bluuebunny/crossref_metadata_2025 huggingface dataset:
A Study on the Automation of Fish Species Recognition and Body Length Measurement System
Authors: Kang Seung-Beom , Kim Seung-Gyu , Lee Sang-Hyun , Im Tae-Ho
Published: September 2024

The rapid depletion of fishery resources has led to the global implementation of Total Allowable Catch (TAC) systems. However, the current manual survey methods employed by land-based inspectors show limitations in accuracy and efficiency. This study proposes an automated system for fish species recognition and body length measurement, utilizing the RT-DETR (Real-Time Detection Transformer) model and ARCore technology to address these issues. The proposed system employs smartphone Time of Flight (ToF) functionality to measure object distance and automatically calculates the weight of 11 TAC-managed fish species by measuring their body length and height. Experimental results reveal that the RT-DETR-x model outperformed the YOLOv8x model by achieving an average mAP50 value 2.3% higher, with a mean recognition accuracy of 96.5% across the 11 species. Furthermore, the ARCore-based length measurement technique exhibited over 95% accuracy for all species. This system is expected to minimize data omissions and streamline labor-intensive processes, thereby contributing to the efficient operation of the TAC system and sustainable management of fishery resources. The study presents an innovative approach that significantly enhances the accuracy and efficiency of fishery resource management, providing a crucial technological foundation for the advancement of future fisheries management policies.
Influence of a Background Shear Flow on Cyclone–Anticyclone Asymmetry in Ageostrophic Balanced Flows
Authors: McKiver William Joseph
Published: September 2024

In this paper, we study how cyclonic and anticyclonic vortices adapt their shape and orientation to a background shear flow in an effort to understand geophysical vortices. Here we use a balanced model that incorporates the effects of rotation and density stratification to model the case of an isolated vortex of uniform potential vorticity subjected to a background shear flow that mimics the effect of surrounding vortices. We find equilibrium states and analyze their linear stability to determine the vortex characteristics at the margin of stability. Differences are found between the cyclonic and anticyclonic equilibria depending on the background flow parameters. When there is only horizontal strain, the vertical aspect ratio of the vortex does not change, whereas increasing the imposed background strain rate causes a change in the horizontal cross section, with cyclones being more deformed than anticyclones for a given value of strain. Vertical shear not only causes changes in the vertical axis but also causes the vortex to tilt away from it upright position. Overall, anticyclonic equilibria tend to have a more circular horizontal cross section, a longer vertical axis, and a larger tilt angle with respect to cyclonic equilibria. The strongest asymmetry between the horizontal cross section of cyclonic and anticyclonic vortices occurs for low values of vertical shear, while the strongest asymmetry in the vertical axes and tilt angle occurs for large vertical shear. Finally, by expanding the vortex shape and orientation in terms of the strain rate, we derive simple formulas that provide insights into how the vortex equilibria depend on the background flow.
Enzymatic Preparation, Identification by Transmembrane Channel-like 4 (TMC4) Protein, and Bioinformatics Analysis of New Salty Peptides from Soybean Protein Isolate
Authors: Zhao Ziying , Yang Mingzhe , Li Zhijiang , Tang Huacheng , Song Xuejian , Wang Xinhui
Published: September 2024

To address the public health challenges posed by high-salt diets, this study utilized pepsin and flavourzyme for the continuous enzymatic hydrolysis of a soy protein isolate (SPI). The separation, purification, and identification of salt-containing peptides in SPI hydrolysate were conducted using ultrafiltration (UF), gel filtration chromatography (GFC), and Liquid Chromatography–Mass Spectrometry/Mass Spectrometry (LC-MS/MS). Subsequently, a molecular docking model was constructed between salt receptor protein transmembrane channel 4 (TMC4) and the identified peptides. Basic bioinformatics screening was performed to obtain non-toxic, non-allergenic, and stable salt peptides. After the enzymatic hydrolysis, separation, and purification of SPI, a component with a sensory evaluation score of 7 and an electronic tongue score of 10.36 was obtained. LC-MS/MS sequencing identified a total of 1697 peptides in the above component, including 84 potential salt-containing peptides. A molecular docking analysis identified seven peptides (FPPP, GGPW, IPHF, IPKF, IPRR, LPRR, and LPHF) with a strong theoretical salty taste. Furthermore, residues Glu531, Asp491, Val495, Ala401, and Phe405 of the peptides bound to the TMC4 receptor through hydrogen bonds, hydrophobic interactions, and electrostatic interactions, thereby imparting a significant salty taste. A basic bioinformatics analysis further revealed that IPHF, LPHF, GGPW, and IPKF were non-toxic, non-allergenic, and stable salt-containing peptides. This study not only provides a new sodium reduction strategy for the food industry, but also opens up new avenues for improving the public’s healthy eating habits.
Positive Selection Drives the Evolution of the Structural Maintenance of Chromosomes (SMC) Complexes
Authors: Forni Diego , Mozzi Alessandra , Sironi Manuela , Cagliani Rachele
Published: September 2024

Structural Maintenance of Chromosomes (SMC) complexes are an evolutionary conserved protein family. In most eukaryotes, three SMC complexes have been characterized, as follows: cohesin, condensin, and SMC5/6 complexes. These complexes are involved in a plethora of functions, and defects in SMC genes can lead to an increased risk of chromosomal abnormalities, infertility, and cancer. To investigate the evolution of SMC complex genes in mammals, we analyzed their selective patterns in an extended phylogeny. Signals of positive selection were identified for condensin NCAPG, for two SMC5/6 complex genes (SMC5 and NSMCE4A), and for all cohesin genes with almost exclusive meiotic expression (RAD21L1, REC8, SMC1B, and STAG3). For the latter, evolutionary rates correlate with expression during female meiosis, and most positively selected sites fall in intrinsically disordered regions (IDRs). Our results support growing evidence that IDRs are fast evolving, and that they most likely contribute to adaptation through modulation of phase separation. We suggest that the natural selection signals identified in SMC complexes may be the result of different selective pressures: a host-pathogen arms race in the condensin and SMC5/6 complexes, and an intragenomic conflict for meiotic cohesin genes that is similar to that described for centromeres and telomeres.
Humanist Anecdotes in Hard Times: F. C. Weiskopf and Lenka Reinerová
Authors: Schonfield Ernest
Published: September 2024

This article examines humanist anecdotes about the turbulent times of the mid-twentieth century by F. C. Weiskopf and Lenka Reinerová. It provides a comparative reading of Weiskopf’s Elend und Größe unserer Tage. Anekdoten 1933–1947 (1950) and Reinerová’s “Tragischer Irrtum und richtige Diagnose” (published in Mandelduft, 1998). The anecdotal form of these texts harks back to the popular Enlightenment (Volksaufklärung) anecdotes of Heinrich von Kleist and Johann Peter Hebel, published in 1810–1811 during the Napoleonic Wars. The anecdote as a literary form is particularly well suited to the representation of wartime and political repression. While Weiskopf’s anecdotes explore cruelty and heroism under the Nazi dictatorship, Reinerová’s autobiographical text juxtaposes crisis points in her own life—her time as a political prisoner in France in 1939 and in Czechoslovakia in 1952–1953; her return to Prague as her family’s sole survivor; and her periodic cancer treatment from 1948 onwards. Reinerová describes how the kindness of ordinary people, and her own optimism and resilience, helped her through the worst times. Her lived experience gives her authority as a storyteller in Walter Benjamin’s sense. Both authors contrast human extremes—the good and the bad—yet both remain optimistic about the human capacity for good.
Lateral and Medial Elbow Tendinopathy and Previous Injuries to Adjacent Joints: A Multicenter Observational Study
Authors: Vinolo-Gil Maria Jesus , García-Campanario Ismael , Estebanez-Pérez María José , Rodríguez-Huguet Manuel , Linares-Gago Marta , Martin-Vega Francisco Javier
Published: September 2024

Background: Lateral and medial elbow tendinopathies are common soft tissue disorders affecting 1–3% of the general population, causing significant pain and functional impairment in the elbow and upper limb. While often associated with overuse and repetitive strain, their exact etiology, including potential associations with prior injuries in adjacent joints, remains unclear. This preliminary study aims to explore the distribution of lateral and medial elbow tendinopathies and investigate the occurrence of previous lesions in adjacent joints among diagnosed individuals, providing foundational insights for future research. Methods: A multicenter cross-sectional observational study was conducted involving 90 subjects diagnosed with lateral and/or medial elbow tendinopathy. The data collection occurred during the initial consultations, including demographic information, clinical assessments, and history of prior injuries in adjacent joints. Results: Among the sample, 44.4% reported prior injuries to adjacent joints in the affected upper limb, with 45.6% of these injuries identified as musculotendinous in nature. The analysis also showed that the type of elbow tendinopathy was significantly associated with sex (p = 0.01) and occupational origin (p = 0.022). Conclusions: While a notable percentage of the subjects reported prior musculoskeletal injuries in the same limb, the study’s geographic limitations and reliance on self-reported data introduce potential recall bias. These preliminary findings suggest a possible relationship between prior adjacent joint injuries and elbow tendinopathy. Further research with larger sample sizes and more rigorous study design is needed to confirm these observations and explore the underlying mechanisms.
Varying Light Intensities Affect Lettuce Growth and Physiology in Controlled Indoor Environments
Authors: Mayorga-Gomez Andres M. , van Iersel Marc W. , Ferrarezi Rhuanito Soranz
Published: September 2024

Agriculture in controlled environments has gained popularity over time. Compared to traditional agriculture, controlled environments emerge as an alternative to mitigate the negative impacts of conventional farming methods. However, controlled environment agriculture, particularly plant factories with artificial lighting, incurs higher electricity costs, primarily for supplemental lighting and dehumidification of the cultivation area. Given these high costs, it is crucial to understand how efficiently plants utilize available light to convert it into biomass. This understanding can be used to design lighting strategies to reduce electricity usage. In this study, we cultivated ‘Rex’ lettuce (Lactuca sativa) plants on a soilless substrate and used an ebb-and-flow system for irrigation and fertilization. Plants grew in varying photosynthetic photon flux density (PPFD) levels ranging from 125 to 375 µmol·m−2·s−1 and were assessed for various physiological responses. Our findings revealed that plants exposed to higher light levels exhibited greater final dry weight, increased photosynthetic activity, higher water use efficiency, and accelerated growth compared to those under lower light conditions. Notably, plants subjected to higher light intensities did not show a significant increase in transpiration, suggesting a potential trade-off between energy expenditure on supplemental lighting and dehumidification. This finding opens the possibility of reducing energy consumption for dehumidification and achieving economic savings by subjecting plants to optimal growing conditions for shorter durations. This depends on whether higher savings on dehumidification are achieved compared to the energy required to maintain high PPFD levels.
Climate Influence on Leaf Appearance and Ligustroflavone and Rhoifolin Compounds of Turpinia arguta (Lindl.) Seem. from Different Chinese Habitats
Authors: Ji Hongli , Cai Junhuo , Chen Chao , Song Xiaomin , Luo Yun , Yu Jinbao , Zhang Yang , Tao Xiuhua
Published: September 2024

The dry leaf of Turpinia arguta (Lindl.) Seem. is used in traditional Chinese medicine as a quick-acting product for sore throat and pharyngitis relief. Samples of T. arguta were collected from 40 different habitats mostly located in Jiangxi Province, and leaf appearance traits and dry matter yield were analyzed. HPLC was used to quantify ligustroflavone and rhoifolin, the pharmacological-quality markers for this species, according to the 2020 Edition of Chinese Pharmacopoeia. The correlations between leaf-measurable traits, ligustroflavone and rhoifolin contents, and climate factors were subsequently assessed using Pearson’s two-tailed correlation test and redundancy analysis. The highest dry matter yields were found in locations S(G-mt), Q(J-t), and A(X-t). Ligustroflavone and rhoifolin contents ranged from 0.023% to 1.336% and 0.008% to 0.962%, respectively; the highest levels of ligustroflavone and rhoifolin compounds were found in locations A(X-t) and Y(B-mt). Leaf morphology was influenced by the mean temperature of the warmest quarter, while leaf thickness was affected by the minimum temperature of the coldest month, precipitation seasonality, and solar radiation. Larger and thicker leaves predicted higher yields of ligustroflavone and rhoifolin compounds in T. arguta under Chinese southern conditions, such as those in Anyuan and Quannan counties. Our findings suggest that enhancing the mean diurnal temperature range and implementing appropriate shading during cultivation can enhance the ligustroflavone and rhoifolin compounds of T. arguta.
Workplace Bullying and Harassment in Higher Education Institutions: A Scoping Review
Authors: Hodgins Margaret , Kane Rhona , Itzkovich Yariv , Fahie Declan
Published: September 2024

Workplace bullying is broadly defined as a detrimental form of negative micro-political interaction(s) incorporating a range of aggressive interpersonal behaviours. While targeted toxic behaviour based upon legally protected grounds such as ethnicity, gender, or sexual orientation is conceptualised as harassment, this paper positions harassment as a constituent subset of workplace bullying—distinct, but inextricably linked to the broader landscape of workplace predation and incivility. Meta-analyses of cross-sectional and longitudinal studies demonstrate a robust relationship between being bullied and compromised health, and some sectors, e.g., education, display higher than average levels of exposure, suggesting that contexts matter. The higher education sector is the focus of this scoping review. High rates of bullying have been reported in Higher Education Institutions (HEIs), where many of the organisational factors that drive bullying are present. One systematic literature review has been carried out on bullying in HEIs, reviewing papers prior to 2013. Since the sector has seen considerable contextual change since that time, another review is timely. This systematic scoping review aims to identify the volume, range, nature, and characteristics of studies of workplace bullying in HEIs between 2003 and 2023, with a specific focus on how the context of HEIs contributes to the enactment and/or the response to workplace bullying. To this end, 3179 records were identified, with 140 papers charted to identify methods, institution, population, and country. Forty-seven papers were subjected to full-text review for the exploration of contextual factors. Priorities for future research lie in addressing the pernicious effects of neoliberal governance models as well as the complex and intersecting power relations that are unique to higher education.
Microcredit Pricing Model for Microfinance Institutions under Basel III Banking Regulations
Authors: Durango-Gutiérrez Patricia , Lara-Rubio Juan , Navarro-Galera Andrés , Buendía-Carrillo Dionisio
Published: September 2024

Purpose. The purpose of this research is to propose a tool for designing a microcredit risk pricing strategy for borrowers of microfinance institutions (MFIs). Design/methodology/approach. Considering the specific characteristics of microcredit borrowers, we first estimate and measure microcredit risk through the default probability, applying a parametric technique such as logistic regression and a non-parametric technique based on an artificial neural network, looking for the model with the highest predictive power. Secondly, based on the Basel III internal ratings-based (IRB) approach, we use the credit risk measurement for each borrower to design a pricing model that sets microcredit interest rates according to default risk. Findings. The paper demonstrates that the probability of default for each borrower is more accurately adjusted using the artificial neural network. Furthermore, our results suggest that, given a profitability target for the MFI, the microcredit interest rate for clients with a lower level of credit risk should be lower than a standard, fixed rate to achieve the profitability target. Practical implications. This tool allows us, on the one hand, to measure and assess credit risk and minimize default losses in MFIs and, secondly, to promote their competitiveness by reducing interest rates, capital requirements, and credit losses, favoring the financial self-sustainability of these institutions. Social implications. Our findings have the potential to make microfinance institutions fairer and more equitable in their lending practices by providing microcredit with risk-adjusted pricing. Furthermore, our findings can contribute to the design of government policies aimed at promoting the financial and social inclusion of vulnerable people. Originality. The personal characteristics of microcredit clients, mainly reputation and moral solvency, are crucial to the default behavior of microfinance borrowers. These factors should have an impact on the pricing of microcredit.
CEP-1347 Boosts Chk2-Mediated p53 Activation by Ionizing Radiation to Inhibit the Growth of Malignant Brain Tumor Cells
Authors: Mitobe Yuta , Suzuki Shuhei , Nakamura Kazuki , Nakagawa-Saito Yurika , Takenouchi Senri , Togashi Keita , Sugai Asuka , Sonoda Yukihiko , Kitanaka Chifumi , Okada Masashi
Published: September 2024

Radiation therapy continues to be the cornerstone treatment for malignant brain tumors, the majority of which express wild-type p53. Therefore, the identification of drugs that promote the ionizing radiation (IR)-induced activation of p53 is expected to increase the efficacy of radiation therapy for these tumors. The growth inhibitory effects of CEP-1347, a known inhibitor of MDM4 expression, on malignant brain tumor cell lines expressing wild-type p53 were examined, alone or in combination with IR, by dye exclusion and/or colony formation assays. The effects of CEP-1347 on the p53 pathway, alone or in combination with IR, were examined by RT-PCR and Western blot analyses. The combination of CEP-1347 and IR activated p53 in malignant brain tumor cells and inhibited their growth more effectively than either alone. Mechanistically, CEP-1347 and IR each reduced MDM4 expression, while their combination did not result in further decreases. CEP-1347 promoted IR-induced Chk2 phosphorylation and increased p53 expression in concert with IR in a Chk2-dependent manner. The present results show, for the first time, that CEP-1347 is capable of promoting Chk2-mediated p53 activation by IR in addition to inhibiting the expression of MDM4 and, thus, CEP-1347 has potential as a radiosensitizer for malignant brain tumors expressing wild-type p53.
Large Extracellular Vesicles Derived from Natural Killer Cells Affect the Functions of Monocytes
Authors: Sokolov Dmitry , Gorshkova Alina , Tyshchuk Elizaveta , Grebenkina Polina , Zementova Maria , Kogan Igor , Totolian Areg
Published: September 2024

Communication between natural killer cells (NK cells) and monocytes/macrophages may play an important role in immunomodulation and regulation of inflammatory processes. The aim of this research was to investigate the impact of NK cell-derived large extracellular vesicles on monocyte function because this field is understudied. We studied how NK-cell derived large extracellular vesicles impact on THP-1 cells characteristics after coculturing: phenotype, functions were observed with flow cytometry. In this study, we demonstrated the ability of large extracellular vesicles produced by NK cells to integrate into the membranes of THP-1 cells and influence the viability, phenotype, and functional characteristics of the cells. The results obtained demonstrate the ability of large extracellular vesicles to act as an additional component in the immunomodulatory activity of NK cells in relation to monocytes.
Spatial Transcriptomics Analysis: Maternal Obesity Impairs Myogenic Cell Migration and Differentiation during Embryonic Limb Development
Authors: Gao Yao , Hossain Md Nazmul , Zhao Liang , Deavila Jeanene Marie , Law Nathan C. , Zhu Mei-Jun , Murdoch Gordon K. , Du Min
Published: September 2024

Limb muscle is responsible for physical activities and myogenic cell migration during embryogenesis is indispensable for limb muscle formation. Maternal obesity (MO) impairs prenatal skeletal muscle development, but the effects of MO on myogenic cell migration remain to be examined. C57BL/6 mice embryos were collected at E13.5. The GeoMx DSP platform was used to customize five regions along myogenic cell migration routes (myotome, dorsal/ventral limb, limb stroma, limb tip), and data were analyzed by GeomxTools 3.6.0. A total of 2224 genes were down-regulated in the MO group. The GO enrichment analysis showed that MO inhibited migration-related biological processes. The signaling pathways guiding myogenic migration such as hepatocyte growth factor signaling, fibroblast growth factor signaling, Wnt signaling and GTPase signaling were down-regulated in the MO E13.5 limb tip. Correspondingly, the expression levels of genes involved in myogenic cell migration, such as Pax3, Gab1, Pxn, Tln2 and Arpc, were decreased in the MO group, especially in the dorsal and ventral sides of the limb. Additionally, myogenic differentiation-related genes were down-regulated in the MO limb. MO impedes myogenic cell migration and differentiation in the embryonic limb, providing an explanation for the impairment of fetal muscle development and offspring muscle function due to MO.
Thanatin: A Promising Antimicrobial Peptide Targeting the Achilles’ Heel of Multidrug-Resistant Bacteria
Authors: Liu Qianhui , Wu Qian , Xu Tianming , Malakar Pradeep K. , Zhu Yongheng , Liu Jing , Zhao Yong , Zhang Zhaohuan
Published: September 2024

Antimicrobial resistance poses an escalating threat to human health, necessitating the development of novel antimicrobial agents capable of addressing challenges posed by antibiotic-resistant bacteria. Thanatin, a 21-amino acid β-hairpin insect antimicrobial peptide featuring a single disulfide bond, exhibits broad-spectrum antibacterial activity, particularly effective against multidrug-resistant strains. The outer membrane biosynthesis system is recognized as a critical vulnerability in antibiotic-resistant bacteria, which thanatin targets to exert its antimicrobial effects. This peptide holds significant promise for diverse applications. This review begins with an examination of the structure–activity relationship and synthesis methods of thanatin. Subsequently, it explores thanatin’s antimicrobial activity, detailing its various mechanisms of action. Finally, it discusses prospective clinical, environmental, food, and agricultural applications of thanatin, offering valuable insights for future research endeavors.
Differentiation and Growth-Arrest-Related lncRNA (DAGAR): Initial Characterization in Human Smooth Muscle and Fibroblast Cells
Authors: de la Cruz-Thea Benjamin , Natali Lautaro , Ho-Xuan Hung , Bruckmann Astrid , Coll-Bonfill Núria , Strieder Nicholas , Peinado Víctor I. , Meister Gunter , Musri Melina M.
Published: September 2024

Vascular smooth muscle cells (SMCs) can transition between a quiescent contractile or “differentiated” phenotype and a “proliferative-dedifferentiated” phenotype in response to environmental cues, similar to what in occurs in the wound healing process observed in fibroblasts. When dysregulated, these processes contribute to the development of various lung and cardiovascular diseases such as Chronic Obstructive Pulmonary Disease (COPD). Long non-coding RNAs (lncRNAs) have emerged as key modulators of SMC differentiation and phenotypic changes. In this study, we examined the expression of lncRNAs in primary human pulmonary artery SMCs (hPASMCs) during cell-to-cell contact-induced SMC differentiation. We discovered a novel lncRNA, which we named Differentiation And Growth Arrest-Related lncRNA (DAGAR) that was significantly upregulated in the quiescent phenotype with respect to proliferative SMCs and in cell-cycle-arrested MRC5 lung fibroblasts. We demonstrated that DAGAR expression is essential for SMC quiescence and its knockdown hinders SMC differentiation. The treatment of quiescent SMCs with the pro-inflammatory cytokine Tumor Necrosis Factor (TNF), a known inducer of SMC dedifferentiation and proliferation, elicited DAGAR downregulation. Consistent with this, we observed diminished DAGAR expression in pulmonary arteries from COPD patients compared to non-smoker controls. Through pulldown experiments followed by mass spectrometry analysis, we identified several proteins that interact with DAGAR that are related to cell differentiation, the cell cycle, cytoskeleton organization, iron metabolism, and the N-6-Methyladenosine (m6A) machinery. In conclusion, our findings highlight DAGAR as a novel lncRNA that plays a crucial role in the regulation of cell proliferation and SMC differentiation. This paper underscores the potential significance of DAGAR in SMC and fibroblast physiology in health and disease.
Exploring the Relationship of rs2802292 with Diabetes and NAFLD in a Southern Italian Cohort—Nutrihep Study
Authors: Forte Giovanna , Donghia Rossella , Lepore Signorile Martina , Tatoli Rossella , Bonfiglio Caterina , Losito Francesco , De Marco Katia , Manghisi Andrea , Guglielmi Filomena Anna , Disciglio Vittoria , Fasano Candida , Sanese Paola , Cariola Filomena , Buonadonna Antonia Lucia , Grossi Valentina , Giannelli Gianluigi , Simone Cristiano
Published: September 2024

Background: The minor G-allele of FOXO3 rs2802292 is associated with human longevity. The aim of this study was to test the protective effect of the variant against the association with type 2 Diabetes and NAFLD. Methods: rs2802292 was genotyped in a large population of middle-aged subjects (n = 650) from a small city in Southern Italy. All participants were interviewed to collect information about lifestyle and dietary habits; clinical characteristics were recorded, and blood samples were collected from all subjects. The association between rs2802292 and NAFLD or diabetes was tested using a logistic model and mediation analysis adjusted for covariates. Results: Overall, the results indicated a statistical association between diabetes and rs2802292, especially for the TT genotype (OR = 2.14, 1.01 to 4.53 95% C.I., p = 0.05) or in any case for those who possess the G-allele (OR = 0.45, 0.25 to 0.81 95% C.I., p = 0.008). Furthermore, we found a mediation effect of rs2802292 on diabetes (as mediator) and NAFLD. There is no direct relationship between rs2802292 and NAFLD, but the effect is direct (β = 0.10, −0.003 to 0.12 95% C.I., p = 0.04) on diabetes, but only in TT genotypes. Conclusions: The data on our cohort indicate that the longevity-associated FOXO3 variant may have protective effects against diabetes and NAFLD.
Prediction of Multiple Degenerative Diseases Based on DNA Methylation in a Co-Physiology Mechanisms Perspective
Authors: Zhang Li , Cai Ruirui , Wang Chencai , Liu Jialong , Kuang Zhejun , Wang Han
Published: September 2024

Degenerative diseases oftentimes occur within the continuous process of aging, and the corresponding clinical manifestations may be neurodegeneration, neoplastic diseases, or various human complex diseases. DNA methylation provides the opportunity to explore aging and degenerative diseases as epigenetic traits. It has already been applied to age prediction and disease diagnosis. It has been shown that various degenerative diseases share co-physiology mechanisms with each other, clues of which may be gained from studying the aging process. Here, we endeavor to predict the risk of degenerative diseases in an aging-relevant comorbid mechanism perspective. Firstly, an epigenetic clock method was implemented based on a multi-scale convolutional neural network, and a Shapley feature attribution analysis was applied to discover the aging-related CpG sites. Then, these sites were further screened to a smaller subset composed of 196 sites by using biomics analysis according to their biological functions and mechanisms. Finally, we constructed a multilayer perceptron (MLP)-based degenerative disease risk prediction model, Mlp-DDR, which was well trained and tested to accurately classify nine degenerative diseases. Recent studies also suggest that DNA methylation plays a significant role in conditions like osteoporosis and osteoarthritis, broadening the potential applications of our model. This approach significantly advances the ability to understand degenerative diseases and represents a substantial shift from traditional diagnostic methods. Despite the promising results, limitations regarding model complexity and dataset diversity suggest directions for future research, including the development of tissue-specific epigenetic clocks and the inclusion of a wider range of diseases.
The Current Landscape of Secondary Malignancies after CAR T-Cell Therapies: How Could Malignancies Be Prevented?
Authors: Bouziana Stella , Bouzianas Dimitrios
Published: September 2024

Chimeric antigen receptor (CAR) T-cell therapies have revolutionised the field of haematological malignancies by achieving impressive remission rates in patients with highly refractory haematological malignancies, improving overall survival. To date, six commercial anti-CD19 and anti-BCMA CAR T-cell products have been approved by the Food and Drug Administration (FDA) for the treatment of relapsed/refractory B-cell haematological malignancies and multiple myeloma. The indications for CAR T-cell therapies are gradually expanding, with these therapies being investigated in a variety of diseases, including non-malignant ones. Despite the great success, there are several challenges surrounding CAR T-cell therapies, such as non-durable responses and high-grade toxicities. In addition, a new safety concern was added by the FDA on 28 November 2023 following reports of T-cell malignancies in patients previously treated with either anti-CD19 or anti-BCMA autologous CAR T-cell therapies both in clinical trials and in the real-world setting. Since then, several reports have been published presenting the incidence and analysing the risks of other secondary malignancies after CAR T-cell therapies. In this opinion article, the current landscape of secondary malignancies after CAR T-cell therapies is presented, along with a proposed strategy for future research aiming at potentially diminishing or abrogating the risk of developing secondary malignancies after CAR T-cell therapies.
The Pathological Mechanisms and Therapeutic Molecular Targets in Arteriovenous Fistula Dysfunction
Authors: Yan Ruiwei , Song Anni , Zhang Chun
Published: September 2024

The number of patients with end-stage renal disease (ESRD) requiring hemodialysis is increasing worldwide. Although arteriovenous fistula (AVF) is the best and most important vascular access (VA) for hemodialysis, its primary maturation failure rate is as high as 60%, which seriously endangers the prognosis of hemodialysis patients. After AVF establishment, the venous outflow tract undergoes hemodynamic changes, which are translated into intracellular signaling pathway cascades, resulting in an outward and inward remodeling of the vessel wall. Outward remodeling refers to the thickening of the vessel wall and the dilation of the lumen to accommodate the high blood flow in the AVF, while inward remodeling is mainly characterized by intimal hyperplasia. More and more studies have shown that the two types of remodeling are closely related in the occurrence and development of, and jointly determining the final fate of, AVF. Therefore, it is essential to investigate the underlying mechanisms involved in outward and inward remodeling for identifying the key targets in alleviating AVF dysfunction. In this review, we summarize the current clinical diagnosis, monitoring, and treatment techniques for AVF dysfunction and discuss the possible pathological mechanisms related to improper outward and inward remodeling in AVF dysfunction, as well as summarize the similarities and differences between the two remodeling types in molecular mechanisms. Finally, the representative therapeutic targets of potential clinical values are summarized.
The Impact of Liver Failure on the Immune System
Authors: Dąbrowska Alicja , Wilczyński Bartosz , Mastalerz Jakub , Kucharczyk Julia , Kulbacka Julita , Szewczyk Anna , Rembiałkowska Nina
Published: September 2024

Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune response. This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation, which might result from acute-on-chronic liver failure (ACLF) and cirrhosis. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.
MicroRNAs Regulate the Expression of Genes Related to the Innate Immune and Inflammatory Response in Rabbits Infected with Lagovirus europaeus GI.1 and GI.2 Genotypes
Authors: Ostrycharz-Jasek Ewa , Fitzner Andrzej , Siennicka Aldona , Budkowska Marta , Hukowska-Szematowicz Beata
Published: September 2024

MicroRNAs (miR) are a group of small, non-coding RNAs of 17–25 nucleotides that regulate gene expression at the post-transcriptional level. Dysregulation of miRNA expression or function may contribute to abnormal gene expression and signaling pathways, leading to disease pathology. Lagovirus europaeus (L. europaeus) causes severe disease in rabbits called rabbit hemorrhagic disease (RHD). The symptoms of liver, lung, kidney, and spleen degeneration observed during RHD are similar to those of acute liver failure (ALF) and multi-organ failure (MOF) in humans. In this study, we assessed the expression of miRs and their target genes involved in the innate immune and inflammatory response. Also, we assessed their potential impact on pathways in L. europaeus infection—two genotypes (GI.1 and GI.2)—in the liver, lungs, kidneys, and spleen. The expression of miRs and target genes was determined using quantitative real-time PCR (qPCR). We assessed the expression of miR-155 (MyD88, TAB2, p65, NLRP3), miR-146a (IRAK1, TRAF6), miR-223 (TLR4, IKKα, NLRP3), and miR-125b (MyD88). We also examined biomarkers of inflammation: IL-1β, IL-6, TNF-α, and IL-18 in four tissues at the mRNA level. Our study shows that the main regulators of the innate immune and inflammatory response in L. europaeus/GI.1 and GI.2 infection, as well as RHD, are miR-155, miR-223, and miR-146a. During infection with L. europaeus/RHD, miR-155 has both pro- and anti-inflammatory effects in the liver and anti-inflammatory effects in the kidneys and spleen; miR-146a has anti-inflammatory effects in the liver, lungs and kidneys; miR-223 has anti-inflammatory effects in all tissues; however, miR-125b has anti-inflammatory effects only in the liver. In each case, such an effect may be a determinant of the pathogenesis of RHD. Our research shows that miRs may regulate three innate immune and inflammatory response pathways in L. europaeus infection. However, the result of this regulation may be influenced by the tissue microenvironment. Our research shows that infection of rabbits with L. europaeus/GI.1 and GI.2 genotypes causes an overexpression of two critical acute phase cytokines: IL-6 in all examined tissues and TNF-α (in the liver, lungs, and spleen). IL-1β was highly expressed only in the lungs after L. europaeus infection. These facts indicate a strong and rapid involvement of the local innate immune and inflammatory response in L. europaeus infection—two genotypes (GI.1 and GI.2)—and in the pathogenesis of RHD. Profile of biomarkers of inflammation in rabbits infected with L. europaeus/GI.1 and GI.2 genotypes are similar regarding the nature of changes but are different for individual tissues. Therefore, we propose three inflammation profiles for L. europaeus infection for both GI.1 and GI.2 genotypes (pulmonary, renal, liver, and spleen).
Transient Increases in Neural Oscillations and Motor Deficits in a Mouse Model of Parkinson’s Disease
Authors: Wu Yue , Lu Lidi , Qing Tao , Shi Suxin , Fang Guangzhan
Published: September 2024

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor symptoms like tremors and bradykinesia. PD’s pathology involves the aggregation of α-synuclein and loss of dopaminergic neurons, leading to altered neural oscillations in the cortico-basal ganglia-thalamic network. Despite extensive research, the relationship between the motor symptoms of PD and transient changes in brain oscillations before and after motor tasks in different brain regions remain unclear. This study aimed to investigate neural oscillations in both healthy and PD model mice using local field potential (LFP) recordings from multiple brain regions during rest and locomotion. The histological evaluation confirmed the significant dopaminergic neuron loss in the injection side in 6-OHDA lesioned mice. Behavioral tests showed motor deficits in these mice, including impaired coordination and increased forelimb asymmetry. The LFP analysis revealed increased delta, theta, alpha, beta, and gamma band activity in 6-OHDA lesioned mice during movement, with significant increases in multiple brain regions, including the primary motor cortex (M1), caudate–putamen (CPu), subthalamic nucleus (STN), substantia nigra pars compacta (SNc), and pedunculopontine nucleus (PPN). Taken together, these results show that the motor symptoms of PD are accompanied by significant transient increases in brain oscillations, especially in the gamma band. This study provides potential biomarkers for early diagnosis and therapeutic evaluation by elucidating the relationship between specific neural oscillations and motor deficits in PD.
PE/PPE Proteome and ESX-5 Substrate Spectrum in Mycobacterium marinum
Authors: Yan Lili , Lai Hiu Ying , Leung Thomas Chun Ning , Cheng Hiu Fu , Chen Xin , Tsui Stephen Kwok Wing , Ngai Sai Ming , Au Shannon Wing Ngor
Published: September 2024

PE/PPE proteins secreted by the ESX-5 type VII secretion system constitute a major protein repertoire in pathogenic mycobacteria and are essential for bacterial survival, pathogenicity, and host–pathogen interaction; however, little is known about their expression and secretion. The scarcity of arginine and lysine residues in PE/PPE protein sequences and the high homology of their N-terminal domains limit protein identification using classical trypsin-based proteomic methods. This study used endoproteinase AspN and trypsin to characterize the proteome of Mycobacterium marinum. Twenty-seven PE/PPE proteins were uniquely identified in AspN digests, especially PE_PGRS proteins. These treatments allowed the identification of approximately 50% of the PE/PPE pool encoded in the genome. Moreover, EspG5 pulldown assays retrieved 44 ESX-5-associated PPE proteins, covering 85% of the PPE pool in the identified proteome. The identification of PE/PE_PGRS proteins in the EspG5 interactome suggested the presence of PE–PPE pairs. The correlation analysis between protein abundance and phylogenetic relationships found potential PE/PPE pairs, indicating the presence of multiple PE/PE_PGRS partners in one PPE. We validated that EspG5 interacted with PPE31 and PPE32 and mapped critical residues for complex formation. The modified proteomic platform increases the coverage of PE/PPE proteins and elucidates the expression and localization of these proteins.
Identifying microRNAs Possibly Implicated in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Review
Authors: Tsamou Maria , Kremers Fabiënne A. C. , Samaritakis Keano A. , Roggen Erwin L.
Published: September 2024

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are chronic syndromes of unknown etiology, accompanied by numerous symptoms affecting neurological and physical conditions. Despite frequent revisions of the diagnostic criteria, clinical practice guidelines are often outdated, leading to underdiagnosis and ineffective treatment. Our aim was to identify microRNA (miRNA) biomarkers implicated in pathological mechanisms underlying these diseases. A comprehensive literature review using publicly accessible databases was conducted. Interesting miRNAs were extracted from relevant publications on ME/CFS and/or FM, and were then linked to pathophysiological processes possibly manifesting these chronic diseases. Dysregulated miRNAs in ME/CFS and FM may serve as promising biomarkers for these diseases. Key identified miRNAs, such as miR-29c, miR-99b, miR-128, miR-374b, and miR-766, were frequently mentioned for their roles in immune response, mitochondrial dysfunction, oxidative stress, and central sensitization, while miR-23a, miR-103, miR-152, and miR-320 were implicated in multiple crucial pathological processes for FM and/or ME/CFS. In summary, both ME/CFS and FM seem to share many dysregulated biological or molecular processes, which may contribute to their commonly shared symptoms. This miRNA-based approach offers new angles for discovering molecular markers urgently needed for early diagnosis or therapeutics to tackle the pathology of these medically unexplained chronic diseases.
CXCL12 Gene Polymorphisms and Serum Levels: Associations with Multiple Sclerosis Prevalence and Clinical Parameters in Lithuania
Authors: Valiukevicius Paulius , Kaikaryte Kriste , Gedvilaite-Vaicechauskiene Greta , Balnyte Renata , Liutkeviciene Rasa
Published: September 2024

Our study aimed to investigate the associations between CXCL12 rs1029153, rs1801157, and rs2297630 single-nucleotide polymorphisms (SNPs), CXCL12 protein levels, MS prevalence, and clinical parameters. This study included 250 individuals diagnosed with MS and 250 sex- and age-matched healthy control individuals from Lithuania. The SNPs were genotyped with real-time PCR-based assays. The CXCL12 protein concentration was evaluated in serum using the ELISA method. Of the studied CXCL12 SNPs, we found that the rs1801157 CT genotype in the males was associated with 2.3 times reduced MS odds when compared with the CC genotype according to the overdominant and codominant models (p = 0.011 and p = 0.012, respectively). There was a tendency, which did not reach adjusted statistical significance, for a lower CXCL12 protein concentration in the healthy individuals with the rs1801157 CT genotype (p = 0.028). Sensory symptoms were rarer in the women with the rs1801157 TT genotype (p = 0.004); however, this genotype was also associated with a shorter MS disease duration (p = 0.007). CXCL12 rs1801157 was associated with reduced odds of MS occurrence in the male individuals. In women, rs1801157 was associated with a sensory symptom prevalence.
Nitrate Starvation Induces Lateral Root Organogenesis in Triticum aestivum via Auxin Signaling
Authors: Tang Chengming , Zhang Yunxiu , Liu Xiao , Zhang Bin , Si Jisheng , Xia Haiyong , Fan Shoujin , Kong Lingan
Published: September 2024

The lateral root (LR) is an essential component of the plant root system, performing important functions for nutrient and water uptake in plants and playing a pivotal role in cereal crop productivity. Nitrate (NO3−) is an essential nutrient for plants. In this study, wheat plants were grown in 1/2 strength Hoagland’s solution containing 5 mM NO3− (check; CK), 0.1 mM NO3− (low NO3−; LN), or 0.1 mM NO3− plus 60 mg/L 2,3,5-triiodobenzoic acid (TIBA) (LNT). The results showed that LN increased the LR number significantly at 48 h after treatment compared with CK, while not increasing the root biomass, and LNT significantly decreased the LR number and root biomass. The transcriptomic analysis showed that LN induced the expression of genes related to root IAA synthesis and transport and cell wall remodeling, and it was suppressed in the LNT conditions. A physiological assay revealed that the LN conditions increased the activity of IAA biosynthesis-related enzymes, the concentrations of tryptophan and IAA, and the activity of cell wall remodeling enzymes in the roots, whereas the content of polysaccharides in the LRP cell wall was significantly decreased compared with the control. Fourier-transform infrared spectroscopy and atomic microscopy revealed that the content of cell wall polysaccharides decreased and the cell wall elasticity of LR primordia (LRP) increased under the LN conditions. The effects of LN on IAA synthesis and polar transport, cell wall remodeling, and LR development were abolished when TIBA was applied. Our findings indicate that NO3− starvation may improve auxin homeostasis and the biological properties of the LRP cell wall and thus promote LR initiation, while TIBA addition dampens the effects of LN on auxin signaling, gene expression, physiological processes, and the root architecture.