Bioinformatic analysis and experimental validation of six cuproptosis-associated genes as a prognostic signature of breast cancer
Background Breast carcinoma (BRCA) is a life-threatening malignancy in women and shows a poor prognosis. Cuproptosis is a novel mode of cell death but its relationship with BRCA is unclear. This study attempted to develop a cuproptosis-relevant prognostic gene signature for BRCA. Methods Cuproptosis-relevant subtypes of BRCA were obtained by consensus clustering. Differential expression analysis was implemented using the ‘limma’ package. Univariate Cox and multivariate Cox analyses were performed to determine a cuproptosis-relevant prognostic gene signature. The signature was constructed and validated in distinct datasets. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were also conducted using the prognostic signature to uncover the underlying molecular mechanisms. ESTIMATE and CIBERSORT algorithms were applied to probe the linkage between the gene signature and tumor microenvironment (TME). Immunotherapy responsiveness was assessed using the Tumor Immune Dysfunction and Exclusion (TIDE) web tool. Real-time quantitative PCR (RT-qPCR) was performed to detect the expressions of cuproptosis-relevant prognostic genes in breast cancer cell lines. Results Thirty-eight cuproptosis-associated differentially expressed genes (DEGs) in BRCA were mined by consensus clustering and differential expression analysis. Based on univariate Cox and multivariate Cox analyses, six cuproptosis-relevant prognostic genes, namely SAA1, KRT17, VAV3, IGHG1, TFF1, and CLEC3A, were mined to establish a corresponding signature. The signature was validated using external validation sets. GSVA and GSEA showed that multiple cell cycle-linked and immune-related pathways along with biological processes were associated with the signature. The results ESTIMATE and CIBERSORT analyses revealed significantly different TMEs between the two Cusig score subgroups. Finally, RT-qPCR analysis of cell lines further confirmed the expressional trends of SAA1, KRT17, IGHG1, and CLEC3A. Conclusion Taken together, we constructed a signature for projecting the overall survival of BRCA patients and our findings authenticated the cuproptosis-relevant prognostic genes, which are expected to provide a basis for developing prognostic molecular biomarkers and an in-depth understanding of the relationship between cuproptosis and BRCA.
Chen et al. (2024) Bioinformatic analysis and experimental validation of six cuproptosis-associated genes as a prognostic signature of breast cancer. PeerJ 12:e17419 https://doi.org/10.7717/peerj.17419
Serum proteomics study on cognitive impairment after cardiac valve replacement surgery: a prospective observational study
Objective The incidence of perioperative neurocognitive disorders (PND) is high, especially after cardiac surgeries, and the underlying mechanisms remain elusive. Here, we conducted a prospective observational study to observe serum proteomics differences in PND patients after cardiac valve replacement surgery. Methods Two hundred and twenty-six patients who underwent cardiac valve surgery were included. They were categorized based on scoring into non-PND group (group non-P) and PND group (group P’). The risk factors associated with PND were analyzed. These patients were further divided into group C and group P by propensity score matching (PSM) to investigate the serum proteome related to the PND by serum proteomics. Results The postoperative 6-week incidence of PND was 16.8%. Risk factors for PND include age, chronic illness, sufentanil dosage, and time of cardiopulmonary bypass (CPB). Proteomics identified 31 down-regulated proteins and six up-regulated proteins. Finally, GSTO1, IDH1, CAT, and PFN1 were found to be associated with PND. Conclusion The occurrence of PND can impact some oxidative stress proteins. This study provided data for future studies about PND to general anaesthesia and surgeries.
Ma et al. (2024) Serum proteomics study on cognitive impairment after cardiac valve replacement surgery: a prospective observational study. PeerJ 12:e17536 https://doi.org/10.7717/peerj.17536
Genome-wide identification, characterization and expression analysis of the DUF668 gene family in tomato
The domain of unknown function 668 (DUF668) is a gene family that may play a key role in plant growth and development as well as in responding to adversity coercion stresses. However, the DUF668 gene family has not yet been well identified and characterized in tomato. In this study, a total of nine putative SlDUF668 genes were identified in tomato, distributed on six chromosomes. Phylogenetic analyses revealed that SlDUF668 proteins were classified into two major groups. Members within the same group largely displayed analogous gene structure and conserved motif compositions. Several cis-elements were exhibited in the upstream sequences of the SlDUF668 genes, including elements implicated in plant growth and development processes, abiotic stress and hormone responses. Further, the study assessed the expression patterns of the SlDUF668 gene family in various tomato tissues, five plant hormones treatments, three abiotic stresses using qRT-PCR. The SlDUF668 genes expressed ubiquitously in various tissues, and five genes (SlDUF668-04, SlDUF668-06, SlDUF668-07, SlDUF668-08 and SlDUF668-09) showed tissue specificity. And SlDUF668 genes responded to abiotic stresses such as salt, drought and cold to varying degrees. Overall, our study provided a base for the tomato DUF668 gene family and laid a foundation for further understanding the functional characteristics of DUF668 genes in tomato plants.
Li et al. (2024) Genome-wide identification, characterization and expression analysis of the DUF668 gene family in tomato. PeerJ 12:e17537 https://doi.org/10.7717/peerj.17537
Identification of key genes as potential diagnostic biomarkers in sepsis by bioinformatics analysis
Background Sepsis, an infection-triggered inflammatory syndrome, poses a global clinical challenge with limited therapeutic options. Our study is designed to identify potential diagnostic biomarkers of sepsis onset in critically ill patients by bioinformatics analysis. Methods Gene expression profiles of GSE28750 and GSE74224 were obtained from the Gene Expression Omnibus (GEO) database. These datasets were merged, normalized and de-batched. Weighted gene co-expression network analysis (WGCNA) was performed and the gene modules most associated with sepsis were identified as key modules. Functional enrichment analysis of the key module genes was then conducted. Moreover, differentially expressed gene (DEG) analysis was conducted by the “limma” R package. Protein-protein interaction (PPI) network was created using STRING and Cytoscape, and PPI hub genes were identified with the cytoHubba plugin. The PPI hub genes overlapping with the genes in key modules of WGCNA were determined to be the sepsis-related key genes. Subsequently, the key overlapping genes were validated in an external independent dataset and sepsis patients recruited in our hospital. In addition, CIBERSORT analysis evaluated immune cell infiltration and its correlation with key genes. Results By WGCNA, the greenyellow module showed the highest positive correlation with sepsis (0.7, p = 2e − 19). 293 DEGs were identified in the merged datasets. The PPI network was created, and the CytoHubba was used to calculate the top 20 genes based on four algorithms (Degree, EPC, MCC, and MNC). Ultimately, LTF, LCN2, ELANE, MPO and CEACAM8 were identified as key overlapping genes as they appeared in the PPI hub genes and the key module genes of WGCNA. These sepsis-related key genes were validated in an independent external dataset (GSE131761) and sepsis patients recruited in our hospital. Additionally, the immune infiltration profiles differed significantly between sepsis and non-sepsis critical illness groups. Correlations between immune cells and these five key genes were assessed, revealing that plasma cells, macrophages M0, monocytes, T cells regulatory, eosinophils and NK cells resting were simultaneously and significantly associated with more than two key genes. Conclusion This study suggests a critical role of LTF, LCN2, ELANE, MPO and CEACAM8 in sepsis and may provide potential diagnostic biomarkers and therapeutic targets for the treatment of sepsis.
Lin et al. (2024) Identification of key genes as potential diagnostic biomarkers in sepsis by bioinformatics analysis. PeerJ 12:e17542 https://doi.org/10.7717/peerj.17542
Behavioral responses of a clonal fish to perceived predation risk
Predation threat is a major driver of behavior in many prey species. Animals can recognize their relative risk of predation based on cues in the environment, including visual and/or chemical cues released by a predator or from its prey. When threat of predation is high, prey often respond by altering their behavior to reduce their probability of detection and/or capture. Here, we test how a clonal fish, the Amazon molly (Poecilia formosa), behaviorally responds to predation cues. We measured aggressive and social behaviors both under ‘risk’, where chemical cues from predatory fish and injured conspecifics were present, and control contexts (no risk cues present). We predicted that mollies would exhibit reduced aggression towards a simulated intruder and increased sociability under risk contexts as aggression might increase their visibility to a predator and shoaling should decrease their chance of capture through the dilution effect. As predicted, we found that Amazon mollies spent more time with a conspecific when risk cues were present, however they did not reduce their aggression. This highlights the general result of the ‘safety in numbers’ behavioral response that many small shoaling species exhibit, including these clonal fish, which suggests that mollies may view this response as a more effective anti-predator response compared to limiting their detectability by reducing aggressive conspecific interactions.
Aguiñaga et al. (2024) Behavioral responses of a clonal fish to perceived predation risk. PeerJ 12:e17547 https://doi.org/10.7717/peerj.17547
Knowledge, attitudes, and practices (KAPs) regarding tick-borne rickettsial disease among medical staff in endemic areas of China
Tick-borne rickettsial disease (TBRD) is a perilous acute infection that often eludes diagnosis in its early stages. The triad of knowledge, attitudes, and practices (KAPs) among medical professionals is key to reducing missed diagnosis rates. Therefore, a meticulous evaluation of KAPs is imperative. This study aimed to delve into the understanding of TBRD and explore the beliefs and practices related to personal prevention methods among individuals in Lu’an, a hotspot for TBRD. During the summer months of 2023, convenience sampling was employed by circulating a confidential questionnaire to 1,206 participants in the endemic regions of China. This questionnaire painted a comprehensive picture of the participants’ sociodemographic profiles and their KAPs levels vis-à-vis TBRD. The findings revealed that participants scored a mere 55.78% in knowledge, while their attitudes and practices garnered impressive scores of 90.09% and 90.83%, respectively. Upon further analysis using multiple linear regression, several intriguing patterns emerged. Male participants, employed in the Infectious Disease Department, held vice-senior or higher titles, or had prior medical training demonstrated superior knowledge scores. On the other hand, medical personnel who were younger than 30, possessed graduate degrees or higher qualifications, and had training excelled in attitudes and practices. Notably, when employing the Boston Consulting Group (BCG) matrix, a significant distribution of medical personnel was observed across the four quadrants. Specifically, 37.43%, 13.19%, 19.61%, and 29.77% fell into the first, second, third, and fourth quadrants. This survey underscores the commendable attitudes and practices of medical staff towards TBRD in endemic regions of China. However, their knowledge level remains wanting and demands urgent improvement.
Shao et al. (2024) Knowledge, attitudes, and practices (KAPs) regarding tick-borne rickettsial disease among medical staff in endemic areas of China. PeerJ 12:e17562 https://doi.org/10.7717/peerj.17562
Hypertrophic effects of low-load blood flow restriction training with different repetition schemes: a systematic review and meta-analysis
Objective This systematic review and meta-analysis analyzed the effect of low-load resistance training (LL-RT) with blood flow restriction (BFR) versus high-load resistance training (HL-RT) on muscle hypertrophy focusing on the repetition scheme adopted. Methods Four databases were searched to identify randomized controlled trials that compared the effect of LL-RT with BFR versus HL-RT on muscle hypertrophy. Standardized mean differences (SMD) were pooled in a random effects meta-analysis. Results The overall analysis did not demonstrate significant differences between conditions (SMD = 0.046; p = 0.14). A similar result was observed when we separately analyzed studies that used sets to momentary muscle failure (SMD = 0.033; p = 0.520), sets of 15 repetitions (SMD = 0.005; p = 0.937) and a fixed repetition scheme composed of 75 repetitions (SMD = 0.088; p = 0.177). The analysis considering body region indicates no difference in lower limb exercise between HL-RT and LL-RT with BFR (SMD = 0.00066; p = 0.795) while upper limb exercise favors HL-RT (SMD = 0.231; p = 0.005). Conclusion LL-RT with BFR elicits muscle hypertrophy similar to HL-RT regardless of the employed repetition scheme, although there appears to be a small beneficial effect in favor of HL-RT in upper limb exercise.
de Queiros et al. (2024) Hypertrophic effects of low-load blood flow restriction training with different repetition schemes: a systematic review and meta-analysis. PeerJ 12:e17195 https://doi.org/10.7717/peerj.17195
Pedagogical control scales of vertical jumping performance in untrained adolescents (13–16 years): research by strata
Background A scale is used to establish performance ranges in different sciences, it being necessary to design specialized biological and pedagogical indicators in physical activity, sport and health. Objective To design a scale for the pedagogical control of the vertical jumping ability in untrained adolescents (13–16 years), stratifying the sample by age range, ethnicity, urban and rural area, socioeconomic level, and gender. Methods A representative sample of the Ecuadorian population (n = 3,705) is studied, classifying it into the aforementioned strata, controlling the vertical jump by ISAK I and II level experts, applying the Sargent Test to measure vertical jumps on a multi-force wall, establishing scales with seven percentile levels, and making comparisons related to chronological age, gender, socioeconomic, and genetic indicators. Results Significant differences in the vertical jumping performance were determined according to the category or age range (13–14 ≠ 15–16 years) and by gender (w = 0.000). Various levels of performance were determined, classifying the maximum level as talented in the female gender (≥40 cm; and ≥42 cm) and male gender (≥47 cm; and ≥57 cm) in the 13‒14 and 15‒16 years categories, respectively. Sampling comparisons by geographical area only determined significant differences in the male gender, with the jumping ability being higher in urban areas (13‒14 years: w = 0.046; 15‒16 years: w = 0.013). The comparison by ethnic groups showed significant differences (k = 0.030), favoring the Afro-Ecuadorian ethnic group in both genders, while there are significant differences by socioeconomic level, especially between the middle and lower classes. Conclusions The present research solves the lack of a tool for making correct didactic decisions related to the vertical jumping ability, taking into account various important stratified indicators. The complementary conclusions show significant differences according to the category stratum or age range, the gender stratum, and the ethnic stratum in females and males, where the best average rank favored the Afro-Ecuadorian ethnic group in both genders. There are significant differences in the geographical area stratum in the male gender, and differences in the socioeconomic stratum in favor of the upper and middle classes.
Calero-Morales et al. (2024) Pedagogical control scales of vertical jumping performance in untrained adolescents (13–16 years): research by strata. PeerJ 12:e17298 https://doi.org/10.7717/peerj.17298
Choice-based severity scale (CSS): assessing the relative severity of procedures from a laboratory animal’s perspective
One primary goal of laboratory animal welfare science is to provide a comprehensive severity assessment of the experimental and husbandry procedures or conditions these animals experience. The severity, or degree of suffering, of these conditions experienced by animals are typically scored based on anthropocentric assumptions. We propose to (a) assess an animal’s subjective experience of condition severity, and (b) not only rank but scale different conditions in relation to one another using choice-based preference testing. The Choice-based Severity Scale (CSS) utilizes animals’ relative preferences for different conditions, which are compared by how much reward is needed to outweigh the perceived severity of a given condition. Thus, this animal-centric approach provides a common scale for condition severity based on the animal’s perspective. To assess and test the CSS concept, we offered three opportunistically selected male rhesus macaques (Macaca mulatta) choices between two conditions: performing a cognitive task in a typical neuroscience laboratory setup (laboratory condition) versus the monkey’s home environment (cage condition). Our data show a shift in one individual’s preference for the cage condition to the laboratory condition when we changed the type of reward provided in the task. Two additional monkeys strongly preferred the cage condition over the laboratory condition, irrespective of reward amount and type. We tested the CSS concept further by showing that monkeys’ choices between tasks varying in trial duration can be influenced by the amount of reward provided. Altogether, the CSS concept is built upon laboratory animals’ subjective experiences and has the potential to de-anthropomorphize severity assessments, refine experimental protocols, and provide a common framework to assess animal welfare across different domains.
Cassidy et al. (2024) Choice-based severity scale (CSS): assessing the relative severity of procedures from a laboratory animal’s perspective. PeerJ 12:e17300 https://doi.org/10.7717/peerj.17300
Preliminary studies of selected Lemna species on the oxygen production potential in relation to some ecological factors
Dissolved oxygen is fundamental for chemical and biochemical processes occurring in natural waters and critical for the life of aquatic organisms. Many organisms are responsible for altering organic matter and oxygen transfers across ecosystem or habitat boundaries and, thus, engineering the oxygen balance of the system. Due to such Lemna features as small size, simple structure, vegetative reproduction and rapid growth, as well as frequent mass occurrence in the form of thick mats, they make them very effective in oxygenating water. The research was undertaken to assess the impact of various species of duckweed (L. minor and L. trisulca) on dissolved oxygen content and detritus production in water and the role of ecological factors (light, atmospheric pressure, conductivity, and temperature) in this process. For this purpose, experiments were carried out with combinations of L. minor and L. trisulca. On this basis, the content of oxygen dissolved in water was determined depending on the growth of duckweed. Linear regression models were developed to assess the dynamics of changes in oxygen content and, consequently, organic matter produced by the Lemna. The research showed that the presence of L. trisulca causes an increase in dissolved oxygen content in water. It was also shown that an increase in atmospheric pressure had a positive effect on the ability of duckweed to produce oxygen, regardless of its type. The negative correlation between conductivity and water oxygenation, obtained in conditions of limited light access, allows us to assume that higher water conductivity limits oxygen production by all combinations of duckweeds when the light supply is low. Based on the developed models, it was shown that the highest increase in organic matter would be observed in the case of mixed duckweed and the lowest in the presence of the L. minor species, regardless of light conditions. Moreover, it was shown that pleustophytes have different heat capacities, and L. trisulca has the highest ability to accumulate heat in water for the tested duckweed combinations. The provided knowledge may help determine the good habitat conditions of duckweed, indicating its role in purifying water reservoirs as an effect of producing organic matter and shaping oxygen conditions with the participation of various Lemna species.
Sender et al. (2024) Preliminary studies of selected Lemna species on the oxygen production potential in relation to some ecological factors. PeerJ 12:e17322 https://doi.org/10.7717/peerj.17322