title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=110 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Mitigative effect of sodium alginate on streptozotocin (STZ)-induced diabetic neuropathy through regulation of redox status and miR-146a in the rat sciatic nerve link: https://peerj.com/articles/19046 last-modified: 2025-03-24 description: Diabetic peripheral neuropathy (DPN) is a significant complication of diabetes with limited effective therapeutic options. Sodium alginate (SA), a natural polysaccharide from brown algae, has demonstrated health benefits, however, whether it can treat streptozotocin (STZ)-induced DPN remains unclear. The present experiment aimed to test the preventive role of SA on STZ-induced DPN in rats and explored the possible mechanisms. The DPN rat model was established in rats by intraperitoneal injection of a single dose of 40 mg/kg b.w. STZ, and SA (200 mg/kg b.w./day) was orally administered for 28 days after type 2 diabetes mellitus (T2DM) induction. The obtained findings revealed that STZ significantly increased serum levels of FBG, HOMA-IR, TC, TG, VLDL-C, and LDL-C, while decreased serum insulin, incretin GLP-1, HDL-C, and lipase activity. In the sciatic nerves, STZ significantly increased proinflammatory cytokine levels (IL-1β, IL-6, and TNF-α), caspase-3 (a pro-apoptotic protein), markers of oxidative stress (MDA and NO), and AGEs. In parallel, STZ induced a significant decline in the activities of enzymatic antioxidants, viz., SOD, CAT, and GPx, and non-enzymatic GSH. These changes were accompanied by a low expression of miR-146a in the sciatic nerves of DPN rats. Except for HOMA-IR, SA treatment to STZ injected rats significantly improved these parameters and helped to rescue the neurological morphology of the sciatic nerve fibers. In conclusion, SA mitigated experimental DPN, and this might be due to its ability to suppress hyperglycemic-hyperlipidemic effects, counteract the overactivation of inflammatory molecules, increase miR-146a expression, modulate oxidative dysregulation, and reduce cell apoptosis. creator: Nema A. Mohamed creator: Naeimah M. Shouran creator: Amina E. Essawy creator: Ashraf M. Abdel-Moneim creator: Sherine Abdel Salam uri: https://doi.org/10.7717/peerj.19046 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Mohamed et al. title: Demographics and physical and mental health of clients at a sports center with and without exercise addiction link: https://peerj.com/articles/19002 last-modified: 2025-03-24 description: BackgroundWhile exercise is widely recognized for its health benefits, excessive engagement can lead to exercise addiction (EA), a behavioral condition characterized by compulsive and harmful physical activity. Limited research exists on the demographic, physical, and mental health profiles of individuals with EA. This descriptive cross-sectional study examines demographic factors and related health outcomes among clients at a university sports center with and without EA.MethodsA total of 386 participants were randomly recruited through convenience sampling at the Chulalongkorn University Sports Center in Bangkok, Thailand. EA, physical well-being, and mental well-being were assessed using the Exercise Addiction Inventory (EAI), the Knee and Osteoarthritis Outcome Score (KOOS), and the Questionnaire for Eudaimonic Well-Being (QEWB), respectively. Demographic and exercise-related variables, psychological well-being, and knee outcomes were compared between participants with and without EA using Chi-square tests. Logistic regression analysis was performed to identify predictors of EA.ResultsThe majority of participants were male (55.2%), with a mean age of 27.5 years (SD = 10.9). Among the 386 participants, 322 (83.4%) exhibited partial symptoms, and 35 (9.1%) exhibited full symptoms of EA. Full symptoms of EA were significantly associated with gender, exercise frequency, smoking status, hours spent walking, hours spent in other sports, cognitive focus on metabolism during exercise, and poor knee outcomes (P < 0.05). Logistic regression revealed that being male was the sole significant predictor of EA (OR = 2.65, P = 0.024).ConclusionsEA was prevalent among clients at the sports center and was associated with adverse knee outcomes. Being male was identified as a key predictor of EA. Future research should explore additional factors associated with EA and its effects on physical and mental health. creator: Rasmon Kalayasiri creator: Chayamon Rattanawijarn uri: https://doi.org/10.7717/peerj.19002 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Kalayasiri and Rattanawijarn title: Moving beyond the physical impervious surface impact and urban habitat fragmentation of Alaska: quantitative human footprint inference from the first large scale 30 m high-resolution Landscape metrics big data quantification in R and the cloud link: https://peerj.com/articles/18894 last-modified: 2025-03-24 description: With increased globalization, man-made climate change, and urbanization, the landscape–embedded within the Anthropocene-becomes increasingly fragmented. With wilderness habitats transitioning and getting lost, globally relevant regions considered ‘pristine’, such as Alaska, are no exception. Alaska holds 60% of the U.S. National Park system’s area and is of national and international importance, considering the U.S. is one of the wealthiest nations on earth. These characteristics tie into densities and quantities of human features, e.g., roads, houses, mines, wind parks, agriculture, trails, etc., that can be summarized as ‘impervious surfaces.’ Those are physical impacts and actively affecting urban-driven landscape fragmentation. Using the remote sensing data of the National Land Cover Database (NLCD), here we attempt to create the first quantification of this physical human impact on the Alaskan landscape and its fragmentation. We quantified these impacts using the well-established landscape metrics tool ‘Fragstats’, implemented as the R package “landscapemetrics” in the desktop software and through the interface of a Linux Cloud-computing environment. This workflow allows for the first time to overcome the computational limitations of the conventional Fragstats software within a reasonably quick timeframe. Thereby, we are able to analyze a land area as large as approx. 1,517,733 km2 (state of Alaska) while maintaining a high assessment resolution of 30 m. Based on this traditional methodology, we found that Alaska has a reported physical human impact of c. 0.067%. We additionally overlaid other features that were not included in the input data to highlight the overall true human impact (e.g., roads, trails, airports, governance boundaries in game management and park units, mines, etc.). We found that using remote sensing (human impact layers), Alaska’s human impact is considerably underestimated to a meaningless estimate. The state is more seriously fragmented and affected by humans than commonly assumed. Very few areas are truly untouched and display a high patch density with corresponding low mean patch sizes throughout the study area. Instead, the true human impact is likely close to 100% throughout Alaska for several metrics. With these newly created insights, we provide the first state-wide landscape data and inference that are likely of considerable importance for land management entities in the state of Alaska, and for the U.S. National Park systems overall, especially in the changing climate. Likewise, the methodological framework presented here shows an Open Access workflow and can be used as a reference to be reproduced virtually anywhere else on the planet to assess more realistic large-scale landscape metrics. It can also be used to assess human impacts on the landscape for more sustainable landscape stewardship and mitigation in policy. creator: Moriz Steiner creator: Falk Huettmann uri: https://doi.org/10.7717/peerj.18894 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Steiner and Huettmann title: The prognostic model of low-grade glioma based on m6A-associated immune genes and functional study of FBXO4 in the tumor microenvironment link: https://peerj.com/articles/19194 last-modified: 2025-03-21 description: Backgroundm6A plays a dual role in regulating the expression of oncogenes and tumor suppressor genes, and is crucial in tumorigenesis and progression. The immune system is closely involved in tumorigenesis and development, playing a key role in tumor therapy and resistance. However, research on m6A-related immune markers in low-grade gliomas is still limited and requires further investigation.MethodsAll data was obtained from the Chinese Glioma Genome Atlas database and The Cancer Genome Atlas. The construction of the prognostic model and the online application of the dynamic nomogram relied on univariate Cox analysis, LASSO regression, and multivariate Cox analysis. Two different clustering analyses were performed on all samples, resulting in high, medium, and low expression groups of m6A regulatory and immune genes, followed by an analysis of the correlations between these scores. Finally, the biological role of FBXO4 in glioma cells was determined through quantitative reverse transcription polymerase chain reaction, cell proliferation assays, and cell migration experiments.ResultsThe prognostic model for low-grade glioma demonstrated strong performance, with an AUC over 0.9 in the training group. In the internal validation group, AUC values ranged from 0.831 to 0.894, while in the external validation group, the AUC ranged from 0.623 to 0.813. Additionally, the online application of the dynamic nomogram allowed for relatively accurate predictions of LGG patients’ survival time. Further analysis revealed that the high-expression groups of m6A regulatory genes and m6A-related immune genes exhibited higher levels of immune cells and stromal cells, lower tumor purity, and poorer survival rates. GSEA enrichment analysis suggested that these findings might be related to the activation of multiple signaling pathways. This may explain the lower survival rates observed in this group. Furthermore, the m6A score was significantly associated with moderate to high expression of immune genes and high expression of m6A regulatory genes, and it showed a positive correlation with most immune cell types. Finally, in vitro experiments confirmed that silencing FBXO4 significantly inhibited proliferation and migration in glioma cell lines, further supporting the biological relevance of our model.ConclusionBased on multi-dimensional clustering analysis and experimental validation, the prognostic model developed in this study can effectively assess the prognosis of LGG patients and their relationship with the immune microenvironment. Furthermore, the correlation analysis between m6A scores and the tumor microenvironment provides a foundation for further exploration of the disease’s pathophysiology. Additionally, we suggest that FBXO4 may serve as an important biomarker for the diagnosis and prognosis of LGG. creator: Yiling Zhang creator: Na Luo creator: Xiaoyu Li creator: Chuanfei Zeng creator: Xin Chen creator: Xiaohong Peng creator: Yuanyuan Zhang creator: Guangyuan Hu uri: https://doi.org/10.7717/peerj.19194 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Zhang et al. title: Classification of red beet and sugar beet for drought tolerance using morpho-physiological and stomatal traits link: https://peerj.com/articles/19133 last-modified: 2025-03-21 description: Drought is a global phenomenon that endangers agricultural production by creating water scarcity. Selecting drought-tolerant cultivars, varieties, and species is essential for maintaining the food supply and advancing breeding efforts. The study aimed to compare red beet (Beta vulgaris L. var. cruenta) and sugar beet (B. vulgaris L. var. altissima Döll.) for drought tolerance at the early growth stage considering morpho-physiological and stomatal parameters. Three red beet cultivars (Bicores, BT Pancina, and Yakut) and three sugar beet cultivars (Mohican, Orthega KWS, and Valentina) were subjected to various drought stress (Control, 10%, and 20% PEG-6000) for 30 days at the four-leaf stage. Fresh and dry plant weight, leaf area, dry matter, chlorophyll content (SPAD), leaf temperature, relative water content, membrane stability index, stomatal density, and size were investigated. The results revealed that the cultivars exhibited different responses to drought stress, and a greater percentage reduction in morphological parameters was observed in red beet cultivars. Drought markedly reduced the fresh and dry weights, leaf area, relative water content, membrane stability, and stomatal size. Enhanced dry matter and stomatal density were identified. The stomatal density increased from 158 to 215 mm−2 while the stomatal size decreased from 433 to 342 µm2 in the plants subjected to 20% PEG. Moderate drought stress effectively distinguished drought-tolerant sugar beet and red beet genotypes. It was concluded that sugar beet appeared to be more drought-tolerant than red beet and that the membrane stability index, relative water content, and stomatal density could be effectively used for selecting drought-tolerant beet genotypes. creator: Gamze Kaya creator: Nurgül Ergin uri: https://doi.org/10.7717/peerj.19133 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Kaya and Ergin title: Comparative genomic analysis of emerging non-typeable Haemophilus influenzae (NTHi) causing emerging septic arthritis in Atlanta link: https://peerj.com/articles/19081 last-modified: 2025-03-21 description: BackgroundHaemophilus influenzae is a Gram-negative bacterium that can exist as a commensal organism or cause a range of diseases, from ear infections to invasive conditions like meningitis. While encapsulated H. influenzae strains have historically been linked to severe diseases, non-typeable Haemophilus influenzae (NTHi) strains, lacking an intact capsule locus, have emerged as the leading cause of invasive H. influenzae infections, particularly following the widespread use of the H. influenzae serotype b (Hib) vaccine.MethodsIn response to a significant increase in invasive NTHi infections among persons living with HIV in metropolitan Atlanta during 2017–2018, we conducted a comparative genomic analysis of two predominant NTHi clones, C1 and C2, identified during this period. These clones correspond to multilocus sequence types ST164 and ST1714, respectively. We analyzed the genomic characteristics of C1 and C2 using whole genome sequencing data and compared them to a broader pangenome of H. influenzae strains to identify potential virulence factors and genetic adaptations.ResultsBoth C1 and C2 isolates were highly related within their clusters, with C1 showing a maximum of 132 SNPs and C2 showing 149 SNPs within their respective core genomes. Genomic analysis revealed significant deletions in known virulence genes, surprisingly suggesting possible attenuation of virulence. No unique accessory genes were identified that distinguished C1 and C2 from other H. influenzae strains, although both clusters exhibited a consistent loss of the pxpB gene (encoding 5-oxoprolinase subunit), replaced by a mobile cassette containing genes potentially involved in sugar metabolism. All C1 and C2 isolates showed potential enrichment in accessory genes associated with systemic infections.ConclusionsOur study suggests that while C1 and C2 clones possess some genetic markers potentially linked to systemic infections, there are no definitive unique genetic factors that distinguish these clones as more virulent than other H. influenzae strains. The expansion of these clones in a vulnerable population may reflect both chance introduction and potential adaptations to the host environment. Further research is needed to understand the implications of these genetic findings on the clinical management and prevention of invasive NTHi infections. creator: Brianna J. Bixler creator: Charlotte J. Royer creator: Robert A. Petit III creator: Abraham G. Moller creator: Samantha Sefton creator: Stepy Thomas creator: Amy Tunali creator: Lauren F. Collins creator: Monica M. Farley creator: Sarah W. Satola creator: Timothy D. Read uri: https://doi.org/10.7717/peerj.19081 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Bixler et al. title: Construction of an immunoinformatics-based multi-epitope vaccine candidate targeting Kyasanur forest disease virus link: https://peerj.com/articles/18982 last-modified: 2025-03-21 description: Kyasanur forest disease (KFD) is one of the neglected tick-borne viral zoonoses. KFD virus (KFDV) was initially considered endemic to the Western Ghats region of Karnataka state in India. Over the years, there have been reports of its spread to newer areas within and outside Karnataka. The absence of an effective treatment for KFD mandates the need for further research and development of novel vaccines. The present study was designed to develop a multi-epitope vaccine candidate against KFDV using immunoinformatics approaches. A total of 74 complete KFDV genome sequences were analysed for genetic recombination followed by phylogeny. Computational prediction of B- and T-cell epitopes belonging to envelope protein was performed and epitopes were prioritised based on IFN-Gamma, IL-4, IL-10 stimulation and checked for allergenicity and toxicity. The eight short-listed epitopes (three MHC-Class 1, three MHC-Class 2 and two B-cell) were then combined using various linkers to construct the vaccine candidate. Molecular docking followed by molecular simulations revealed stable interactions of the vaccine candidate with immune receptor complex namely Toll-like receptors (TLR2-TLR6). Codon optimization followed by in-silico cloning of the designed multi-epitope vaccine construct into the pET30b (+) expression vector was carried out. Immunoinformatics analysis of the multi-epitope vaccine candidate in the current study has potential to significantly accelerate the initial stages of vaccine development. Experimental validation of the potential multi-epitope vaccine candidate remains crucial to confirm effectiveness and safety in real-world conditions. creator: Sunitha Manjari Kasibhatla creator: Lekshmi Rajan creator: Anita Shete creator: Vinod Jani creator: Savita Yadav creator: Yash Joshi creator: Rima Sahay creator: Deepak Y. Patil creator: Sreelekshmy Mohandas creator: Triparna Majumdar creator: Uddhavesh Sonavane creator: Rajendra Joshi creator: Pragya Yadav uri: https://doi.org/10.7717/peerj.18982 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Kasibhatla et al. title: Quantitative MRI reveals infrapatellar fat pad changes after running a marathon link: https://peerj.com/articles/19123 last-modified: 2025-03-20 description: BackgroundMarathon running, while offering health benefits, is associated with a high incidence of knee injuries. The infrapatellar fat pad (IFP) plays a critical role in knee joint homeostasis and injury mitigation. This study investigated IFP adaptations to the acute stress of marathon running using quantitative magnetic resonance imaging (MRI).MethodsFourteen amateur marathon runners (12 male, two female) were prospectively enrolled and underwent 3.0T MRI (GE SIGNA Architect) one week before and after the marathon. Left knee imaging included MAGiC and IDEAL-IQ sequences. MAGiC sequences provide T1, T2, and proton density (PD) maps. IDEAL-IQ sequences yield fat fraction (FF), representing the relative amount of fat within the IFP, and the transverse relaxation rate (R2*) within the IFP. IFP volume and maximum cross-sectional area were quantified. Two experienced radiologists independently analyzed the images using dedicated software. Inter-observer reliability for quantitative MRI measurements was assessed using intraclass correlation coefficients (ICCs). Paired t-tests were used to compare pre- and post-marathon measurements of T1, T2, FF, R2* values, IFP volume and maximum cross-sectional area. Pearson correlation analysis explored relationships between changes in IFP parameter changes and participant characteristics. P < 0.05 was considered statistically significant for all analyses.ResultsPost-marathon, IFP FF significantly increased (p < 0.05), while IFP volume significantly decreased (p < 0.05), T1 and T2 values showed a decreasing trend. IFP appeared morphologically compressed post-marathon. A significant negative correlation was found between FF change and both body weight and body mass index (BMI) (p < 0.05).ConclusionsThis study provides novel evidence of robust IFP adaptation to marathon running, characterized by increased FF and potential fluid shifts, suggesting enhanced cushioning and load dissipation. These findings highlight the importance of considering individual biomechanics in understanding IFP function and injury susceptibility. Future research should clarify the clinical implications of these adaptations for runner injury prevention and rehabilitation. creator: Xiang Bo Zhao creator: Haifeng Zhao creator: Wen Juan Du creator: Hao Zhang uri: https://doi.org/10.7717/peerj.19123 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2025 Zhao et al. title: Fatty acid profiles of highly migratory resources from the Southeastern Pacific Ocean, Chile: a potential tool for biochemical and nutritional traceability link: https://peerj.com/articles/19101 last-modified: 2025-03-20 description: The traceability of fish species and their resulting food products is essential to maintain the global supply of these goods, allowing us to distinguish and reconstruct the origin and history of their production chain. One way to trace food is through biochemical determinations, which aid in identifying their geographical origin quickly. This study analyzed the fatty acid (FA) profiles of highly migratory fishery resource species (HMRS) from the Southeastern Pacific Ocean (SEPO), and their use as potential tools to determine the geographic origin and nutritional condition of these marine resources. The fatty acids (FAs) presented in fillet or muscle tissue of 18 HMRS were measured as FA methyl esters by gas chromatography. Our results reveal that the swordfish Xiphias gladius presented the greatest variety of FAs, strongly characterized by the presence of saturated, monounsaturated, and polyunsaturated FAs. A similar trend of high diversity in all classes of FAs was observed in tuna species (i.e., Thunnus alalunga; T. albacares; T. obesus), oilfish (Ruvettus pretiosus) and escolar fish (Lepidocybium flavobrunneum). In turn, Lampris guttatus, Makaira indica, and Tetrapturus audax presented an intermediate variety of FAs and the highest amount of saturated and monounsaturated FAs of the evaluated species. Finally, Luvarus imperialis, Coryphaena hippurus and the sharks (Lamna nasus; Alopias vulpinus; Prionace glauca; Isurus oxyrinchus; Sphyrna zygaena) presented a low diversity of FAs, with only saturated FAs strongly predominating. Regarding the total concentration of FAs, the highest average values were recorded in X. gladius, L. flavobrunneum and R. pretiosus. The present study revealed notable differences in the FA compositions of the muscle of diverse HMRS from the SEPO off the coast of Chile, with the swordfish showing the healthiest FAs (i.e., mono and polyunsaturated) for human consumption. The data on FAs collected for HMRS could be used as a reference to characterize the FA profiles of other fisheries in the SEPO (e.g., coastal pelagic fishes). In an ecosystem approach, our findings help us to understand how essential nutrients (i.e., FA biomolecules) are transferred through the marine food web in the SEPO, revealing the diet type and/or feeding habits of HMRS considered as top predators. Furthermore, identifying the FA profiles of fishery resources at a spatial level provides crucial information for their management and conservation, particularly in those resources that are overexploited and also have a critical nutritional importance for human consumption. creator: Fabián Guzmán-Rivas creator: Marco Quispe-Machaca creator: Jorge Lazo creator: Juan Carlos Ortega creator: Sergio Mora creator: Patricio Barría Martínez creator: Ángel Urzúa uri: https://doi.org/10.7717/peerj.19101 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Guzmán-Rivas et al. title: NCBP2 predicts the prognosis and the immunotherapy response of cancers: a pan-cancer analysis link: https://peerj.com/articles/19050 last-modified: 2025-03-20 description: BackgroundThe cap-binding complex (CBC) plays a crucial role in facilitating gene expression by safeguarding mRNA from nonsense-mediated decay, promoting mRNA splicing, 3′-end processing, and facilitating nuclear export. Nevertheless, the precise biological functions and clinical implications of CBC in cancer remain ambiguous, necessitating further investigation for clarification.MethodsThe present study utilized the cBioPortal database to investigate the genetic alterations of nuclear cap binding protein subunit 2 (NCBP2) in pan-cancer. The Cancer Genome Atlas (TCGA) and online web tools were employed to analyze the correlation between NCBP2 and prognosis, genome instability, immune infiltration, immune response, cancer stemness, and chemotherapeutic efficacy in pan-cancer. Furthermore, the expression of NCBP2 was confirmed by immunohistochemistry (IHC) and functional analysis at the single-cell level was conducted using the CancerSEA database.ResultsNCBP2 exhibited distinct genetic alterations in pan-cancer with an increased expression in 24/32, while decreased expression in 3/32, types of cancers. IHC confirmed the aberrant expression of NCBP2 in lung squamous cell carcinoma (LUSC), pancreatic adenocarcinoma (PAAD), kidney renal papillary cell carcinoma (KIRP) and kidney renal clear cell carcinoma (KIRC). NCBP2 was correlated with overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) in various cancers. Importantly, it was identified as a risk factor for OS, DSS and PFS in PAAD and uterine corpus endometrial carcinoma (UCEC). Gene Set Enrichment Analysis (GSEA) demonstrated that elevated NCBP2 was linked to immune and proliferation related pathways across multiple cancer types. Furthermore, a negative association between NCBP2 and stromal score, immune score, and ESTIMATE score was detected, and a positive correlation was observed between NCBP2 and diverse immune cells as well as stemness-indexes in the majority of cancer types. Drug sensitivity analysis revealed that drugs associated with NCBP2 primarily targeted DNA replication, chromatin histone methylation, ABL signaling, cell cycle, and PI3K signaling. Additionally, an examination at the single-cell level indicated that NCBP2 was positively correlated with cell cycle progression, DNA damage, DNA repair, invasion, and stemness in most cancer types, while negatively correlated with apoptosis, inflammation, and hypoxia in certain cancers.ConclusionIn this study, we revealed the correlation of NCBP2 with prognosis, microenvironment and stemness, indicating that NCBP2 might be a potential therapeutic target for more effective and personalized therapy strategies in pan-cancer. creator: Shichao Li creator: Yulan Wang creator: Xi Yang creator: Miao Li creator: Guoxiang Li creator: Qiangqiang Song creator: Junyu Liu uri: https://doi.org/10.7717/peerj.19050 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2025 Li et al.