title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=419 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Expression profiles of circular RNAs and interaction networks of competing endogenous RNAs in neurogenic bladder of rats following suprasacral spinal cord injury link: https://peerj.com/articles/16042 last-modified: 2023-09-18 description: BackgroundNeurogenic bladder (NB) following suprasacral spinal cord injury (SSCI) is an interstitial disease with the structural remodeling of bladder tissue and matrix over-deposition. Circular RNAs (circRNAs) are involved in fibrotic disease development through their post-transcriptional regulatory functions. This study aimed to use transcriptome high-throughput sequencing to investigate the process of NB and bladder fibrosis after SSCI.MethodsSpinal cord transection at the T10–T11 level was used to construct the SSCI model in rats (10–week–old female Wistar rats, weighing 200 ± 20 g). The bladders were collected without (sham group) and with (SSCI 1–3 groups) NB status. Morphological examination was conducted to assess the extent of bladder fibrosis. Additionally, RNA sequencing was utilized to determine mRNAs and circRNAs expression patterns. The dynamic changes of differentially expressed mRNAs (DEMs) and circRNAs (DECs) in different periods of SSCI were further analyzed.ResultsBladder weight, smooth muscle cell hypertrophy, and extracellular matrix gradually increased after SSCI. Compared with the sham group, 3,255 DEMs and 1,339 DECs, 3,449 DEMs and 1,324 DECs, 884 DEMs, and 1,151 DECs were detected in the SSCI 1–3 groups, respectively. Specifically, circRNA3621, circRNA0617, circRNA0586, and circRNA4426 were significant DECs common to SSCI 1–3 groups compared with the sham group. Moreover, Gene Ontology (GO) enrichment suggested that inflammatory and chronic inflammatory responses were the key events in NB progression following SSCI. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment associated with the “Chemokine signaling pathway”, the “IL-17 signaling pathway”, and the “TGF-beta signaling pathway” suggests their potential involvement in regulating biological processes. The circRNA–miRNA–mRNA interaction networks of DECs revealed rno-circ-2239 (micu2) as the largest node, indicating that the rno-circ-2239–miRNA–mRNA–mediated network may play a critical role in the pathogenesis of SSCI-induced NB.ConclusionsThis study offers a comprehensive outlook on the possible roles of DEMs and DECs in bladder fibrosis and NB progression following SSCI. These findings have the potential to serve as novel biomarkers and therapeutic targets. creator: Jimeng Ruan creator: Xin Cui creator: Hao Yan creator: Chunsong Jia creator: Tongwen Ou creator: Zhenhua Shang uri: https://doi.org/10.7717/peerj.16042 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Ruan et al. title: A new gnathosaurine (Pterosauria, Archaeopterodactyloidea) from the Late Jurassic of Portugal link: https://peerj.com/articles/16048 last-modified: 2023-09-18 description: An incomplete, yet remarkably-sized dentated rostrum and associated partial cervical vertebrae of a pterosaur (ML 2554) were recently discovered from the Late Jurassic (Late Kimmeridgian-Early Tithonian) Lourinhã Formation of Praia do Caniçal, of central west Portugal. This specimen exhibits features such as a spatulated anterior expansion of the rostrum, robust comb-like dentition, and pronounced rims of the tooth alveoli, indicating gnathosaurine affinities. Based on its further unique tooth and dentary morphology, a new genus and species, Lusognathus almadrava gen. et spec. nov., is proposed, making this the first named pterosaur species found within Portugal. The presence of this taxon adds yet another element to the fluvio-deltaic lagoonal environment that has been suggested as representative of the Lourinhã Formation in the Late Jurassic, further contributing to the diversity and distribution of gnathosaurines worldwide. creator: Alexandra E. Fernandes creator: Victor Beccari creator: Alexander W. A. Kellner creator: Octávio Mateus uri: https://doi.org/10.7717/peerj.16048 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Fernandes et al. title: Performance of multigene testing in cytologically indeterminate thyroid nodules and molecular risk stratification link: https://peerj.com/articles/16054 last-modified: 2023-09-18 description: ObjectiveThyroid cancer is the third most prevalent cancer among females. Genetic testing based on next-generation sequencing may provide an auxiliary diagnosis to reduce cytologically diagnostic uncertainty. However, commercial multigene tests are not widely available and are not well-tested in the Chinese population.MethodsIn this study, we designed a multigene testing panel and evaluated its performance in 529 cytologically indeterminate thyroid nodules (Bethesda III, IV and V). The molecular data of the DNA mutations and RNA fusions of fine needle aspiration samples were reviewed in conjunction with a clinical diagnosis, pathological reports, and definitive surgery for retrospective analysis. Then, the molecular risk stratification was investigated for its accuracy in malignant risk prediction.ResultsThe overall combined consistency revealed substantial agreement (Kappa = 0.726) with the sensitivity, specificity, positive predictive value, and negative predictive values of 97.80%, 82.14%, 98.99%, and 67.65%, respectively. The most common aberration was BRAFV600E (82.59%), followed by NRAS mutants (4.07%), RET fusions (3.70%), and KRAS mutants (3.15%). Two cases (0.44%) were categorized into a high-risk group, 426 cases (94.67%) were categorized into a BRAF-like group with totally histopathologic papillary patterned tumors, and 22 cases (4.89%) were categorized into a RAS-like group with 14 papillary and eight follicular patterned tumors when the cohort concurrent aberrations were excluded. Potentially aggressive features may be related to concurrent molecular alterations of BRAFV600E with TERTQ302R, and AKT1L52R, NRASG12C, NRASQ61R, and CCDC6-RET fusions. ConclusionsThis study provided a multigene panel for identifying benign nodules from cytologically indeterminate thyroid nodules to avoid unnecessary surgery. We provide further evidence for using molecular risk stratification as a promising predictor of disease outcomes. The results of this study may be limited by the extremely high prevalence of cancer in the cohort for clinical reference. creator: Yuanyuan Zhou creator: Xinping Wu creator: Yuzhi Zhang creator: Zhiqiang Li creator: Xia Ge creator: Hao Chen creator: Yuan Mao creator: Wenbo Ding uri: https://doi.org/10.7717/peerj.16054 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Zhou et al. title: Whole-genome resequencing analysis of the medicinal plant Gardenia jasminoides link: https://peerj.com/articles/16056 last-modified: 2023-09-18 description: BackgroundGardenia jasminoides is a species of Chinese medicinal plant, which has high medicinal and economic value and rich genetic diversity, but the study on its genetic diversity is far not enough.MethodsIn this study, one wild and one cultivated gardenia materials were resequenced using IlluminaHiSeq sequencing platform and the data were evaluated to understand the genomic characteristics of G. jasminoides.ResultsAfter data analysis, the results showed that clean data of 11.77G, Q30 reached 90.96%. The average comparison rate between the sample and reference genome was 96.08%, the average coverage depth was 15X, and the genome coverage was 85.93%. The SNPs of FD and YP1 were identified, and 3,087,176 and 3,241,416 SNPs were developed, respectively. In addition, SNP non-synonymous mutation, InDel mutation, SV mutation and CNV mutation were also detected between the sample and the reference genome, and KEGG, GO and COG database annotations were made for genes with DNA level variation. The structural gene variation in the biosynthetic pathway of crocin and gardenia, the main medicinal substance of G. jasminoides was further explored, which provided basic data for molecular breeding and genetic diversity of G. jasminoides in the future. creator: Xinyu Xu creator: Bihua Chen creator: Juan Zhang creator: Siren Lan creator: Shasha Wu uri: https://doi.org/10.7717/peerj.16056 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Xu et al. title: In vitro and ex vitro propagation of Turkish myrtles through conventional and plantform bioreactor systems link: https://peerj.com/articles/16061 last-modified: 2023-09-18 description: The myrtle (Myrtus communis) plant naturally grows in the temperate Mediterranean and subtropical regions and is used for various purposes; thus, it is among the promising species of horticultural crops. This study aimed to evaluate and compare the performance of different propagation systems, including rooting, solid media propagation, rooting, and with the Plantform bioreactor system, in achieving healthy and rapid growth of four myrtle genotypes with diverse genetic origins and well-regional adaptation. The selection of myrtle genotypes with distinct genetic backgrounds and proven adaptability to specific regions allowed for a comprehensive assessment of the propagation systems under investigation. Present findings proved that the Plantform system, the new-generation tissue culture system, was quite successful in micropropagation and rooting myrtle genotypes. We succeeded in vitro micropropagation and rooting of diverse wild myrtle genotypes, enabling year-round propagation without reliance on specific seasons or environmental conditions. The process involved initiating cultures from explants and multiplying them through shoot proliferation in a controlled environment. This contributes to sustainable plant propagation, preserving and utilizing genetic resources for conservation and agriculture. creator: Özhan Şimşek creator: Dicle Dönmez creator: Mehmet Ali Sarıdaş creator: Emine Acar creator: Yıldız Aka Kaçar creator: Sevgi Paydaş Kargı creator: Tolga İzgü uri: https://doi.org/10.7717/peerj.16061 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Şimşek et al. title: The mediating roles of coping styles and academic burnout in the relationship between stressors and depressive symptoms among Chinese postgraduates link: https://peerj.com/articles/16064 last-modified: 2023-09-18 description: BackgroundSince few studies have incorporated factors like stressors, coping styles, and academic burnout into the same model to analyze their impacts on depressive symptoms, this research attempts to establish an optimal structural model to explore the direct and indirect effects of these factors on depressive symptoms.MethodsA total of 266 postgraduates completed questionnaires regarding coping styles, academic burnout, stressors, and depressive symptoms. The path analysis was applied for investigating the roles of coping styles and academic burnout in mediating the relationship between stressors and depressive symptoms.ResultsThe total and direct effects of stressors on depressive symptoms were 0.53 and 0.31, respectively. The proportion of the direct effect of stressors on depressive symptoms to its total effect amounted to 58.50%. The indirect effects of academic burnout, positive coping style, and negative coping style on the association between stressors and depressive symptoms were 0.11, 0.04, and 0.03, taking up 20.75%, 7.55%, and 5.66% of the total effect, respectively. The serial indirect effect of positive coping style and academic burnout was 0.02, accounting for 3.77% of the total effect, while that of negative coping style and academic burnout was 0.02, taking up 3.77% of the total effect.ConclusionsCoping styles and academic burnout chain jointly mediate the relationship between stressors and depressive symptoms among postgraduates. Thus, encouraging postgraduates to tackle stress positively may reduce the likelihood of the development of academic burnout and further reduce depressive symptoms. creator: Hong Shi creator: Hanfang Zhao creator: Minfu He creator: Zheng Ren creator: Shixun Wang creator: Li Cui creator: Jieyu Zhao creator: Wenjun Li creator: Yachen Wei creator: Wenjing Zhang creator: Ziqiang Chen creator: Hongjian Liu creator: Xiumin Zhang uri: https://doi.org/10.7717/peerj.16064 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Shi et al. title: Evidence for the utility of cfDNA plasma concentrations to predict disease severity in COVID-19: a retrospective pilot study link: https://peerj.com/articles/16072 last-modified: 2023-09-18 description: BackgroundCOVID-19 is a worldwide pandemic caused by the highly infective SARS-CoV-2. There is a need for biomarkers not only for overall prognosis but also for predicting the response to treatments and thus for improvements in the clinical management of patients with COVID-19. Circulating cell-free DNA (cfDNA) has emerged as a promising biomarker in the assessment of various pathological conditions. The aim of this retrospective and observational pilot study was to investigate the range of cfDNA plasma concentrations in hospitalized COVID-19 patients during the first wave of SARS-CoV-2 infection, to relate them to established inflammatory parameters as a correlative biomarker for disease severity, and to compare them with plasma levels in a healthy control group.MethodsLithium-Heparin plasma samples were obtained from COVID-19 patients (n = 21) during hospitalization in the University Medical Centre of Mainz, Germany between March and June 2020, and the cfDNA concentrations were determined by quantitative PCR yielding amplicons of long interspersed nuclear elements (LINE-1). The cfDNA levels were compared with those of an uninfected control group (n = 19).ResultsPlasma cfDNA levels in COVID-19 patients ranged from 247.5 to 6,346.25 ng/ml and the mean concentration was 1,831 ± 1,388 ng/ml (± standard deviation), which was significantly different from the levels of the uninfected control group (p < 0.001). Regarding clinical complications, the highest correlation was found between cfDNA levels and the myositis (p = 0.049). In addition, cfDNA levels correlated with the “WHO clinical progression scale”. D-Dimer and C-reactive protein (CRP) were the clinical laboratory parameters with the highest correlations with cfDNA levels.ConclusionThe results of this observational pilot study show a wide range in cfDNA plasma concentrations in patients with COVID-19 during the first wave of infection and confirm that cfDNA plasma concentrations serve as a predictive biomarker of disease severity in COVID-19. creator: Katharina Hoeter creator: Elmo Neuberger creator: Susanne Fischer creator: Manuel Herbst creator: Ema Juškevičiūtė creator: Kira Enders creator: Heidi Rossmann creator: Martin F. Sprinzl creator: Perikles Simon creator: Marc Bodenstein creator: Michael Schaefer uri: https://doi.org/10.7717/peerj.16072 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Hoeter et al. title: Identification of two short peptide motifs from serine/arginine-rich protein ribonucleic acid recognition motif-1 domain acting as splicing regulators link: https://peerj.com/articles/16103 last-modified: 2023-09-18 description: BackgroundSerine/arginine-rich (SR) proteins regulate pre-mRNA splicing. However, structurally similar proteins often behave differently in splicing regulation and the underlying mechanisms are largely unknown. Here, using SMN1/2 minigenes we extensively analyzed four SR proteins, SRSF1/5/6/9.MethodsIn this study, the effects of these proteins on SMN1/2 exon 7 splicing when tethered at either intron 6 or 7 were evaluated using an MS2-tethering assay. Deletion analysis in four SR proteins and co-overexpression analysis were performed.ResultsSplicing outcomes varied among all four SR proteins, SRSF1 and SRSF5 function the same at the two sites, acting as repressor and stimulator, respectively; while SRSF6 and SRSF9 promote exon 7 inclusion at only one site. Further, the key domains of each SR proteins were investigated, which identified a potent inhibitory nonapeptide in the C-terminus of SRSF1/9 ribonucleic acid recognition motif-1 (RRM1) and a potent stimulatory heptapeptide at the N-terminus of SRSF5/6 RRM1.ConclusionThe insight of the four SR proteins and their domains in affecting SMN gene splicing brings a new perspective on the modes of action of SR proteins; and the functional peptides obtained here offers new ideas for developing splice switching-related therapies. creator: Tao Jiang creator: Li Wang creator: Liang Tang creator: Azhar Zeb creator: Yanjun Hou uri: https://doi.org/10.7717/peerj.16103 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Jiang et al. title: Lower-limb sagittal joint angles during gait can be predicted based on foot acceleration and angular velocity link: https://peerj.com/articles/16131 last-modified: 2023-09-18 description: Background and purposeContinuous monitoring of lower-limb movement may help in the early detection and control/reduction of diseases (such as the progression of orthopedic diseases) by applying suitable interventions. Therefore, it is invaluable to calculate the lower-limb movement (sagittal joint angles) while walking daily for continuous evaluation of such risks. Although cameras in a motion capture system are necessary for calculating lower-limb sagittal joint angles during gait, the method is unrealistic considering the setting is difficult to achieve in daily life. Therefore, the estimation of lower-limb sagittal joint angles during walking based on variables, which can be measured using wearable sensors (e.g., foot acceleration and angular velocity), is important. This study estimates the lower-limb sagittal joint angles during gait from the norms of foot acceleration and angular velocity using machine learning and validates the accuracy of the estimated joint angles with those obtained using a motion capture system.MethodsHealthy adults (n = 200) were asked to walk at a comfortable speed (10 trials), and their lower-limb sagittal joint angles, foot accelerations, and angular velocities were obtained. Using these variables, we established a feedforward neural network and estimated the lower-limb sagittal joint angles.ResultsThe average root mean squared errors of the lower-limb sagittal joint angles during gait ranged between 2.5°–7.0° (hip: 7.0°; knee: 4.0°; and ankle: 2.5°).ConclusionThese results show that we can estimate the lower-limb sagittal joint angles during gait using only the norms of foot acceleration and angular velocity, which can help calculate the lower-limb sagittal joint angles during daily walking. creator: Takuma Inai creator: Tomoya Takabayashi uri: https://doi.org/10.7717/peerj.16131 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Inai and Takabayashi title: miR-200a-3p overexpression alleviates diabetic cardiomyopathy injury in mice by regulating autophagy through the FOXO3/Mst1/Sirt3/AMPK axis link: https://peerj.com/articles/15840 last-modified: 2023-09-15 description: ObjectiveHyperglycemia and insulin resistance or deficiency are characteristic features of diabetes. Diabetes is accompanied by cardiomyocyte hypertrophy, fibrosis and ventricular remodeling, and eventually heart failure. In this study, we established a diabetic cardiomyopathy (DCM) mouse model to explore the role and mechanism of miR-200a-3p in DCM.MethodsWe used db/db mice to simulate the animal model of DCM and the expression of miR-200a-3p was then examined by RT-qPCR. Tail vein injection of mice was done with rAAV-miR-200a-3p for 8 weeks, and cardiac function was assessed by cardiac ultrasound. The levels of myocardial tissue injury, fibrosis, inflammation, apoptosis and autophagy in mice were detected by histological staining, TUNEL and other molecular biological experiments.ResultsmiR-200a-3p expression levels were significantly decreased in the myocardium of DCM mice. Diabetic mice developed cardiac dysfunction and presented pathological changes such as myocardial injury, myocardial interstitial fibrosis, cardiomyocyte apoptosis, autophagy, and inflammation. Overexpression of miR-200a-3p expression significantly ameliorated diabetes induced-cardiac dysfunction and myocardial injury, myocardial interstitial fibrosis, cardiomyocyte apoptosis, and inflammation, and enhanced autophagy. Mechanistically, miR-200a-3p interacted with FOXO3 to promote Mst1 expression and reduce Sirt3 and p-AMPK expression.ConclusionIn type 2 diabetes, increased miR-200a-3p expression enhanced autophagy and participated in the pathogenic process of cardiomyopathy throug7 Mst1/Sirt3/AMPK axis regulation by its target gene FOXO3. This conclusion provides clues for the search of new gene targeted therapeutic approaches for diabetic cardiomyopathy. creator: Penghua You creator: Haichao Chen creator: Wenqi Han creator: Jizhao Deng uri: https://doi.org/10.7717/peerj.15840 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 You et al.