bluuebunny/crossref_metadata_2025 huggingface dataset:
A Metabolite Perspective on the Involvement of the Gut Microbiota in Type 2 Diabetes
Authors: Fu Yifeng , Li Siying , Xiao Yunhua , Liu Gang , Fang Jun
Published: October 2023

Type 2 diabetes (T2D) is a commonly diagnosed condition that has been extensively studied. The composition and activity of gut microbes, as well as the metabolites they produce (such as short-chain fatty acids, lipopolysaccharides, trimethylamine N-oxide, and bile acids) can significantly impact diabetes development. Treatment options, including medication, can enhance the gut microbiome and its metabolites, and even reverse intestinal epithelial dysfunction. Both animal and human studies have demonstrated the role of microbiota metabolites in influencing diabetes, as well as their complex chemical interactions with signaling molecules. This article focuses on the importance of microbiota metabolites in type 2 diabetes and provides an overview of various pharmacological and dietary components that can serve as therapeutic tools for reducing the risk of developing diabetes. A deeper understanding of the link between gut microbial metabolites and T2D will enhance our knowledge of the disease and may offer new treatment approaches. Although many animal studies have investigated the palliative and attenuating effects of gut microbial metabolites on T2D, few have established a complete cure. Therefore, conducting more systematic studies in the future is necessary.
Zinc Oxide Nanoparticles Affect Early Seedlings’ Growth and Polar Metabolite Profiles of Pea (Pisum sativum L.) and Wheat (Triticum aestivum L.)
Authors: Stałanowska Karolina , Szablińska-Piernik Joanna , Okorski Adam , Lahuta Lesław B.
Published: October 2023

The growing interest in the use of zinc oxide nanoparticles (ZnO NPs) in agriculture creates a risk of soil contamination with ZnO NPs, which can lead to phytotoxic effects on germinating seeds and seedlings. In the present study, the susceptibility of germinating seeds/seedlings of pea and wheat to ZnO NPs of various sizes (≤50 and ≤100 nm) applied at concentrations in the range of 100–1000 mg/L was compared. Changes in metabolic profiles in seedlings were analyzed by GC and GC-MS methods. The size-dependent harmful effect of ZnO NPs on the seedling’s growth was revealed. The more toxic ZnO NPs (50 nm) at the lowest concentration (100 mg/L) caused a 2-fold decrease in the length of the wheat roots. In peas, the root elongation was slowed down by 20–30% only at 1000 mg/L ZnO NPs. The metabolic response to ZnO NPs, common for all tested cultivars of pea and wheat, was a significant increase in sucrose (in roots and shoots) and GABA (in roots). In pea seedlings, an increased content of metabolites involved in the aspartate–glutamate pathway and the TCA cycle (citrate, malate) was found, while in wheat, the content of total amino acids (in all tissues) and malate (in roots) decreased. Moreover, a decrease in products of starch hydrolysis (maltose and glucose) in wheat endosperm indicates the disturbances in starch mobilization.
GPER: An Estrogen Receptor Key in Metastasis and Tumoral Microenvironments
Authors: Tirado-Garibay Ana Carolina , Falcón-Ruiz Elba Andrea , Ochoa-Zarzosa Alejandra , López-Meza Joel E.
Published: October 2023

Estrogens and their role in cancer are well-studied, and some cancer types are classified in terms of their response to them. In recent years, a G protein-coupled estrogen receptor (GPER) has been described with relevance in cancer. GPER is a pleiotropic receptor with tissue-specific activity; in normal tissues, its activation is related to correct development and homeostasis, while in cancer cells, it can be pro- or anti-tumorigenic. Also, GPER replaces estrogen responsiveness in estrogen receptor alpha (ERα)-lacking cancer cell lines. One of the most outstanding activities of GPER is its role in epithelial–mesenchymal transition (EMT), which is relevant for metastasis development. In addition, the presence of this receptor in tumor microenvironment cells contributes to the phenotypic plasticity required for the dissemination and maintenance of tumors. These characteristics suggest that GPER could be a promising therapeutic target for regulating cancer development. This review focuses on the role of GPER in EMT in tumorigenic and associated cells, highlighting its role in relation to the main hallmarks of cancer and possible therapeutic options.
Frontotemporal Dementia P301L Mutation Potentiates but Is Not Sufficient to Cause the Formation of Cytotoxic Fibrils of Tau
Authors: Wang Kuang-Wei , Zhang Gary , Kuo Min-Hao
Published: October 2023

The P301L mutation in tau protein is a prevalent pathogenic mutation associated with neurodegenerative frontotemporal dementia, FTD. The mechanism by which P301L triggers or facilitates neurodegeneration at the molecular level remains unclear. In this work, we examined the effect of the P301L mutation on the biochemical and biological characteristics of pathologically relevant hyperphosphorylated tau. Hyperphosphorylated P301L tau forms cytotoxic aggregates more efficiently than hyperphosphorylated wildtype tau or unphosphorylated P301L tau in vitro. Mechanistic studies establish that hyperphosphorylated P301L tau exacerbates endoplasmic reticulum (ER) stress-associated gene upregulation in a neuroblastoma cell line when compared to wildtype hyperphosphorylated tau treatment. Furthermore, the microtubule cytoskeleton is severely disrupted following hyperphosphorylated P301L tau treatment. A hyperphosphorylated tau aggregation inhibitor, apomorphine, also inhibits the harmful effects caused by P301L hyperphosphorylated tau. In short, the P301L single mutation within the core repeat domain of tau renders the underlying hyperphosphorylated tau more potent in eliciting ER stress and cytoskeleton damage. However, the P301L mutation alone, without hyperphosphorylation, is not sufficient to cause these phenotypes. Understanding the conditions and mechanisms whereby selective mutations aggravate the pathogenic activities of tau can provide pivotal clues on novel strategies for drug development for frontotemporal dementia and other related neurodegenerative tauopathies, including Alzheimer’s disease.
Development of a Cytotoxic Antibody–Drug Conjugate Targeting Membrane Immunoglobulin E-Positive Cells
Authors: Rodak Aleksandra , Stadlbauer Katharina , Bobbili Madhusudhan Reddy , Smrzka Oskar , Rüker Florian , Wozniak Knopp Gordana
Published: October 2023

High numbers of membrane immunoglobulin E (IgE)-positive cells are characteristic of allergic conditions, atopic dermatitis, or IgE myeloma. Antibodies targeting the extracellular membrane-proximal domain of the membranous IgE-B-cell receptor (BCR) fragment can be used for specific depletion of IgE-BCR-positive cells. In this study, we derivatized such an antibody with a toxin and developed an antibody–drug conjugate (ADC) that showed strong cytotoxicity for an IgE-positive target cell line. Site-specific conjugation with maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl-monomethyl-auristatin E via a newly introduced single cysteine residue was used to prepare a compound with a drug–antibody ratio of 2 and favorable biophysical properties. The antibody was rapidly taken up by the target cells, showing almost complete internalization after 4 h of treatment. Its cytotoxic effect was potentiated upon cross-linking mediated by an anti-human IgG F(ab’)2 fragment. Because of its fast internalization and strict target specificity, this antibody–drug conjugate presents a valuable starting point for the further development of an anti-IgE cell-depleting agent, operating by the combined action of receptor cross-linking and toxin-mediated cytotoxicity.
FGF3 Directs the Pathfinding of Prethalamic GABAergic Axons
Authors: Huang Hong , Chen Qingyi , Xu Zhengang , Liu Fang
Published: October 2023

The thalamus plays a crucial role in ensuring the faithful transfer of sensory information, except olfactory signals, to corresponding cortical areas. However, thalamic function is not simply restricted to relaying information to and from the cerebral cortex. The ability to modulate the flow of sensory information is supported by a second abundant neuronal type in the prethalamus, the inhibitory gamma-aminobutyric acid (GABAergic) neurons, which project inhibitory GABAergic axons to dorsal thalamic glutamatergic neurons. Interestingly, during the trajectory of pioneer prethalamic axons, morphogen fibroblast growth factor (FGF)-3 is expressed in the ventral chick hypothalamus. Using in vitro analyses in chick explants, we identify a chemorepellent effect of FGF3 on nearby prethalamic GABAergic axons. Furthermore, inhibition of FGF3 guidance functions indicates that FGF3 signaling is necessary to navigate prethalamic axons correctly. Gene expression analyses and loss of function studies demonstrate that FGF3 mediates prethalamic axonal guidance through the downstream pathway of the FGF receptor (FGFR)-1. Together, these results suggest that FGF3 expressed in the hypothalamus functions as a chemorepellent molecule to direct the pathway selection of neighboring GABAergic axons.
Genome-Wide Identification and Characterization of WRKY Transcription Factors in Betula platyphylla Suk. and Their Responses to Abiotic Stresses
Authors: Yu Jiajie , Zhang Xiang , Cao Jiayu , Bai Heming , Wang Ruiqi , Wang Chao , Xu Zhiru , Li Chunming , Liu Guanjun
Published: October 2023

The WRKY transcription factor (TF) family is one the largest plant-specific transcription factor families. It has been proven to play significant roles in multiple plant biological processes, especially stress response. Although many WRKY TFs have been identified in various plant species, WRKYs in white birch (Betula platyphylla Suk.) remain to be studied. Here, we identified a total of 68 BpWRKYs, which could be classified into four main groups. The basic physiochemical properties of these TFs were analyzed using bioinformatics tools, including molecular weight, isoelectric point, chromosome location, and predicted subcellular localization. Most BpWRKYs were predicted to be located in the nucleus. Synteny analysis found 17 syntenic gene pairs among BpWRKYs and 52 syntenic gene pairs between BpWRKYs and AtWRKYs. The cis-acting elements in the promoters of BpWRKYs could be enriched in multiple plant biological processes, including stress response, hormone response, growth and development, and binding sites. Tissue-specific expression analysis using qRT-PCR showed that most BpWRKYs exhibited highest expression levels in the root. After ABA, salt (NaCl), or cold treatment, different BpWRKYs showed different expression patterns at different treatment times. Furthermore, the results of the Y2H assay proved the interaction between BpWRKY17 and a cold-responsive TF, BpCBF7. By transient expression assay, BpWRKY17 and BpWRKY67 were localized in the nucleus, consistent with the previous prediction. Our study hopes to shed light for research on WRKY TFs and plant stress response.
Fast and High-Efficiency Synthesis of Capsanthin in Pepper by Transient Expression of Geminivirus
Authors: Lin Zhimin , Ali Muhammad Moaaz , Yi Xiaoyan , Zhang Lijuan , Wang Shaojuan
Published: October 2023

The color of the chili fruit is an important factor that determines the quality of the chili, as red chilies are more popular among consumers. The accumulation of capsanthin is the main cause of reddening of the chili fruit. Capsanthin is an important metabolite in carotenoid metabolism, and its production level is closely linked to the expression of the genes for capsanthin/capsorubin synthase (CCS) and carotenoid hydroxylase (CrtZ). We reported for the first time that the synthesis of capsanthin in chili was enhanced by using a geminivirus (Bean Yellow Dwarf Virus). By expressing heterologous β-carotenoid hydroxylase (CrtZ) and β-carotenoid ketolase (CrtW) using codon optimization, the transcription level of the CCS gene and endogenous CrtZ was directly increased. This leads to the accumulation of a huge amount of capsanthin in a very short period of time. Our results provide a platform for the rapid enhancement of endogenous CCS activity and capsanthin production using geminivirus in plants.
Keras/TensorFlow in Drug Design for Immunity Disorders
Authors: Dragan Paulina , Joshi Kavita , Atzei Alessandro , Latek Dorota
Published: October 2023

Homeostasis of the host immune system is regulated by white blood cells with a variety of cell surface receptors for cytokines. Chemotactic cytokines (chemokines) activate their receptors to evoke the chemotaxis of immune cells in homeostatic migrations or inflammatory conditions towards inflamed tissue or pathogens. Dysregulation of the immune system leading to disorders such as allergies, autoimmune diseases, or cancer requires efficient, fast-acting drugs to minimize the long-term effects of chronic inflammation. Here, we performed structure-based virtual screening (SBVS) assisted by the Keras/TensorFlow neural network (NN) to find novel compound scaffolds acting on three chemokine receptors: CCR2, CCR3, and one CXC receptor, CXCR3. Keras/TensorFlow NN was used here not as a typically used binary classifier but as an efficient multi-class classifier that can discard not only inactive compounds but also low- or medium-activity compounds. Several compounds proposed by SBVS and NN were tested in 100 ns all-atom molecular dynamics simulations to confirm their binding affinity. To improve the basic binding affinity of the compounds, new chemical modifications were proposed. The modified compounds were compared with known antagonists of these three chemokine receptors. Known CXCR3 compounds were among the top predicted compounds; thus, the benefits of using Keras/TensorFlow in drug discovery have been shown in addition to structure-based approaches. Furthermore, we showed that Keras/TensorFlow NN can accurately predict the receptor subtype selectivity of compounds, for which SBVS often fails. We cross-tested chemokine receptor datasets retrieved from ChEMBL and curated datasets for cannabinoid receptors. The NN model trained on the cannabinoid receptor datasets retrieved from ChEMBL was the most accurate in the receptor subtype selectivity prediction. Among NN models trained on the chemokine receptor datasets, the CXCR3 model showed the highest accuracy in differentiating the receptor subtype for a given compound dataset.
A Catalog of Coding Sequence Variations in Salivary Proteins’ Genes Occurring during Recent Human Evolution
Authors: Di Pietro Lorena , Boroumand Mozhgan , Lattanzi Wanda , Manconi Barbara , Salvati Martina , Cabras Tiziana , Olianas Alessandra , Flore Laura , Serrao Simone , Calò Carla M. , Francalacci Paolo , Parolini Ornella , Castagnola Massimo
Published: October 2023

Saliva houses over 2000 proteins and peptides with poorly clarified functions, including proline-rich proteins, statherin, P-B peptides, histatins, cystatins, and amylases. Their genes are poorly conserved across related species, reflecting an evolutionary adaptation. We searched the nucleotide substitutions fixed in these salivary proteins’ gene loci in modern humans compared with ancient hominins. We mapped 3472 sequence variants/nucleotide substitutions in coding, noncoding, and 5′-3′ untranslated regions. Despite most of the detected variations being within noncoding regions, the frequency of coding variations was far higher than the general rate found throughout the genome. Among the various missense substitutions, specific substitutions detected in PRB1 and PRB2 genes were responsible for the introduction/abrogation of consensus sequences recognized by convertase enzymes that cleave the protein precursors. Overall, these changes that occurred during the recent human evolution might have generated novel functional features and/or different expression ratios among the various components of the salivary proteome. This may have influenced the homeostasis of the oral cavity environment, possibly conditioning the eating habits of modern humans. However, fixed nucleotide changes in modern humans represented only 7.3% of all the substitutions reported in this study, and no signs of evolutionary pressure or adaptative introgression from archaic hominins were found on the tested genes.
Blood-Based Transcriptomic Biomarkers Are Predictive of Neurodegeneration Rather Than Alzheimer’s Disease
Authors: Shvetcov Artur , Thomson Shannon , Spathos Jessica , Cho Ann-Na , Wilkins Heather M. , Andrews Shea J. , Delerue Fabien , Couttas Timothy A. , Issar Jasmeen Kaur , Isik Finula , Kaur Simranpreet , Drummond Eleanor , Dobson-Stone Carol , Duffy Shantel L. , Rogers Natasha M. , Catchpoole Daniel , Gold Wendy A. , Swerdlow Russell H. , Brown David A. , Finney Caitlin A.
Published: October 2023

Alzheimer’s disease (AD) is a growing global health crisis affecting millions and incurring substantial economic costs. However, clinical diagnosis remains challenging, with misdiagnoses and underdiagnoses being prevalent. There is an increased focus on putative, blood-based biomarkers that may be useful for the diagnosis as well as early detection of AD. In the present study, we used an unbiased combination of machine learning and functional network analyses to identify blood gene biomarker candidates in AD. Using supervised machine learning, we also determined whether these candidates were indeed unique to AD or whether they were indicative of other neurodegenerative diseases, such as Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Our analyses showed that genes involved in spliceosome assembly, RNA binding, transcription, protein synthesis, mitoribosomes, and NADH dehydrogenase were the best-performing genes for identifying AD patients relative to cognitively healthy controls. This transcriptomic signature, however, was not unique to AD, and subsequent machine learning showed that this signature could also predict PD and ALS relative to controls without neurodegenerative disease. Combined, our results suggest that mRNA from whole blood can indeed be used to screen for patients with neurodegeneration but may be less effective in diagnosing the specific neurodegenerative disease.
Graphitic Carbon Nitride/Zinc Oxide-Based Z-Scheme and S-Scheme Heterojunction Photocatalysts for the Photodegradation of Organic Pollutants
Authors: Panthi Gopal , Park Mira
Published: October 2023

Graphitic carbon nitride (g-C3N4), a metal-free polymer semiconductor, has been recognized as an attractive photocatalytic material for environmental remediation because of its low band gap, high thermal and photostability, chemical inertness, non-toxicity, low cost, biocompatibility, and optical and electrical efficiency. However, g-C3N4 has been reported to suffer from many difficulties in photocatalytic applications, such as a low specific surface area, inadequate visible-light utilization, and a high charge recombination rate. To overcome these difficulties, the formation of g-C3N4 heterojunctions by coupling with metal oxides has triggered tremendous interest in recent years. In this regard, zinc oxide (ZnO) is being largely explored as a self-driven semiconductor photocatalyst to form heterojunctions with g-C3N4, as ZnO possesses unique and fascinating properties, including high quantum efficiency, high electron mobility, cost-effectiveness, environmental friendliness, and a simple synthetic procedure. The synergistic effect of its properties, such as adsorption and photogenerated charge separation, was found to enhance the photocatalytic activity of heterojunctions. Hence, this review aims to compile the strategies for fabricating g-C3N4/ZnO-based Z-scheme and S-scheme heterojunction photocatalytic systems with enhanced performance and overall stability for the photodegradation of organic pollutants. Furthermore, with reference to the reported system, the photocatalytic mechanism of g-C3N4/ZnO-based heterojunction photocatalysts and their charge-transfer pathways on the interface surface are highlighted.
Aggregation, Transmission, and Toxicity of the Microtubule-Associated Protein Tau: A Complex Comprehension
Authors: Hu Jiaxin , Sha Wenchi , Yuan Shuangshuang , Wu Jiarui , Huang Yunpeng
Published: October 2023

The microtubule-associated protein tau is an intrinsically disordered protein containing a few short and transient secondary structures. Tau physiologically associates with microtubules (MTs) for its stabilization and detaches from MTs to regulate its dynamics. Under pathological conditions, tau is abnormally modified, detaches from MTs, and forms protein aggregates in neuronal and glial cells. Tau protein aggregates can be found in a number of devastating neurodegenerative diseases known as “tauopathies”, such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), corticobasal degeneration (CBD), etc. However, it is still unclear how the tau protein is compacted into ordered protein aggregates, and the toxicity of the aggregates is still debated. Fortunately, there has been considerable progress in the study of tau in recent years, particularly in the understanding of the intercellular transmission of pathological tau species, the structure of tau aggregates, and the conformational change events in the tau polymerization process. In this review, we summarize the concepts of tau protein aggregation and discuss the views on tau protein transmission and toxicity.
Multiple Sclerosis-Associated Gut Microbiome in the Israeli Diverse Populations: Associations with Ethnicity, Gender, Disability Status, Vitamin D Levels, and Mediterranean Diet
Authors: Nitzan Zehavit , Staun-Ram Elsebeth , Volkowich Anat , Miller Ariel
Published: October 2023

Microbiome dysbiosis is increasingly being recognized as implicated in immune-mediated disorders including multiple sclerosis (MS). The microbiome is modulated by genetic and environmental factors including lifestyle, diet, and drug intake. This study aimed to characterize the MS-associated gut microbiome in the Israeli populations and to identify associations with demographic, dietary, and clinical features. The microbiota from 57 treatment-naive patients with MS (PwMS) and 43 age- and gender-matched healthy controls (HCs) was sequenced and abundance compared. Associations between differential microbes with demographic or clinical characteristics, as well as diet and nutrient intake, were assessed. While there was no difference in α- or β-diversity of the microbiome, we identified 40 microbes from different taxonomic levels that differ in abundance between PwMS and HCs, including Barnesiella, Collinsella, Egerthella, Mitsuokella, Olsenella Romboutsia, and Succinivibrio, all enhanced in PwMS, while several members of Lacnospira were reduced. Additional MS-differential microbes specific to ethnicity were identified. Several MS-specific microbial patterns were associated with gender, vitamin D level, Mediterranean diet, nutrient intake, or disability status. Thus, PwMS have altered microbiota composition, with distinctive patterns related to geographic locations and population. Microbiome dysbiosis seem to be implicated in disease progression, gender-related differences, and vitamin D-mediated immunological effects recognized in MS. Dietary interventions may be beneficial in restoring a “healthy microbiota” as part of applying comprehensive personalized therapeutic strategies for PwMS.
The MADF-BESS Protein CP60 Is Recruited to Insulators via CP190 and Has Redundant Functions in Drosophila
Authors: Melnikova Larisa , Molodina Varvara , Babosha Valentin , Kostyuchenko Margarita , Georgiev Pavel , Golovnin Anton
Published: October 2023

Drosophila CP190 and CP60 are transcription factors that are associated with centrosomes during mitosis. CP190 is an essential transcription factor and preferentially binds to housekeeping gene promoters and insulators through interactions with architectural proteins, including Su(Hw) and dCTCF. CP60 belongs to a family of transcription factors that contain the N-terminal MADF domain and the C-terminal BESS domain, which is characterized by the ability to homodimerize. In this study, we show that the conserved CP60 region adjacent to MADF is responsible for interacting with CP190. In contrast to the well-characterized MADF-BESS transcriptional activator Adf-1, CP60 is recruited to most chromatin sites through its interaction with CP190, and the MADF domain is likely involved in protein–protein interactions but not in DNA binding. The deletion of the Map60 gene showed that CP60 is not an essential protein, despite the strong and ubiquitous expression of CP60 at all stages of Drosophila development. Although CP60 is a stable component of the Su(Hw) insulator complex, the inactivation of CP60 does not affect the enhancer-blocking activity of the Su(Hw)-dependent gypsy insulator. Overall, our results indicate that CP60 has an important but redundant function in transcriptional regulation as a partner of the CP190 protein.
Customer Shopping Behavior Analysis Using RFID and Machine Learning Models
Authors: Alfian Ganjar , Octava Muhammad Qois Huzyan , Hilmy Farhan Mufti , Nurhaliza Rachma Aurya , Saputra Yuris Mulya , Putri Divi Galih Prasetyo , Syahrian Firma , Fitriyani Norma Latif , Atmaji Fransiskus Tatas Dwi , Farooq Umar , Nguyen Dat Tien , Syafrudin Muhammad
Published: October 2023

Analyzing customer shopping habits in physical stores is crucial for enhancing the retailer–customer relationship and increasing business revenue. However, it can be challenging to gather data on customer browsing activities in physical stores as compared to online stores. This study suggests using RFID technology on store shelves and machine learning models to analyze customer browsing activity in retail stores. The study uses RFID tags to track product movement and collects data on customer behavior using receive signal strength (RSS) of the tags. The time-domain features were then extracted from RSS data and machine learning models were utilized to classify different customer shopping activities. We proposed integration of iForest Outlier Detection, ADASYN data balancing and Multilayer Perceptron (MLP). The results indicate that the proposed model performed better than other supervised learning models, with improvements of up to 97.778% in accuracy, 98.008% in precision, 98.333% in specificity, 98.333% in recall, and 97.750% in the f1-score. Finally, we showcased the integration of this trained model into a web-based application. This result can assist managers in understanding customer preferences and aid in product placement, promotions, and customer recommendations.
The Importance of Being Casiopeina as Polypharmacologycal Profile (Mixed Chelate–Copper (II) Complexes and Their In Vitro and In Vivo Activities)
Authors: Aguilar-Jiménez Zenayda , Espinoza-Guillén Adrián , Resendiz-Acevedo Karen , Fuentes-Noriega Inés , Mejía Carmen , Ruiz-Azuara Lena
Published: October 2023

In this review, we present a timeline that shows the origin of mixed chelate copper (II) complexes, registered as Mark Title Casiopeínas®, as the first copper (II) compounds proposed as anticancer drugs in 1988 and 1992. In the late twentieth century, the use of essential metals as anticancer agents was not even considered, except for their antifungal or antibacterial effects; also, copper, as gold salts, was used for arthritis problems. The use of essential metals as anticancer drugs to diminish the secondary toxic effects of Cisplatin was our driving force: to find less toxic and even more economical compounds under the rational design of metal chelate complexes. Due to their chemical properties, copper compounds were the choice to continue anticancer drug development. In this order of ideas, the rational designs of mixed chelate–copper (II) complexes (Casiopeínas, (Cas) homoleptic or heteroleptic, depending on the nature of the secondary ligand) were synthesized and fully characterized. In the search for new, more effective, and less toxic drugs, Casiopeína® (Cas) emerged as a family of approximately 100 compounds synthesized from coordinated Cu(II) complexes with proven antineoplastic potential through cytotoxic action. The Cas have the general formula [Cu(N–N)(N–O)]NO3 and [Cu(N–N)(O–O)]NO3, where N–N is an aromatic substituted diimine (1,10-phenanthroline or 2,2′-bipyridine), and the oxygen donor (O–O) is acetylacetonate or salicylaldehyde. Lately, some similar compounds have been developed by other research groups considering a similar hypothesis after Casiopeína’s discoveries had been published, as described herein. As an example of translational medicine criteria, we have covered each step of the established normative process for drug development, and consequently, one of the molecules (Casiopeína III ia (CasIIIia)) has reached the clinical phase I. For these copper compounds, other activities, such as antibacterial, antiparasitic and antiviral, have been discovered.
Application of AI-Based Techniques on Moody’s Diagram for Predicting Friction Factor in Pipe Flow
Authors: Mishra Ritusnata , Ojha Chandra Shekhar Prasad
Published: October 2023

The friction factor is a widely used parameter in characterizing flow resistance in pipes and open channels. Recently, the application of machine learning and artificial intelligence (AI) has found several applications in water resource engineering. With this in view, the application of artificial intelligence techniques on Moody’s diagram for predicting the friction factor in pipe flow for both transition and turbulent flow regions has been considered in the present study. Various AI methods, like Random Forest (RF), Random Tree (RT), Support Vector Machine (SVM), M5 tree (M5), M5Rules, and REPTree models, are applied to predict the friction factor. While performing the statistical analysis (root-mean-square error (RMSE), mean absolute error (MAE), squared correlation coefficient (R2), and Nash–Sutcliffe efficiency (NSE)), it was revealed that the predictions made by the Random Forest model were the most reliable when compared to other AI tools. The main objective of this study was to highlight the limitations of artificial intelligence (AI) techniques when attempting to effectively capture the characteristics and patterns of the friction curve in certain regions of turbulent flow. To further substantiate this behavior, the conventional algebraic equation was used as a benchmark to test how well the current AI tools work. The friction factor estimates using the algebraic equation were found to be even more accurate than the Random Forest model, within a relative error of ≤±1%, in those regions where the AI models failed to capture the nature and variation in the friction factor.
A Review of Optimization and Measurement Techniques of the Friction Stir Welding (FSW) Process
Authors: Prabhakar D. A. P. , Korgal Akash , Shettigar Arun Kumar , Herbert Mervin A. , Chandrashekharappa Manjunath Patel Gowdru , Pimenov Danil Yurievich , Giasin Khaled
Published: October 2023

This review reports on the influencing parameters on the joining parts quality of tools and techniques applied for conducting process analysis and optimizing the friction stir welding process (FSW). The important FSW parameters affecting the joint quality are the rotational speed, tilt angle, traverse speed, axial force, and tool profile geometry. Data were collected corresponding to different processing materials and their process outcomes were analyzed using different experimental techniques. The optimization techniques were analyzed, highlighting their potential advantages and limitations. Process measurement techniques enable feedback collection during the process using sensors (force, torque, power, and temperature data) integrated with FSW machines. The use of signal processing coupled with artificial intelligence and machine learning algorithms produced better weld quality was discussed.
Dynamic Multi-Period Maritime Accident Susceptibility Assessment Based on AIS Data and Random Forest Model
Authors: Zhu Weihua , Wang Shoudong , Liu Shengli , Yang Libo , Zheng Xinrui , Li Bohao , Zhang Lixiao
Published: October 2023

Maritime accidents, such as ship collisions and oil spills, directly affect maritime transportation, pollute the water environment, and indirectly threaten life and property safety. Predicting the maritime accident susceptibility and taking measures in advance can effectively avoid the accident probability and reduce the risk. Therefore, this study established dynamic multi-period (monthly, yearly, and five-yearly) maritime accident prediction models based on the random forest (RF) algorithm and Automatic Identification System (AIS) data for susceptibility assessment. First, based on historical maritime accidents and influencing factor data, we generated the feature matrixes and selected the conditioning factors using the Pearson correlation coefficient. Then, we constructed the accident susceptibility models using the RF method and evaluated the model performances based on the accuracy, recall, precision, F1-measure, ROC, and AUC values. Finally, we developed accident susceptibility maps for different period scales. The results show that the monthly, yearly, and five-yearly models performed well according to the validation values. And the three-period susceptibility maps show similar patterns. The high-susceptibility areas are close to the shore, especially from the Shanghai shore to the Guangxi shore. In addition, the ship density and bathymetry are the most critical factors among the ten influencing factors in the three models, contributing around 25% and 20% of the total information. These models and maps can provide technological support for maritime accident susceptibility assessment on a multi-period scale, which can be helpful for route planning and resource allocation in marine management.
Psychodynamic Therapies for the Treatment of Substance Addictions: A PRISMA Meta-Analysis
Authors: Zuccon Marco , Topino Eleonora , Musetti Alessandro , Gori Alessio
Published: October 2023

The aim of this meta-analysis was to compare psychodynamic with other treatments in studies of substance addiction. The literature search was conducted using the PubMed, Web of Science, Cohcrane library, SCOPUS, and Onesearch databases. All studies comparing psychodynamic therapy with other types of psychological interventions for Substance Use Disorder were eligible. Three outcomes were considered to compare intervention performance: substance use, participation in treatment and other symptomatic conditions (OSCs). Hedges’ G was used to measure effect size. The Revised Cochrane Risk of Bias tool for randomized trials was used to assess quality of evidence and possible bias, Egger regression analyses for publication bias, and Q and I-square statistics were used to assess heterogeneity. The alcohol group showed no differences between treatments on the three outcomes. The cocaine group showed no significant differences in the two outcomes, while for OSCs, available data was insufficient. The opioids group showed small but significant differences regarding participation in favor of non-psychodynamic interventions and no significant results for other outcomes. Based on the three measures of recovery considered in this meta-analysis, psychodynamic interventions were shown to be as effective as other psychological treatments in treating substance dependence and proved to be an empirically-supported treatment for the above addictions.
A Multi-Hazard Risk Assessment Framework for Urban Disaster Prevention Planning: A Case Study of Xiamen, China
Authors: Zhou Shutian , Zhai Guofang
Published: October 2023

Understanding and measuring the relative risk level of a city facing multi-hazards is fundamental to improving its disaster prevention planning and schemes. A comprehensive risk evaluation approach stands at the intersection of risk management and disaster system theory. It is also an important interdisciplinary field of catastrophology, economics, and urban infrastructure planning. We believe that current attempts to define and measure comprehensive urban natural disaster risks have certain limitations. Therefore, we propose an Urban Multi-hazards Risk Assessment Framework (UMRAF) which draws on definitions, methods, and experience from risk management, evaluation of property, the value of statistical life, and disaster system theory. It contains local disaster identification, place-based risk assessment (taking into account more than one hazard at a time), urban anti-disaster capability assessment, and relative composite risk index measurement. In our case study of Xiamen, China, to check the feasibility of our UMRAF, we examined local multi-hazards risk distribution and urban anti-disaster capacity layout. We then expanded and visualised the spatial distribution of the relative composite risk index of each evaluation unit across the city via our analyst tool, thereby helping to tailor measures that can reduce risk at a local level.
Mapping Urban Structure Types Based on Remote Sensing Data—A Universal and Adaptable Framework for Spatial Analyses of Cities
Authors: Braun Andreas , Warth Gebhard , Bachofer Felix , Schultz Michael , Hochschild Volker
Published: October 2023

In the face of growing 21st-century urban challenges, this study emphasizes the role of remote sensing data in objectively defining urban structure types (USTs) based on morphology. While numerous UST delineation approaches exist, few are universally applicable due to data constraints or impractical class schemes. This article attempts to tackle this challenge by summarizing important approaches dealing with the computation of USTs and to condense their contributions to the field of research within a single comprehensive framework. Hereby, this framework not only serves as a conjunctive reference for currently existing implementations, but is also independent regarding the input data, spatial scale, or targeted purpose of the mapping. It consists of four major steps: (1) the collection of suitable data sources to describe the building morphology as a key input, (2) the definition of a spatial mapping unit, (3) the parameterization of the mapping units, and (4) the final classification of the mapping units into urban structure types. We outline how these tasks can lead to a UST classification which fits the users’ needs based on their available input data. At the same time, the framework can serve as a protocol for future studies where USTs are mapped, or new approaches are presented. This article closes with an application example for three different cities to underline the flexibility and applicability of the proposed framework while maintaining maximized objectivity and comparability. We recommend this framework as a guideline for the use-specific mapping of USTs and hope to contribute to past and future research on this topic by fostering the implementation of this concept for the spatial analysis and a better understanding of complex urban environments.
Root-Knot-Nematode-Encoded CEPs Increase Nitrogen Assimilation
Authors: Mishra Shova , Hu Weiming , DiGennaro Peter
Published: October 2023

C-terminally encoded peptides (CEPs) are plant developmental signals that regulate growth and adaptive responses to nitrogen stress conditions. These small signal peptides are common to all vascular plants, and intriguingly have been characterized in some plant parasitic nematodes. Here, we sought to discover the breadth of root-knot nematode (RKN)-encoded CEP-like peptides and define the potential roles of these signals in the plant–nematode interaction, focusing on peptide activity altering plant root phenotypes and nitrogen uptake and assimilation. A comprehensive bioinformatic screen identified 61 CEP-like sequences encoded within the genomes of six root-knot nematode (RKN; Meloidogyne spp.) species. Exogenous application of an RKN CEP-like peptide altered A. thaliana and M. truncatula root phenotypes including reduced lateral root number in M. truncatula and inhibited primary root length in A. thaliana. To define the role of RKN CEP-like peptides, we applied exogenous RKN CEP and demonstrated increases in plant nitrogen uptake through the upregulation of nitrate transporter gene expression in roots and increased 15N/14N in nematode-formed root galls. Further, we also identified enhanced nematode metabolic processes following CEP application. These results support a model of parasite-induced changes in host metabolism and inform endogenous pathways to regulate plant nitrogen assimilation.
Penetrating Offenders in Hemifacial Spasm: Surgical Tactics and Prognosis
Authors: Lee Hyun-Seok , Park Kwan
Published: October 2023

(1) Background: In cases of hemifacial spasm (HFS), there are various patterns related to the vascular compression of the facial nerve, including a very rare form that is seen when the offending vessel penetrates the facial nerve. However, there have been few reports in the literature regarding the associated surgical techniques and postoperative prognosis. (2) Methods: A retrospective review was conducted of 4755 patients who underwent microvascular decompression (MVD) surgery from April 1997 to June 2023. In total, 8 out of the 4755 patients (0.2%) exhibited a penetrating offending vessel; the medical and surgical records of these 8 patients were then analyzed. Surgery was then attempted to maximally decompress the penetrating offender. (3) Results: Seven out of the eight patients (87.5%) were spasm-free immediately after surgery, and one had only 10% residual spasm compared to their preoperative condition. That patient was also spasm-free one year later. Postoperative facial palsy occurred in one patient (12.5%) who was assessed as grade II in the House–Brackmann grading system. In another patient, the resection of a small facial nerve bundle did not result in facial palsy. There were no cases of hearing loss or other complications. (4) Conclusions: Decompressing the penetrating offender did not increase the incidence of facial palsy, and the prognosis for hemifacial spasms was good. Therefore, when a penetrating pattern was encountered during MVD surgery, decompression between the penetrating offender and the facial nerve may offer good results.
(2aR,2a1S,5aR,9bR)-4-Isopropyl-7,8-dimethoxy-2a1-methyl-2,2a,2a1,3,5a,9b-hexahydrofluoreno[9,1-bc]furan
Authors: Ilyina Irina V. , Li-Zhulanov Nikolai S. , Gatilov Yuri V. , Volcho Konstantin P. , Sidorenko Alexander Yu. , Agabekov Vladimir E. , Salakhutdinov Nariman F.
Published: October 2023

The development of highly efficient methods for the synthesis of chemical products by using renewable raw materials is one of the topical areas of medicinal chemistry. The paper presents the synthesis of (2aR,2a1S,5aR,9bR)-4-isopropyl-7,8-dimethoxy-2a1-methyl-2,2a,2a1,3,5a,9b-hexahydrofluoreno[9,1-bc]furan. The title compound was obtained through Prins–Friedel–Crafts cascade reactions of trans-4-hydroxymethyl-2-carene, which was synthesized from 3-carene, one of the main components of gum turpentine. The product yield after purification was 48%. The compound’s structure was confirmed by X-ray diffraction analysis.
Potassium 6-Oxo-7,13,16,22-tetraazatetracyclo[12.6.2.18,12.017,21]tricosa-1(20),8(23),9,11,14,16,18,21-octaen-2-yne-15-carboxylate
Authors: Blouet Camille , Letast Stéphanie , Robert Thomas , Bach Stéphane , Pinaud Noël , Joubert Nicolas , Viaud-Massuard Marie-Claude , Guillon Jean , Logé Cédric , Denevault-Sabourin Caroline
Published: October 2023

Potassium 6-oxo-7,13,16,22-tetraazatetracyclo[12.6.2.18,12.017,21]tricosa-1(20),8(23),9,11,14,16,18,21-octaen-2-yne-15-carboxylate was synthesized through a multi-step pathway, starting from commercially available 3-iodo-1,2-phenylenediamine. Structure characterization of this new substituted macrocyclic quinoxaline compound was achieved using 1H NMR, 13C NMR, and HRMS spectral analysis. This new macrocyclic derivative demonstrated submicromolar potency on both Pim-1 and Pim-2 isoforms, with an interesting selectivity profile against a selected panel of human kinases.
3D Composite U(VI) Adsorbents Based on Alginate Hydrogels and Oxidized Biochar Obtained from Luffa cylindrica
Authors: Ayiotis Andreas , Georgiou Efthalia , Ioannou Panagiotis S. , Pashalidis Ioannis , Krasia-Christoforou Theodora
Published: October 2023

3D naturally derived composites consisting of calcium alginate hydrogels (CA) and oxidized biochar obtained from Luffa cylindrica (ox-LC) were synthesized and further evaluated as adsorbents for the removal of U(VI) from aqueous media. Batch-type experiments were conducted to investigate the effect of various physicochemical parameters on the adsorption performance of materials. The maximum adsorption capacity (qmax) was 1.7 mol kg−1 (404.6 mg·g−1) at pH 3.0 for the CA/ox-LC with a 10% wt. ox-LC content. FTIR spectroscopy indicated the formation of inner-sphere complexes between U(VI) and the surface-active moieties existing on both CA and ox-LC, while thermodynamic data revealed that the adsorption process was endothermic and entropy-driven. The experimental data obtained from the adsorption experiments were well-fitted by the Langmuir and Freundlich models. Overall, the produced composites exhibited enhanced adsorption efficiency against U(VI), demonstrating their potential use as effective adsorbents for the recovery of uranium ions from industrial effluents and seawater.
An Improved Grain Growth Model and Its Application in Gradient Heat Treatment of Aero-Engine Turbine Discs
Authors: Liu Zhaofeng , Wang Chao , Cheng Junyi , Guo Jianzheng
Published: October 2023

A new grain growth model was developed by introducing the ultimate grain size to the traditional model. The grain growth behavior and its ultimate size under the Zenner pinning force are also discussed. This model was applied to the nickel-based superalloy and integrated into an FEM code. The grain evolution of a forged third-generation powder superalloy heat treated at different temperatures and holding times was studied. A gradient heat treatment setup was designed and implemented for a full-size turbine disc based on the model prediction to meet the accurate dual-microstructure requirements of an advanced aero-engine turbine disc design. The predicted temperature was validated by thermal couple measurements. The relative error between the prediction and the measurements is less than 2%. The metallographic examination of the whole turbine disk through sectioning showed that the grain size was ASTM 7-8 at the rim area and ASTM 11-12 at the bore region, which agrees well with the prediction. The predicted values of the three measurement areas are ASTM 12.1, ASTM 9.1, and ASTM 7.1, respectively, with a maximum error of 5% compared to the measured values. The proposed model was validated and successfully applied to help manufacture a dual-microstructure aero-engine turbine disc.