Ferroptosis and its implications in bone-related diseases
Ferroptosis, a recently recognized form of regulated cell death (RCD) characterized by iron-dependent lipid peroxide accumulation, has emerged as a noteworthy regulator in various bone-related diseases, including osteoporosis (OP), osteoarthritis (OA), and osteosarcoma (OS). OS primarily afflicts the elderly, rendering them susceptible to fractures due to increased bone fragility. OA represents the most prevalent arthritis in the world, often observed in the aging population. OS predominantly manifests during adolescence, exhibiting an aggressive nature and bearing a significantly unfavorable prognosis. In this review article, we present an overview of the characteristics and mechanism of ferroptosis and its involvement in bone-related diseases, with a particular focus on OP, OA, and OS. Furthermore, we summarize chemical compounds or biological factors that impact bone-related diseases by regulating ferroptosis. Through an in-depth exploration of ferroptosis based on current research findings, this review provides promising insights for potential therapeutic approaches to effectively manage and mitigate the impact of these bone-related pathological conditions.
Wang et al. (2024) Ferroptosis and its implications in bone-related diseases. PeerJ 12:e18626 https://doi.org/10.7717/peerj.18626
Effect of basal luteinizing hormone/follicle-stimulating hormone ratio on clinical outcome of In Vitro fertilization in patients with polycystic ovarian syndrome: a retrospective cohort study
Background The basal luteinizing hormone (LH) and the prior LH to follicle-stimulating hormone (FSH) ratio (LH/FSH) in polycystic ovarian syndrome (PCOS) are generally higher than those in non-PCOS patients and the general population. The potential negative effects of elevated LH on human reproductive function are highly controversial, as are the effects of down-regulation of LH on reproductive function. The purpose of this study was to evaluate the effect of the basal LH/FSH ratio on the live birth rate of PCOS patients undergoing in vitro fertilization (IVF) cycles. Methods A retrospective analysis was conducted on 698 patients with polycystic ovary syndrome undergoing IVF treatments with a mild stimulation protocol (n = 95) and a gonadotropin-releasing hormone (GnRH) agonist protocol (n = 603). The basal LH/FSH ratio of 2 was used as the cut-off value for further subgroup analysis. The demographic properties, controlled ovarian hyperstimulation (COH) processes, and clinical pregnancy outcomes were compared between groups under each ovulation stimulation protocol. Results The live birth rate for patients with a LH/FSH ratio ≥ 2 group (56.38%, n = 149) was not statistically different from that of the ones with a ratio < 2 (53.74%, n = 454) in the GnRH agonist protocol (P = 0.576). Correspondingly, the live birth rate for the LH/FSH ratio ≥ 2 group (43.48%, n = 23) also showed no statistical difference from the ratio < 2 group (48.61%, n = 72) in the mild stimulation protocol (P = 0.668). Additionally, LH/FSH ratios had no significant effect on the live birth rate after adjusting for confounders both in the GnRH agonist protocol (adjusted OR: 1.111; 95% CI [0.467–2.642], P = 0.812) and in the mild stimulation protocol (adjusted OR: 4.057; 95% CI [0.431–38.195], P = 0.221). Furthermore, there was no significant difference in the live birth rate between different ovulation stimulation protocols in PCOS patients with the LH/FSH ratio ≥ 2. Conclusions The live birth rate in IVF outcomes was not affected by an elevated basal LH/FSH ratio in patients with polycystic ovary syndrome. The choice of the GnRH agonist protocol or mild stimulation protocol for ovulation stimulation does not affect the final clinical outcomes either for PCOS patients with a basal LH/FSH ratio ≥ 2.
Shan et al. (2024) Effect of basal luteinizing hormone/follicle-stimulating hormone ratio on clinical outcome of In Vitro fertilization in patients with polycystic ovarian syndrome: a retrospective cohort study. PeerJ 12:e18635 https://doi.org/10.7717/peerj.18635
Method selection affects the estimates of residency and site fidelity in bottlenose dolphins: testing sensitivity and performance of different methods using mark-resight data
Residency (R) and site fidelity (SF) are important parameters in population ecology, yet their quantification poses challenges in marine mammals. Based on a previous review, this study used simulated and empirical mark-resight data to assess the variations and performance of the most used R (n = 8) and SF (n = 11) indices in peer-reviewed literature under different scenarios. We applied the Jolly-Seber model to simulate thousands of bottlenose dolphin populations varying resighting (p) and survival (Phi) probabilities, and performed calibration, sensitivity, and validation analyses. Our results underscore the effects of p and Phi on individual categorization within the diverse simulated conditions, representing the often-overlooked heterogeneity in residency classification for Tursiops populations. All SF indices showed similar and consistent performance (>0.70 Gower’s distance) across the simulated scenarios, even when compared to field study data from wild dolphin populations (i.e., Savannah, USA, and Alvarado, Mexico); thus, SF should be a critical parameter for interstudy comparisons. Conversely, R indices were remarkably different based on their definitions and classification criteria. The different thresholds among definitions largely biased the proportion of residents and transient individuals (or occasional visitors) even leading to counterintuitive outcomes. This emphasizes the importance of considering trade-offs in R index selection aligned with project goals, specific sampling efforts, and population dynamics. For instance, the simplified binomial categorization of R defined by Conway (2017) (https://digitalcommons.coastal.edu/etd/10/) easier to interpret but R indices incorporating temporal components (e.g., monthly, seasonal, and annual) outperformed (>0.70 Gower’s distance) other R indices lacking such criteria. This allowed for a more detailed representation of the temporal structure of the population, and higher consistency and accuracy while classifying individuals. Also, although the residency categories proposed by Möller, Allen & Harcourt (2002) (DOI 10.1071/AM02011) did not perform as well, these seemed to fit better when dealing with data gaps across spatial and temporal scales. Our results contribute to the ongoing discussion on methodological implications for the interpretation of ecological patterns, facilitating a nuanced understanding of population dynamics, aiding scientists, and conservation agencies in making informed decisions for bottlenose dolphin populations worldwide.
Huesca-Domínguez et al. (2024) Method selection affects the estimates of residency and site fidelity in bottlenose dolphins: testing sensitivity and performance of different methods using mark-resight data. PeerJ 12:e18329 https://doi.org/10.7717/peerj.18329
Testing the ‘parasite-mediated domestication’ hypothesis: a comparative approach to the wild boar and domestic pig as model species
The mechanisms underlying the domestication process have already been well explained. Starting with Belyaev’s pioneering experiment on silver foxes, which showed that selection for tameness (reduced fear response, changes in the ‘hypothalamic-pituitary-adrenal system’—HPA axis) leads to destabilisation of the regulatory systems that control morphological and behavioural development, resulting in the changes characteristic of the domestication syndrome. Later, the thyroid rhythm hypothesis and the neural crest cell (NCC) hypothesis provided additional explanations. Recently, the parasite-mediated domestication hypothesis (PMD) has been proposed, suggesting an important role of endoparasites in the domestication process. Since parasites either directly or indirectly affect all mechanisms underlying the domestication syndrome (HPA, thyroid, NCC), the PMD proposes that they may be an important trigger of domestication. PMD can be tested either experimentally or comparatively. One of the basic assumptions of PMD is that parasite-susceptible, genetically less resistant/more tolerant wild animals were originally domesticated and that the susceptibility to parasites has been passed on to today’s domestic animals. This can be verified primarily by comparing the parasite susceptibility of existing wild and domestic populations of the same species. We, therefore, followed a systematic comparative approach by analysing the parasite load in wild boar (WB) and free-ranging domestic pig (DP) populations from a comparable environment in a geographically close area. Fresh faeces from WB and DP populations, one each from Slovenia (SI) and Croatia (HR), were sampled. A total of 59 individual faecal samples were collected (SI: 12 WB, 20 DP; HR: 14 WB, 13 DP). Parasitological diagnostics were carried out using the sedimentation and floatation method. Five different taxa were found in WB and seven in DP. Three parasite taxa were found exclusively in DP (Cystoisospora suis, Trichuris sp., Balantidium coli), and one (Strongyloides sp.) only in WB. Of the parasites found in both cohorts, strongyles/Oesophagostomum sp. were significantly more abundant in DP, while Eimeria sp. was found in equal amounts in both (but in HR only in WB). According to the preliminary study presented here, there is evidence to support the PMD baselines in the wild boar—domestic pig association. However, we cannot draw a definitive conclusion as there are many aspects that may bias the interpretation based on parasite load alone, which are also discussed here. Therefore, comparative studies should be supported by a more focussed methodology, including an experimental approach.
Oleinic et al. (2024) Testing the ‘parasite-mediated domestication’ hypothesis: a comparative approach to the wild boar and domestic pig as model species. PeerJ 12:e18463 https://doi.org/10.7717/peerj.18463
Effect of kinematics on ground reaction force during single-leg jump landing in children: a causal decomposition approach in jumpers and non-jumpers
Background The interaction between joint kinematics and kinetics is usually assessed by linear correlation analysis, which does not imply causality. Understanding the causal links between these variables may help develop landing interventions to improve technique and create joint-specific strengthening programs to reduce reaction forces and injury risk. Objective Therefore, the aim of this study was to analyze the causal interaction between lower limb sagittal kinematics and vertical ground reaction force (VGRF) during single-leg jump landing in children who are jumpers (volleyball and gymnastics) and non-jumpers, using the causal empirical decomposition method. Our hypothesis is that children who participate in jumping sports, compared to those who do not, employ a different joint strategy to regulate ground reaction forces during landing, particularly at the ankle level. Methods Two groups were compared: the jumpers group (n = 14) and the non-jumpers (control group, n = 11). The causal interaction between sagittal kinematics and VGRF was assessed using ensemble empirical mode decomposition (EEMD) and time series instantaneous phase dependence in bi-directional causality. The relative causal strength (RCS) between the time series was quantified as the relative ratio of absolute cause strength between kinematics and VGRF. Results A significant interaction between joint and group was found for RCS (p = 0.035, η2p = 0.14). The post-hoc analysis showed the jumpers group had higher ankle-to-VGRF RCS than the control group (p = 0.017, d = 1.03), while in the control group the hip-to-VGRF RCS was higher than the ankle-to-VGRF RCS (p = 0.004, d = 0.91). Conclusion Based on the causal decomposition approach, our results indicate that practicing jumping sports increases the causal effect of ankle kinematics on ground reaction forces in children. While non-jumper children rely more on the hip to modulate reaction forces, jumper children differ from non-jumpers by their greater use of the ankle joint. These findings could be used to develop specific training programs to improve landing techniques according to practice level, potentially helping to reduce the risk of injury in both athletes and non-athletes.
Cruz-Montecinos et al. (2024) Effect of kinematics on ground reaction force during single-leg jump landing in children: a causal decomposition approach in jumpers and non-jumpers. PeerJ 12:e18502 https://doi.org/10.7717/peerj.18502
Analysis of differential expression of hair follicle tissue transcriptome in Hetian sheep undergoing different periodic changes
Background This study provides new information on long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in the hair follicles of Hetian sheep via the sequencing and analysis of the transcriptome of skin hair follicles during three periods of periodicity change. This is important for improving the quality of carpet wool, providing a preliminary basis for further research on the targeting relationship of these mRNAs and their target genes, and providing a scientific basis for marker-assisted selection of Hetian sheep. Methods The periodic variation of anagen (P I, May, n = 3), catagen (p II, October, n = 3), and telogen (p III, January, n = 3) of the skin hair follicle tissue of three Hetian sheep ewes were selected. Skin samples were collected from the right mid-side of each sampled sheep at three hair follicle developmental stages. The three sheep were used for each developmental stage as biological and technical replicates for transcriptome sequencing and analysis. Results The statistical power of this experimental design, calculated in RNASeqPower, was 0.92. Differential expression analysis revealed 81 lncRNAs that were differentially expressed (46 up-regulated and 35 down-regulated) and 129 mRNAs that were differentially expressed (46 up-regulated and 83 down-regulated) during the PI and PII periods. Between the PI and PIII periods, a total of 144 differentially expressed lncRNAs and 693 differentially expressed mRNAs were identified. Of these, 73 lncRNAs were significantly up-regulated and 71 were significantly down-regulated, while 474 mRNAs were significantly up-regulated and 219 were down-regulated. Additionally, a total of 87 lncRNAs were found to be differentially expressed, with 40 up-regulated and 47 down-regulated, along with 39 differentially expressed mRNAs (23 up-regulated and 16 down-regulated), between the PII and PIII stages. The functional assessment revealed that the mRNA expressed in the cells is related to the membrane, cell processes, metabolism, extracellular region, and other GO items. It is enriched in thyroid hormone synthesis, choline metabolism, cancer, AMPK, Hedgehog, and other signaling pathways. Conclusion A total of 2,286 lncRNAs (including 965 known and 1,321 novel lncRNAs) and 20,879 mRNAs were identified. These co-expressed differentially expressed genes could be used as candidate genes for studying the periodic changes of the hair follicles in Hetian sheep.
Chen et al. (2024) Analysis of differential expression of hair follicle tissue transcriptome in Hetian sheep undergoing different periodic changes. PeerJ 12:e18542 https://doi.org/10.7717/peerj.18542
Diversity, antibacterial and phytotoxic activities of actinomycetes associated with Periplaneta fuliginosa
Background Insect-associated actinomycetes represent a potentially rich source for discovering bioactive metabolites. However, the diversity, antibacterial and phytotoxic activities of symbiotic actinomycetes associated with Periplaneta fuliginosa have not yet been conducted. Results A total of 86 strains of actinomycetes were isolated from the cornicles and intestines of both nymphs and adults of P. fuliginosa. Diversity analysis revealed that the isolated strains were preliminarily identified as 17 species from two genera, and the dominant genus was Streptomyces. A total of 36 crude extracts (60%) obtained from the supernatant of the 60 fermented strains exhibited a potent antibacterial activity against at least one tested pathogenic bacterium. Among these active strains, 27 crude extracts (75%) exhibited phytotoxic activity against the radicle of Echinochloa crusgalli. Furthermore, seven known compounds, including methoxynicotine (1), (3Z,6Z)-3-(4-methoxybenzylidene)-6-(2-methylpropyl) piperazine-2,5-dione (2), XR334 (3), 1-hydroxy-4-methoxy-2-naphthoic acid (4), nocapyrone A (5), β-daucosterol (6), and β-sitosterol (7) were isolated from an active rare actinomycete Nocardiopsis sp. ZLC-87 which was isolated from the gut of adult P. fuliginosa. Among them, compound 4 exhibited moderate antibacterial activity against Micrococcus tetragenus, Staphylococcus aureus, Escherichia coli, and Pseudomonas syringae pv. actinidiae with the zone of inhibition (ZOI) of 14.5, 12.0, 12.5, and 13.0 mm at a concentration of 30 μg/disc, respectively, which was weaker than those of gentamicin sulfate (ZOI of 29.5, 19.0, 18.5, and 24.5 mm). In addition, the compound 4 had potent phytotoxic activity against the radicle of E. crusgalli and Abutilon theophrasti with the inhibition rate of 65.25% and 92.68% at the concentration of 100 μg/mL. Conclusion Based on these findings, this study showed that P. fuliginosa-associated actinomycetes held promise for the development of new antibiotic and herbicide resources.
Liu et al. (2024) Diversity, antibacterial and phytotoxic activities of actinomycetes associated with Periplaneta fuliginosa. PeerJ 12:e18575 https://doi.org/10.7717/peerj.18575
Feldspathic sandstone as an emerging soil stabilizer for aeolian sand in the Mu Us Sandy Land: insights into particle size distribution
Stabilization of aeolian sand is essential for achieving desertification control, soil and water conservation, and agricultural development in sandy lands. Feldspathic sandstone is a soft clay rock widely found in the Mu Us Sandy Land. The purpose of this study was to ascertain the mechanism for aeolian sand stabilization with feldspathic sandstone from the perspective of particle size distribution. Feldspathic sandstone was added to aeolian sand at different ratios (mf:ms = 1:0, 1:1, 1:2, 1:5, and 0:1, where mf is the mass of feldspathic sandstone and ms is the mass of aeolian sand). The results showed that the soil texture was modified upon addition of feldspathic sandstone. The content of particles <0.05 mm increased with increasing addition ratio of feldspathic sandstone, in contrast to the downward trend observed for particles >0.05 mm. Consequently, the soil texture changed from sand to sandy loam, then loam, and finally silty loam. The addition of feldspathic sandstone ameliorated aeolian sand, resulting in a broader particle size distribution and lower particle size uniformity. Continuously well-graded soil was obtained at mf:ms = 1:5 (coefficient of uniformity: 54.71; coefficient of curvature: 2.54) or 1:2 (coefficient of uniformity: 76.21; coefficient of curvature: 1.12). While the addition of feldspathic sandstone solved the problem of single particle size distribution in aeolian sand, the presence of aeolian sand prevented soil compaction caused by the high clay content of feldspathic sandstone. Findings of this study indicate that the addition of feldspathic sandstone to aeolian sand leads to the mixing of various sized particles and continuous gradation of the soil. Although a higher addition ratio of feldspathic sandstone is more favorable for soil texture improvement, mf:ms = 1:5 is recommended for practical application in terms of particle gradation and cost effectiveness.
Environmental Contamination and Remediation
Zhang et al. (2024) Feldspathic sandstone as an emerging soil stabilizer for aeolian sand in the Mu Us Sandy Land: insights into particle size distribution. PeerJ 12:e18577 https://doi.org/10.7717/peerj.18577
Balance training in older adults enhances feedback control after perturbations
Background As we age, avoiding falls becomes increasingly challenging. While balance training can mitigate such challenges, the specific mechanisms through which balance control improves remains unclear. Methods We investigated the impact of balance training in older adults on feedback control after perturbations, focusing on kinematic balance recovery strategies and muscle synergy activation. Twenty older adults aged over 65 underwent short-term (one session) and long-term (3-weeks, 10 sessions) balance training, and their recovery from unpredictable mediolateral perturbations was assessed. Perturbations consisted of 8° rotations of a robot-controlled platform on which participants were balancing on one leg. We measured full-body 3D kinematics and activation of 15 leg and trunk muscles, from which linear and rotational kinematic balance recovery responses and muscle synergies were obtained. Results Our findings revealed improved balance performance after long-term training, characterized by reduced centre of mass acceleration and (rate of change of) angular momentum. Particularly during the later stage of balance recovery the use of angular momentum to correct centre of mass displacement was reduced after training, decreasing the overshoot in body orientation. Instead, more ankle torque was used to correct centre of mass displacement, but only for perturbations in medial direction. These situation and strategy specific changes indicate adaptations in feedback control. Activation of muscle synergies during balance recovery was also affected by training, specifically the synergies responsible for leg stiffness and ankle torques. Training effects on angular momentum and the leg stiffness synergy were already evident after short-term training. Conclusion We conclude that balance training in older adults refines feedback control through the tuning of control strategies, ultimately enhancing the ability to recover balance.
Koster et al. (2024) Balance training in older adults enhances feedback control after perturbations. PeerJ 12:e18588 https://doi.org/10.7717/peerj.18588
Risk factors and prediction models for recurrent acute ischemic stroke: a retrospective analysis
Background Ischemic stroke is one of the leading causes of disability and death worldwide, with a high risk of recurrence that severely impacts the quality of life of patients. Therefore, identifying and analyzing the risk factors for recurrent ischemic stroke is crucial for the prevention and management of this disease. Methods A total of 114 cases of recurrent acute ischemic stroke patients admitted from July 2017 to March 2021 were selected as the observation group, and another 409 cases of initial ischemic stroke patients from the same period as the control group. The clinical data of the observation group and the control group were compared to analyze the risk factors associated with the readmission of ischemic stroke. A single-factor analysis (Model 1), Least Absolute Shrinkage and Selection Operator (LASSO) regression, and machine learning methods (Model 2) were used to screen important variables, and a multi-factor COX Proportional Hazards Model regression stroke recurrence risk prediction model was constructed. The predictive performance of the model was evaluated by the consistency index (C-index). Results Multivariate COX regression analysis revealed that history of hypertension (Hazard Ratio [HR] = 2.549; 95% Confidence Interval (CI) [1.503–4.321]; P = 0.001), history of cerebral infarction (HR = 1.709; 95% CI [1.066–2.738]; P = 0.026), cerebral artery stenosis (HR = 0.534; 95% CI [0.306–0.931]; P = 0.027), carotid arteriosclerosis (HR = 1.823; 95% CI [1.137–2.924]; P = 0.013), systolic blood pressure (HR = 0.981; 95% CI [0.971–0.991]; P < 0.0001), red cell distribution width-coefficient of variation (RDW-CV) (HR = 1.251; 95% CI [1.019–1.536]; P = 0.033), mean platelet volume (MPV) (HR = 1.506; 95% CI [1.148–1.976]; P = 0.003), uric acid (UA) (HR = 0.995; 95% CI [0.991–1.000]; P = 0.049) were found significantly associated with acute ischemic stroke. The C-index of the full COX model was 0.777 (0.732~0.821), showing a good discrimination between Model 1 and Model 2. Conclusions History of hypertension, history of cerebral infarction, cerebral artery stenosis, carotid atherosclerosis, systolic blood pressure, UA, RDW-CV, and MPV were identified as risk factors for acute ischemic stroke recurrence. The model can be used to predict the recurrence of acute ischemic stroke.
Ke et al. (2024) Risk factors and prediction models for recurrent acute ischemic stroke: a retrospective analysis. PeerJ 12:e18605 https://doi.org/10.7717/peerj.18605