bluuebunny/crossref_metadata_2025 huggingface dataset:
A Plasma Membrane Intrinsic Protein Gene OfPIP2 Involved in Promoting Petal Expansion and Drought Resistance in Osmanthus fragrans
Authors: Lu Xinke , Kong En , Shen Lixiao , Ye Yong , Wang Yiguang , Dong Bin , Zhong Shiwei
Published: October 2024

Osmanthus fragrans, a native to China, is renowned as a highly popular gardening plant. However, this plant faces significant challenges from drought stress, which can adversely affect its flowering. In this study, we found that the plasma membrane-localized gene OfPIP2 exhibited a substantial upregulation during the flowering stages and in response to drought stress. GUS staining has illustrated that the OfPIP2 promoter can drive GUS activity under drought conditions. The overexpression of OfPIP2 was found to enhance petal size by modulating epidermal cell dimensions in Petunia and tobacco. Moreover, this overexpression also bolstered drought tolerance, as evidenced by a reduction in stomatal aperture in both species. Furthermore, yeast one-hybrid (Y1H) and dual-luciferase (Dual-LUC) assays have indicated that the transcription factor OfMYB28 directly binds to the OfPIP2 promoter, thereby regulating its expression. Together, we speculated that a module of OfMYB28-OfPIP2 was not only involved in the enhancement of petal size but also conferred the improvement of drought tolerance in O. fragrans. These results contribute valuable insights into the molecular function of the OfPIP2 gene and lay a foundation for molecular breeding strategies in O. fragrans.
Alignment of a Trivalent Chromosome on the Metaphase Plate Is Associated with Differences in Microtubule Density at Each Kinetochore
Authors: Borseth Ashley B. , Kianersi Hedyeh D. , Galloway Paige , Gercken Grace , Stowe Emily L. , Pizzorno Marie , Paliulis Leocadia V.
Published: October 2024

Chromosome alignment on the metaphase plate is a conserved phenomenon and is an essential function for correct chromosome segregation for many organisms. Organisms with naturally-occurring trivalent chromosomes provide a useful system for understanding how chromosome alignment is evolutionarily regulated, as they align on the spindle with one kinetochore facing one pole and two facing the opposite pole. We studied chromosome alignment in a praying mantid that has not been previously studied chromosomally, the giant shield mantis Rhombodera megaera. R. megaera has a chromosome number of 2n = 27 in males. Males have X1, X2, and Y chromosomes that combine to form a trivalent in meiosis I. Using live-cell imaging of spermatocytes in meiosis I, we document that sex trivalent Y chromosomes associate with one spindle pole and the two X chromosomes associate with the opposing spindle pole. Sex trivalents congress alongside autosomes, align with them on the metaphase I plate, and then the component chromosomes segregate alongside autosomes in anaphase I. Immunofluorescence imaging and quantification of brightness of kinetochore–microtubule bundles suggest that the X1 and X2 kinetochores are associated with fewer microtubules than the Y kinetochore, likely explaining the alignment of the sex trivalent at the spindle equator with autosomes. These observations in R. megaera support the evolutionary significance of the metaphase alignment of chromosomes and provide part of the explanation for how this alignment is achieved.
ABCG Transporters in the Adaptation of Rice to Salt Stresses
Authors: Zhang Dan , Hu Yuanyi , Tang Li , Du Yaxi , Mao Ruihua , Sheng Xiabing , Liu Huimin , Liu Xiaolin , Zhao Bingran , Lei Dongyang
Published: October 2024

The ATP-binding cassette (ABC) proteins are a diverse family of transmembrane transporter proteins widely identified in various organisms. The ABCG transporters belong to the G subfamily of the ABC transporter family. Rarely research on ABCG transporters involved in salt tolerance of rice was found. In this study, the evolutionary relationships, conserved motifs, intra- and inter-species homologous genes, and cis-acting elements of ABCG subfamily members were analyzed, and the expression changes of these genes under salt stress at 0 h, 3 h, and 24 h were detected. Based on these results, the candidate gene OsABCG7, which is induced by salt stress, was selected for further studies. Yeast experiments confirmed that the OsABCG7 gene might be involved in the regulation of salt tolerance. The abcg7 mutant showed a higher degree of leaf wilting and a lower survival rate, exhibiting a salt-sensitive phenotype. Systematic analysis of this family in rice helps design effective functional analysis strategies and provides data support for understanding the role of ABCG transporters under salt stress.
Apelin Counteracts the Effects of Fusobacterium nucleatum on the Migration of Periodontal Ligament Cells In Vitro
Authors: Cores Ziskoven Pablo , Nogueira Andressa V. B. , Eick Sigrun , Deschner James
Published: October 2024

To better understand the link between periodontitis and metabolic diseases, our in vitro study aimed to assess the influence of the adipokine apelin and/or the periodontal pathogen Fusobacterium nucleatum on periodontal cells. Periodontal ligament (PDL) cells were exposed to F. nucleatum in the presence and absence of apelin. Scratch assays were used to analyze the in vitro wound healing and velocity of cell migration. To investigate if F. nucleatum and/or apelin have a regulatory effect on cell proliferation and apoptosis, proliferation and viability assays were performed as well as an analysis of caspase 9 expression. Both the in vitro wound closure and the cell migration rate were significantly reduced by F. nucleatum. Simultaneous incubation with apelin counteracted the adverse effects of F. nucleatum. The proliferation assay demonstrated that neither apelin nor F. nucleatum significantly affected PDL cell proliferation. Furthermore, neither apelin nor F. nucleatum was cytotoxic or affected apoptosis after 48 h. Apelin could play a modulatory role in the pathogenesis of periodontitis, as it was able to compensate for the inhibitory effects of the periodontal pathogen F. nucleatum on PDL cell migration in vitro.
Enzymatic Kinetic Resolution of Racemic 1-(Isopropylamine)-3-phenoxy-2-propanol: A Building Block for β-Blockers
Authors: Chałupka Joanna , Marszałł Michał Piotr , Sikora Adam
Published: October 2024

This study aimed to optimize the kinetic resolution of building blocks for the synthesis of β-blockers using Candida rugosa lipases, which could be potentially used to synthesize enantiomerically pure β-blockers further. Reaction mixtures were incubated in a thermostated shaker. Qualitative and quantitative analyses of the reaction mixtures were performed using chiral stationary phases and the UPLC-IT-TOF system. Of the 24 catalytic systems prepared, a system containing lipase from Candida rugosa MY, [EMIM][BF4] and toluene as a two-phase reaction medium and isopropenyl acetate as an acetylating agent was optimal. This resulted in a product with high enantiomeric purity produced via biotransformation, whose enantioselectivity was E = 67.5. Using lipases from Candida rugosa enables the enantioselective biotransformation of the β-blockers building block. The biocatalyst used, the reaction environment, and the acetylating agent significantly influence the efficiency of performer kinetic resolutions. The studies made it possible to select an optimum system, a prerequisite for obtaining a product of high enantiomeric purity. As a result of the performed biotransformation, the (S)-enantiomer of the β-blocker derivative was obtained, which can be used to further synthesize enantiomerically pure β-blockers.
Cytotoxicity, Proapoptotic Activity and Drug-like Potential of Quercetin and Kaempferol in Glioblastoma Cells: Preclinical Insights
Authors: Kusaczuk Magdalena , Tovar-Ambel Elena , Martín-Cabrera Paola , Lorente Mar , Salvador-Tormo Nélida , Mikłosz Agnieszka , Chabowski Adrian , Velasco Guillermo , Naumowicz Monika
Published: October 2024

Despite the increasing understanding of the pathogenesis of glioblastoma (GBM), treatment options for this tumor remain limited. Recently, the therapeutic potential of natural compounds has attracted great interest. Thus, dietary flavonoids quercetin (QCT) and kaempferol (KMF) were investigated as potential cytostatic agents in GBM. Moreover, the physicochemical properties of QCT and KMF, determining their bioavailability and therapeutic efficiency, were evaluated. We proved that both polyphenols significantly reduced the viability of GBM cells. We also demonstrated that both QCT and KMF evoked the cytotoxic effect in T98G cells via induction of apoptotic cell death as shown by increased activity of caspase 3/7 and caspase 9 together with an overexpression of the cleaved form of PARP. Apoptosis was additionally accompanied by the activation of stress responses in QCT- and KMF-treated cells. Both polyphenols caused oxidative stress and endoplasmic reticulum (ER) stress, as demonstrated by the increased generation of reactive oxygen species (ROS), deregulated expressions of superoxide dismutases (SOD2 and Sod1 on protein and transcriptomic levels, respectively), as well as an overexpression of ERO1α, GRP78, p-JNK, and an up-regulation of Chop, Atf4 and Atf6α genes. The antitumor effect of QCT and KMF was also confirmed in vivo, showing reduced growth of tumor xenografts in the chick chorioallantoic membrane (CAM) experiment. Moreover, electrophoretic light scattering (ELS) was used to measure the zeta potential of cell membranes upon exposition to QCT and KMF. Additionally, on the basis of existing physicochemical data, the drug-likeness score of QCT and KMF was evaluated. Analyses showed that both compounds accomplish Lipinski’s Rule of 5, and they both fit into the criteria of good central nervous system (CNS) drugs. Altogether, our data support the idea that QCT and KMF might be plausible candidates for evaluation as therapeutic agents in preclinical models of glioblastoma.
Transcriptomic Analysis of Genes Associated with Stinger Development at Different Life Stages of Apis mellifera
Authors: Zhou Shiwen , Zhang Juan , Yang Zhenhui , Fu Yunxi , Lai Yu , Xu Xueling , Xu Ruixin , Lü Yang , Li Zhiguo , Zhao Ping , Su Songkun , Nie Hongyi
Published: October 2024

Stingers, evolved from ovipositors, are an important defense organ for the Apidae, Vespidae, and Formicidae species. However, the molecular mechanism of stinger development remains unclear. Here, we show that the earliest time point for the appearance of stingers in Apis mellifera is at the 1-day-old worker pupal stage based on morphological observations and anatomy from the pre-pupal to adult stages. To discover the genes related to stinger development, we first comprehensively compared the stinger transcriptome at different stages and screened 1282, 186, and 166 highly expressed genes in the stingers of 1- and 5-day-old worker pupae and newly emerged worker bees (NEBs), respectively, then identified 25 DEGs involved in the early stage of stinger development. We found that Dll was a key candidate gene in the early development of A. mellifera stingers by combining analyses of the protein–protein interaction network and spatiotemporal expression patterns. An RNAi experiment showed that about 20% of individuals exhibited tip bending in the piercing parts of their stingers in the Dll-dsRNA-treated group, with the morphology presenting as side–side or front–back tip bending. This indicates that Dll plays a vital role in the early development of A. mellifera stingers. Together, our study provides insight into the molecular mechanism of Hymenoptera stinger development and an inspiration for the molecular breeding of gentle honeybee species with stinger abnormalities.
Platelet Proteomics and Tissue Metabolomics Investigation for the Mechanism of Aspirin Eugenol Ester on Preventive Thrombosis Mechanism in a Rat Thrombosis Model
Authors: Tao Qi , Fan Li-Ping , Feng Ji , Zhang Zhi-Jie , Liu Xi-Wang , Qin Zhe , Li Jian-Yong , Yang Ya-Jun
Published: October 2024

Platelet activation is closely related to thrombosis. Aspirin eugenol ester (AEE) is a novel medicinal compound synthesized by esterifying aspirin with eugenol using the pro-drug principle. Pharmacological and pharmacodynamic experiments showed that AEE has excellent anti-inflammatory, antioxidant, and inhibitory platelet activation effects, preventing thrombosis. However, the regulatory network and action target of AEE in inhibiting platelet activation remain unknown. This study aimed to investigate the effects of AEE on platelets of thrombosed rats to reveal its regulatory mechanism via a multi-omics approach. The platelet proteomic results showed that 348 DEPs were identified in the AEE group compared with the model group, of which 87 were up- and 261 down-regulated. The pathways in this result were different from previous results, including mTOR signaling and ADP signaling at P2Y purinoceptor 12. The metabolomics of heart and abdominal aortic tissue results showed that the differential metabolites were mainly involved in steroid biosynthesis, the citric acid cycle, phenylalanine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and glutathione metabolism. Molecular docking results showed that AEE had a better binding force to both the COX-1 and P2Y12 protein. AEE could effectively inhibit platelet activation by inhibiting COX-1 protein and P2Y12 protein activity, thereby inhibiting platelet aggregation. Therefore, AEE can have a positive effect on inhibiting platelet activation.
Relationship between the GABA Pathway and Signaling of Other Regulatory Molecules
Authors: Kabała Katarzyna , Janicka Małgorzata
Published: October 2024

GABA (gamma-aminobutyric acid) is an amino acid whose numerous regulatory functions have been identified in animal organisms. More and more research indicate that in plants, this molecule is also involved in controlling basic growth and development processes. As recent studies have shown, GABA plays an essential role in triggering plant resistance to unfavorable environmental factors, which is particularly important in the era of changing climate. The main sources of GABA in plant cells are glutamic acid, converted in the GABA shunt pathway, and polyamines subjected to oxidative degradation. The action of GABA is often related to the activity of other messengers, including phytohormones, polyamines, NO, H2O2, or melatonin. GABA can function as an upstream or downstream element in the signaling pathways of other regulators, acting synergistically or antagonistically with them to control cellular processes. Understanding the role of GABA and its interactions with other signaling molecules may be important for developing crop varieties with characteristics that enable adaptation to a changing environment.
The 419th Aspartic Acid of Neural Membrane Protein Enolase 2 Is a Key Residue Involved in the Axonal Growth of Motor Neurons Mediated by Interaction between Enolase 2 Receptor and Extracellular Pgk1 Ligand
Authors: Lee Bing-Chang , Tsai Jui-Che , Huang Yi-Hsin , Wang Chun-Cheng , Lee Hung-Chieh , Tsai Huai-Jen
Published: October 2024

Neuron-specific Enolase 2 (Eno2) is an isozyme primarily distributed in the central and peripheral nervous systems and neuroendocrine cells. It promotes neuronal survival, differentiation, and axonal regeneration. Recent studies have shown that Eno2 localized on the cell membrane of motor neurons acts as a receptor for extracellular phosphoglycerate kinase 1 (ePgk1), which is secreted by muscle cells and promotes the neurite outgrowth of motor neurons (NOMN). However, interaction between Eno1, another isozyme of Enolase, and ePgk1 failed to return the same result. To account for the difference, we constructed seven point-mutations of Eno2, corresponding to those of Eno1, and verified their effects on NOMN. Among the seven Eno2 mutants, eno2-siRNA-knockdown NSC34 cells transfected with plasmid encoding the 419th aspartic acid mutated into serine (Eno2-[D419S]) or Eno2-[E420K] showed a significant reduction in neurite length. Moreover, the Eno2-ePgk1-interacted synergic effect on NOMN driven by Eno2-[D419S] was more profoundly reduced than that driven by Eno2-[E420K], suggesting that D419 was the more essential residue involved in NOMN mediated by Eno2-ePgk1 interaction. Eno2-ePgk1-mediated NOMN appeared to increase the level of p-Cofilin, a growth cone collapse marker, in NSC34 cells transfected with Eno2-[D419S] and incubated with ePgk1, thereby inhibiting NOMN. Furthermore, we conducted in vivo experiments using zebrafish transgenic line Tg(mnx1:GFP), in which GFP is tagged in motor neurons. In the presence of ePgk1, the retarded growth of axons in embryos injected with eno2-specific antisense morpholino oligonucleotides (MO) could be rescued by wobble-eno2-mRNA. However, despite the addition of ePgk1, the decreased defective axons and the increased branched neurons were not significantly improved in the eno2-[D419S]-mRNA-injected embryos. Collectively, these results lead us to suggest that the 419th aspartic acid of mouse Eno2 is likely a crucial site affecting motor neuron development mediated by Eno2-ePgk1 interaction, and, hence, mutations result in a significant reduction in the degree of NOMN in vitro and axonal growth in vivo.
The Hidden Dangers of Sedentary Living: Insights into Molecular, Cellular, and Systemic Mechanisms
Authors: Diniz Daniel Guerreiro , Bento-Torres João , da Costa Victor Oliveira , Carvalho Josilayne Patricia Ramos , Tomás Alessandra Mendonça , Galdino de Oliveira Thaís Cristina , Soares Fernanda Cabral , de Macedo Liliane Dias e Dias , Jardim Naina Yuki Vieira , Bento-Torres Natáli Valim Oliver , Anthony Daniel Clive , Brites Dora , Picanço Diniz Cristovam Wanderley
Published: October 2024

With the aging of the global population, neurodegenerative diseases are emerging as a major public health issue. The adoption of a less sedentary lifestyle has been shown to have a beneficial effect on cognitive decline, but the molecular mechanisms responsible are less clear. Here we provide a detailed analysis of the complex molecular, cellular, and systemic mechanisms underlying age-related cognitive decline and how lifestyle choices influence these processes. A review of the evidence from animal models, human studies, and postmortem analyses emphasizes the importance of integrating physical exercise with cognitive, multisensory, and motor stimulation as part of a multifaceted approach to mitigating cognitive decline. We highlight the potential of these non-pharmacological interventions to address key aging hallmarks, such as genomic instability, telomere attrition, and neuroinflammation, and underscore the need for comprehensive and personalized strategies to promote cognitive resilience and healthy aging.
On the Potential Energy Surface of the Pyrene Dimer
Authors: Czernek Jiří , Brus Jiří
Published: October 2024

Knowledge of reliable geometries and associated intermolecular interaction energy (ΔE) values at key fragments of the potential energy surface (PES) in the gas phase is indispensable for the modeling of various properties of the pyrene dimer (PYD) and other important aggregate systems of a comparatively large size (ca. 50 atoms). The performance of the domain-based local pair natural orbital (DLPNO) variant of the coupled-cluster theory with singles, doubles and perturbative triples in the complete basis set limit [CCSD(T)/CBS] method for highly accurate predictions of the ΔE at a variety of regions of the PES was established for a representative set of pi-stacked dimers, which also includes the PYD. For geometries with the distance between stacked monomers close to a value of such a distance in the ΔE minimum structure, an excellent agreement between the canonical CCSD(T)/CBS results and their DLPNO counterparts was found. This finding enabled us to accurately characterize the lowest-lying configurations of the PYD, and the physical origin of their stabilization was thoroughly analyzed. The proposed DLPNO-CCSD(T)/CBS procedure should be applied with the aim of safely locating a global minimum of the PES and firmly establishing the pertaining ΔE of even larger dimers in studies of packing motifs of organic electronic devices and other novel materials.
Genomic Sequencing to Detect Cross-Breeding Quality in Dogs: An Example Studying Disorders in Sexual Development
Authors: de Gennaro Luciana , Burgio Matteo , Lacalandra Giovanni Michele , Petronella Francesco , L’Abbate Alberto , Ravasini Francesco , Trombetta Beniamino , Rizzo Annalisa , Ventura Mario , Cicirelli Vincenzo
Published: October 2024

Disorders of sexual development (DSDs) in dogs, similar to humans, arise from genetic mutations, gonadal differentiation, or phenotypic sex development. The French Bulldog, a breed that has seen a surge in popularity and demand, has also shown a marked increase in DSD incidence. This study aims to characterize the genetic underpinnings of DSDs in a French Bulldog named Brutus, exhibiting ambiguous genitalia and internal sexual anatomy, and to explore the impact of breeding practices on genetic diversity within the breed. We utilized a comprehensive approach combining conventional cytogenetics, molecular techniques, and deep sequencing to investigate the genetic profile of Brutus. The sequence data were compared to three other male French Bulldogs’ genome sequences with typical reproductive anatomy, including Brutus’s father and the canine reference genome (CanFam6). We found a Robertsonian fusion involving chromosome 23 previously reported in dogs as a causative mutation responsible for sex reversal syndrome. Our findings revealed a 22% mosaicism (78,XX/77,XX), the absence of the sex-determining region (SRY) gene, and the presence of 43 unique Single Nucleotide Variants (SNVs) not inherited from the father. Notably, the run of homozygosity (ROH) analysis showed Brutus has a higher number of homozygous segments compared to other Bulldogs, with a total length of these fragments 50% greater than the average, strongly suggesting this dog is the product of the mating between siblings. Although no direct causative genes for the DSD phenotype were identified, four candidate loci warrant further investigation. Our study highlighted the need for a better annotated and curated reference dog genome to define genes causative of any specific phenotype, suggests a potential genetic basis for the DSD phenotype in dogs, and underscores the consequences of uncontrolled breeding practices in French Bulldogs. These findings highlight the importance of implementing strategic genetic management to preserve genetic health and diversity in canine populations.
3′,4′-Dihydroxyflavonol Inhibits Fibrotic Response in a Rabbit Model of Glaucoma Filtration Surgery
Authors: Pasvanis Zoe , Kong Roy C. K. , Shah Manisha H. , Chan Elsa C. , Fan Gaskin Jennifer C.
Published: October 2024

Post-operative fibrosis of the filtering bleb limits the success of glaucoma filtration surgery (GFS). To minimise subconjunctival scarring following GFS, treatment with antimetabolites such as Mitomycin C (MMC) has become standard practice; however, their use is associated with considerable side effects. This study aimed to investigate the anti-scarring properties of 3′,4′-dihydroxyflavonol (DiOHF). GFS was performed in New Zealand white rabbits who received eye drops of DiOHF three times daily and vehicle eye drops after surgery (n = 5) or a single intraoperative treatment of MMC (n = 5). Blebs were imaged immediately following surgery and on days 7, 15, 21, and 28 for clinical examination. On day 28, eyes were harvested to assess collagen deposition, expression of α-SMA, oxidative stress, angiogenesis, fibroblast activity, and inflammation in the conjunctiva/Tenon’s layer. At 7 and 28 days post-GFS, MMC-treated blebs were more ischaemic than DiOHF- or vehicle-treated blebs. On day 28, DiOHF treatment significantly suppressed collagen accumulation, CD31 expression, Vimentin expression, and CD45 expression compared to the vehicle control. No difference was observed in 3-Nitrotyrosine or αSMA expression between treatment groups. Treatment with DiOHF reduced conjunctival scarring and angiogenesis in rabbits with GFS, which was comparable to MMC. DiOHF may be a safer and more effective wound-modulating agent than conventional antifibrotic therapy in GFS.
Cannabinoids and Genetic Epilepsy Models: A Review with Focus on CDKL5 Deficiency Disorder
Authors: Massey Sean , Quigley Anita , Rochfort Simone , Christodoulou John , Van Bergen Nicole J.
Published: October 2024

Pediatric genetic epilepsies, such as CDKL5 Deficiency Disorder (CDD), are severely debilitating, with early-onset seizures occurring more than ten times daily in extreme cases. Existing antiseizure drugs frequently prove ineffective, which significantly impacts child development and diminishes the quality of life for patients and caregivers. The relaxation of cannabis legislation has increased research into potential therapeutic properties of phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). CBD’s antiseizure properties have shown promise, particularly in treating drug-resistant genetic epilepsies associated with Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). However, specific research on CDD remains limited. Much of the current evidence relies on anecdotal reports of artisanal products lacking accurate data on cannabinoid composition. Utilizing model systems like patient-derived iPSC neurons and brain organoids allows precise dosing and comprehensive exploration of cannabinoids’ pharmacodynamics. This review explores the potential of CBD, THC, and other trace cannabinoids in treating CDD and focusing on clinical trials and preclinical models to elucidate the cannabinoid’s potential mechanisms of action in disrupted CDD pathways and strengthen the case for further research into their potential as anti-epileptic drugs for CDD. This review offers an updated perspective on cannabinoid’s therapeutic potential for CDD.
Genome-Wide Identification and Expression Analysis of the BTB Gene Superfamily Provides Insight into Sex Determination and Early Gonadal Development of Alligator sinensis
Authors: Li Pengfei , Liu Peng , Zang Dongsheng , Li Changcheng , Wang Chong , Zhu Yunzhen , Liu Mengqin , Lu Lilei , Wu Xiaobing , Nie Haitao
Published: October 2024

The BTB gene superfamily is widely distributed among higher eukaryotes and plays a significant role in numerous biological processes. However, there is limited knowledge about the structure and function of BTB genes in the critically endangered species Alligator sinensis, which is endemic to China. A total of 170 BTB genes were identified from the A. sinensis genome, classified into 13 families, and unevenly distributed across 16 chromosomes. Analysis of gene duplication events yielded eight pairs of tandem duplication genes and six pairs of segmental duplication genes. Phylogenetics shows that the AsBTB genes are evolutionarily conserved. The cis-regulatory elements in the AsBTB family promoter region reveal their involvement in multiple biological processes. Protein interaction network analysis indicates that the protein interactions of the AsBTB genes are centered around CLU-3, mainly participating in the regulation of biological processes through the ubiquitination pathway. The expression profile and protein interaction network analysis of AsBTB genes during sex differentiation and early gonadal development indicate that AsBTB genes are widely expressed in this process and involves numerous genes and pathways for regulation. This study provides a basis for further investigation of the role of the BTB gene in sex differentiation and gonadal development in A. sinensis.
Piperonylic Acid Promotes Hair Growth by Activation of EGFR and Wnt/β-Catenin Pathway
Authors: Han Seung Hyun , Jo Kyung Won , Kim Younghyun , Kim Kyong-Tai
Published: October 2024

Dermal papilla cells (DPCs) are located at the bottom of the hair follicle and play a critical role in hair growth, shape, and cycle. Epidermal growth factor receptor (EGFR) and Wnt/β-catenin signaling pathways are essential in promoting keratinocyte activation as well as hair follicle formation in DPCs. Piperonylic acid is a small molecule that induces EGFR activation in keratinocytes. However, the effects of piperonylic acid on DPCs in regard to the stimulation of hair growth have not been studied. In the present study, piperonylic acid was shown to activate the Wnt/β-catenin signaling pathway in addition to the EGFR signaling pathway in DPCs. Piperonylic acid suppressed DKK1 expression, which presumably promoted the accumulation of β-catenin in the nucleus. In addition, piperonylic acid promoted cyclin D upregulation and cell growth and increased the expression of alkaline phosphatase (ALP), a DPC marker. In a clinical study, the group that applied a formulation containing piperonylic acid had a significantly higher number of hairs per unit area than the placebo group. These results identify piperonylic acid as a promising new candidate for hair loss treatment.
Development and Validation of a Comprehensive Prognostic and Depression Risk Index for Gastric Adenocarcinoma
Authors: Tian Sheng , Liu Yixin , Liu Pan , Nomura Sachiyo , Wei Yongchang , Huang Tianhe
Published: October 2024

Depressive disorder contributes to the initiation and prognosis of patients with cancer, but the interaction between cancer and depressive disorder remains unclear. We generated a gastric adenocarcinoma patient-derived xenograft mice model, treated with chronic unpredictable mild stimulation. Based on the RNA-sequence from the mouse model, patient data from TCGA, and MDD-related (major depressive disorder) genes from the GEO database, 56 hub genes were identified by the intersection of differential expression genes from the three datasets. Molecular subtypes and a prognostic signature were generated based on the 56 genes. A depressive mouse model was constructed to test the key changes in the signatures. The signature was constructed based on the NDUFA4L2, ANKRD45, and AQP3 genes. Patients with high risk-score had a worse overall survival than the patients with low scores, consistent with the results from the two GEO cohorts. The comprehensive results showed that a higher risk-score was correlated with higher levels of tumor immune exclusion, higher infiltration of M0 macrophages, M2 macrophages, and neutrophils, higher angiogenetic activities, and more enriched epithelial–mesenchymal transition signaling pathways. A higher risk score was correlated to a higher MDD score, elevated MDD-related cytokines, and the dysfunction of neurogenesis-related genes, and parts of these changes showed similar trends in the animal model. With the Genomics of Drug Sensitivity in Cancer database, we found that the gastric adenocarcinoma patients with high risk-score may be sensitive to Pazopanib, XMD8.85, Midostaurin, HG.6.64.1, Elesclomol, Linifanib, AP.24534, Roscovitine, Cytarabine, and Axitinib. The gene signature consisting of the NDUFA4L2, ANKRD45, and AQP3 genes is a promising biomarker to distinguish the prognosis, the molecular and immune characteristics, the depressive risk, and the therapy candidates for gastric adenocarcinoma patients.
Unveiling the Anticancer Potential: Computational Exploration of Nitrogenated Derivatives of (+)-Pancratistatin as Topoisomerase I Inhibitors
Authors: Mohamed Magdi Awadalla , Elsaman Tilal , Elderdery Abozer Y. , Alsrhani Abdullah , Ghanem Heba Bassiony , Alruwaili Majed Mowanes , Hamza Siddiqa M. A. , Mekki Salma Elhadi Ibrahim , Alotaibi Hazim Abdullah , Mills Jeremy
Published: October 2024

Cancer poses a substantial global health challenge, driving the need for innovative therapeutic solutions that offer improved effectiveness and fewer side effects. Topoisomerase I (Topo I) has emerged as a validated molecular target in the pursuit of developing anticancer drugs due to its critical role in DNA replication and transcription. (+)-Pancratistatin (PST), a naturally occurring compound found in various Amaryllidaceae plants, exhibits promising anticancer properties by inhibiting Topo I activity. However, its clinical utility is hindered by issues related to limited chemical availability and aqueous solubility. To address these challenges, molecular modelling techniques, including virtual screening, molecular docking, molecular mechanics with generalised born and surface area solvation (MM-GBSA) calculations, and molecular dynamics simulations were utilised to evaluate the binding interactions and energetics of PST analogues with Topo I, comparing them with the well-known Topo I inhibitor, Camptothecin. Among the compounds screened for this study, nitrogenated analogues emerged as the most encouraging drug candidates, exhibiting improved binding affinities, favourable interactions with the active site of Topo I, and stability of the protein-ligand complex. Structural analysis pinpointed key molecular determinants responsible for the heightened potency of nitrogenated analogues, shedding light on essential structural modifications for increased activity. Moreover, in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions highlighted favourable drug-like properties and reduced toxicity profiles for the most prominent nitrogenated analogues, further supporting their potential as effective anticancer agents. In summary, this screening study underscores the significance of nitrogenation in augmenting the anticancer efficacy of PST analogues targeting Topo I. The identified lead compounds exhibit significant potential for subsequent experimental validation and optimisation, thus facilitating the development of novel and efficacious anticancer therapeutics with enhanced pharmacological profiles.
Macrophages: Key Players in the Battle against Triple-Negative Breast Cancer
Authors: Padzińska-Pruszyńska Irena , Kucharzewska Paulina , Matejuk Agata , Górczak Małgorzata , Kubiak Małgorzata , Taciak Bartłomiej , Król Magdalena
Published: October 2024

Triple-negative breast cancer (TNBC) is a challenging subtype of breast cancer characterized by the absence of estrogen and progesterone receptors and HER2 expression, leading to limited treatment options and a poorer prognosis. TNBC is particularly prevalent in premenopausal African-descent women and is associated with aggressive tumor behavior and higher metastatic potential. Tumor-associated macrophages (TAMs) are abundantly present within the TNBC microenvironment and play pivotal roles in promoting tumor growth, progression, and metastasis through various mechanisms, including immune suppression and enhancement of angiogenesis. This review provides an in-depth overview of TNBC, focusing on its epidemiology, its molecular characteristics, and the critical influence of TAMs. It discusses the pathological and molecular aspects that define TNBC’s aggressive nature and reviews current and emerging therapeutic strategies aimed at targeting these dynamics. Special attention is given to the role of TAMs, exploring their potential as therapeutic targets due to their significant impact on tumor behavior and patient outcomes. This review aims to highlight the complexities of the TNBC landscape and to present the innovative approaches that are currently being pursued to improve therapeutic efficacy and patient survival.
Heterogeneous Transcriptional Landscapes in Human Sporadic Parathyroid Gland Tumors
Authors: Verdelli Chiara , Carrara Silvia , Maggiore Riccardo , Dalino Ciaramella Paolo , Corbetta Sabrina
Published: October 2024

The expression of several key molecules is altered in parathyroid tumors due to gene mutations, the loss of heterozygosity, and aberrant gene promoter methylation. A set of genes involved in parathyroid tumorigenesis has been investigated in sporadic parathyroid adenomas (PAds). Thirty-two fresh PAd tissue samples surgically removed from patients with primary hyperparathyroidism (PHPT) were collected and profiled for gene, microRNA, and lncRNA expression (n = 27). Based on a gene set including MEN1, CDC73, GCM2, CASR, VDR, CCND1, and CDKN1B, the transcriptomic profiles were analyzed using a cluster analysis. The expression levels of CDC73 and CDKN1B were the main drivers for clusterization. The samples were separated into two main clusters, C1 and C2, with the latter including two subgroups of five PAds (C2A) and nineteen PAds (C2B), both differing from C1 in terms of their lower expression of CDC73 and CDKN1B. The C2A PAd profile was also associated with the loss of TP73, an increased expression of HAR1B, HOXA-AS2, and HOXA-AS3 lncRNAs, and a trend towards more severe PHPT compared to C1 and C2B PAds. C2B PAds were characterized by a general downregulated gene expression. Moreover, CCND1 levels were also reduced as well as the expression of the lncRNAs NEAT1 and VLDLR-AS1. Of note, the deregulated lncRNAs are predicted to interact with the histones H3K4 and H3K27. Patients harboring C2B PAds had lower ionized and total serum calcium levels, lower PTH levels, and smaller tumor sizes than patients harboring C2A PAds. In conclusion, PAds display heterogeneous transcriptomic profiles which may contribute to the modulation of clinical and biochemical features. The general downregulated gene expression, characterizing a subgroup of PAds, suggests the tumor cells behave as quiescent resting cells, while the severity of PHPT may be associated with the loss of p73 and the lncRNA-mediated deregulation of histones.
An Easily Customizable Approach for Automated Species-Specific Detection of Anuran Calls Using the European Green Toad as an Example
Authors: Landler Lukas , Kornilev Yurii V. , Burgstaller Stephan , Siebert Janette , Krall Maria , Spießberger Magdalena , Dörler Daniel , Heigl Florian
Published: October 2024

Machine learning approaches for pattern recognition are increasingly popular. However, the underlying algorithms are often not open source, may require substantial data for model training, and are not geared toward specific tasks. We used open-source software to build a green toad breeding call detection algorithm that will aid in field data analysis. We provide instructions on how to reproduce our approach for other animal sounds and research questions. Our approach using 34 green toad call sequences and 166 audio files without green toad sounds had an accuracy of 0.99 when split into training (70%) and testing (30%) datasets. The final algorithm was applied to amphibian sounds newly collected by citizen scientists. Our function used three categories: “Green toad(s) detected”, “No green toad(s) detected”, and “Double check”. Ninety percent of files containing green toad calls were classified as “Green toad(s) detected”, and the remaining 10% as “Double check”. Eighty-nine percent of files not containing green toad calls were classified as “No green toad(s) detected”, and the remaining 11% as “Double check”. Hence, none of the files were classified in the wrong category. We conclude that it is feasible for researchers to build their own efficient pattern recognition algorithm.
An Independent Learning System for Flutter Cross-Platform Mobile Programming with Code Modification Problems
Authors: Kinari Safira Adine , Funabiki Nobuo , Aung Soe Thandar , Wai Khaing Hsu , Mentari Mustika , Puspitaningayu Pradini
Published: October 2024

Nowadays, with the common use of smartphones in daily lives, mobile applications have become popular around the world, which will lead to a rise in Flutter framework. Developed by Google, Flutter with Dart programming provides a cross-platform development environment to create visually appealing and responsive user interfaces across mobile, web, and desktop platforms using a single codebase. However, due to time and staff limitations, the Flutter/Dart programming course is not included in curricula, even in IT departments in universities. Therefore, independent learning environments for students are essential to meet this growing popularity. Previously, we have developed programming learning assistant system (PLAS) as a web-browser-based self-learning platform for novice students. PLAS offers various types of exercise problems designed to cultivate programming skills step-by-step through a lot of code reading and code writing practices. Among them, one particular type is the code modification problem (CMP), which asks to modify the given source code to satisfy the new specifications. CMP is expected to be solved by novices with little effort if they have knowledge of other programming languages. Thus, PLAS with CMP will be an excellent platform for independent learning. In this paper, we present PLAS with CMP for the independent learning of Flutter/Dart programming. To improve the readability of the source code by students, we provided rich comments on grammar or behaviors. Besides, the code can be downloaded so that students can check and run it on an IDE. For evaluations, we generated 38 CMP instances for basic and multimedia/storage topics in Flutter/Dart programming and assigned them to 21 master students at Okayama University, Japan, who have never studied it. The results confirm the validity of the proposal.
System Reliability Analysis of Concrete Arch Dams Considering Foundation Rock Wedges Movement: A Discussion on the Limit Equilibrium Method
Authors: Soltani Narjes , Escuder-Bueno Ignacio , Klun Mateja
Published: October 2024

In this paper, a discussion on the applicability and limitations of the limit equilibrium method is presented. In this manner, the reliability of a concrete arch dam-foundation system under static loading is evaluated by considering a set of potentially moveable rock wedges in the foundation. The safety of the system is assessed utilizing a quasi-analytical method, which employs the limit equilibrium method and numerical analysis to calculate the sliding safety factors and the dam trust forces, respectively. The reliability is evaluated using the Latin Hypercube Sampling method. Random variables in the system are the friction angle, cohesion, and the Grout Curtain Efficiency Coefficient. In the end, the influence of two parametric variables of discontinuities, elastic slip and rock mass deformability modulus, on the rock wedges’ sliding safety factor is evaluated by comparing the results of the quasi-analytical method with the purely numerical method. The results show that in the case of complicated geotechnical conditions, the limit equilibrium method may not reflect real-world failure scenarios.
Structural Health Monitoring and Performance Evaluation of Bridges and Structural Elements
Authors: Mehrabi Armin , Khedmatgozar Dolati Seyed Saman
Published: October 2024

Bridges and other structures that support critical services necessary for communities constitute an important part of surface infrastructure [...]
Comparison of Growth and Composition of Black Soldier Fly (Hermetia illucens L.) Larvae Reared on Sugarcane By-Products and Other Substrates
Authors: Zandi-Sohani Nooshin , Tomberlin Jeffery K.
Published: October 2024

Black soldier fly larvae (BSFL) can convert organic waste into high-quality biomass. In this study, we tested the potential of sugarcane by-products as a food source for BSFL and compared larval development and nutritional value with some other organic substrates. Seven different substrates were used, including carrot pomace (C), carrot pomace and leftover bread (CB) (50/50), bagasse and vinasse (BV), bagasse and molasses (BM), bagasse, vinasse, and molasses (BVM), a mixture of all the above treatments (MX), and university canteen leftovers (UCLs). The larval weight and length were measured for two weeks from day 5 to 19. Then, the BSFL were harvested and analyzed for dry matter, crude protein, oil, ash, mineral, and fatty acid composition. Larval weight and length varied depending on the feeding substrate provided. University canteen leftovers resulted in the BSFL having at least 18% greater length (17.00 mm) and 56% greater weight (3.15 g) compared to other treatments. The highest amounts of protein (38.9%) and oil (39.06%) were observed in the UCL treatment, while the BV treatment larvae had the highest quantities of ash (28.9%) and dry matter (28.0%). The fatty acid profile of the BSFL revealed three-times-higher levels of saturated fatty acids than unsaturated fatty acids in the UCL treatment and was at least twice as high in other treatments. Overall, the BSFL had the best growth on the UCL substrate, and the combination of bagasse and vinasse (BV) was the most appropriate substrate for BSFL development among the sugarcane by-products.
Identification and Characterization of Four Novel Viruses in Balclutha incisa
Authors: Xiao Jiajing , Yang Guang , Liu Renyi , Ge Danfeng
Published: October 2024

Balclutha incisa (Cicadellidae: Deltocephalinae), a leafhopper prevalent in tropical and temperate regions, is notably abundant in grasses and rice. The virome of B. incisa was investigated using deep transcriptome sequencing, leading to the first identification of four viruses belonging to the families Aliusviridae, Iflaviridae, and Totiviridae in B. incisa. These viruses have been provisionally named B. incisa ollusvirus 1 (BiOV1), B. incisa ollusvirus 2 (BiOV2), B. incisa iflavirus 1 (BiIV1), and B. incisa totivirus 1 (BiTV1). The complete genome sequences of these viruses were obtained through rapid amplification of cDNA ends (RACE). BiOV1 has a linear genome of 15,125 nucleotides (nt), while BiOV2 possesses a circular genome of 14,853 nt. The BiIV1 genome, excluding the poly(A) tail, is 10,903 nt in length and encodes a single open reading frame (ORF) for a polyprotein consisting of 3194 amino acids (aa). The BiTV1 genome is 4357 nt long and contains two overlapping ORFs, with the viral RNA-dependent RNA polymerase (RdRp) translated via a −1 ribosomal frameshift. Phylogenetic and sequence identity analyses suggest that all these viruses are novel members of their respective families. This study significantly expands our understanding of the virome associated with B. incisa by reporting and characterizing these novel viruses.