Carboxypeptidase E is a prognostic biomarker co-expressed with osteoblastic genes in osteosarcoma
Osteosarcoma (OS) is a rare primary malignant bone tumor in adolescents and children with a poor prognosis. The identification of prognostic genes lags far behind advancements in treatment. In this study, we identified differential genes using mRNA microarray analysis of five paired OS tissues. Hub genes, gene set enrichment analysis, and pathway analysis were performed to gain insight into the pathway alterations of OS. Prognostic genes were screened using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, then overlapped with the differential gene dataset. The carboxypeptidase E (CPE) gene, found to be an independent risk factor, was further validated using RT-PCR and Gene Expression Omnibus (GEO) datasets. Additionally, we explored the specific expression of CPE in OS tissues by reanalyzing single-cell genomics. Interestingly, CPE was found to be co-expressed with osteoblast lineage cell clusters that expressed RUNX2, SP7, SPP1, and IBSP marker genes in OS. These results suggest that CPE could serve as a prognostic factor in osteoblastic OS and should be further investigated as a potential therapeutic target.
Chen et al. (2023) Carboxypeptidase E is a prognostic biomarker co-expressed with osteoblastic genes in osteosarcoma. PeerJ 11:e15814 https://doi.org/10.7717/peerj.15814
Identification and characterization of novel sesquiterpene synthases TPS9 and TPS12 from Aquilaria sinensis
Sesquiterpenes are characteristic components and important quality criterions for agarwood. Although sesquiterpenes are well-known to be biosynthesized by sesquiterpene synthases (TPSs), to date, only a few TPS genes involved in agarwood formation have been reported. Here, two new TPS genes, namely, TPS9 and TPS12, were isolated from Aquilaria sinensis (Lour.) Gilg, and their functions were examined in Escherichia coli BL21(DE3), with farnesyl pyrophosphate (FPP) and geranyl pyrophosphate (GPP) as the substrate of the corresponding enzyme activities. They were both identified as a multiproduct enzymes. After incubation with FPP, TPS9 liberated β-farnesene and cis-sesquisabinene hydrate as main products, with cedrol and another unidentified sesquiterpene as minor products. TPS12 catalyzes the formation of β-farnesene, nerolidol, γ-eudesmol, and hinesol. After incubation with GPP, TPS9 generated citronellol and geraniol as main products, with seven minor products. TPS12 converted GPP into four monoterpenes, with citral as the main product, and three minor products. Both TPS9 and TPS12 showed much higher expression in the two major tissues emitting floral volatiles: flowers and agarwood. Further, RT-PCR analysis showed TPS9 and TPS12 are typical genes mainly expressed during later stages of stress response, which is better known than that of chromone derivatives. This study will advance our understanding of agarwood formation and provide a solid theoretical foundation for clarifying its mechanism in A. sinensis.
Yu et al. (2023) Identification and characterization of novel sesquiterpene synthases TPS9 and TPS12 from Aquilaria sinensis. PeerJ 11:e15818 https://doi.org/10.7717/peerj.15818
Intestinal GPDH-1 regulates high glucose diet induced lifespan extension in aged worms
A high glucose diet (HGD) is associated with many metabolic diseases including type 2 diabetes, and cardiovascular diseases. Additionally, a HGD increases the oxidative stress resistance of young animals but shortens their lifespan. To investigate the role of HGD feeding on the aging of aged animals, we tested for oxidative stress resistance and changes in lifespan using C. elegans. We showed that a HGD extends the lifespan of aged worms that are dependent on oxidative stress resistance. Furthermore, we measured the lifespan of oxidative stress responding genes of HGD-fed worms. We found that gpdh-1 and col-92 are highly expressed in HGD and paraquat (PQ) treated worms. Further experiments indicated that intestinal gpdh-1 is essential for the HGD induced lifespan extension of aged worms. Our studies provide new insights into understanding the correlation between glucose metabolism, oxidative stress resistance, and aging.
Mo et al. (2023) Intestinal GPDH-1 regulates high glucose diet induced lifespan extension in aged worms. PeerJ 11:e15845 https://doi.org/10.7717/peerj.15845
Developing bottom drifters to better understand the stranding locations of cold-stunned sea turtles in Cape Cod Bay, Massachusetts
Every fall, juvenile sea turtles in the Northwest Atlantic Ocean are threatened by rapidly declining water temperatures. When sea turtles become hypothermic, or cold-stunned, they lose mobility—either at the surface, subsurface, or the bottom of the water column—and eventually strand at the shoreline where rescue teams associated with the Sea Turtle Stranding and Salvage Network may search for them. Understanding the effects of ocean currents on the potential stranding locations of cold-stunned sea turtles is essential to better understand stranding hotspots and increase the probability of successful discovery and recovery of turtles before they die in the cold temperatures. Traditional oceanographic drifters—instruments used to track currents—have been used to examine relationships between current and stranding locations in Cape Cod Bay, but these drifters are not representative of sea turtle morphology and do not assess how bottom currents affect stranding locations. To address these knowledge gaps, we designed new drifters that represent the shape and dimensions of sea turtles—one that can float at the surface and one that sinks to the bottom—to track both surface and bottom currents in Cape Cod Bay. We found a marked difference between the trajectories of our new drifter models and those that were previously used for similar research. These findings bring us one step closer to identifying the transport pathways for cold-stunned sea turtles and optimizing cold-stunned sea turtle search and rescue efforts in Cape Cod.
Spatial and Geographic Information Science
Page et al. (2023) Developing bottom drifters to better understand the stranding locations of cold-stunned sea turtles in Cape Cod Bay, Massachusetts. PeerJ 11:e15866 https://doi.org/10.7717/peerj.15866
Profiling of primary and phytonutrients in edible mahlab cherry (Prunus mahaleb L.) seeds in the context of its different cultivars and roasting as analyzed using molecular networking and chemometric tools
Prunus mahaleb L. (mahlab cherry) is a deciduous plant that is native to the Mediterranean region and central Europe with a myriad of medicinal, culinary and cosmetic uses. The present study explored different cultivars of mahlab (white from Egypt and Greece, red from Egypt and post roasting). UPLC-MS led to the detection of 110 primary and secondary metabolites belonging to different classes including phenylpropanoids (hydroxy cinnamates, coumaroyl derivatives), organic acids, coumarins, cyanogenic glycosides, flavonoids, nitrogenous compounds, amino acids and fatty acids, of which 39 are first time to be detected in Prunus mahaleb L. A holistic assessment of metabolites was performed for further analysis of dataset using principal component analysis (PCA) among mahlab cultivars to assess variance within seeds. The results revealed that phenolic acids (coumaric acid-O-hexoside, ferulic acid-O-hexoside, ferulic acid-O-hexoside dimer, dihydrocoumaroyl-O-hexoside dimer and ferulic acid), coumarins (coumarin and herniarin) and amino acids (pyroglutamic acid) were abundant in white mahlab cultivars (cvs.) from different locations. In contrast, red mahlab and its roasted seeds were more rich in organic acids (citric and malic acids), amygdalin derivative and sphingolipids. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) revealed for markers in red mahlab and in response to roasting, where red mahlab was rich in nitrogenous compounds viz. nonamide, deoxy fructosyl leucine, glutaryl carnitine and isoleucine, while roasted product (REM) was found to be enriched in choline.
Mostafa et al. (2023) Profiling of primary and phytonutrients in edible mahlab cherry (Prunus mahaleb L.) seeds in the context of its different cultivars and roasting as analyzed using molecular networking and chemometric tools. PeerJ 11:e15908 https://doi.org/10.7717/peerj.15908
Sources of intraspecific variation in the isotopic niche of a semi-aquatic predator in a human-modified landscape
Intraspecific variation modulates patterns of resource use by species, potentially affecting the structure and stability of food webs. In human-modified landscapes, habitat disturbance modifies trophic interactions and intraspecific niche variation, impacting population persistence. Here, we investigated the relationship of sex, ontogeny, and habitat factors with the trophic niche of Caiman crocodilus in an agricultural landscape. We evaluated temporal variation in the trophic niche parameters using carbon and nitrogen stable isotope analysis from different body tissues. We found that caimans exploit the same carbon and nitrogen pools through time, with low isotopic variability between seasons, partly due to the slow isotope turnover rates of tissues in crocodilians. Conversely, the trophic niche of caimans varied across habitats, but with no evidence of a difference between natural and anthropogenic habitats. It apparently results from the influence of habitat suitability, connectivity, and caiman movements during the foraging. Our findings highlight the broader niches of juvenile caimans relative to adults, possibly in response of territorialism and opportunistic foraging strategy. Although using similar resources, females had a larger niche than males, probably associated with foraging strategies during nesting. Considering the sex and body size categories, caimans occupied distinct isotopic regions in some habitats, indicating apparent niche segregation. Ontogenetic trophic shifts in the isotopes (δ13C and δ15N) depended on sex, leading to resource partitioning that can potentially reduce intraspecific competition. Decision-makers and stakeholders should consider the trophic dynamics of sex and body size groups for the sustainable management and conservation of caiman populations, which implies in the maintenance of wetland habitats and landscape heterogeneity in the Formoso River floodplain.
Pereira et al. (2023) Sources of intraspecific variation in the isotopic niche of a semi-aquatic predator in a human-modified landscape. PeerJ 11:e15915 https://doi.org/10.7717/peerj.15915
Co-inhibition of adenosine 2b receptor and programmed death-ligand 1 promotes the recruitment and cytotoxicity of natural killer cells in oral squamous cell carcinoma
Adenosine promotes anti-tumor immune responses by modulating the functions of T-cells and natural killer (NK) cells in the tumor microenvironment; however, the role of adenosine receptors in the progression of oral squamous cell carcinoma (OSCC) and its effects on immune checkpoint therapy remain unclear. In this study, we obtained the tumor tissues from 80 OSCC patients admitted at the Shandong University Qilu Hospital between February 2014 and December 2016. Thereafter, we detected the expression of adenosine 2b receptor (A2BR) and programmed death-ligand 1 (PD-L1) using immunohistochemical staining and analyzed the association between their expression in different regions of the tumor tissues, such as tumor nest, border, and paracancer stroma. To determine the role of A2BR in PD-L1 expression, CAL-27 (an OSCC cell line) was treated with BAY60-6583 (an A2BR agonist), and PD-L1 expression was determined using western blot and flow cytometry. Furthermore, CAL-27 was treated with a nuclear transcription factor-kappa B (NF-κ B) inhibitor, PDTC, to determine whether A2BR regulates PD-L1 expression via the NF-κ B signaling pathway. Additionally, a transwell assay was performed to verify the effect of A2BR and PD-L1 on NK cell recruitment. The results of our study demonstrated that A2BR and PD-L1 are co-expressed in OSCC. Moreover, treatment with BAY60-6583 induced PD-L1 expression in the CAL-27 cells, which was partially reduced in cells pretreated with PDTC, suggesting that A2BR agonists induce PD-L1 expression via the induction of the NF-κ B signaling pathway. Furthermore, high A2BR expression in OSCC was associated with lower infiltration of NK cells. Additionally, our results demonstrated that treatment with MRS-1706 (an A2BR inverse agonist) and/or CD274 (a PD-L1-neutralizing antibody) promoted NK cell recruitment and cytotoxicity against OSCC cells. Altogether, our findings highlight the synergistic effect of co-inhibition of A2BR and PD-L1 in the treatment of OSCC via the modulation of NK cell recruitment and cytotoxicity.
Wang et al. (2023) Co-inhibition of adenosine 2b receptor and programmed death-ligand 1 promotes the recruitment and cytotoxicity of natural killer cells in oral squamous cell carcinoma. PeerJ 11:e15922 https://doi.org/10.7717/peerj.15922
Development and validation of a nomogram for assessment postoperative sodium disturbance in PAs patients: a retrospective cohort study
Background Pituitary adenomas (PAs) are neuroendocrine tumors located in the sellar region. Surgery, being the primary treatment option for most PAs, is known to cause disruptions in sodium metabolism. Objective To develop and validate a nomogram for assessment the incidence of postoperative sodium disturbance (SD) in patients with PAs. Methods In this retrospective study, 208 patients with PAs who underwent resection surgery between 2013 and 2020 were included. Various demographic characteristics, clinical features and laboratory data were analyzed as potential predictors of postoperative sodium disturbance (SD). LASSO regression were used to identify independent preoperative variables associated with SD. Logistic regression was employed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). A nomogram was constructed to visualize these results and evaluated using metrics such as the area under the curve (AUC) for discrimination, the Hosmer-Lemeshow test for calibration and decision curve for usefulness assessment. Results The incidence of SD was 44.23% (92 cases out of 208). Six preoperative factors, including sex, types of PAs, phosphocreatine kinase (CK), serum iron (Fe), free fatty acids (NEFA) and mean corpuscular volume (MCV), were identified for constructing a predictive nomogram. The nomogram showed high accuracy, with AUC values of 0.851 (95% CI [0.799–0.923]) and 0.771 (95% CI [0.681–0.861]) in the training and validation datasets, respectively. Calibration assessment and decision curve analysis confirmed its good agreement and clinical utility. Conclusion A practical and effective nomogram for predicting SD after PAs surgery is presented in this study.
Li et al. (2023) Development and validation of a nomogram for assessment postoperative sodium disturbance in PAs patients: a retrospective cohort study. PeerJ 11:e15946 https://doi.org/10.7717/peerj.15946
Regulation of HDAC11 gene expression in early myogenic differentiation
Histone acetylation and deacetylation affect the patterns of gene expression in cellular differentiation, playing pivotal roles in tissue development and maintenance. For example, the intrinsic histone acetyltransferase activity of transcriptional coactivator p300 is especially required for the expression of myogenic regulatory factors including Myf5 and MyoD, and consequently for skeletal myogenesis. On the other hand, histone deacetylases (HDACs) remove the acetyl group from histones, which is critical for gene repression in stem cell fate transition. Through integrative omic analyses, we found that while some HDACs were differentially expressed at the early stage of skeletal myoblast differentiation, Hdac11 gene expression was significantly enhanced by nuclear receptor signaling. In addition, p300 and MyoD control Hdac11 expression in milieu of normal and signal-enhanced myoblast differentiation. Thus, HDAC11 may be essential to differential gene expression at the onset of myoblast differentiation.
Li et al. (2023) Regulation of HDAC11 gene expression in early myogenic differentiation. PeerJ 11:e15961 https://doi.org/10.7717/peerj.15961
Histological study of seventeen organs from dugong (Dugong dugon)
Background Dugongs are marine mammals with a crescent-shaped tail fluke and a concave trailing margin that belong to the family Dugongidae., They are distributed widely in the warm coastal waters of the Indo-Pacific region. Importantly, the population of dugongs has decreased over the past decades as they have been classified as rare marine mammals. Previous studies have investigated the habitat and genetic diversity of dugongs. However, a comprehensive histological investigation of their tissue has not yet been conducted. This study provides unique insight into the organs of dugongs and compares them with other mammal species. Methods Tissue sections were stained with Harris’s hematoxylin and eosin Y. The histological structure of 17 organ tissues obtained from eight systems was included in this study. Tissue sections were obtained from the urinary system (kidney), muscular system (striated skeletal muscle and smooth muscle), cardiovascular system (cardiac muscle (ventricle), coronary artery, and coronary vein), respiratory system (trachea and lung), gastrointestinal system (esophagus, stomach, small intestine, liver, and pancreas), reproductive system (testis), lymphatic system (spleen and thymus), and endocrine system (pancreas). Results While most structures were similar to those of other mammal species, there were some differences in the tissue sections of dugongs when compared with other mammalian species and manatees. These include the kidneys of dugongs, which were non-lobular and had a smooth, elongated exterior resulting in a long medullary crest, whereas the dugong pyloric epithelium did not have overlying stratified squamous cells and was noticably different from the Florida manatee. Discussion Histological information obtained from various organs of the dugong can serve as an essential foundation of basal data for future microanatomical studies. This information can also be used as high-value data in the diagnosis and pathogenesis of sick dugongs or those with an unknown cause of death.
Kaewmong et al. (2023) Histological study of seventeen organs from dugong (Dugong dugon). PeerJ 11:e15859 https://doi.org/10.7717/peerj.15859