title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=512 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Tandem mass tag-based quantitative proteomic analysis identification of succinylation related proteins in pathogenesis of thoracic aortic aneurysm and aortic dissection link: https://peerj.com/articles/15258 last-modified: 2023-05-11 description: BackgroundThoracic aortic aneurysm and dissection (TAAD) are devastating cardiovascular diseases with a high rate of disability and mortality. Lysine succinylation, a newly found post-translational modification, has been reported to play an important role in cardiovascular diseases. However, how succinylation modification influences TAAD remains obscure.MethodsAscending aortic tissues were obtained from patients with thoracic aortic aneurysm (TAA, n = 6), thoracic aortic dissection (TAD) with pre-existing aortic aneurysm (n = 6), and healthy subjects (n = 6). Global lysine succinylation level was analyzed by Western blotting. The differentially expressed proteins (DEPs) were analyzed by tandem mass tag (TMT) labeling and mass spectrometry. Succinylation-related proteins selected from the literature review and AmiGO database were set as a reference inventory for further analysis. Then, the pathological aortic sections were chosen to verify the proteomic results by Western blotting and qRT-PCR.ResultsThe level of global lysine succinylation significantly increased in TAA and TAD patients compared with healthy subjects. Of all proteins identified by proteomic analysis, 197 common DEPs were screened both in TAA and TAD group compared with the control group, of which 93 proteins were significantly upregulated while 104 were downregulated. Among these 197 DEPs, OXCT1 overlapped with the succinylation-related proteins and was selected as the target protein involved in thoracic aortic pathogenesis. OXCT1 was further verified by Western blotting and qRT-PCR, and the results showed that OXCT1 in TAA and TAD patients was significantly lower than that in healthy donors (p < 0.001), which was consistent with the proteomic results.ConclusionsOXCT1 represents novel biomarkers for lysine succinylation of TAAD and might be a therapeutic target in the future. creator: Yu Zhang creator: Hongwei Zhang creator: Haiyue Wang creator: Chenhao Wang creator: Peng Yang creator: Chen Lu creator: Yu Liu creator: Zhenyuan Xu creator: Yi Xie creator: Jia Hu uri: https://doi.org/10.7717/peerj.15258 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Zhang et al. title: m6A eraser ALKBH5 mitigates the apoptosis of cardiomyocytes in ischemia reperfusion injury through m6A/SIRT1 axis link: https://peerj.com/articles/15269 last-modified: 2023-05-11 description: Recent studies have shown that the potential regulatory role of N6-methyladenine (m6A) modification may affect the occurrence and development of various cardiovascular diseases. However, the regulatory mechanism of m6A modification on myocardial ischemia reperfusion injury (MIRI) is rarely reported. A mouse model of myocardial ischemia reperfusion (I/R) was established by ligation and perfusion of the left anterior descending coronary artery, and a cellular model of hypoxia/reperfusion (H/R) was conducted in cardiomyocytes (CMs). We found that the protein expression of ALKBH5 in myocardial tissues and cells were decreased, accompanied by increased m6A modification level. Overexpression of ALKBH5 significantly inhibited H/R-induced oxidative stress and apoptosis in CMs. Mechanistically, there was an enriched m6A motif in the 3′-UTR of SIRT1 genome, and ALKBH5 overexpression promoted the stability of SIRT1 mRNA. Furthermore, results using overexpression or knockdown of SIRT1 confirmed the protective effect of SIRT1 on H/R induced CMs apoptosis. Together, our study reveals a critical role of ALKBH5-medicated m6A on CM apoptosis, supplying an important regulating effect of m6A methylation in ischemic heart disease. creator: Liangliang Liu creator: Zhen Liu uri: https://doi.org/10.7717/peerj.15269 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Liu and Liu title: Incidence, genetic diversity, and antimicrobial resistance profiles of Vibrio parahaemolyticus in seafood in Bangkok and eastern Thailand link: https://peerj.com/articles/15283 last-modified: 2023-05-11 description: BackgroundEmergence of Vibrio parahaemolyticus pandemic strain O3:K6 was first documented in 1996. Since then it has been accounted for large outbreaks of diarrhea globally. In Thailand, prior studies on pandemic and non-pandemic V. parahaemolyticus had mostly been done in the south. The incidence and molecular characterization of pandemic and non-pandemic strains in other parts of Thailand have not been fully characterized. This study examined the incidence of V. parahaemolyticus in seafood samples purchased in Bangkok and collected in eastern Thailand and characterized V. parahaemolyticus isolates. Potential virulence genes, VPaI-7, T3SS2, and biofilm were examined. Antimicrobial resistance (AMR) profiles and AMR genes (ARGs) were determined.MethodsV. parahaemolyticus was isolated from 190 marketed and farmed seafood samples by a culture method and confirmed by polymerase chain reaction (PCR). The incidence of pandemic and non-pandemic V. parahaemolyticus and VPaI-7, T3SS2, and biofilm genes was examined by PCR. AMR profiles were verified by a broth microdilution technique. The presence of ARGs was verified by genome analysis. V. parahaemolyticus characterization was done by multilocus sequence typing (MLST). A phylogenomic tree was built from nucleotide sequences by UBCG2.0 and RAxML softwares.ResultsAll 50 V. parahaemolyticus isolates including 21 pathogenic and 29 non-pathogenic strains from 190 samples had the toxRS/old sequence, indicating non-pandemic strains. All isolates had biofilm genes (VP0950, VP0952, and VP0962). None carried T3SS2 genes (VP1346 and VP1367), while VPaI-7 gene (VP1321) was seen in two isolates. Antimicrobial susceptibility profiles obtained from 36 V. parahaemolyticus isolates revealed high frequency of resistance to colistin (100%, 36/36) and ampicillin (83%, 30/36), but susceptibility to amoxicillin/clavulanic acid and piperacillin/tazobactam (100%, 36/36). Multidrug resistance (MDR) was seen in 11 isolates (31%, 11/36). Genome analysis revealed ARGs including blaCARB (100%, 36/36), tet(34) (83%, 30/36), tet(35) (42%, 15/36), qnrC (6%, 2/36), dfrA6 (3%, 1/36), and blaCTX-M-55 (3%, 1/36). Phylogenomic and MLST analyses classified 36 V. parahaemolyticus isolates into 5 clades, with 12 known and 13 novel sequence types (STs), suggesting high genetic variation among the isolates.ConclusionsAlthough none V. parahaemolyticus strains isolated from seafood samples purchased in Bangkok and collected in eastern Thailand were pandemic strains, around one third of isolates were MDR V. parahaemolyticus strains. The presence of resistance genes of the first-line antibiotics for V. parahaemolyticus infection raises a major concern for clinical treatment outcome since these resistance genes could be highly expressed under suitable circumstances. creator: Chartchai Changsen creator: Somsak Likhitrattanapisal creator: Kamonwan Lunha creator: Wiyada Chumpol creator: Surasak Jiemsup creator: Anuphap Prachumwat creator: Darin Kongkasuriyachai creator: Supawadee Ingsriswang creator: Soraya Chaturongakul creator: Aekarin Lamalee creator: Suganya Yongkiettrakul creator: Sureemas Buates uri: https://doi.org/10.7717/peerj.15283 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Changsen et al. title: Kekveus brevisulcatus sp. nov., a new featherwing beetle from mid-Cretaceous amber of northern Myanmar (Coleoptera: Ptiliidae) link: https://peerj.com/articles/15306 last-modified: 2023-05-11 description: Ptiliidae (featherwing beetles) is a group of minute staphylinoid beetles with a scarce fossil record. Here a second member of the Mesozoic genus Kekveus Yamamoto et al. is reported from mid-Cretaceous Burmese amber, with detailed morphology obtained through confocal microscopy. Kekveus brevisulcatus Li, Yamamoto, Newton & Cai sp. nov. shares with K. jason Yamamoto et al. the unpaired medial pronotal fovea and narrowly separated transverse metacoxae, but can be separated from the latter based on its less elongate body, shorter pronotal foveae, and much weaker transverse depression on the head. Our phylogenetic analyses support the discheramocephalin affinity of Kekveus, although its relationship with other members of Discheramocephalini cannot be confidently resolved. creator: Yan-Da Li creator: Shûhei Yamamoto creator: Alfred F. Newton creator: Chen-Yang Cai uri: https://doi.org/10.7717/peerj.15306 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Li et al. title: Bone marrow mesenchymal stem cell-derived exosomes protect podocytes from HBx-induced ferroptosis link: https://peerj.com/articles/15314 last-modified: 2023-05-11 description: IntroductionHepatitis B virus-associated glomerulonephritis (HBV-GN) is a common secondary kidney disease in China, the pathogenesis of which is not completely clear, and there is still a lack of effective treatment.MethodsThe mechanism of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) was investigated by using HBx-transfected human renal podocytes. Cell viability was detected by CCK8 assay. Iron and malondialdehyde (MDA) contents were detected by using commercial kits. Reactive oxygen species (ROS) levels were measured by flow cytometry analysis. The expression of ferroptosis related molecules was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. The effect of miR-223-3p transferred by BMSC-derived exosomes on HBx-overexpressing podocytes was proved by using miR-223-3p inhibitor.ResultsThe cell viability of podocytes reduced at 72 h or 96 h after the transfection of lentivirus overexpressing HBx protein (p < 0.05). Ferroptosis-related proteins, including glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were down-regulated upon HBx overexpression, while acyl-CoA synthetase long-chain family member 4 (ACSL4) was up-regulated (p < 0.05). Intracellular levels of iron, MDA, and ROS were also enhanced (p < 0.05). BMSC-derived exosomes protected against ferroptosis induced by HBx overexpression in podocytes. miR-223-3p was enriched in BMSC-derived exosomes. Application of miR-223-3p inhibitor reversed the protective effect of BMSC-derived exosomes on HBx-induced ferroptosis in podocytes.ConclusionBMSC-derived exosomes inhibit HBx-induced podocyte ferroptosis by transferring miR-223-3p. creator: Xiaoqian Yang creator: Yani Yu creator: Baoshuang Li creator: Yueqi Chen creator: Moxuan Feng creator: Yongzheng Hu creator: Wei Jiang uri: https://doi.org/10.7717/peerj.15314 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Yang et al. title: Multi-omics analysis of pyroptosis regulation patterns and characterization of tumor microenvironment in patients with hepatocellular carcinoma link: https://peerj.com/articles/15340 last-modified: 2023-05-11 description: BackgroundHepatocellular carcinoma (HCC) is a primary malignant tumor of the liver, and pyroptosis has been identified as a novel cellular program that plays a role in numerous diseases including cancer. However, the functional role of pyroptosis in HCC remains unclear. The purpose of this study is to explore the relationship between the two found hub genes and provide targets for clinical treatment.MethodsThe Cancer Genome Atlas (TCGA) database was used to collect the gene data and clinically-related information of patients with HCC. After the differentially expressed genes (DEGs) were identified, they were intersected with the genes related to pyroptosis, and a risk prediction model was established to predict the overall survival (OS). Subsequently, drug sensitivity analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) was used to analyze the biological characteristics of the DEGs. Different immune cell infiltration and related pathways were analyzed, and hub genes were identified by protein-protein interaction (PPI). Finally, the expression of hub genes was verified by real-time quantitative PCR (qRT-PCR) and immunohistochemistry.ResultsWe conducted a comprehensive bioinformatics analysis to investigate the molecular mechanisms of pyroptosis in hepatocellular carcinoma (HCC). A total of 8,958 differentially expressed genes were identified, and 37 differentially expressed genes were associated with pyroptosis through intersection. Moreover, we developed an OS model with excellent predictive ability and discovered the differences in biological function, drug sensitivity, and immune microenvironment between high-risk and low-risk groups. Through enrichment analysis, we found that the differentially expressed genes are related to various biological processes. Then, 10 hub genes were identified from protein-protein interaction networks. Finally, midkine (MDK) was screened from the 10 hub genes and further verified by PCR and immunohistochemistry, which revealed its high expression in HCC.ConclusionWe have developed a reliable and consistent predictive model based on the identification of potential hub genes, which can be used to accurately forecast the prognosis of patients, thus providing direction for further clinical research and treatment. creator: Bingbing Shang creator: Ruohan Wang creator: Haiyan Qiao creator: Xixi Zhao creator: Liang Wang creator: Shaoguang Sui uri: https://doi.org/10.7717/peerj.15340 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Shang et al. title: Temperament and character in an Australian sample: examining cross-sectional associations of personality with age, sex, and satisfaction with life link: https://peerj.com/articles/15342 last-modified: 2023-05-11 description: ObjectivePersonality can influence how we interpret and react to our day-to-day life circumstances. Temperament and character are the primary dimensions of personality, and both are influenced genetically. Temperament represents our emotional core, while character reflects our goals and values as we develop through life. Research shows that where people live, their social, economic, and physical environment can influence attitudes and behaviors, and these have links to variations in personality traits. There are few studies that focus on Australian personality as temperament and character. Using an Australian general population sample, we examined the psychometric properties of the Temperament and Character Inventory (TCIR140) and investigated the associations between TCIR140 traits with both sociodemographic variables and measures of well-being. In addition, we investigated differences in temperament and character between our Australian general population sample and published results of similar studies from other countries.MethodsAustralians (N = 1,510) completed the Temperament and Character Inventory (TCIR-140), the Positive and Negative Affect Scale and the Satisfaction with Life Scale. Cronbach’s alpha and confirmatory factor analysis (CFA) examined the TCIR-140 psychometrics. Correlation analyzes, independent sample t-tests and ANOVA with post-hoc comparisons analyzed the sample.ResultsCronbach’s alphas were high, ranging from α = 0.78–0.92, and the CFA confirmed two constructs of temperament and character. Females were higher in Harm Avoidance (p < 0.001), Reward Dependence (p < 0.001), and Cooperativeness (p < 0.001) compared to males, who were higher in Self-Directedness (p < 0.001). Age groups showed significant differences among all temperament and character traits (p < 0.001) except for Reward Dependence (p = 0.690). Young adults had the least resilient personality profile and poorest measures of well-being. Correlations with measures of temperament and character, well-being and affect were all in the expected direction.ConclusionsTemperament and character are related to indicators of wellbeing and differs by age and sex. This Australian sample demonstrate a temperament that is high in Persistence and a character high in Self-Directedness and Cooperativeness with an overall postive affect and a general satisfaction with life. In comparison to other countries, Australians in this sample differ in levels of several traits, demonstrating a cautious and independent temperament with a character that is cooperative, industrious, and self-reliant. Young-adults in comparison to older groups have a temperament and character profile that is prone to negative emotions and a lower satisfaction with life. creator: Diann S. Eley creator: Vikas Bansal creator: C. Robert Cloninger creator: Janni Leung uri: https://doi.org/10.7717/peerj.15342 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Eley et al. title: The role of solar radiation and tidal emersion on oxidative stress and glutathione synthesis in mussels exposed to air link: https://peerj.com/articles/15345 last-modified: 2023-05-11 description: Preparation for oxidative stress (POS) is a widespread adaptive response to harsh environmental conditions, whose hallmark is the upregulation of antioxidants. In contrast to controlled laboratory settings, animals are exposed to multiple abiotic stressors under natural field conditions. Still, the interplay between different environmental factors in modulating redox metabolism in natural settings remains largely unexplored. Here, we aim to shed light on this topic by assessing changes in redox metabolism in the mussel Brachidontes solisianus naturally exposed to a tidal cycle. We compared the redox biochemical response of mussels under six different natural conditions in the field along two consecutive days. These conditions differ in terms of chronology, immersion/emersion, and solar radiation, but not in terms of temperature. Animals were collected after being exposed to air early morning (7:30), immersed during late morning and afternoon (8:45–15:30), and then exposed to air again late afternoon towards evening (17:45–21:25), in two days. Whole body homogenates were used to measure the activity of antioxidant (catalase, glutathione transferase and glutathione reductase) and metabolic (glucose 6-phosphate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase and pyruvate kinase) enzymes, reduced (GSH) and disulfide (GSSG) glutathione levels, and oxidative stress markers (protein carbonyl and thiobarbituric acid reactive substances). Air and water temperature remained stable between 22.5 °C and 26 °C during both days. Global solar radiation (GSR) greatly differed between days, with a cumulative GSR of 15,381 kJ/m2 for day 1 and 5,489 kJ/m2 for day 2, whose peaks were 2,240 kJ/m2/h at 14:00 on day 1 and 952 kJ/m2/h at 12:00 on day 2. Compared with animals underwater, emersion during early morning did not elicit any alteration in redox biomarkers in both days. Air exposure for 4 h in the late afternoon towards evening caused oxidative damage to proteins and lipids and elicited GSH synthesis in animals that had been previously exposed to high GSR during the day. In the following day, when GSR was much lower, exposure to air under the same conditions (duration, time, and temperature) had no effect on any redox biomarker. These findings suggest that air exposure under low-intensity solar radiation is not sufficient to trigger POS in B. solisianus in its natural habitat. Thus, natural UV radiation is possibly a key environmental factor that combined to air exposure induces the POS-response to the stressful event of tidal variation in this coastal species. creator: Daniel C. Moreira creator: Marcus Aurélio da Costa Tavares Sabino creator: Marina Minari creator: Felipe Torres Brasil Kuzniewski creator: Ronaldo Angelini creator: Marcelo Hermes-Lima uri: https://doi.org/10.7717/peerj.15345 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Moreira et al. title: The effect of FMT and vitamin C on immunity-related genes in antibiotic-induced dysbiosis in mice link: https://peerj.com/articles/15356 last-modified: 2023-05-11 description: Antibiotics are double-edged swords. Although antibiotics are used to inhibit pathogenic bacteria, they also run the risk of destroying some of the healthy bacteria in our bodies. We examined the effect of penicillin on the organism through a microarray dataset, after which 12 genes related to immuno-inflammatory pathways were selected by reading the literature and validated using neomycin and ampicillin. The expression of genes was measured using qRT-PCR. Several genes were significantly overexpressed in antibiotic-treated mice, including CD74 and SAA2 in intestinal tissues that remained extremely expressed after natural recovery. Moreover, transplantation of fecal microbiota from healthy mice to antibiotic-treated mice was made, where GZMB, CD3G, H2-AA, PSMB9, CD74, and SAA1 were greatly expressed; however, SAA2 was downregulated and normal expression was restored, and in liver tissue, SAA1, SAA2, SAA3 were extremely expressed. After the addition of vitamin C, which has positive effects in several aspects, to the fecal microbiota transplantation, in the intestinal tissues, the genes that were highly expressed after the fecal microbiota transplantation effectively reduced their expression, and the unaffected genes remained normally expressed, but the CD74 gene remained highly expressed. In liver tissues, normally expressed genes were not affected, but the expression of SAA1 was reduced and the expression of SAA3 was increased. In other words, fecal microbiota transplantation did not necessarily bring about a positive effect of gene expression restoration, but the addition of vitamin C effectively reduced the effects of fecal microbiota transplantation and regulated the balance of the immune system. creator: Xiaorong Huang creator: Yv Zhang creator: Junsong Huang creator: Wenli Gao creator: Xie Yongfang creator: Chuisheng Zeng creator: Chao Gao uri: https://doi.org/10.7717/peerj.15356 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Huang et al. title: Higher serum β2-microglobulin is a predictive biomarker for cognitive impairment in spinal cord injury link: https://peerj.com/articles/15372 last-modified: 2023-05-11 description: ObjectiveRecent studies have suggested that high levels of β2-microglobulin are linked to cognitive deterioration; however, it is unclear how this connects to spinal cord injury (SCI). This study sought to determine whether there was any association between cognitive decline and serum β2-microglobulin levels in patients with SCI.MethodsA total of 96 patients with SCI and 56 healthy volunteers were enrolled as study participants. At the time of enrollment, specific baseline data including age, gender, triglycerides (TG), low-density lipoprotein (LDL), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), smoking, and alcohol use were recorded. Each participant was assessed by a qualified physician using the Montreal cognitive assessment (MoCA) scale. Serum β2-microglobulin levels were measured using an enzyme-linked immunosorbent assay (ELISA) reagent for β2-microglobulin.ResultsA total of 152 participants were enrolled, with 56 in the control group and 96 in the SCI group. There were no significant baseline data differences between the two groups (p > 0.05). The control group had a MoCA score of 27.4 ± 1.1 and the SCI group had a score of 24.3 ± 1.5, with the difference being significant (p < 0.05). The serum ELISA results revealed that the levels of β2-microglobulin in the SCI group were considerably higher (p < 0.05) than those in the control group (2.08 ± 0.17 g/mL compared to 1.57 ± 0.11 g/mL). The serum β2-microglobulin level was used to categorize the patients with SCI into four groups. As serum β2-microglobulin levels increased, the MoCA score reduced (p < 0.05). After adjustment of baseline data, further regression analysis showed that serum β2-microglobulin level remained an independent risk factor for post-SCI cognitive impairment.ConclusionsPatients with SCI had higher serum levels of β2-microglobulin, which may be a biomarker for cognitive decline following SCI. creator: Zhonghao Cui creator: Shuai Wang creator: Yanke Hao creator: Yuanzhen Chen uri: https://doi.org/10.7717/peerj.15372 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Cui et al.