homojunction significantly improved the transport of photogenerated charge carriers (electron–hole pairs) and thus resulted in enhanced H2 production efficiency (366.34 μmol g−1 h−1) as compared to pristine ZnV (229.09 μmol g−1 h−1) and CdV (274.91 μmol g−1 h−1) using methanol as a sacrificial reagent (SR) with water under visible-light illumination. The synergistic effect of Cd on ZnV NPs resulted in band gap reduction and broadened visible light absorption which was attributed to enhanced H2 production. The current study explains how a homojunction affects various features of important factors behind photocatalytic activity, which supports significant insights into the advancement of materials in the future.
Exploring Borate-Modified Calcium Phosphate Ceramics: Antimicrobial Potential and Cytocompatibility Assessment
Authors: Fadeeva Inna V. , Barbaro Katia , Altigeri Annalisa , Forysenkova Anna A. , Gafurov Marat R. , Mamin Georgy V. , Knot’ko Alexander V. , Yankova Viktoriya G. , Zhukova Anna A. , Russo Fabrizio , Rau Julietta V.
Published: March 2024

Addressing periprosthetic infections, which present significant healing challenges that often require revision surgeries, necessitates the development of novel antibacterial materials and implants. Current research focuses on creating materials that hinder bacterial adhesion, colonization, and proliferation in surrounding tissues. Boron (B)-containing compounds are known for their antibacterial properties and potential in bone metabolism for regenerative medicine. In this study, we synthesized B-containing tricalcium phosphate (0.3B-TCP) with 1.1 wt.% B content via precipitation from aqueous solutions and sintering at 1100 °C. X-ray diffraction confirmed the ceramic’s primary crystalline phase as β-TCP, with B evenly distributed according to energy-dispersive spectroscopy data. Electron paramagnetic resonance (EPR) data verified stable paramagnetic borate anions, indicating successful BO33− substitution for phosphate groups. The microstructural properties of 0.3B-TCP ceramic were assessed before and after soaking in a saline solution. Its bending strength was approximately 30 MPa, and its porosity was about 33%. 0.3B-TCP ceramic demonstrated significant antimicrobial efficacy against various bacterial strains and a fungus. Cytotoxicity evaluation using equine adipose tissue-derived mesenchymal stem cells and osteogenic differentiation assessment were conducted. The combination of antibacterial efficacy and good cytocompatibility suggests 0.3B-TCP ceramic as a promising bone substitute material.
An Evaluation of the Effects of Pineapple-Extract and Bromelain-Based Treatment after Mandibular Third Molar Surgery: A Randomized Three-Arm Clinical Study
Authors: Colletti Alessandro , Procchio Chiara , Pisano Mariaelena , Martelli Alma , Pellizzato Marzia , Cravotto Giancarlo
Published: March 2024

A three-arm, randomized, placebo-controlled clinical study was conducted to assess the impact of lyophilized pineapple extract with titrated bromelain (Brome-Inf®) and purified bromelain on pain, swelling, trismus, and quality of life (QoL) following the surgical extraction of the mandibular third molars. Furthermore, this study examined the need for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) by comparing their effects with a placebo group. This study enrolled 42 individuals requiring the extraction of a single mandibular third molar under local anesthesia. The patients were randomly assigned to receive Brome-Inf®, purified bromelain, or a placebo orally, initiating treatment on the day of surgery and continuing for the next 7 days. The primary outcome measured was the requirement for NSAIDs in the three groups. Pain, swelling, and trismus were secondary outcome variables, evaluated postoperatively at 1, 3, and 7 days. This study also assessed the comparative efficacy of freeze-dried pineapple extract and single-component bromelain. Ultimately, the placebo group showed a statistically higher need for ibuprofen (from days 1 to 7) at the study’s conclusion (p < 0.0001). In addition, reductions in pain and swelling were significantly higher in both the bromelain and pineapple groups (p < 0.0001 for almost all patients, at all intervals) than in the placebo group. The active groups also demonstrated a significant difference in QoL compared to the placebo group (p < 0.001). A non-significant reduction in trismus occurred in the treatment groups compared to the placebo group. Therefore, the administration of pineapple extract titrated in bromelain showed significant analgesic and anti-edema effects in addition to improving QoL in the postoperative period for patients who had undergone mandibular third molar surgery. Moreover, both bromelain and Brome-Inf® supplementation reduced the need for ibuprofen to comparable extents, proving that they are good alternatives to NSAIDs in making the postoperative course more comfortable for these patients. A further investigation with larger samples is necessary to assess the pain-relieving and anti-inflammatory impacts of the entire pineapple phytocomplex in surgical procedures aside from mandibular third molar surgery.