bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and Testing of an Integrated Corn Stubble Residual Film-Recycling Machine
Authors: Wei Le , Liu Xiaolong , Sun Wei , Zhao Wuyun , Li Hui , Zhang Hua , Li Hongling , Liang Jiadong , Li Yongzhi , Zhou Yuhang , Zhao Ningning
Published: October 2024

The existing residual film-recycling machines struggle to efficiently recover and separate film stubble in a single operation. With roller-type film-rolling device unloading difficulties and other problems, in order to improve the recovery efficiency of film stubble and the separation effect while reducing human labor and to improve work efficiency, we designed an automatic hydraulic unloading film stubble-recycling integrated residual film-recycling machine. The angle of the membrane lifting device was determined by theoretical calculations using the method of coupled simulation of EDEM and ANSYS Workbench. We analyzed the amount of resistance as well as the maximum stress and deformation during the working process of the membrane-lifting device and focused on the design of the membrane–soil separating device and membrane-rolling device. The depth of the film shovel, the forward speed of the machine, and the rotational speed of the driving wheel of the jogging chain were selected as the test factors, and the residual film recovery rate was taken as the evaluation index. A three-factor, three-level test was designed by applying the principles of the Box–Behnken experimental design. The results show that when the forward speed is 1.36 m/s, the soil depth is 147.16 mm, and the rotational speed of the driving wheel of the shaking chain is 77.89 r/min, the recovery rate of the residual film is 87.56%, and the relative error between the experimental value and the optimized value is 2.73%. The experimental results can provide a theoretical basis for the design of the residual film-recycling machine.
Biochemical Parameters of Fallow Light Soil Enriched with Sewage Sludge
Authors: Żukowska Grażyna , Futa Barbara , Myszura-Dymek Magdalena
Published: October 2024

One way to manage sewage sludge, which is consistent with the assumptions of the European Green Deal, is to use it in agriculture. The study focused on the possibility of using soil enzyme activity and the GMea index (the geometric mean of enzyme activities) in connection with the total organic carbon (TOC) and the total nitrogen (TN) content to assess the quality of fallow light soil after exogenous organic matter (EOM) fertilization. Exogenous organic matter in the form of stabilized municipal sewage sludge was introduced into the soil. The experiment included five variants: one control site and four sites with 30, 75, 150, and 300 Mg ha−1 of sewage sludge added to the soil. The contents of TOC, TN and heavy metals (Zn, Cu, Pb, Cd) in the soil material were assayed. In addition, the activity of soil enzymes, i.e., neutral phosphatase, urease, protease and dehydrogenase, was examined, and the geometric mean of the enzyme activities (GMea index) was calculated. Fertilization of light soil with sewage sludge resulted in an increase in TOC and TN proportionally to the EOM dose. The addition of sewage sludge increased the content of tested heavy metals in the soil and did not exceed the levels considered acceptable. The introduction of sewage sludge contributed to the stimulation of biological life in the soil. This was evidenced by an intensification of soil enzyme activity. However, individual enzymes showed a different response to EOM fertilization, while GMea showed a significant increase in the quality of the fallowed soils as the EOM rate increased to 150 Mg ha−1.
Real-Time Detection and Localization of Weeds in Dictamnus dasycarpus Fields for Laser-Based Weeding Control
Authors: Xu Yanlei , Liu Zehao , Li Jian , Huang Dongyan , Chen Yibing , Zhou Yang
Published: October 2024

Traditional Chinese medicinal herbs have strict environmental requirements and are highly susceptible to weed damage, while conventional herbicides can adversely affect their quality. Laser weeding has emerged as an effective method for managing weeds in precious medicinal herbs. This technique allows for precise weed removal without chemical residue and protects the surrounding ecosystem. To maximize the effectiveness of this technology, accurate detection and localization of weeds in the medicinal herb fields are crucial. This paper studied seven species of weeds in the field of Dictamnus dasycarpus, a traditional Chinese medicinal herb. We propose a lightweight YOLO-Riny weed-detection algorithm and develop a YOLO-Riny-ByteTrack Multiple Object Tracking method by combining it with the ByteTrack algorithm. This approach enables accurate detection and localization of weeds in medicinal fields. The YOLO-Riny weed-detection algorithm is based on the YOLOv7-tiny network, which utilizes the FasterNet lightweight structure as the backbone, incorporates a lightweight upsampling operator, and adds structure reparameterization to the detection network for precise and rapid weed detection. The YOLO-Riny-ByteTrack Multiple Object Tracking method provides quick and accurate feedback on weed identification and location, reducing redundant weeding and saving on laser weeding costs. The experimental results indicate that (1) YOLO-Riny improves detection accuracy for Digitaria sanguinalis and Acalypha australis, ultimately amounting to 5.4% and 10%, respectively, compared to the original network. It also diminishes the model size by 2 MB and inference time by 10 ms, making it more suitable for resource-constrained edge devices. (2) YOLO-Riny-ByteTrack enhances Multiple Object Tracking accuracy by 3%, reduces ID switching by 14 times, and improves overall tracking accuracy by 3.4%. The proposed weed-detection and localization method for Dictamnus dasycarpus offers fast detection speed, high localization accuracy, and stable tracking, supporting the implementation of laser weeding during the seedling stage of Dictamnus dasycarpus.
A Critical Review on Soil Gas Analysis: Modern Technologies and Problems
Authors: Bannov Alexander G. , Trubin Igor’ V. , Zakharov Ilya K. , Maksimovskiy Evgeny A. , Kurmashov Pavel B.
Published: October 2024

In this review article, the main techniques for spectroscopic studies of gases in field conditions are considered. The issues related to the study of gas emissions from soils and the determination of their concentrations are analysed. The main types of spectroscopy used in portable devices for soil gas analysis, along with their design features and sampling approaches, are provided. Various studies aimed at optimising the operation of devices for analysing gases emitted from the soil, taking into account agronomic, agrochemical, and ecological specifics, are also presented. The effect of using different types of lasers and reflecting elements on the accuracy of optical measurements and the sensitivity to various substances in the gases is analysed.
The Path of African Millets (Pennisetum glaucum and Sorghum bicolor) to Iberia
Authors: Pérez-Jordà Guillem , Peña-Chocarro Leonor , Sabato Diego , Peralta Gómez Antonio , Ribera Agustí , García Borja Pablo , Negre Joan , Martín Civantos Jose María
Published: October 2024

Pearl millet (Pennisetum glaucum) is the most widely cultivated millet in Africa and India but has not yet been identified in Europe, while the earliest remains of sorghum (Sorghum bicolor) are attested in Italy in the fifth century AD. This paper presents evidence that pearl millet was introduced to Iberia during the 11th–12th centuries AD. This is the first documented evidence for this African crop in Europe. Sorghum, on the other hand, appears as a later introduction (14th century AD) in Iberia. We present archaeobotanical data from eight Andalusi sites in Valencia and Andalucía (southern Iberia) where both crops have been found. We have also examined medieval textual data where references to pearl millet appeared to be absent, and we conclude that the word “dacsa”, currently used to refer to sorghum, should be understood as a reference to pearl millet. From the 16th century onwards, this term was given to maize, when the American cereal replaced the African millets.
Evaluation of Two Commercial ELISA Kits for Measuring Equine Serum Gastrin Compared to Radioimmunoassay
Authors: Vokes Jessica R. , Gedye Kristene R. , Lovett Amy L. , de Kantzow Max C. , Shan Ran , Steel Catherine M. , Sykes Benjamin W.
Published: October 2024

Gastrin is an important hormone involved in gastric acid secretion. Despite its importance, validated methods other than radioimmunoassay (RIA) to assess serum gastrin concentrations in horses are lacking. This study aims to determine the agreement between ELISA and RIA in quantifying equine serum gastrin concentrations. Serum gastrin concentrations were quantified using two ELISA kits and RIA. Samples (196) from 14 horses at different time points were analyzed using one ELISA kit and RIA, selected samples (7) were analyzed using a second ELISA kit, and the correlation between methods was calculated. The level of agreement was analyzed by Bland-Altman analysis and differences between ELISA and RIA were plotted against averages for each sample. The Pearson correlation between gastrin concentrations measured by ELISA and the RIA was 0.27 and −0.32 for ELISA kit 1 and kit 2, respectively. Mean bias (ELISA-RIA) was 198.40 pg/mL (95% CI: −142.95–539.76) and −17.90 pg/mL (95% CI: −89.98–54.19) for ELISA kit 1 and kit 2, respectively. Measurements of horse gastrin by both ELISA methods were highly variable, with an unacceptable correlation to the reference method, RIA. Using non-validated ELISA methods to quantify horse gastrin cannot be recommended.
SNP-Based and Kmer-Based eQTL Analysis Using Transcriptome Data
Authors: Ge Mei , Li Chenyu , Zhang Zhiyan
Published: October 2024

Traditional expression quantitative trait locus (eQTL) mapping associates single nucleotide polymorphisms (SNPs) with gene expression, where the SNPs are derived from large-scale whole-genome sequencing (WGS) data or transcriptome data. While WGS provides a high SNP density, it also incurs substantial sequencing costs. In contrast, RNA-seq data, which are more accessible and less expensive, can simultaneously yield gene expressions and SNPs. Thus, eQTL analysis based on RNA-seq offers significant potential applications. Two primary strategies were employed for eQTL in this study. The first involved analyzing expression levels in relation to variant sites detected between populations from RNA-seq data. The second approach utilized kmers, which are sequences of length k derived from RNA-seq reads, to represent variant sites and associated these kmer genotypes with gene expression. We discovered 87 significant association signals involving eGene on the basis of the SNP-based eQTL analysis. These genes include DYNLT1, NMNAT1, and MRLC2, which are closely related to neurological functions such as motor coordination and homeostasis, play a role in cellular energy metabolism, and function in regulating calcium-dependent signaling in muscle contraction, respectively. This study compared the results obtained from eQTL mapping using RNA-seq identified SNPs and gene expression with those derived from kmers. We found that the vast majority (23/30) of the association signals overlapping the two methods could be verified by haplotype block analysis. This comparison elucidates the strengths and limitations of each method, providing insights into their relative efficacy for eQTL identification.
Synchronously Mature Intersex Japanese Flounder (Paralichthys olivaceus): A Rare Case
Authors: Han Tian , Cao Wei , San Lize , Xu Zixiong , Wang Guixing , He Zhongwei , Liu Yufeng , Ren Yuqin , Wang Yufen , Zhang Xiaoyan , Hou Jilun
Published: October 2024

Japanese flounder is usually gonochoristic, with gonads that are either testes or ovaries. Here, we report an unusual case of hermaphroditism in Japanese flounder captured from the Bohai Sea. In the intersex flounder, the membrane of the upper ovary was closely connected to the abdominal muscles and internal organs, and the eggs filled the entire abdomen. The lower ovary was small and closely connected to the testes. The testes contained few fully mature sperm. Both eggs and sperm were capable of fertilization. The levels of several reproduction-related hormones (17β-estradiol, 11-ketotestosterone, 17α, 20β-dihydroxyprogesterone, luteinizing hormone, follicle-stimulating hormone, and testosterone) in the intersex flounder were intermediate, between those in females and males. The results showed that the heterozygosity of the intersex flounder was 0.632, and there were 28 single-nucleotide polymorphisms in the cyp21a gene. Compared with that of wild flounder, the activity of 21-hydroxylase was reduced by approximately 20.0%, and expressions of cyp19a, amh, and dmrt1 differed. We present the first report of its kind, detailing the anatomy, hormonal endocrinology, molecular biology, and physiology of the intersex Japanese flounder.
Mitochondrial Genomes of Korean Native Black Goats Reveal Shared Phylogeographic Patterns and Demographic History
Authors: Kim Gaeun , Lee Eundo , Kim Kwanwoo , Kim Dongkyo , Kim Seungchang , Jin Daehyeok , Song Huimang , Mun Seongsil , Jeong Hankyeol , Kim Jaemin , Choi Bonghwan
Published: October 2024

This study explores the phylogeny of Korean native black goats through analysis of their complete mitochondrial DNA. The National Institute of Animal Science has gathered genetic material on purebred goats from isolated regions such as Tongyeong, Dangjin, and Jangsu, and is actively breeding them on a national level. These populations, however, are small and exhibit high inbreeding rates, highlighting the urgent need to preserve genetic diversity. The haplotype diversity within this native group is 0.659, with 39 haplotypes identified. By contrast, including international breeds in the analysis increases the overall haplotype diversity to 0.925 with 203 haplotypes identified, highlighting the limited genetic diversity among native black goats. For phylogenetic assessment, a neighbor-joining tree and median-joining network were constructed using identified haplogroups (A, B, C, D, G, and F) from prior studies. The results pinpoint the native black goats as closely related to, but distinct from, Haplogroup A with a bootstrap value of 98, establishing them as a separate clade (A’). This supports the notion of a shared ancestry with various global populations. This research provides essential data on the origins and evolutionary history of Korean native black goats, supporting conservation and breeding efforts aimed at enhancing genetic diversity.
Taurine Protects against Silica Nanoparticle-Induced Apoptosis and Inflammatory Response via Inhibition of Oxidative Stress in Porcine Ovarian Granulosa Cells
Authors: Chen Fenglei , Sun Jiarong , Ye Rongrong , Virk Tuba Latif , Liu Qi , Yuan Yuguo , Xu Xianyu
Published: October 2024

Silica nanoparticles (SNPs) induce reproductive toxicity through ROS production, which significantly limits their application. The protective effects of taurine (Tau) against SNP-induced reproductive toxicity remain unexplored. So this study aims to investigate the impact of Tau on SNP-induced porcine ovarian granulosa cell toxicity. In vitro, granulosa cells were exposed to SNPs combined with Tau. The localization of SNPs was determined by TEM. Cell viability was examined by CCK-8 assay. ROS levels were measured by CLSM and FCM. SOD and CAT levels were evaluated using ELISA and qPCR. Cell apoptosis was detected by FCM, and pro-inflammatory cytokine transcription levels were measured by qPCR. The results showed that SNPs significantly decreased cell viability, while increased cell apoptosis and ROS levels. Moreover, SOD and CAT were decreased, while IFN-α, IFN-β, IL-1β, and IL-6 were increased after SNP exposures. Tau significantly decreased intracellular ROS, while it increased SOD and CAT compared to SNPs alone. Additionally, Tau exhibited anti-inflammatory effects and inhibited cell apoptosis. On the whole, these findings suggest that Tau mitigates SNP-induced cytotoxicity by reducing oxidative stress, inflammatory response, and cell apoptosis. Tau may be an effective strategy to alleviate SNP-induced toxicity and holds promising application prospects in the animal husbandry and veterinary industry.
Association Between Dairy Production System and Milk Functionality Based on Analysis of miRNAs in Exosomes from Milk
Authors: Abou el qassim Loubna , Golan-Gerstl Regina , Reif Shimon , Royo Luis J.
Published: October 2024

Dairy farming practices significantly affect the nutritional and functional properties of milk. This study compares miRNAs in milk exosomes from extensive and intensive dairy systems and explores their potential implications for human consumers. Extensive systems are believed to produce milk of higher quality with better animal welfare compared to intensive systems. Milk samples from eight extensive and nine intensive dairy farms were analysed. Milk-derived extracellular vesicles were isolated through sequential ultracentrifugation and characterised through Dynamic Light Scattering and Nanosight to determine the size and the concentration of the extracellular vesicles, in addition to immunoblotting to ensure the presence of exosome-specific proteins in their membrane. miRNA levels were quantified using RT-qPCR, and metabolic pathways associated with miRNAs showing significant differences between farm groups were analysed. EVs from extensive farms had higher concentrations. Notably, bta-miR-451 levels were significantly higher in milk from extensive farms (p = 0.021). Like human miRNA hsa-miR-451, it is linked to pathways related to Parkinson’s disease and cancer. Our research suggests that milk production in extensive systems not only provides socioeconomic and environmental benefits but may also have positive effects on human health. Further research is warranted to explore the bioactive potential of these miRNAs and their implications for human health.
The Role of Antioxidant Transcription Factor Nrf2 and Its Activating Compounds in Systemic Lupus Erythematosus
Authors: Liu Lu , de Leeuw Karina , van Goor Harry , Westra Johanna
Published: October 2024

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which kidney involvement, so-called lupus nephritis (LN), is common and one of the most severe manifestations. Oxidative stress (OS) may play a role in the pathogenesis of LN through the exacerbation of inflammation and immune cell dysfunction/dysregulation. Nuclear factor erythroid 2-related factor 2 (Nrf2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene and is regarded as a central regulator of the antioxidative response. Nrf2-activating compounds have been shown to alleviate oxidative stress in cells and tissues of lupus-prone mice. Although the precise mechanisms of Nrf2 activation on the immune system in SLE remain to be elucidated, Nrf2-activating compounds are considered novel therapeutical options to suppress OS and thereby might alleviate disease activity in SLE, especially in LN. This review therefore summarizes the role of the Nrf2 signaling pathway in the pathogenesis of SLE with LN and describes compounds modulating this pathway as potential additional clinical interventions.
Stochastic Parameterization of Moist Physics Using Probabilistic Diffusion Model
Authors: Wang Leyi , Wang Yiming , Hu Xiaoyu , Wang Hui , Zhou Ruilin
Published: October 2024

Deep-learning-based convection schemes have garnered significant attention for their notable improvements in simulating precipitation distribution and tropical convection in Earth system models. However, these schemes struggle to capture the stochastic nature of moist physics, which can degrade the simulation of large-scale circulations, climate means, and variability. To address this issue, a stochastic parameterization scheme called DIFF-MP, based on a probabilistic diffusion model, is developed. Cloud-resolving data are coarse-grained into resolved-scale variables and subgrid contributions, which serve as conditional inputs and outputs for DIFF-MP. The performance of DIFF-MP is compared with that of generative adversarial networks and variational autoencoders. The results demonstrate that DIFF-MP consistently outperforms these models in terms of prediction error, coverage ratio, and spread–skill correlation. Furthermore, the standard deviation, skewness, and kurtosis of the subgrid contributions generated by DIFF-MP more closely match the test data than those produced by the other models. Interpretability experiments confirm that DIFF-MP’s parameterization of moist physics is physically consistent.
Si3N4-Assisted Densification Sintering of Na3Zr2Si2PO12 Ceramic Electrolyte toward Solid-State Sodium Metal Batteries
Authors: Sun Wenwen , Li Yang , Sun Chen , Sun Zheng , Jin Haibo , Zhao Yongjie
Published: October 2024

The solid-state metal battery with solid-state electrolytes has been considered the next generation of energy storage technology owing to its superior safety and high energy density. But, unfavorable ionic conductivity and interfacial problems make it difficult to widely use in practice. In this work, Si3N4 was rationally introduced into the NASICON matrix as a sintering aid, and the influence of Si3N4 on the crystal phase, microstructure, electrochemical and electrical performance of Na3Zr2Si2PO12 (NZSP) ceramic was systematically studied. The results demonstrate that the introduction of Si3N4 can effectively lower the densification sintering temperature of Na3Zr2Si2PO12 electrolyte and enhance the room temperature ionic conductivity of the NZSP to 3.82 × 10−4 S cm−1. In addition, since Si3N4 has a high thermal conductivity and can inhibit the transmission of electrons between the grains of the electrolyte matrix, it will effectively hinder the generation of sodium metal dendrites and relieve the concentration of the heat source. Moreover, owing to the desirable interface compatibility of the Na and NZSP-Si3N4 electrolyte, the Na/NZSP-1150-1%Si3N4/Na symmetric battery exhibits excellent stability, and the electrode/electrolyte interface still maintains good integrity even after long-term cycling. The assembled Na/NZSP-1150-1%Si3N4/Na3.5V0.5Mn0.5Fe0.5Ti0.5(PO4)3 cell manifests an initial specific capacity of 152.5 mA h g−1, together with an initial Coulombic efficiency of 99.8%. Furthermore, after 200 cycles, the battery displays a capacity retention rate of 82%.
Manipulating Electrolyte Interface Chemistry Enables High-Performance TiO2 Anode for Sodium-Ion Batteries
Authors: Wang Qi , Zhang Rui , Sun Dan , Wang Haiyan , Tang Yougen
Published: October 2024

Titanium dioxide (TiO2) has emerged as a candidate anode material for sodium-ion batteries (SIBs). However, their applications still face challenges of poor rate performance and low initial coulomb efficiency (ICE), which are induced by the unstable solid-electrolyte interface (SEI) and sluggish Na+ diffusion kinetics in conventional ester-based electrolytes. Herein, inspired by the electrode/electrolyte interfacial chemistry, tetrahydrofuran (THF) is exploited to construct an advanced electrolyte and reveal the relationship between the improved electrochemical performance and the derived SEI film on TiO2 anode. The robust and homogeneously distributed F-rich SEI film formed in THF electrolyte favors fast interfacial charge transfer dynamics and excellent interfacial stability. As a result, the THF electrolyte endows the TiO2 anode with greatly improved ICE (64.5%), exceptional rate capabilities (186 mAh g−1 at 5.0 A g−1), and remarkable cycling stability. This study elucidates the control of interfacial chemistry by rational electrolyte design and offers insights into the development of high-performance and long-lifetime TiO2 anode.
Development of Biomaterials to Modulate the Function of Macrophages in Wound Healing
Authors: Li Jiacheng , Xie Jiatong , Wang Yaming , Li Xixian , Yang Liqun , Zhao Muxin , Chen Chaoxian
Published: October 2024

Wound healing is a complex and precisely regulated process that encompasses multiple stages, including inflammation, anti-inflammation, and tissue repair. It involves various cells and signaling molecules, with macrophages demonstrating a significant degree of plasticity and playing a crucial regulatory role at different stages. In recent years, the use of biomaterials, which include both natural and synthetic polymers or macromolecules, has proliferated for the purpose of enhancing wound healing. This review summarizes how these diverse biomaterials promote wound healing by modulating macrophage behavior and examines the broader implications of these modulations. Additionally, we discuss the limitations associated with the clinical application of immunomodulatory biomaterials and propose potential solutions. Finally, we look towards future developments in the design of immunomodulatory biomaterials intended to enhance wound healing.
Genetic Testing as a Source of Information Driving Diagnosis and Therapeutic Plan in a Multidisciplinary Case
Authors: Grippaudo Cristina , Cafiero Concetta , Grande Nicola Maria , Dassatti Leonardo , Palmirotta Raffaele , Castagnola Raffaella , Isola Gaetano
Published: October 2024

In many cases, the etiopathogenesis of oral cavity diseases depends on the presence of variants in some genes. Being able to identify these variants defines the possibilities and limits of therapies. This multidisciplinary case describes several pathologies of the oral cavity in a young patient affected by type 1 diabetes. The patient presented with an impacted palatal canine. Further investigation revealed cervical root resorption of the upper right central incisor. Genetic testing was performed for interleukin, VDR receptor genes, and the evaluation of periodontopathogenic bacteria. The mutational analysis carried out for the VDR polymorphisms and the IL1A, IL1B, IL6, and IL10 polymorphisms showed the presence of pathogenetic variants. The results for bacterial load showed the presence of periodontal pathogenes. The first intervention was the intentional replantation of the incisor. The second intervention was the orthodontic recovery of the impacted canine, using light forces and a hybrid anchorage with a miniscrew. At the end of orthodontic treatment, a crack was found in the upper left first premolar, which was extracted. Throughout treatment, non-invasive periodontal interventions were performed periodically to control periodontal inflammation. This case is an example of the integration of genetic analyses into the multidisciplinary diagnostic pathway.
Modulation of Carnitine Palmitoyl Transferase 1b Expression and Activity in Muscle Pathophysiology in Osteoarthritis and Osteoporosis
Authors: Greggi Chiara , Montanaro Manuela , Scioli Maria Giovanna , Puzzuoli Martina , Gino Grillo Sonia , Scimeca Manuel , Mauriello Alessandro , Orlandi Augusto , Gasbarra Elena , Iundusi Riccardo , Pucci Sabina , Tarantino Umberto
Published: October 2024

In the pathophysiology of osteoarthritis and osteoporosis, articular cartilage and bone represent the target tissues, respectively, but muscle is also involved. Since many changes in energy metabolism occur in muscle with aging, the aim of the present work was to investigate the involvement of carnitine palmitoyl transferase 1b (Cpt1b) in the muscle pathophysiology of the two diseases. Healthy subjects (CTR, n = 5), osteoarthritic (OA, n = 10), and osteoporotic (OP, n = 10) patients were enrolled. Gene expression analysis conducted on muscle and myoblasts showed up-regulation of CPT1B in OA patients; this result was confirmed by immunohistochemical and immunofluorescence analyses and enzyme activity assay, which showed increased Cpt1b activity in OA muscle. In addition, CPT1B expression resulted down-regulated in cultured OP myoblasts. Given the potential involvement of Cpt1b in the modulation of oxidative stress, we investigated ROS levels, which were found to be lower in OA myoblasts, and gene expression of nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4 (Nox4), which resulted up-regulated in OA cells. Finally, the immunofluorescence of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) showed a decreased expression in OP myoblasts, with respect to CTR and OA. Contextually, through an ultrastructural analysis conducted by Transmission Electron Microscopy (TEM), the presence of aberrant mitochondria was observed in OP muscle. This study highlights the potential role of Cpt1b in the regulation of muscle homeostasis in both osteoarthritis and osteoporosis, allowing for the expansion of the current knowledge of what are the molecular biological pathways involved in the regulation of muscle physiology in both diseases.
Human Herpesvirus-6B Infection and Alterations of Gut Microbiome in Patients with Fibromyalgia: A Pilot Study
Authors: Ievina Lauma , Fomins Nikita , Gudra Dita , Kenina Viktorija , Vilmane Anda , Gravelsina Sabine , Rasa-Dzelzkaleja Santa , Murovska Modra , Fridmanis Davids , Nora-Krukle Zaiga
Published: October 2024

Fibromyalgia (FM) is a chronic disorder characterized by widespread musculoskeletal pain often accompanied by fatigue, sleep disturbances, memory issues, and mood disorders. The exact cause of FM remains unknown, and diagnosis is typically based on a history of persistent widespread pain, as there are no objective biomarkers usable in diagnosis of this disorder available. The aim of this study was to identify measurable indicators specific to FM with potential as biomarkers. This study included 17 individuals diagnosed with FM and 24 apparently healthy persons. Using real-time polymerase chain reaction (qPCR), we detected the presence of human herpesvirus (HHV)-6A and B genomic sequences in DNA isolated from peripheral blood mononuclear cells (PBMCs) and buccal swabs. HHV-6-specific IgG and IgM class antibodies, along with proinflammatory cytokine levels, were measured using enzyme-linked immunosorbent assay (ELISA) and bead-based multiplex assays. Additionally, the gut microbiome was analyzed through next-generation sequencing. HHV-6B was more frequently detected in the PBMCs of FM patients. FM patients with a body mass index (BMI) of 30 or higher exhibited elevated cytokine levels compared to the control group with the same BMI range. Gut microbiome analysis revealed significant differences in both α-diversity and β-diversity between the FM and control groups, indicating a shift in species abundance in the FM group.
Phosphatidylserine: A Novel Target for Ischemic Stroke Treatment
Authors: Guo Jiaqi , He Jiachen , Xu Shuaili , Chen Xi , Zhu Zhanwei , Ji Xunming , Wu Di
Published: October 2024

Over the past 40 years, research has heavily emphasized stroke treatments that directly target ischemic cascades after stroke onset. Much attention has focused on studying neuroprotective drugs targeting one aspect of the ischemic cascade. However, the single-target therapeutic approach resulted in minimal clinical benefit and poor outcomes in patients. Considering the ischemic cascade is a multifaceted and complex pathophysiological process with many interrelated pathways, the spotlight is now shifting towards the development of neuroprotective drugs that affect multiple aspects of the ischemic cascade. Phosphatidylserine (PS), known as the “eat-me” signal, is a promising candidate. PS is involved in many pathophysiological changes in the central nervous system after stroke onset, including apoptosis, inflammation, coagulation, and neuronal regeneration. Moreover, PS might also exert various roles in different phases after stroke onset. In this review, we describe the synthesis, regulation, and function of PS under physiological conditions. Furthermore, we also summarize the different roles of PS after stroke onset. More importantly, we also discuss several treatment strategies that target PS. We aim to advocate a novel stroke care strategy by targeting PS through a translational perspective.
Unveiling the Complexities of Hereditary Angioedema
Authors: Tutunaru Cristina Violeta , Ică Oana Maria , Mitroi George G. , Neagoe Carmen Daniela , Mitroi George F. , Orzan Olguța Anca , Bălăceanu-Gurău Beatrice , Ianoși Simona Laura
Published: October 2024

Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic disorder, constituting approximately 2% of all clinical cases of angioedema, with a global prevalence estimated between 1 in 50,000 and 1 in 150,000 individuals. The condition affects individuals of all genders and ethnic backgrounds without significant variation. HAE is classified into three types. Type I HAE, which accounts for 85% of cases, is characterized by a deficiency of the C1 esterase inhibitor (C1-INH) gene. Type II HAE, making up 15% of cases, involves a dysfunctional C1-INH. Type III HAE, which represents about 5% to 10% of cases, is often estrogen-dependent and although several mutations have been identified, it typically involves normal C1-INH activity. Despite the differences in C1-INH functionality, all three types of HAE manifest with similar clinical symptoms. HAE leads to recurrent episodes of non-pruritic angioedema, which occurs in the absence of urticaria. Breakthroughs in understanding HAE pathophysiology have revolutionized treatment, leading to the development of highly targeted therapies for both acute management and long-term prevention. Meanwhile, cutting-edge advancements in omics technologies are unlocking new possibilities for biomarker discovery, paving the way for more precise diagnoses and personalized treatment strategies that could significantly enhance patient outcomes. This review will delve into the intricate pathophysiology, diverse clinical presentations, and diagnostic challenges of HAE while exploring emerging biomarkers and innovative approaches to therapeutic management and prevention strategies. Additionally, it will underscore the vital importance of screening family members of affected individuals, even when symptoms are not present.
Yap Is a Nutrient Sensor Sensitive to the Amino Acid L-Isoleucine and Regulates the Expression of Ctgf in Cardiomyocytes
Authors: Nelson Victoria L. , Eadie Ashley L. , Perez Lester , Madhu Malav , Platt Mathew , Mercer Angella , Pulinilkunnil Thomas , Kienesberger Petra , Simpson Jeremy A. , Brunt Keith R.
Published: October 2024

Myocardial infarction and reperfusion constitute a complex injury consisting of many distinct molecular stress patterns that influence cardiomyocyte survival and adaptation. Cell signalling, which is essential to cardiac development, also presents potential disease-modifying opportunities to recover and limit myocardial injury or maladaptive remodelling. Here, we hypothesized that Yap signalling could be sensitive to one or more molecular stress patterns associated with early acute ischemia. We found that Yap, and not Taz, expression patterns differed in a post-myocardial infarct compared to a peri-infarct region of rat hearts post-myocardial infarction, suggesting cell specificity that would be challenging to resolve for causation in vivo. Using H9c2 ventricular myotubes in vitro as a model, Yap levels were determined to be more sensitive to nutrient deprivation than other stress patterns typified by ischemia within the first hour of stress. Moreover, this is mediated by amino acid availability, predominantly L-isoleucine, and influences the expression of connective tissue growth factor (Ctgf)—a major determinant of myocardial adaptation after injury. These findings present novel opportunities for future therapeutic development and risk assessment for myocardial injury and adaptation.
Flow Cytometric Immunophenotyping: Minimal Differences in Fresh and Cryopreserved Peripheral Blood Mononuclear Cells versus Whole Blood
Authors: Tompa Andrea , Johansson Junko , Islander Ulrika , Faresjö Maria
Published: October 2024

Background/Objectives: Flow cytometry is a convenient tool in immunophenotyping for monitoring the status of immunological conditions and diseases. The aim of this study was to investigate the effect of isolation and cryopreservation by flow cytometric analysis on subpopulations of CD4+ T helper (Th), T regulatory (Treg), CD8+ T cytotoxic (Tc), CD56+ NK, CD19+ B and monocytes. Freshly isolated and cryopreserved peripheral blood mononuclear cells (PBMCs) were compared to fresh whole blood. Methods: Peripheral blood was collected from healthy donors and prepared for flow cytometric analysis using the same panels of antibodies throughout the study. Results: Comparisons between fresh (F)- and cryopreserved (C)-PBMCs showed no major differences in percentages of CD4+, Th1, Th2 and CD4+CD25+CD127low Treg cells. No differences in percentage of CD8+ or subpopulations of naive/stem, central or effector memory cells were observed between F- and C-PBMCs. The percentage of CD56+ NK cells, CD19+ B cells or classical and nonclassical monocytes did not differ between F-and C-PBMCs either. On the contrary, whole blood had lower percentages of Th and NK cells but higher percentages of Th1, Th17, Th1Th17, Tregs, Tc and B cells compared to C-PBMCs, while it had a higher proportion of Tc compared to F-PBMCs. Conclusions: Flow cytometric immunophenotyping minimally differs between freshly isolated and cryopreserved PBMCs. This implies the possibility of cryostorage of cohorts for later analysis. Importantly, care must be taken when comparing results from whole blood with isolated and cryopreserved PBMCs. Collectively, these results can contribute to the standardization of flow cytometric protocols in both clinical and research settings.
Spasmolytic Activity and Anti-Inflammatory Effect of Novel Mebeverine Derivatives
Authors: Stoyanova Mihaela , Milusheva Miglena , Gledacheva Vera , Stefanova Iliyana , Todorova Mina , Kircheva Nikoleta , Angelova Silvia , Pencheva Mina , Stojnova Kirila , Tsoneva Slava , Nikolova Stoyanka
Published: October 2024

Background: Irritable bowel syndrome (IBS) has a major negative influence on quality of life, causing cramps, stomach pain, bloating, constipation, etc. Antispasmodics have varying degrees of efficacy. Mebeverine, for example, works by controlling bowel movements and relaxing the muscles of the intestines but has side effects. Therefore, more efficient medication is required. Methods: In the current study, we investigated the synthesis of novel mebeverine analogs and determined ex vivo their spasmolytic and in vitro and ex vivo anti-inflammatory properties. The ability to influence both contractility and inflammation provides a dual-action approach, offering a comprehensive solution for the prevention and treatment of both conditions. Results: The results showed that all the compounds have better spasmolytic activity than mebeverine and good anti-inflammatory potential. Among the tested compounds, 3, 4a, and 4b have been pointed out as the most active in all the studies conducted. To understand their mechanism of activity, molecular docking simulation was investigated. The docking analysis explained the biological activities with their calculated Gibbs energies and possibilities for binding both centers of albumin. Moreover, the calculations showed that molecules can bind also the two muscarinic receptors and interleukin-β, hence these structures would exert a positive therapeutic effect owed to interaction with these specific receptors/cytokine. Conclusions: Three of the tested compounds have emerged as the most active and effective in all the studies conducted. Future in vivo and preclinical experiments will contribute to the establishment of these novel mebeverine derivatives as potential drug candidates against inflammatory diseases in the gastrointestinal tract.
Comparative Analysis of Resmetirom vs. FGF21 Analogs vs. GLP-1 Agonists in MASLD and MASH: Network Meta-Analysis of Clinical Trials
Authors: Ayesh Hazem , Beran Azizullah , Suhail Sajida , Ayesh Suhail , Niswender Kevin
Published: October 2024

Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic-Dysfunction Associated Steatohepatitis (MASH) are linked to obesity, type 2 diabetes, and metabolic syndrome, increasing liver-related morbidity and cardiovascular risk. Recent therapies, including Resmetirom, FGF21 analogs, and GLP-1 agonists, have shown promise. This network meta-analysis evaluates their comparative efficacy and safety. Methods: A literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library. Included clinical trials addressed MASLD or MASH with Resmetirom, FGF21 analogs, or GLP-1 agonists. Statistical analyses used a random-effects model, calculating mean differences (MD) and relative risks (RR), with heterogeneity assessed using τ2, I2, and Q statistics. Results: MASH resolution was significantly higher for FGF21 (RR 4.84, 95% CI: 2.59 to 9.03), Resmetirom showed the most significant reduction in MRI-PDFF (MD −18.41, 95% CI: −23.60 to −13.22) and >30% fat reduction (RR 3.56, 95% CI: 2.41 to 5.26). Resmetirom significantly reduced ALT (MD −15.71, 95% CI: −23.30 to −8.13), AST (MD −12.28, 95% CI: −21.07 to −3.49), and GGT (MD −19.56, 95% CI: −34.68 to −4.44). FGF21 and GLP-1 also reduced these markers. Adverse events were significantly higher with Resmetirom (RR 1.47, 95% CI: 1.24 to 1.74), while GLP-1 and FGF21 showed non-significant trends towards increased risk. Conclusions: Resmetirom and FGF21 show promise in treating MASLD and MASH, with Resmetirom particularly effective in reducing liver fat and improving liver enzymes. GLP-1 agonists also show benefits but to a lesser extent. Further long-term studies are needed to validate these findings and assess cost-effectiveness.
Luteolin (LUT) Induces Apoptosis and Regulates Mitochondrial Membrane Potential to Inhibit Cell Growth in Human Cervical Epidermoid Carcinoma Cells (Ca Ski)
Authors: Pei Sung-Nan , Lee Kuan-Ting , Rau Kun-Ming , Lin Tsung-Ying , Tsai Tai-Hsin , Hsu Yi-Chiang
Published: October 2024

Background/Objectives: Luteolin (LUT) is a natural flavonoid with known anti-inflammatory, antioxidant, and anti-cancer properties. Cervical cancer, particularly prevalent in certain regions, remains a significant health challenge due to its high recurrence and poor response to treatment. This study aimed to investigate the anti-tumor effects of LUT on human cervical epidermoid carcinoma cells (Ca Ski), focusing on cell growth inhibition, apoptosis induction, and regulation of mitochondrial membrane potential. Methods: Ca Ski cells were treated with varying concentrations of LUT (0, 25, 50, 100 µM) for different time periods (24, 48, 72 hours). Cell viability was measured using the MTT assay, apoptosis was assessed by flow cytometry with annexin V-FITC/PI staining, and changes in mitochondrial membrane potential were evaluated using JC-1 staining. Caspase-3 activation was examined by flow cytometry, and expression of apoptosis-related proteins (caspase-3, -8, -9, AIF) was analyzed via Western blotting. Results: LUT significantly inhibited the growth of Ca Ski cells in a dose- and time-dependent manner, with the most pronounced effects observed at 100 µM over 72 hours. Flow cytometry confirmed that LUT induced apoptosis without causing necrosis. Mitochondrial membrane potential was reduced after LUT treatment, coinciding with increased caspase-3 activation. Western blot analysis revealed the upregulation of pro-apoptotic proteins caspase-3, -8, -9, and AIF, indicating that LUT induces apoptosis through the intrinsic mitochondrial pathway. Conclusions: Luteolin effectively inhibits cervical cancer cell proliferation and induces apoptosis by disrupting mitochondrial membrane potential and activating caspases. These findings suggest that LUT holds potential as a therapeutic agent for cervical cancer, with further studies needed to explore its in vivo efficacy and broader clinical applications.
Remarks on Selected Morphological Aspects of Cancer Neuroscience: A Microscopic Photo Review
Authors: Iżycka-Świeszewska Ewa , Gulczyński Jacek , Sejda Aleksandra , Kitlińska Joanna , Galli Susana , Rogowski Wojciech , Sigorski Dawid
Published: October 2024

Background: This short review and pictorial essay presents a morphological insight into cancer neuroscience, which is a complex and dynamic area of the pathobiology of tumors. Methods: We discuss the different methods and issues connected with structural research on tumor innervation, interactions between neoplastic cells and the nervous system, and dysregulated neural influence on cancer phenotypes. Results: Perineural invasion (PNI), the most-visible cancer–nerve relation, is briefly presented, focusing on its pathophysiology and structural diversity as well as its clinical significance. The morphological approach to cancer neurobiology further includes the analysis of neural density/axonogenesis, neural network topographic distribution, and composition of fiber types and size. Next, the diverse range of neurotransmitters and neuropeptides and the neuroendocrine differentiation of cancer cells are reviewed. Another morphological area of cancer neuroscience is spatial or quantitative neural-related marker expression analysis through different detection, description, and visualization methods, also on experimental animal or cellular models. Conclusions: Morphological studies with systematic methodologies provide a necessary insight into the structure and function of the multifaceted tumor neural microenvironment and in context of possible new therapeutic neural-based oncological solutions.
Differential Resting-State Brain Characteristics of Skeleton Athletes and Non-Athletes: A Preliminary Resting-State fMRI Study
Authors: Jin Xinhong , Chen Shuying , Qi Yapeng , Zhou Qichen , Wang Jian , Wang Yingying , Zhou Chenglin
Published: October 2024

(1) Background: This study investigates the resting-state brain characteristics of skeleton athletes compared to healthy age-matched non-athletes, using resting-state fMRI to investigate long-term skeleton-training-related changes in the brain. (2) Methods: Eleven skeleton athletes and twenty-three matched novices with no prior experience with skeleton were recruited. Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity analyses were explored to investigate resting-state functional magnetic resonance imaging (rs-fMRI) data, aiming to elucidate differences in resting-state brain function between the two groups. (3) Results: Compared to the control group, skeleton athletes exhibited significantly higher ALFF in the left fusiform, left inferior temporal gyrus, right inferior frontal gyrus, left middle temporal gyrus, left and right insula, left Rolandic operculum, left inferior frontal gyrus, and left superior temporal gyrus. Skeleton athletes exhibit stronger functional connectivity in brain regions associated with cognitive and motor control (superior frontal gyrus, insula), as well as those related to reward learning (putamen), visual processing (precuneus), spatial cognition (inferior parietal), and emotional processing (amygdala), during resting-state brain function. (4) Conclusions: The study contributes to understanding how motor training history shapes skeleton athletes’ brains, which have distinct neural characteristics compared to the control population, indicating potential adaptations in brain function related to their specialized training and expertise in the sport.