bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Recycling Antibodies: Crovalimab’s Molecular Design Enables Four-Weekly Subcutaneous Injections for PNH Treatment
Authors: Sampei Zenjiro , Haraya Kenta , Gan Siok Wan , Muraoka Masaru , Hayasaka Akira , Fukuzawa Taku , Shida-Kawazoe Meiri , Tsuboi Yoshinori , Gotoh Akihiko , Obara Naoshi , Ueda Yasutaka
Published: October 2024

The advent of recycling antibodies, leveraging pH-dependent antigen binding and optimized FcRn interaction, has advanced the field of antibody therapies, enabling extended durability and reduced dosages. Eculizumab (Soliris®) demonstrated the efficacy of C5 inhibitors for paroxysmal nocturnal hemoglobinuria (PNH), while its derivative, ravulizumab (Ultomiris®), recognized as a recycling antibody, extended the dosing intervals. However, limitations including intravenous administration and inefficacy in patients with the R885H single-nucleotide polymorphism (SNP) in C5 could necessitate alternative solutions. Crovalimab (PiaSky®), a next-generation recycling antibody, overcomes these challenges with innovative charge engineering, achieving the enhanced cellular uptake of C5–crovalimab complexes and targeting a unique C5 epitope, allowing for efficacy regardless of the R885H SNP. This study highlights crovalimab’s distinctive molecular features, showing its eliminated binding to Fcγ receptors and C1q, alongside its optimized antigen binding characteristics. The impact of charge engineering was reconfirmed in mice, demonstrating faster C5 clearance than recycling antibodies. Notably, in the maintenance dosing regimen, crovalimab neutralizes approximately seven C5 molecules per antibody on average. Furthermore, its design also reduces the viscosity to facilitate high-concentration formulations suitable for subcutaneous delivery. Consequently, crovalimab offers a four-weekly subcutaneous injection regimen for PNH, marking a substantial improvement in treatment convenience and potentially transforming patients’ quality of life.
What Is a Biofilm? Lessons Learned from Interactions with Immune Cells
Authors: Krzyżek Paweł
Published: October 2024

Biofilms are unique, multicellular life forms that challenge our understanding of the microbial functioning. The last decades of research on biofilms have allowed us to better understand their importance in the context of both health and various pathologies in the human body, although many knowledge gaps hindering their correct comprehension still exist. Biofilms are classically described as mushroom-shaped structures attached to the substrate; however, an increasing body of evidence shows that their morphology in clinical conditions may differ significantly from that classically presented. Although this may result partly from the unique physicochemical conditions within the host, the interaction between microbes and immune cells during development of a biofilm should not be underestimated. The current Opinion confronts the classical view on biofilms with the latest scientific research describing the vitality of interactions with immune cells as a modulator of the biofilm phenotype and behavior in clinical conditions.
Novel Calcitonin Gene-Related Peptide (CGRP) Interfering Migraine Therapies and Stroke—A Review
Authors: Eller Michael Thomas , Frank Florian , Kaltseis Katharina , Karisik Anel , Knoflach Michael , Broessner Gregor
Published: October 2024

Migraine and stroke are neurological disorders with significant global prevalence and impact. Recent advances in migraine therapy have focused on the calcitonin gene-related peptide (CGRP) pathway. This review examines the shared pathomechanisms between migraine and stroke, with emphasis on the role of CGRP. We analyze the current literature on CGRP’s functions in cerebrovascular regulation, edema formation, neuroinflammation, and neuroprotection. CGRP acts as a potent vasodilator and plays a crucial role in trigeminovascular activation during migraine attacks. In stroke, CGRP has demonstrated neuroprotective effects by improving collateral circulation and reducing ischemia-reperfusion injury. Concerns have been raised about the potential impact of CGRP inhibitors on stroke risk and outcomes. Studies in animals suggest that CGRP receptor antagonists may worsen cerebral ischemia by impairing collateral flow. We discuss the implications of these findings for the use of CGRP-targeting therapies in migraine patients, especially those at increased risk of stroke. Additionally, we explore the complex interplay between CGRP, endothelial function, and platelet activity in both conditions. This review highlights the need for further research to elucidate the long-term cerebrovascular safety of CGRP pathway inhibitors and to identify potential subgroups of migraine patients who may be at higher risk of adverse cerebrovascular events with these novel therapies.
How Do Gepotidacin and Zoliflodacin Stabilize DNA Cleavage Complexes with Bacterial Type IIA Topoisomerases? 1. Experimental Definition of Metal Binding Sites
Authors: Morgan Harry , Nicholls Robert A. , Warren Anna J. , Ward Simon E. , Evans Gwyndaf , Long Fei , Murshudov Garib N. , Duman Ramona , Bax Benjamin D.
Published: October 2024

One of the challenges for experimental structural biology in the 21st century is to see chemical reactions happen. Staphylococcus aureus (S. aureus) DNA gyrase is a type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology. Drugs, such as gepotidacin, zoliflodacin and the quinolone moxifloxacin, can stabilize these normally transient DNA strand breaks and kill bacteria. Crystal structures of uncleaved DNA with a gepotidacin precursor (2.1 Å GSK2999423) or with doubly cleaved DNA and zoliflodacin (or with its progenitor QPT-1) have been solved in the same P61 space-group (a = b ≈ 93 Å, c ≈ 412 Å). This suggests that it may be possible to observe the two DNA cleavage steps (and two DNA-religation steps) in this P61 space-group. Here, a 2.58 Å anomalous manganese dataset in this crystal form is solved, and four previous crystal structures (1.98 Å, 2.1 Å, 2.5 Å and 2.65 Å) in this crystal form are re-refined to clarify crystal contacts. The structures clearly suggest a single moving metal mechanism—presented in an accompanying (second) paper. A previously published 2.98 Å structure of a yeast topoisomerase II, which has static disorder around a crystallographic twofold axis, was published as containing two metals at one active site. Re-refined coordinates of this 2.98 Å yeast structure are consistent with other type IIA topoisomerase structures in only having one metal ion at each of the two different active sites.
Amino Acid Compound 2 (AAC2) Treatment Counteracts Insulin-Induced Synaptic Gene Expression and Seizure-Related Mortality in a Mouse Model of Alzheimer’s Disease
Authors: Deng Zhijie , Lee Aejin , Lin Tao , Taneja Sagarika , Kowdley Devan , Leung Jacob H. , Hill Marykate , Tao Tianyi , Fitzgerald Julie , Yu Lianbo , Blakeslee Joshua J. , Townsend Kristy , Weil Zachary M. , Parquette Jon R. , Ziouzenkova Ouliana
Published: October 2024

Diabetes is a major risk factor for Alzheimer’s disease (AD). Amino acid compound 2 (AAC2) improves glycemic and cognitive functions in diabetic mouse models through mechanisms distinct from insulin. Our goal was to compare the effects of AAC2, insulin, and their nanofiber-forming combination on early asymptomatic AD pathogenesis in APP/PS1 mice. Insulin, but not AAC2 or the combination treatment (administered intraperitoneally every 48 h for 120 days), increased seizure-related mortality, altered the brain fat-to-lean mass ratio, and improved specific cognitive functions in APP/PS1 mice. NanoString and pathway analysis of cerebral gene expression revealed dysregulated synaptic mechanisms, with upregulation of Bdnf and downregulation of Slc1a6 in insulin-treated mice, correlating with insulin-induced seizures. In contrast, AAC2 promoted the expression of Syn2 and Syp synaptic genes, preserved brain composition, and improved survival. The combination of AAC2 and insulin counteracted free insulin’s effects. None of the treatments influenced canonical amyloidogenic pathways. This study highlights AAC2’s potential in regulating synaptic gene expression in AD and insulin-induced contexts related to seizure activity.
A Prospective Observational Study on Analyzing Lung Cancer Gene Mutation Variant Allele Frequency (VAF) and Its Correlation with Treatment Efficacy
Authors: Shinozaki Yusuke , Morikawa Kei , Kida Hirotaka , Handa Hiroshi , Saji Hisashi , Nakamura Seiji , Sato Yoshiharu , Ueda Yumi , Suzuki Fumihiko , Matoba Ryo , Mineshita Masamichi
Published: October 2024

A few studies have reported on the variability of the variant allele frequency (VAF) of gene mutations and the relationship between VAF and the therapeutic effect of molecular-targeted drugs. This joint study was conducted from May 2020 to January 2022 between St. Marianna University School of Medicine and the DNA Chip Research Institute. Cytology samples were used to verify the usefulness of a lung cancer compact panel test, which is a high-sensitivity next-generation sequencing (NGS) gene panel test. We analyzed the distribution of VAF and the duration of the initial molecular-targeted drug administration in patients with advanced-stage epidermal growth factor receptor (EGFR) mutations. Of the 196 patients diagnosed with non-small cell carcinoma (NSCLC), gene mutations were detected in 114 (58.2%) cases and in 68.7% of patients with adenocarcinomas (an increased detection rate). A VAF of 30% or more for DNA mutations was confirmed in 35 patients (33.7%), 10% to <30% in 38 (36.5%), and <10% in 31 (29.8%), including 18 patients (17.3%) with <6%, which is considered the lower limit of the LOD for other companion diagnostic kits. EGFR mutations were detected in 59 patients (30%), of whom 35 were in an advanced stage and received molecular-targeted drugs as their initial treatment. Groups A and B comprised patients with a VAF of ≥10% and <10%, respectively, with 27 patients (median VAF 30.6%, range 11.4–77%) in group A and 8 (median VAF 5.4%, range 0.1–8.5%) in group B. The duration of the administration of molecular-targeted drugs was 17 months (range 3–42 months) in group A and 14 months (range 1–45 months) in group B, with no statistically significant difference between the two groups (p-value = 0.7). Twenty-seven percent of patients had a VAF < 10%. Even in patients with a low VAF for gene mutations, sufficient therapeutic effects were observed with molecular-targeted drugs, suggesting the importance of detecting mutations using a highly sensitive method at initial diagnosis. Further prospective validation studies of a larger number of cases are warranted.
Asymmetric Synthesis and Biological Activity of Contact Pheromone of Western Flower Thrips, Frankliniella occidentalis
Authors: Lin Chuanwen , Zhu Wenya , Wu Shuai , Bian Qinghua , Zhong Jiangchun
Published: October 2024

Western flower thrips, Frankliniella occidentalis, is a serious worldwide pest of agriculture and horticulture, and its contact pheromone is 7-methyltricosane. Two enantiomers of 7-methyltricosane were synthesized for the first time. The centra of our strategy were chiral auxiliaries to introduce stereocenter, and Wittig coupling to connect two blocks. The overall yields of our synthesis were 29–30% with seven steps. The electroantennogram (EAG) and the contact behavioral responses revealed that (R)-, (S)- and racemic 7-methyltricosane were separately bioactive, and the racemate was the most bioactive in the male arrestant activity and the female EAG test. This result provides valuable insights, showing that the racemate could be used for the support of the control of western flower thrips, which could be more easily prepared relative to more expensive enantiopure pheromone.
Comprehensive Phytochemical Profiling of Ulva lactuca from the Adriatic Sea
Authors: Mutavski Zorana , Jerković Igor , Nikolić Nada Ćujić , Radman Sanja , Flanjak Ivana , Aladić Krunoslav , Šubarić Drago , Vulić Jelena , Jokić Stela
Published: October 2024

The potential of the green macroalga Ulva lactuca is increasingly recognized, not only for its environmental benefits, but also for its applications in various industries, including food, pharmaceuticals, and cosmetics. Given this insight, a comprehensive analysis of the chemical profile of U. lactuca from the Adriatic Sea was carried out. The hydrodistillate, rich in (Z,Z,Z)-hexadeca-7,10,13-trienal and hexadecanoic acid, underlines its importance for health-related uses, particularly in lipid metabolism and cellular integrity. Fatty acid analysis showed a predominance of palmitic acid and a favorable n-6/n-3 polyunsaturated fatty acid ratio, suggesting that U. lactuca can make a valuable contribution to a balanced diet. In addition, essential amino acids, including leucine, valine, and isoleucine, support its use as a functional ingredient for muscle repair and metabolic health. The ethanol extract contained 56 compounds, including derivatives of fatty acids, phenolic acids, pigments, flavonoids, and steroids. Many of them, such as hexadecasphinganine, azelaic acid, 5-sulfosalicylic acid, and pheophytin a, have proven roles or potentials in promoting human health. These results confirm that U. lactuca is a rich source of bioactive compounds, emphasizing its potential in scientific research and its expanding industrial applications in health, nutrition, and cosmetics.
Potential Anticancer Effects of Isoflavone Prunetin and Prunetin Glycoside on Apoptosis Mechanisms
Authors: Jeong Se Hyo , Kim Hun Hwan , Park Min Yeong , Bhosale Pritam Bhangwan , Abusaliya Abuyaseer , Hwang Kwang Hyun , Moon Yeon Gyu , Heo Jeong Doo , Seong Je Kyung , Ahn Meejung , Park Kwang Il , Won Chung Kil , Kim Gon Sup
Published: October 2024

Cancer is a deadly disease caused by cells that deviate from the normal differentiation and proliferation behaviors and continue to multiply. There is still no definitive cure, and many side effects occur even after treatment. However, apoptosis, one of the programs imprinted on cells, is becoming an important concept in controlling cancer. Flavonoids are polyphenolic compounds found in plants, are naturally bioactive compounds, have been studied for their anticancer effects, and have fewer side effects than chemical treatments. Isoflavones are phytoestrogens belonging to the flavonoid family, and this review discusses in depth the potential anticancer effects of prunetin, one of the many flavonoid families, via the apoptotic mechanism. In addition, a glycoside called prunetin glucoside has been investigated for its anticancer effects through apoptotic mechanisms. The primary intention of this review is to identify the effects of prunetin and its glycoside, prunetin glucoside, on cell death signaling pathways in various cancers to enhance the potential anticancer effects of these natural compounds.
Copy Number Variation and Selection Signal: Exploring the Domestication History and Phenotype Differences Between Duroc and the Chinese Native Ningxiang Pigs
Authors: Yang Fang , Chen Wenwu , Yang Yanda , Meng Yang , Chen Yantong , Ding Xiaoling , Zhang Yuebo , He Jun , Gao Ning
Published: October 2024

The Ningxiang pig, one of the well-known Chinese native pig breeds, has the advantages of tender meat, high intramuscular fat (IMF) content, and roughage tolerance, compared to the commercial lean pig breeds. The genetic basis for complex traits in Ningxiang pigs has been previously studied through other genetic markers, such as Single Nucleotide Polymorphism (SNP), while the characteristics of copy number variation (CNV) and the selection signal have not been investigated yet. In this study, GGP 50 k genotyping data of 2242 Ningxiang pigs (NX) and 1137 Duroc pigs (Duroc) were involved in CNV atlas construction and selection signals identification. Annotations of genes and quantitative trait locus (QTLs) were performed on the target candidate regions, as follows: (1) 162 CNVs were detected in Ningxiang pigs, while 326 CNVs were detected in Duroc pigs, and there are 21 copy number variation regions (CNVRs) shared between them; (2) The CNVRs of Duroc are more abundant, with 192 CNVRs, accounting for 1.61% of the entire genome, while those of Ningxiang pigs only have 98 CNVRs, accounting for 0.49%; (3) The QTLs annotated on CNVs and selected regions of Ningxiang pigs were mainly associated with meat quality and fertility. In contrast, the Duroc QTLs’ notes relate primarily to the carcass and immunity, and explain why they have a higher slaughter rate and immunity; (4) There is a presence of high-frequency acquired CNVs, specifically in Ningxiang pigs, with 24 genes significantly enriched in the sensory receptor-related pathway in this region; (5) Based on the CNVs atlas, candidate genes such as 3 inositol 1,4,5-triphosphate receptor, type 3 (ITPR3), forkhead box protein K2 (FOXK2), G-protein coupled estrogen receptor 1 (GPER1), Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), triosephosphate isomerase 1 (TPI1), and other candidate genes related to fat deposition and differentiation were screened. In general, this study improved our knowledge about copy number variation and selection signal information of Ningxiang pigs, which can not only further explain the genetic differences between Chinese native and Western commercial pig breeds, but also provide new materials for the analysis of the genetic basis of complex traits.
Developing Adventitious Root Meristems Induced by Layering for Plant Chromosome Preparation
Authors: Yan Xu , Wu Zizhou , Wang Honglin , Zuo Yanchun , Du Zhouhe
Published: October 2024

Chromosome numbers and morphology are important characteristics of a species and its evolution. Root tips are the most commonly used tissue as a source of actively dividing cells for chromosome visualization in plants. Previously, rapidly growing root tips were collected from germinating kernels or from seedlings growing in pots or fields. However, the use of adventitious roots (ARs) derived from aerial tissue as meristems for chromosome visualization has always been overlooked. Here, we successfully induced ARs in 12 materials that were investigated, with the exception of Sorghum nitidum. Using ARs meristem we obtained high-quality chromosome spreads for Morus alba, Broussonetia papyrifera, Lolium multiflorum, Sorghum sudanense, S. propinquum, S. bicolor × S. sudanense, Zea mays, Z. mexicana, Glycine max, Medicago sativa, and Brassica napus. The results reported here demonstrate that layering is an alternative and effective method for producing meristematic cells for high-quality chromosome preparation in plant species producing ARs. For species that produce ARs by layering, this protocol is particularly valuable for the development of cost-effective and high-throughput non-invasive cytogenetic studies.
High-Salt Diet Accelerates Neuron Loss and Anxiety in APP/PS1 Mice Through Serpina3n
Authors: Ma Kaige , Zhang Chenglin , Zhang Hanyue , An Chanyuan , Li Ge , Cheng Lixue , Li Mai , Ren Minghe , Bai Yudan , Liu Zichang , Ji Shengfeng , Liu Xiyue , Gao Jinman , Zhang Zhichao , Wu Xiaolin , Chen Xinlin
Published: October 2024

High salt (HS) consumption is an independent risk factor for neurodegenerative diseases such as dementia, stroke, and cerebral small vessel disease related to cognitive decline. Recently, Alzheimer’s disease-like pathology changes have been reported as consequences of a HS diet in wild-type (wt) mice. However, it has not been revealed how HS diets accelerate the progress of Alzheimer’s disease (AD) in APP/PS1 mice. Here, we fed APP/PS1 mice a HS diet or normal diet (ND) for six months; the effects of the HS/ND on wt mice were also observed. The results of our behavior test reveal that the HS diet exacerbates anxiety, β-amyloid overload, neuron loss, and synapse damage in the hippocampi of APP/PS1 mice; this was not observed in HS-treated wt mice. RNA sequencing shows that nearly all serpin family members were increased in the hippocampus of HS-treated APP/PS1 mice. Gene function analysis showed that a HS diet induces neurodegeneration, including axon dysfunction and neuro-ligand-based dysfunction, and regulates serine protein inhibitor activities. The mRNA and protein levels of Serpina3n were dramatically increased. Upregulated Serpina3n may be the key for β-amyloid aggregation and neuronal loss in the hippocampus of HS-treated APP/PS1 mice. Serpina3n inhibition attenuated the anxiety and increased the number of neurons in the hippocampal CA1(cornu ammonis) region of APP/PS1 mice. Our study provides novel insights into the mechanisms by which excessive HS diet deteriorates anxiety in AD mice. Therefore, decreasing daily dietary salt consumption constitutes a pivotal public health intervention for mitigating the progression of neuropathology, especially for old patients and those with neurodegenerative disease.
Trastuzumab-Mediated Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Enhances Natural Killer Cell Cytotoxicity in HER2-Overexpressing Ovarian Cancer
Authors: Hong Sa Deok , Katuwal Nar Bahadur , Kang Min Sil , Ghosh Mithun , Park Seong Min , Kim Tae Hoen , Baek Young Seok , Lee Seung Ryeol , Moon Yong Wha
Published: October 2024

Ovarian cancer is the deadliest gynecologic cancer. Although human epidermal growth factor receptor-2 (HER2) overexpression, a poor prognostic molecular marker in ovarian cancer, is found in almost 30% of ovarian cancer cases, there are no established therapies for HER2-overexpressing ovarian cancer. In this study, we investigated the efficacy of combined samfenet, a biosimilar compound of trastuzumab, and natural killer (NK) cells in preclinical model of HER2-overexpressing ovarian cancer. Firstly, we screened the HER2 expression in three ovarian cancer cell lines and eight ovarian cancer patient-derived tumor xenograft (PDTX) samples. Then, immunohistochemistry and silver in situ hybridization (SISH) were performed following clinical criteria. HER2-overexpressing cells exhibited the highest sensitivity to samfenet compared with low-HER2-expressing cells. In addition, the combination of samfenet with natural killer (NK) cells resulted in significantly enhanced sensitivity to HER2-overexpressing cells and showed a significant antitumor effect on PDTX mice compared with monotherapy. It is known that anti-HER2-humanized IgG1 monoclonal antibodies, including trastuzumab, induce antibody-dependent cellular cytotoxicity (ADCC). Consequently, the combination of samfenet with NK cells demonstrated NK cell-mediated ADCC, as confirmed using an in vitro NK cytotoxicity assay and in vivo antitumor efficacy. A transferase dUTP nick end labeling (TUNEL) assay using xenografted tumors further supported the ADCC effects based on the increase in the number of apoptotic cells in the combination group. Furthermore, high HER2 expression was associated with shorter progression-free survival and overall survival based on public mRNA expression data. In this study, we demonstrated that the combination of samfenet and NK cell therapy could be a promising treatment strategy for patients with HER2-overexpressing ovarian cancer, through ADCC effects. Therefore, this study supports a rationale for further clinical studies of the combination of samfenet and NK cells as a therapy for patients with HER2-overexpressing ovarian cancer.
Transcriptomic Response of Rhizobium leguminosarum to Acidic Stress and Nutrient Limitation Is Versatile and Substantially Influenced by Extrachromosomal Gene Pool
Authors: Żebracki Kamil , Koper Piotr , Wójcik Magdalena , Marczak Małgorzata , Mazur Andrzej
Published: October 2024

Multipartite genomes are thought to confer evolutionary advantages to bacteria by providing greater metabolic flexibility in fluctuating environments and enabling rapid adaptation to new ecological niches and stress conditions. This genome architecture is commonly found in plant symbionts, including nitrogen-fixing rhizobia, such as Rhizobium leguminosarum bv. trifolii TA1 (RtTA1), whose genome comprises a chromosome and four extrachromosomal replicons (ECRs). In this study, the transcriptomic responses of RtTA1 to partial nutrient limitation and low acidic pH were analyzed using high-throughput RNA sequencing. RtTA1 growth under these conditions resulted in the differential expression of 1035 to 1700 genes (DEGs), which were assigned to functional categories primarily related to amino acid and carbohydrate metabolism, ribosome and cell envelope biogenesis, signal transduction, and transcription. These results highlight the complexity of the bacterial response to stress. Notably, the distribution of DEGs among the replicons indicated that ECRs played a significant role in the stress response. The transcriptomic data align with the Rhizobium pangenome analysis, which revealed an over-representation of functional categories related to transport, metabolism, and regulatory functions on ECRs. These findings confirm that ECRs contribute substantially to the ability of rhizobia to adapt to challenging environmental conditions.
Progresses and Pitfalls of Epigenetics in Solid Tumors Clinical Trials
Authors: Rossi Alice , Zacchi Francesca , Reni Anna , Rota Michele , Palmerio Silvia , Menis Jessica , Zivi Andrea , Milleri Stefano , Milella Michele
Published: October 2024

Epigenetic dysregulation has long been recognized as a significant contributor to tumorigenesis and tumor maintenance, impacting all recognized cancer hallmarks. Although some epigenetic drugs have received regulatory approval for certain hematological malignancies, their efficacy in treating solid tumors has so far been largely disappointing. However, recent advancements in developing new compounds and a deeper understanding of cancer biology have led to success in specific solid tumor subtypes through precision medicine approaches. Moreover, epigenetic drugs may play a crucial role in synergizing with other anticancer treatments, enhancing the sensitivity of cancer cells to various anticancer therapies, including chemotherapy, radiation therapy, hormone therapy, targeted therapy, and immunotherapy. In this review, we critically evaluate the evolution of epigenetic drugs, tracing their development from initial use as monotherapies to their current application in combination therapies. We explore the preclinical rationale, completed clinical studies, and ongoing clinical trials. Finally, we discuss trial design strategies and drug scheduling to optimize the development of possible combination therapies.
Catalytic Behavior of NHC–Silver Complexes in the Carboxylation of Terminal Alkynes with CO2
Authors: D’Amato Assunta , Sirignano Marco , Viceconte Francesco , Longo Pasquale , Mariconda Annaluisa
Published: October 2024

A number of N-heterocyclic carbene–silver compounds (NHCs)AgX were tested in the direct carboxylation of terminal alkynes using carbon dioxide as the C1 carbon feedstock. The reactions proceed at a pressure of 1 atm of CO2 at room temperature, in the presence of Cs2CO3, and using silver–NHC complexes as catalysts. Thus, phenylacetylene and several alkynes are converted to the corresponding propiolic acids in good to high conversions. The activity of the catalysts is strongly influenced by the substituents on the NHC backbone and the nature of the counterion. Specifically, the most active compound exhibits iodide as the counterion and is stabilized by a benzimidazole derivative. After 24 h of reaction, a quantitative conversion is obtained utilizing DMF as the solvent and phenylacetylene as the substrate.
Numerical Analysis of the Bond Behaviour of High-Strength Concrete-Filled Steel Square Columns with Different Shear Connectors
Authors: Boudali Errebai Mouloud , Ihaddoudene Abd Nacer Touati , Saidani Messaoud
Published: October 2024

This paper deals with a numerical method of analysis of the performance of shear connectors in transferring load in high-strength concrete-filled steel tube square sections. The novelty of the model is that it considers all the important parameters that affect performance at once: bond strength, the transfer rate of each connector, and the stress distribution and deformation of each element. Four specimens fabricated using different types of connectors were validated using ABAQUS version 2017 software. The deformation of the connectors, concrete damage, and the local instability of the steel tube were extensively investigated. The main parameters considered were the ultimate bond strength and load transfer ratio. The shear connector arrangement consisting of four specimens, namely C1 with 16 studs, a circular rib (C2), a circular rib with 8 studs (C3), and a circular rib with 8 vertical ribs (C4), had a significant influence on the key parameters. Connectors C2, C3, and C4 transferred more than 80% of the total load. The circular rib was more effective in transferring the load and limiting slip than the vertical rib and the studs. The circular rib (C2) transferred the load mainly through the four corners. The deterioration of the concrete and local instability of the steel tube had complex deformations which were influenced by the geometry of the inserted connectors.
Unlocking Genome Editing: Advances and Obstacles in CRISPR/Cas Delivery Technologies
Authors: Kaupbayeva Bibifatima , Tsoy Andrey , Safarova (Yantsen) Yuliya , Nurmagambetova Ainetta , Murata Hironobu , Matyjaszewski Krzysztof , Askarova Sholpan
Published: October 2024

CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats associated with protein 9) was first identified as a component of the bacterial adaptive immune system and subsequently engineered into a genome-editing tool. The key breakthrough in this field came with the realization that CRISPR/Cas9 could be used in mammalian cells to enable transformative genetic editing. This technology has since become a vital tool for various genetic manipulations, including gene knockouts, knock-in point mutations, and gene regulation at both transcriptional and post-transcriptional levels. CRISPR/Cas9 holds great potential in human medicine, particularly for curing genetic disorders. However, despite significant innovation and advancement in genome editing, the technology still possesses critical limitations, such as off-target effects, immunogenicity issues, ethical considerations, regulatory hurdles, and the need for efficient delivery methods. To overcome these obstacles, efforts have focused on creating more accurate and reliable Cas9 nucleases and exploring innovative delivery methods. Recently, functional biomaterials and synthetic carriers have shown great potential as effective delivery vehicles for CRISPR/Cas9 components. In this review, we attempt to provide a comprehensive survey of the existing CRISPR-Cas9 delivery strategies, including viral delivery, biomaterials-based delivery, synthetic carriers, and physical delivery techniques. We underscore the urgent need for effective delivery systems to fully unlock the power of CRISPR/Cas9 technology and realize a seamless transition from benchtop research to clinical applications.
MIMO-Uformer: A Transformer-Based Image Deblurring Network for Vehicle Surveillance Scenarios
Authors: Zhang Jian , Cheng Baoping , Zhang Tengying , Zhao Yongsheng , Fu Tao , Wu Zijian , Tao Xiaoming
Published: October 2024

Motion blur is a common problem in the field of surveillance scenarios, and it obstructs the acquisition of valuable information. Thanks to the success of deep learning, a sequence of CNN-based architecture has been designed for image deblurring and has made great progress. As another type of neural network, transformers have exhibited powerful deep representation learning and impressive performance based on high-level vision tasks. Transformer-based networks leverage self-attention to capture the long-range dependencies in the data, yet the computational complexity is quadratic to the spatial resolution, which makes transformers infeasible for the restoration of high-resolution images. In this article, we propose an efficient transformer-based deblurring network, named MIMO-Uformer, for vehicle-surveillance scenarios. The distinct feature of the MIMO-Uformer is that the basic-window-based multi-head self-attention (W-MSA) of the Swin transformer is employed to reduce the computational complexity and then incorporated into a multi-input and multi-output U-shaped network (MIMO-UNet). The performance can benefit from the operation of multi-scale images by MIMO-UNet. However, most deblurring networks are designed for global blur, while local blur is more common under vehicle-surveillance scenarios since the motion blur is primarily caused by local moving vehicles. Based on this observation, we further propose an Intersection over Patch (IoP) factor and a supervised morphological loss to improve the performance based on local blur. Extensive experiments on a public and a self-established dataset are carried out to verify the effectiveness. As a result, the deblurring behavior based on PSNR is improved at least 0.21 dB based on GOPRO and 0.74 dB based on the self-established datasets compared to the existing benchmarks.
Distributed Neuroadaptive Formation Control for Aerial Base Station-Assisted Hovercraft Systems with Mixed Disturbances
Authors: Ye Peiyun , Yu Renhai , Shan Qihe
Published: October 2024

Effectively addressing the formation control of ABS-assisted hovercraft systems with heterogeneities, unavailable leaders’ convex combination states, nonlinearities, and mixed disturbances poses significant challenges. This paper proposes a distributed neuroadaptive formation tracking strategy of ABS-assisted hovercraft systems for the first time, where aerial base stations (ABSs) are composed of unmanned aerial vehicles (UAVs) for data distribution and computation offloading. Firstly, UAVs are designed to track the virtual-leader while shaping a fixed formation, and the observer is devised for each follower hovercraft to estimate the convex combination states of UAVs. Then, output regulation equations are employed to transform heterogeneous systems into a compact form via the Kronecker product, while neural networks (NNs) are introduced to compensate for model nonlinearities. Furthermore, based on random differential equations (RDEs) combined with Lyapunov theory, the noise-to-state practical stability in probability (NSPS-P) property of the error dynamics under mixed disturbances can be obtained. Finally, simulation examples demonstrate that the outputs of follower hovercrafts rapidly achieve a time-varying formation and rotate around convex combination states of leader UAVs simultaneously.
Underwater Acoustic Target Recognition Based on Sub-Regional Feature Enhancement and Multi-Activated Channel Aggregation
Authors: Zheng Zhongxiang , Liu Peng
Published: October 2024

Feature selection and fusion in ship radiated noise-based underwater target recognition have remained challenging tasks. This paper proposes a novel feature extraction method based on multi-dimensional feature selection and fusion. Redundant features are filtered through feature visualization techniques. The Sub-regional Feature Enhancement modules (SFE) and Multi-activated Channel Aggregation modules (MCA) within the neural network are utilized to achieve underwater target recognition. Experimental results indicate that our network, named Sub-Regional Channel Aggregation Net (SRCA-Net), utilizing 3-s sound segments for ship radiated noise recognition, surpasses existing models, achieving an accuracy of 78.52% on the public DeepShip dataset.
Pulmonary Endometriosis: A Systematic Review
Authors: Nikolettos Konstantinos , Patsouras Alexandros , Kotanidou Sonia , Garmpis Nikolaos , Psilopatis Iason , Garmpi Anna , Effraimidou Eleni I. , Daniilidis Angelos , Dimitroulis Dimitrios , Nikolettos Nikos , Tsikouras Panagiotis , Gerede Angeliki , Papoutsas Dimitrios , Kontomanolis Emmanuel , Damaskos Christos
Published: October 2024

Background/Objectives: Endometriosis is characterized by the presence of ectopic endometrial-like glands and stroma outside the endometrial cavity, which mainly occurs in the pelvic cavity. Pulmonary endometriosis, or thoracic endometriosis syndrome (TES), describes the rare presence of endometrial-like cells in the thoracic cavity and includes catamenial pneumothorax, catamenial hemothorax, hemoptysis, and lung nodules. Our aim is to summarize the results of all reported cases of TES. Methods: Extensive research was conducted through MEDLINE/PUBMED using the keywords “thoracic endometriosis”, “thoracic endometriosis syndrome”, “catamenial pneumothorax”, “catamenial hemoptysis”, and “TES”. Following PRISMA guidelines, all published cases of TES between January 1950 and March 2024 were included. A systematic review of 202 studies in English, including 592 patients, was performed. Results: The median age of women with TES is 33.8 years old. The most common clinical presentation is catamenial pneumothorax (68.4%), while lesions are mainly found in the right lung unilaterally (79.9%). Chest computed tomography (CT) was used alone or after an X-ray to determine the pathological findings. Ground-glass opacity nodules and cystic lesions represent the most common finding in CT, while pneumothorax is the most common finding in X-rays. Video-assisted thoracoscopic surgery (VATS) is the main therapeutic approach, usually in combination with hormonal therapy, including GnRH analogues, progestins, androgens, or combined oral contraceptives. Hormonal therapy was also administered as monotherapy. Symptom recurrence was reported in 10.1% of all cases after the treatment. Conclusions: High clinical awareness and a multidisciplinary approach are necessary for the best clinical outcome for TES patients. More studies are required to extract safer conclusions.
Examining Documentation Tools for Audit and Forensic Accounting Investigations
Authors: Smith Katherine Taken , Smith Lawrence Murphy
Published: October 2024

This study examines some of the documentation tools and techniques that forensic accountants, internal auditors, external auditors, and others can use to document accounting and financial reporting systems under investigation. While prior research has addressed these items piecemeal, this study is the first to incorporate them, along with current related research and theoretical foundation, and relate them in aggregate to the work of forensic accountants, internal auditors, external auditors, and others. Inputs, processes, and outputs of modern accounting and financial reporting systems are often difficult to fully grasp, with weaknesses obscured by the complexities of the system. These weaknesses make a system vulnerable to fraudsters, embezzlers, hackers, and others who will take advantage of system weaknesses to perpetrate financial fraud, embezzlement, or other financial crimes. Documentation tools and techniques examined in this study will be useful to forensic accountants, internal auditors, external auditors, and others for identifying the components, processes, and potential weaknesses of accounting and financial reporting systems.
Negative Dependencies in Turkish
Authors: Kamali Beste , Zeijlstra Hedde
Published: October 2024

In this paper, we provide an overview of negative dependencies in Turkish. The first are elements such as hiçkimse, which sometimes seem to mean ‘anybody’ and sometimes ‘nobody’. We argue that unlike a standard Negative Polarity Item (NPI) like English anybody, these items should be analyzed as neg-words licensed under Negative Concord (NC). We also discuss further properties of these items, including whether they are universals or existentials. The second set of items that display a negative dependency are universal quantifiers such as herkes ‘everybody’. Unlike their counterparts in many languages, these items obligatorily scope under negation, which raises the question of why a universal is sensitive to negation in the way it is. We account for this behavior in terms of negative polarity sensitivity based on a referentiality requirement we dub the Non-Entailment-of-Non-Existence Condition, following a particular analysis of a class of NPIs in Mandarin. The final case of negative dependency we evaluate is modals that have to scope under or above negation. These cases constitute instances of polarity sensitivity in English and beyond, especially clearly in the case of modal PPIs. We show that in Turkish, however, they do not, and the apparent negative dependency follows from the syntax of Tense-aspect-modality (TAM) morphology.
The Effectiveness of Cognitive Behavioral Therapy on Insomnia Severity Among Menopausal Women: A Scoping Review
Authors: Ntikoudi Anastasia , Owens Dimitra Anna , Spyrou Alketa , Evangelou Eleni , Vlachou Eugenia
Published: October 2024

This review explores the impact of cognitive behavioral therapy for insomnia (CBT-I) on menopausal women suffering from insomnia. The transition to menopause is often accompanies by sleep disturbances, which significantly affect women’s quality of life. This review applies a scoping approach to evaluate randomized controlled trials (RCTs) focused on CBT-I interventions for insomnia among menopausal women. The included studies examined variations in the number of CBT-I sessions, the duration of interventions, and their delivery methods (face-to-face, online, or telephone-based). The results consistently showed that CBT-I significantly improves sleep quality and reduces insomnia severity in menopausal women. CBT-I was particularly effective compared to other interventions such as sleep restriction therapy and sleep hygiene education. Sleep quality improvements were observed to persist for up to six months after treatment. These findings support the use of CBT-I as a first-line intervention for insomnia in menopausal women, offering a sustainable solution with fewer side effects compared to pharmacological treatments. However, the review also highlights the need for further research on CBT-I’s efficacy in diverse populations, as most studies focused on predominantly white and well-educated women.
Molbank—Aims and Scope Update
Authors: Leadbeater Nicholas E.
Published: October 2024

Molbank is a unique journal, bringing together one-compound-per-paper short notes on synthetic compounds and natural products [...]
Phosphorus–Nitrogen Interaction in Fire Retardants and Its Impact on the Chemistry of Treated Wood
Authors: Grześkowiak Wojciech Łukasz , Ratajczak Izabela , Zborowska Magdalena , Przybylska Marcelina , Patora Marcin
Published: October 2024

This work focuses on the changes in the chemical composition of wood caused by impregnation with fire retardants such as guanidine carbonate (GC), urea (U), diammonium phosphate (DAP) and their mixtures. The treated wood was tested using the oxygen index (LOI), Py–GC/MS analysis and FTIR Spectroscopy. The wood was vacuum treated at a pressure of 0.8 MPa for 20 min and then subjected to thermal degradation using the LOI. This way, degraded and nondegraded layers were obtained and ground (0.2 mm). All treatment variants achieved the class of non-flammable materials based on LOI tests; the exception was the 5% urea solution, defined as a flame-retardant material. Using the analytical methods, it was found that cellulose and hemicelluloses undergo the fastest thermal degradation. This study found that the variant protected with a 5% mixture of GC and DAP before and after the degradation process had the best fire-retardant properties regarding cellulose content in the wood. The highest content of anhydrosugars characterised the same variants, the amount of which indicates a slowdown in the degradation process and, consequently, a reduction in the release of levoglucosan during combustion, suggesting potential applications in fire safety.
Study on the Morphological Distribution and Modeling Methods of River Particles in Upstream and Downstream Sections
Authors: Hu Zhengbo , Zhang Junhui , Tan Xin , Yang Hao
Published: October 2024

This study investigates the morphological evolution of river particles and their mechanical behavior during sediment transport. River particles exhibit distinct shape differences between upstream and downstream sections, with particles becoming progressively rounded downstream. The rounding process is quantitatively described using morphological indices. The analysis reveals upstream particles are more angular, while downstream particles become increasingly rounded due to erosion and abrasion, modeled by a unified abrasion function. The Loop subdivision method effectively simulates this gradual rounding process. Additionally, the Discrete Element Method (DEM) calculates the natural angle of repose for particles with varying erosion levels, showing angles ranging from 38.2° for angular particles to 34.4° for rounded particles, closely matching field observations. The numerical results effectively demonstrate the interlocking effect caused by particle morphology. This research enhances the understanding of sediment transport dynamics and provides a robust framework for modeling particle shape evolution.
Correction: Emokpaire et al. Effect of Ru on Deformation Mechanism and Microstructure Evolution of Single-Crystal Superalloys under Medium-Temperature and High-Stress Creep. Materials 2023, 16, 2732
Authors: Emokpaire Stephen Okhiai , Wang Nan , Liu Jide , Zhu Chongwei , Wang Xinguang , Li Jinguo , Zhou Yizhou
Published: October 2024

Following publication, concerns were raised regarding the peer-review process related to the publication of this article [...]
Lattice Structures—Mechanical Description with Respect to Additive Manufacturing
Authors: Ráž Karel , Chval Zdeněk , Pereira Mathis
Published: October 2024

Lattice structures, characterized by their repetitive, interlocking patterns, provide an efficient balance of strength, flexibility, and reduced weight, making them essential in fields such as aerospace and automotive engineering. These structures use minimal material while effectively distributing stress, providing high resilience, energy absorption, and impact resistance. Composed of unit cells, lattice structures are highly customizable, from simple 2D honeycomb designs to complex 3D TPMS forms, and they adapt well to additive manufacturing, which minimizes material waste and production costs. In compression tests, lattice structures maintain stiffness even when filled with powder, suggesting minimal effect from the filler material. This paper shows the principles of creating finite element simulations with 3D-printed specimens and with usage of the lattice structure. The comparing of simulation and real testing is also shown in this research. The efficiency in material and energy use underscores the ecological and economic benefits of lattice-based designs, positioning them as a sustainable choice across multiple industries. This research analyzes three selected structures—solid material, pure latices structure, and boxed lattice structure with internal powder. The experimental findings reveal that the simulation error is less than 8% compared to the real measurement. This error is caused by the simplified material model, which is considering the isotropic behavior of the used material PA12GB (not the anisotropic model). The used and analyzed production method was multi jet fusion.