Investigating molecular markers linked to acute myocardial infarction and cuproptosis: bioinformatics analysis and validation in the AMI mice model
Cuproptosis-related key genes play a significant role in the pathological processes of acute myocardial infarction (AMI). However, a complete understanding of the molecular mechanisms behind this participation remains elusive. This study was designed to identify genes and immune cells critical to AMI pathogenesis. Based on the GSE48060 dataset (31 AMI patients and 21 healthy persons, GPL570-55999), we identified genes associated with dysregulated cuproptosis and the activation of immune responses between normal subjects and patients with a first myocardial attack. Two molecular clusters associated with cuproptosis were defined in patients with AMI. Immune infiltration analysis showed that there was significant immunity heterogeneity among different clusters. Multiple immune responses were closely associated with Cluster2-specific differentially expressed genes (DEGs). The generalized linear model machine model presented the best discriminative performance with relatively lower residual and root mean square error, and a higher area under the curve (AUC = 0.870). A final two-gene-based generalized linear model was constructed, exhibiting satisfactory performance in two external validation datasets (AUC = 0.719, GSE66360 and AUC = 0.856, GSE123342). Column graph, calibration curve, and decision curve analyses also proved the accuracy of AMI prediction. We also constructed a mouse C57BL/6 model of AMI (3 h, 48 h, and 1 week) and used qRT-PCR and immunofluorescence to detect the expression changes of CBLB and ZNF302. In this study, we present a systematic analysis of the complex relationship between cuproptosis and a first AMI attack, and provide new insights into the diagnosis and treatment of AMI.
Wang et al. (2024) Investigating molecular markers linked to acute myocardial infarction and cuproptosis: bioinformatics analysis and validation in the AMI mice model. PeerJ 12:e17280 https://doi.org/10.7717/peerj.17280
Genome-wide identification and expression analysis of the WRKY gene family in Rhododendron henanense subsp. lingbaoense
Background This work explored the characteristics of the WRKY transcription factor family in Rhododendron henanense subsp. lingbaoense (Rhl) and the expression patterns of these genes under abiotic stress by conducting bioinformatics and expression analyses. Methods RhlWRKY genes were identified from a gene library of Rhl. Various aspects of these genes were analyzed, including genetic structures, conserved sequences, physicochemical properties, cis-acting elements, and chromosomal location. RNA-seq was employed to analyze gene expression in five different tissues of Rhl: roots, stems, leaves, flowers, and hypocotyls. Additionally, qRT-PCR was used to detect changes in the expression of five RhlWRKY genes under abiotic stress. Result A total of 65 RhlWRKY genes were identified and categorized into three subfamilies based on their structural characteristics: Groups I, II, and III. Group II was further divided into five subtribes, with shared similar genetic structures and conserved motifs among members of the same subtribe. The physicochemical properties of these proteins varied, but the proteins are generally predicted to be hydrophilic. Most proteins are predicted to be in the cell nucleus, and distributed across 12 chromosomes. A total of 84 cis-acting elements were discovered, with many related to responses to biotic stress. Among the identified RhlWRKY genes, there were eight tandem duplicates and 97 segmental duplicates. The majority of duplicate gene pairs exhibited Ka/Ks values <1, indicating purification under environmental pressure. GO annotation analysis indicated that WRKY genes regulate biological processes and participate in a variety of molecular functions. Transcriptome data revealed varying expression levels of 66.15% of WRKY family genes in all five tissue types (roots, stems, leaves, flowers, and hypocotyls). Five RhlWRKY genes were selected for further characterization and there were changes in expression levels for these genes in response to various stresses. Conclusion The analysis identified 65 RhlWRKY genes, among which the expression of WRKY_42 and WRKY_17 were mainly modulated by the drought and MeJA, and WRKY_19 was regulated by the low-temperature and high-salinity conditions. This insight into the potential functions of certain genes contributes to understanding the growth regulatory capabilities of Rhl.
Guo et al. (2024) Genome-wide identification and expression analysis of the WRKY gene family in Rhododendron henanense subsp. lingbaoense. PeerJ 12:e17435 https://doi.org/10.7717/peerj.17435
Effects of high-intensity sprint exercise on neuromuscular function in sprinters: the countermovement jump as a fatigue assessment tool
Background High-intensity sprint exercises (HIS) are central to sprinter training and require careful monitoring of athlete muscle fatigue to improve performance and prevent injury. While the countermovement jump (CMJ) may be used to monitor neuromuscular fatigue (NMF), little is known about the specific effects from HIS. The purpose of this study is to investigate the effects of HIS on the CMJ to assess its utility for assessing NMF following HIS. Methods Ten male collegiate 400 m sprinters completed a 400 m sprint fatigue protocol and underwent five CMJ-testing sessions (baseline, 3 minutes, 10 minutes, 1 hour and 24 hours) over two days. Three CMJ trials, performed on a force plate, were completed each trial, with rating of perceived exertion (RPE) recorded as a subjective fatigue measure. Changes in RPE, CMJ variables, force-time and power-time curves at baseline and post fatigue were assessed. Results Significant changes were observed in most variables following the fatigue protocol. In particular, concentric mean power remained significantly lower after 24 hours compared to baseline. In addition, the force-time curves exhibited a significant reduction in all conditions following the fatigue protocol. This decline was most pronounced within 50–75%of the concentric phase relative to baseline measurements. Conclusion. Results indicate that the CMJ may be a useful tool for monitoring fatigue in at least 400 m sprinters. These data also indicate that HIS may disproportionately reduce force output in during concentric movement. These insights may improve training prescriptions and injury prevention strategies for sprint athletes.
Hasegawa et al. (2024) Effects of high-intensity sprint exercise on neuromuscular function in sprinters: the countermovement jump as a fatigue assessment tool. PeerJ 12:e17443 https://doi.org/10.7717/peerj.17443
Dose-response relationship between weekly physical activity level and the frequency of colds in Chinese middle-aged and elderly individuals
Background Engaging in appropriate physical activity can significantly lower the risk of various diseases among middle-aged and older adults. Investigating optimal levels of physical activity (PA) is crucial for enhancing the health of this demographic. This study aims to explore the dose–response relationship between weekly PA levels and the frequency of colds among Chinese middle-aged and elderly individuals, identifying the necessary PA level to effectively diminish the risk of colds. Methods We conducted a cross-sectional study using a web-based survey targeting individuals aged 40 and older (n = 1, 683) in China. The survey collected information on PA and the frequency of colds. Data was analyzed using Kruskal–Wallis test and the χ2 test. We explored the dose–response relationship between weekly PA and cold frequency over the past year through an ordered multivariate logistic regression model and a restricted cubic spline model. Results (1) Brisk walking emerged as the preferred physical exercise for those over 40. The findings suggest that engaging in moderate (odds ratio (OR) = 0.64, P < 0.001, 95% confidence interval (CI) [0.50–0.81]) and high (OR = 0.64, P < 0.001, 95% CI [0.51–0.79]) levels of PA weekly significantly reduces the risk of catching a cold. Individuals with one (OR = 1.47, P < 0.001, 95% CI [1.20–1.80]) or multiple chronic diseases (OR = 1.56, P < 0.001, 95% CI [1.21–2.00]) were at increased risk. Those residing in central (OR = 1.64, P < 0.001, 95% CI [1.33–02.01]) and western China (OR = 1.49, P = 0.008, 95% CI [1.11–02.00]) faced a higher risk compared to their counterparts in eastern China. (2) According to the restricted cubic spline model, adults who experienced one cold in the past year had a weekly PA level of 537.29 metabolic equivalent-minutes per week (MET-min/wk) with an OR value of 1. For those reporting two or more colds, the PA level was 537.76 MET-min/wk with an OR of 1. Conclusions (1) Brisk walking is the most favored exercise among the Chinese middle-aged and elderly, with the prevalence of colds being affected by the number of chronic diseases and the geographic location. (2) Regular, moderate exercise is linked to a lower risk of colds. To effectively reduce cold frequency, it is recommended that middle-aged and elderly Chinese individuals engage in a minimum of 538 MET-min/wk of exercise.
Tang et al. (2024) Dose-response relationship between weekly physical activity level and the frequency of colds in Chinese middle-aged and elderly individuals. PeerJ 12:e17459 https://doi.org/10.7717/peerj.17459
Effect of SlSAHH2 on metabolites in over-expressed and wild-type tomato fruit
Background Tomato (Solanum lycopersicum) is an annual or perennial herb that occupies an important position in daily agricultural production. It is an essential food crop for humans and its ripening process is regulated by a number of genes. S-adenosyl-l-homocysteine hydrolase (AdoHcyase, EC 3.3.1.1) is widespread in organisms and plays an important role in regulating biological methylation reactions. Previous studies have revealed that transgenic tomato that over-express SlSAHH2 ripen earlier than the wild-type (WT). However, the differences in metabolites and the mechanisms driving how these differences affect the ripening cycle are unclear. Objective To investigate the effects of SlSAHH2 on metabolites in over-expressed tomato and WT tomato. Methods SlSAHH2 over-expressed tomato fruit (OE-5# and OE-6#) and WT tomato fruit at the breaker stage (Br) were selected for non-targeted metabolome analysis. Results A total of 733 metabolites were identified by mass spectrometry using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and the Human Metabolome database (HMDB). The metabolites were divided into 12 categories based on the superclass results and a comparison with the HMDB. The differences between the two databases were analyzed by PLS-DA. Based on a variable important in projection value >1 and P < 0.05, 103 differential metabolites were found between tomato variety OE-5# and WT and 63 differential metabolites were found between OE-6# and WT. These included dehydrotomatine, L-serine, and gallic acid amongst others. Many metabolites are associated with fruit ripening and eight common metabolites were found between the OE-5# vs. WT and OE-6# vs. WT comparison groups. The low L-tryptophan expression in OE-5# and OE-6# is consistent with previous reports that its content decreases with fruit ripening. A KEGG pathway enrichment analysis of the significantly different metabolites revealed that in the OE-5# and WT groups, up-regulated metabolites were enriched in 23 metabolic pathways and down-regulated metabolites were enriched in 11 metabolic pathways. In the OE-6# and WT groups, up-regulated metabolites were enriched in 29 pathways and down-regulated metabolites were enriched in six metabolic pathways. In addition, the differential metabolite changes in the L-serine to flavonoid transformation metabolic pathway also provide evidence that there is a phenotypic explanation for the changes in transgenic tomato. Discussion The metabolomic mechanism controlling SlSAHH2 promotion of tomato fruit ripening has been further elucidated.
Yang et al. (2024) Effect of SlSAHH2 on metabolites in over-expressed and wild-type tomato fruit. PeerJ 12:e17466 https://doi.org/10.7717/peerj.17466
The impact of history of depression and access to weapons on suicide risk assessment: a comparison of ChatGPT-3.5 and ChatGPT-4
The aim of this study was to evaluate the effectiveness of ChatGPT-3.5 and ChatGPT-4 in incorporating critical risk factors, namely history of depression and access to weapons, into suicide risk assessments. Both models assessed suicide risk using scenarios that featured individuals with and without a history of depression and access to weapons. The models estimated the likelihood of suicidal thoughts, suicide attempts, serious suicide attempts, and suicide-related mortality on a Likert scale. A multivariate three-way ANOVA analysis with Bonferroni post hoc tests was conducted to examine the impact of the forementioned independent factors (history of depression and access to weapons) on these outcome variables. Both models identified history of depression as a significant suicide risk factor. ChatGPT-4 demonstrated a more nuanced understanding of the relationship between depression, access to weapons, and suicide risk. In contrast, ChatGPT-3.5 displayed limited insight into this complex relationship. ChatGPT-4 consistently assigned higher severity ratings to suicide-related variables than did ChatGPT-3.5. The study highlights the potential of these two models, particularly ChatGPT-4, to enhance suicide risk assessment by considering complex risk factors.
Shinan-Altman et al. (2024) The impact of history of depression and access to weapons on suicide risk assessment: a comparison of ChatGPT-3.5 and ChatGPT-4. PeerJ 12:e17468 https://doi.org/10.7717/peerj.17468
SlZIP11 mediates zinc accumulation and sugar storage in tomato fruits
Background Zinc (Zn) is a vital micronutrient essential for plant growth and development. Transporter proteins of the ZRT/IRT-like protein (ZIP) family play crucial roles in maintaining Zn homeostasis. Although the acquisition, translocation, and intracellular transport of Zn are well understood in plant roots and leaves, the genes that regulate these pathways in fruits remain largely unexplored. In this study, we aimed to investigate the function of SlZIP11 in regulating tomato fruit development. Methods We used Solanum lycopersicum L. ‘Micro-Tom’ SlZIP11 (Solanum lycopersicum) is highly expressed in tomato fruit, particularly in mature green (MG) stages. For obtaining results, we employed reverse transcription-quantitative polymerase chain reaction (RT-qPCR), yeast two-hybrid assay, bimolecular fluorescent complementation, subcellular localization assay, virus-induced gene silencing (VIGS), SlZIP11 overexpression, determination of Zn content, sugar extraction and content determination, and statistical analysis. Results RT-qPCR analysis showed elevated SlZIP11 expression in MG tomato fruits. SlZIP11 expression was inhibited and induced by Zn deficiency and toxicity treatments, respectively. Silencing SlZIP11 via the VIGS technology resulted in a significant increase in the Zn content of tomato fruits. In contrast, overexpression of SlZIP11 led to reduced Zn content in MG fruits. Moreover, both silencing and overexpression of SlZIP11 caused alterations in the fructose and glucose contents of tomato fruits. Additionally, SlSWEEET7a interacted with SlZIP11. The heterodimerization between SlSWEET7a and SlZIP11 affected subcellular targeting, thereby increasing the amount of intracellularly localized oligomeric complexes. Overall, this study elucidates the role of SlZIP11 in mediating Zn accumulation and sugar transport during tomato fruit ripening. These findings underscore the significance of SlZIP11 in regulating Zn levels and sugar content, providing insights into its potential implications for plant physiology and agricultural practices.
Sun et al. (2024) SlZIP11 mediates zinc accumulation and sugar storage in tomato fruits. PeerJ 12:e17473 https://doi.org/10.7717/peerj.17473
Neoadjuvant chemotherapy efficacy and prognosis in HER2-low and HER2-zero breast cancer patients by HR status: a retrospective study in China
Background The promising efficacy of novel anti-HER2 antibody-drug conjugates (ADC) in HER2-low breast cancer has made HER2-low a research hotspot. However, controversy remains regarding the neoadjuvant chemotherapy (NAC) efficacy, prognosis, and the relationship with hormone receptor (HR) status of HER2-low. Methods A retrospective analysis was conducted on 975 patients with HER2-negative breast cancer undergoing NAC at Tianjin Medical University Cancer Institute and Hospital, evaluating pathological complete response (pCR) rate and prognosis between HER2-low and HER2-zero in the overall cohort and subgroups. Results Overall, 579 (59.4%) and 396 (40.6%) patients were HER2-low and HER2-zero disease, respectively. Compared with HER2-zero, the HER2-low cohort consists of more postmenopausal patients, with lower histological grade and higher HR positivity. In the HR-positive subgroup, HER2-low cases remain to exhibit lower histological grade, while in the HR-negative subgroup, they show higher grade. The HER2-low group had lower pCR rates than the HER2-zero group (16.4% vs. 24.0%). In the HR-positive subgroup, HER2-low consistently showed lower pCR rate (8.1% vs. 15.5%), and served as an independent suppressive factor for the pCR rate. However, no significant difference was observed in the pCR rates between HER2-low and HER2-zero in the HR-negative breast cancer. In the entire cohort and in stratified subgroups based on HR and pCR statuses, no difference in disease-free survival were observed between HER2-low and HER2-zero. Conclusions In the Chinese population, HER2-low breast cancer exhibits distinct characteristics and efficacy of NAC in different HR subgroups. Its reduced pCR rate in HR-positive subgroup is particularly important for clinical decisions. However, HER2-low is not a reliable factor for assessing long-term survival outcomes.
Zhao et al. (2024) Neoadjuvant chemotherapy efficacy and prognosis in HER2-low and HER2-zero breast cancer patients by HR status: a retrospective study in China. PeerJ 12:e17492 https://doi.org/10.7717/peerj.17492
Genome-wide identification and characterization of SPXdomain-containing genes family in eggplant
Phosphorus is one of the lowest elements absorbed and utilized by plants in the soil. SPX domain-containing genes family play an important role in plant response to phosphate deficiency signaling pathway, and related to seed development, disease resistance, absorption and transport of other nutrients. However, there are no reports on the mechanism of SPX domain-containing genes in response to phosphorus deficiency in eggplant. In this study, the whole genome identification and functional analysis of SPX domain-containing genes family in eggplant were carried out. Sixteen eggplant SPX domain-containing genes were identified and divided into four categories. Subcellular localization showed that these proteins were located in different cell compartments, including nucleus and membrane system. The expression patterns of these genes in different tissues as well as under phosphate deficiency with auxin were explored. The results showed that SmSPX1, SmSPX5 and SmSPX12 were highest expressed in roots. SmSPX1, SmSPX4, SmSPX5 and SmSPX14 were significantly induced by phosphate deficiency and may be the key candidate genes in response to phosphate starvation in eggplant. Among them, SmSPX1 and SmSPX5 can be induced by auxin under phosphate deficiency. In conclusion, our study preliminary identified the SPX domain genes in eggplant, and the relationship between SPX domain-containing genes and auxin was first analyzed in response to phosphate deficiency, which will provide theoretical basis for improving the absorption of phosphorus in eggplants through molecular breeding technology.
Zhuomeng et al. (2024) Genome-wide identification and characterization of SPXdomain-containing genes family in eggplant. PeerJ 12:e17341 https://doi.org/10.7717/peerj.17341
Single-cell transcriptome reveals the heterogeneity of malignant ductal cells and the prognostic value of REG4 and SPINK1 in primary pancreatic ductal adenocarcinoma
Background Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths, with very limited therapeutic options available. This study aims to comprehensively depict the heterogeneity and identify prognostic targets for PDAC with single-cell RNA sequencing (scRNA-seq) analysis. Methods ScRNA-seq analysis was performed on 16 primary PDAC and three adjacent lesions. A series of analytical methods were applied for analysis in cell clustering, gene profiling, lineage trajectory analysis and cell-to-cell interactions. In vitro experiments including colony formation, wound healing and sphere formation assay were performed to assess the role of makers. Results A total of 32,480 cells were clustered into six major populations, among which the ductal cell cluster expressing high copy number variants (CNVs) was defined as malignant cells. Malignant cells were further subtyped into five subgroups which exhibited specific features in immunologic and metabolic activities. Pseudotime trajectory analysis indicated that components of various oncogenic pathways were differentially expressed along tumor progression. Furthermore, intensive substantial crosstalk between ductal cells and stromal cells was identified. Finally, genes (REG4 and SPINK1) screened out of differentially expressed genes (DEGs) were upregulated in PDAC cell lines. Silencing either of them significantly impaired proliferation, invasion, migration and stemness of PDAC cells. Conclusions Our findings offer a valuable resource for deciphering the heterogeneity of malignant ductal cells in PDAC. REG4 and SPINK1 are expected to be promising targets for PDAC therapy.
Ji et al. (2024) Single-cell transcriptome reveals the heterogeneity of malignant ductal cells and the prognostic value of REG4 and SPINK1 in primary pancreatic ductal adenocarcinoma. PeerJ 12:e17350 https://doi.org/10.7717/peerj.17350