PeerJ最新文献

Background: Endometriosis (EM) is a disease related to reproductive dysfunction. The mechanism of epigenetic factors (EF) in EM still needs to be studied. Emerging evidence suggests that EF plays a role in the development of EM. However, the specific molecular pathways through which they exert their effects remain incompletely understood, necessitating further in-depth research. This study aimed to explore the mechanisms underlying EF in EM.

Methods: In the study, the differentially expressed genes (DEGs) between EM and control were obtained by analyzing transcriptome data from public databases. Candidate genes were obtained by taking the intersection of DEGs and EF-related genes (EF-RGs), which were further screened using machine learning algorithms, receiver operating characteristic analysis, and expression levels in the EM and control samples to obtain biomarkers. The potential mechanisms of biomarkers in EF were further analyzed by constructing a nomogram model, gene set enrichment analysis (GSEA), immune infiltration analysis, expression profiling in tissues and cells, molecular regulatory networks, and drug prediction. The expression of these biomarkers was validated using in vitro experiments.

Results: Histone deacetylase 9 (HDAC9), YY1-associated factor 2 (YAF2), and cell division cycle 6 (CDC6) were identified as EF-associated biomarkers in EM. These biomarkers had excellent diagnostic ability for EM. HDAC9, CDC6, and YAF2 were respectively significantly enriched in focal adhesion and oxidative phosphorylation pathways. Four types of differentially distributed immune cells were identified between EM and control samples using immune infiltration analysis. The expression of these biomarkers in different tissues varied with age and menstrual cycle. The expression levels of biomarkers were higher in endothelial cells. Ten miRNAs and 24 lncRNAs that targeted these biomarkers were screened, and there were 12 transcription factors (TFs) in which all the biomarkers acted together. All biomarkers worked together for drugs, including bisphenol A, benzo(a)pyrene, and cisplatin. The results of in vitro experiments were consistent with those of the bioinformatics analysis.

Conclusion: This study identified three biomarkers (HDAC9, CDC6, and YAF2) and the potential therapeutic drugs for EM. These results provide new insights into the mechanisms underlying EM development.

Background: Adult scoliosis, which is characterized by a persistent lateral deviation of the spine of at least 10° in the frontal plane along with vertebral rotation in adulthood, can result from various causes, including degenerative changes, untreated childhood scoliosis, spinal trauma, and prior surgeries. Traditionally, spinal curvature is assessed by measuring the Cobb angle via radiographic imaging; however, concerns over radiation exposure have prompted exploration of alternative diagnostic tools.This study aims to evaluate the effectiveness of a newly developed three-dimensional (3D) body scanner, equipped with 12 depth cameras, in assessing spinal alignment and measuring the Cobb angle in patients with adult scoliosis, in comparison with radiographic imaging.

Methods: In this prospective cohort study, 40 patients with adult scoliosis-both idiopathic and degenerative-underwent evaluation using both radiographic imaging and 3D body scanning. Cobb angles were measured by both methods. Pearson and Spearman's rank correlation coefficients were calculated to assess the linear and monotonic relationships between measurements. Measurement accuracy was quantified using the mean bias from Bland-Altman analysis and spatial agreement of spinal positions was further evaluated using the Intersection over Union (IoU) metric. Univariable and multivariable regression analyses were performed to assess whether body habitus (body mass index, waist circumference, waist-to-height ratio, age, and sex) influenced the absolute error between 3D body scanner-predicted and radiographic Cobb angles.

Results: Cobb angle measurements obtained from 3D body scanning were highly correlated with those from radiography (Pearson r = 0.92, P < 0.001; Spearman ρ = 0.85, P < 0.001), indicating strong linear and monotonic agreement. Bland-Altman analysis showed a small mean bias of -1.06 (95% limits of agreement: -10.25 to 8.12). The average IoU was 0.89, indicating substantial spatial agreement in spinal position predictions. Importantly, obesity indices (body mass index, waist circumference, waist-to-height ratio) were not significantly associated with the absolute error between 3D body scanner-predicted and radiographic Cobb angles in either univariable or multivariable analyses.

Conclusions: The 3D body scanner exhibits promise for assessing spinal alignment and measuring the Cobb angle in patients with adult scoliosis, offering a reliable alternative to traditional radiographic methods. Its accuracy was not affected by obesity-related indices, supporting its applicability across diverse patient body types. Future research should focus on refining scanning protocols and integrating patient-reported outcomes to enhance clinical utility.

Glacial cycles operating across Beringia have repeatedly exposed large swathes of the Bering Land Bridge, intermittently isolating and reuniting North American and Eurasian taxa. In high-latitude birds, these cycles are hypothesized to have been important in driving divergence and speciation. These repeated events have resulted in multiple trans-Beringian avian sister populations of varying degrees of taxonomic depth distributed across modern Beringia. We asked how these cyclic pulses have affected the temporal distribution and number of overall divergence events across Beringia. We sequenced full mitogenomes at high depth from 39 lineage pairs of varying levels of divergence, totaling 432 individuals of seven orders, 14 families, and 49 species from both Eurasia and North America. We then used a hierarchical approximate Bayesian comparative (hABC) approach to estimate the number and distribution of divergence events between the population pairs, using subsampled datasets. Net nucleotide divergence (D_A ) and Jukes-Cantor distance (JC-distance) were also calculated for each pairwise comparison to estimate divergence dates between taxa, using calibrated rates appropriate for shallow avian divergence events. Average divergence times were 200,000 ya for population-level taxa (n = 16), 720,000 ya for subspecies (n = 12), and 1 Mya for species (n = 11), although we consider these dating estimates conservative because of a lack of appropriate calibration for data of this quality. We found eighteen taxon pairs to be significantly differentiated (p < 0.05) by F_ST or substantially differentiated by haplotype clade, bounding the number of potential overall divergence events from 1 to 18, and two subsets of the full mitogenomic dataset analyzed in MTML-msBayes strongly supported simultaneous divergence of all Beringian lineages. However, this finding of simultaneous divergence is biologically unusual given the substantial variation in divergence dates among taxa and might indicate a relatively continuous spread of vicariance events, which is difficult to distinguish from a single, simultaneous vicariance event.

Background: Very few true Pseudomonas methylotrophic strains have been described, and in none of them have the pathways for one-carbon (C₁) substrate metabolism been elucidated.

Methods: The genomes of three Pseudomonas strains able to grow on methanol as the sole source of carbon (C) and energy (E) were sequenced and analyzed, and one of the strains was further characterized at the proteomic and physiological level.

Results: None of the three strains possesses a classic methanol dehydrogenase enzyme, and they apparently employ generalist type-I alcohol dehydrogenases (ADHs) to catabolize methanol to formaldehyde. In two of the strains' genomes, the only complete route encoded for incorporating methylotrophic carbon is the Calvin-Benson-Bassham (CBB) cycle, while other more typical pathways for C₁-carbon assimilation (serine cycle, ribulose monophosphate cycle) appear incomplete. The indispensability of the QedA1 alcohol dehydrogenase and of ribulose bisphosphate carboxylase for growth on methanol was demonstrated by insertion mutagenesis of the qedA1 and cbbL genes in one of the strains.

Discussion: To the author's knowledge, all wild-type methylotrophic Pseudomonadota (i.e., "Gram-negative bacteria") so far described employ a specific dehydrogenase distinctively adapted to using methanol as a substrate (MxaFI, XoxFI, or Mdh2). The methylotrophic Pseudomonas strains described here lack MDH and employ generalist ADHs, thus demoting methanol dehydrogenase (MDH) from the position of a critical enzyme for methanol utilization and expanding the range of enzymes (and genes) that enable methylotrophy in nature. The second remarkable result of this work is the discovery of the utilization of the CBB cycle by a Pseudomonas strain during methylotrophic growth, an absolute novelty for this very relevant bacterial genus.

Background: This study aimed to investigate age-related differences in anthropometric characteristics, change of direction (COD) and repeated sprint ability (RSA) performance, with and without ball control, in elite soccer players from U17, U19, and U23 categories.

Methodology: Seventy-two male players (age: 18.9 ± 2.23 years; height: 1.72 ± 0.08 m; body mass: 71.7 ± 5.04 kg; body mass index (BMI): 24.3 ± 2.61 kg/m²) from three professional soccer clubs were assessed (U17 = 24; U19 = 24; U23 = 24). After a two-month period of regular training and competition, anthropometric measures (height, body mass, body mass index) were recorded. In addition, players completed the New Multi-Change of Direction Agility Test (NMAT) and the Bangsbo RSA test, both performed with and without a ball. Testing was standardized for familiarization, warm-up, and environmental conditions.

Results: U23 players were taller and heavier than U17 and U19 players, and they showed superior COD performance without the ball compared to U17, whereas no statistically significant differences were found in COD with ball or RSA performance across age groups. Correlation analyses revealed moderate associations between anthropometric variables and COD performance (r =  - 0.35 to -0.24), while higher BMI values were related to slower agility times (r = 0.24-0.26).

Conclusions: Age-related anthropometric characteristics were associated with better COD performance without the ball, whereas COD with ball and RSA performance appear less age-dependent and more influenced by training specificity. These findings highlight the importance of incorporating technical COD drills and RSA training early in player development to align physical and technical progression.

Background: Studies have shown that vertical jump biomechanics or patterns may be related to physical fitness. This study investigated the relationship between physical fitness and drop vertical jump (DVJ) biomechanics in male college basketball players.

Methods: Health-related physical fitness was measured by 20s sit-up, core endurance and flexibility test; whilst athletic-related physical fitness by Y-balance test and dominant extremity single-leg hop distance test. Kinetics and kinematics during DVJ were evaluated by VICON.

Results: Five-level side bridge correlated negatively with angle displacement of hip adduction (p = 0.014) and positively with moment of knee flexion (p = 0.033); 8-level abdominal bridge correlated positively with moment of knee flexion (p = 0.01); ankle dorsiflexion range of motion correlated negatively with mediolateral ground reaction force (p = 0.025), angle displacement of knee flexion (p = 0.004), moment of ankle plantarflexion (p = 0.009), and positively with angle displacement of ankle plantarflexion (p = 0.015); ankle plantarflexion ROM correlated negatively with angle of knee flexion (p = 0.012); trunk flexion ROM correlated negatively with moment of ankle plantarflexion (p = 0.014).

Conclusion: Health-related physical fitness could be the alternatives for DVJ biomechanics assessment.

Background: Acute kidney injury (AKI) is a serious disease with a high incidence and easy induction. The search for innovative biomarkers and treatment methods is of great significance for improving the prognosis of patients. Autophagy is closely related to the occurrence and development of AKI. This study aims to explore the role of autophagy-related genes (ARGs) as potential biomarkers and therapeutic targets in AKI.

Methods: In this study, the gene microarray data of the GEO dataset were used to explore the molecular profile of AKI, and three machine learning algorithms were used to screen autophagy-related feature genes. To further validate the reliability of the screening results, we constructed a cisplatin-induced AKI rat model to validate potential biomarkers of machine learning screening.

Results: Machine learning analysis identified 17 differentially expressed ARGs and selected the core genes FIZ1 and FBXO21, with area under curve (AUC) values both exceeding 0.7 (95% CI [0.706-0.899]). Immune analysis revealed that the number of Mast cells resting significantly decreased in AKI samples compared to normal samples (P < 0.05). Electron microscopy observations of the cisplatin-induced AKI rat model indicated thickening of the basement membrane, fusion of foot processes, and swelling and rupture of mitochondria in the model group, suggesting a correlation between AKI and mitochondrial autophagy; Western blot results indicated a significant increase in the expression of FIZ1 and a significant decrease in FBXO21 in the AKI group (P < 0.01). The results of IHC staining were also consistent with those of Western blot results.

Conclusion: This study highlights the significant role of ARGs in AKI and identifies FIZ1 and FBXO21 as promising biomarkers with high diagnostic potential, offering new insights into the molecular mechanisms underlying AKI.

Enzymes, as key biocatalysts, are essential for advancing sustainable green technologies across diverse industrial sectors. The discovery of novel enzymes is essential for expanding their applications. In this study, we identified new lipases using an integrated screening strategy. This approach combines both structural and sequence-based methods on a large-scale metagenomic database. This strategy enabled the identification of new lipases with low sequence identity to known reference proteins. Our approach, therefore, circumvents the limitations of traditional sequence-only methods, which often fail to identify functionally similar enzymes with low sequence similarity. We first used Foldseek, a state-of-the-art structural homology search tool, to rapidly screen the database for proteins with structures similar to widely used lipases. This was followed by a rigorous sequence similarity filtering against public protein databases, yielding 711 putative novel lipases. We selected and experimentally validated three candidates, confirming their lipase activity. Further biochemical characterization revealed their notable properties including thermostability with optimal activity at 50-55 °C, and distinct alkaline activity profiles, maximal at pH of 8.0-9.0. Their unique properties, including high activity at elevated temperatures and alkaline pH, suggest potential for applications in detergent formulations, bioremediation, and industrial biocatalysis. Beyond identifying these promising enzymes, this study demonstrates the power of a combined structural and sequence-based approach for finding novel biocatalysts. This methodological innovation has broad implications for future enzyme discovery from metagenomic resources.

The transition from the Early to the Middle Jurassic was marked by significant restructuring of plesiosaur communities. While knowledge of the earliest Middle Jurassic plesiosaurs is generally limited, Toarcian plesiosaur occurrences are abundant, though the vast majority of specimens have been unearthed in the United Kingdom and Germany. Here, we reassess Lusonectes sauvagei, an early-diverging plesiosaur from the lower to middle upper Toarcian of the São Gião Formation in Portugal. Originally described as Plesiosaurus sp., it was later established as a distinct taxon closely related to taxa currently encompassed within Microcleididae. Our firsthand examination of the holotype of L. sauvagei resulted in differing interpretations of certain aspects of its morphology, prompting a detailed osteological, taxonomic, and phylogenetic reevaluation. We provide a redescription of L. sauvagei, propose a new diagnosis, and investigate its phylogenetic affinities. Although the specimen is fragmentary and poorly preserved, our study suggests that, contrary to the original interpretation, L. sauvagei is not affiliated with Microcleidus spp. The taxon remains problematic and may represent either an early-diverging pliosaurid or a plesiosauroid. Lusonectes is one of the few diagnosable plesiosaurs from the upper Lower Jurassic found outside the classic British and German localities and thus offers insights into the diversity of plesiosaurs just prior to a major event in the evolutionary history of the clade.