Up-regulated IL-17 and Tnf signaling in bone marrow cells of young male osteogenesis imperfecta mice
Osteogenesis imperfecta (OI) is a congenital bone dysplasia mainly caused by either defective production or assembly of type I collagen. The skeletal phenotypes especially fractures are often seen in OI adolescents. Studies have found that an increased number of osteoclasts and excessive bone resorption existed in collagen-related OI, which has not been well understood. Emerging evidence has suggested that inflammation may be associated with OI. We speculated that the bone marrow (BM) niche had similar inflammatory changes and performed RNA-sequencing (RNA-seq) in BM cells derived from young male mice to analyze the related differentially expressed genes (DEGs) and pathways. Data showed that there were 117 shared DEGs (Q ≤ 0.05, |log2FC| ≥ 1) in BM cells isolated from two types of OI murine models that respectively simulate different OI types. Gene Ontology (GO) (Q ≤ 0.05) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) (Q ≤ 0.05) analysis and real-time PCR validation indicated the dysregulated biology process of cellular response to interferon (Ifn) together with upregulated IL-17 signaling, tumor necrosis factor (Tnf) signaling and osteoclast differentiation in OI BM niche. Either defective collagen production or abnormal collagen assembly shared similar alterations in gene profiles and pathways involving inflammation and osteoclast activation. Data presented here not only contributed to understanding of the mechanism of the enhanced bone absorption in the bones of OI, but also provided more evidence to develop potential anti-inflammation therapies.
Shao et al. (2022) Up-regulated IL-17 and Tnf signaling in bone marrow cells of young male osteogenesis imperfecta mice. PeerJ 10:e13963 https://doi.org/10.7717/peerj.13963
Soil microbial community and physicochemical properties together drive soil organic carbon in Cunninghamia lanceolata plantations of different stand ages
Carbon sequestration in forest soil is critical for reducing atmospheric greenhouse gas concentrations and slowing down global warming. However, little is known about the difference in soil organic carbon (SOC) among different stand ages and the relative importance of biotic and abiotic variations such as soil microbial community and soil physicochemical properties in the regulation of SOC in forests. In the present study, we measured the SOC of the topsoil (0-10 cm) in Chinese subtropical Cunninghamia lanceolata plantations of three different stand ages (young plantation of 6 years, middle-aged plantation of 12 years, and mature plantation of 25 years). We further measured microbial community composition by phospholipid fatty acid (PLFA) analysis and soil organic carbon physical fractions by wet sieving and density floating as well as other physicochemical properties. The effects of the main impact factors on SOC were investigated. The results showed that: the middle-aged plantation had significantly higher SOC (10.63 g kg−1) than the young plantation (5.33 g kg−1), and that of the mature plantation (7.83 g kg−1) was in between. Besides, the soil total PLFAs and all the functional groups (i.e., bacteria, fungi, actinomycetes, Gram-positive bacteria, and Gram-negative bacteria) of PLFAs were significantly higher in the middle-aged plantation than in the young plantation and the mature plantation. Soil physicochemical properties, including physical fractions, differed among plantations of the three stand ages. Notably, the proportion of organic carbon protected within microaggregates was significantly higher in the middle-aged plantation (40.4%) than those in the young plantation (29.2%) and the mature plantation (27.8%), indicating that the middle-aged Cunninghamia lanceolata plantation had stronger soil organic carbon stability. Both soil microbial community and physicochemical properties exerted dominant effects on SOC and jointly explained 82.7% of the variance of SOC among different stand ages. Among them, total and all the functional groups of PLFAs, nitrate nitrogen, total nitrogen, and organic carbon protected within microaggregates had a significant positive correlation with SOC. These results highlight the important role of soil biotic and abiotic factors in shaping the contents of SOC in forests of different stand ages. This study provides a theoretical basis for forestry management and forest carbon cycling models.
Yuan et al. (2022) Soil microbial community and physicochemical properties together drive soil organic carbon in Cunninghamia lanceolata plantations of different stand ages. PeerJ 10:e13873 https://doi.org/10.7717/peerj.13873
C1orf74 positively regulates the EGFR/AKT/mTORC1 signaling in lung adenocarcinoma cells
Background Lung adenocarcinoma (LUAD) is a major type of lung cancer with poor prognosis and low 5-year survival rate, which urgently needs further investigation in order to elucidate its mechanisms completely and discover novel therapeutic targets. C1orf74 is a novel protein with unknown function either in normal cells or cancer cells. The aim of this study is to investigate the expression and function of C1orf74 in LUAD cells. Methods The expression of C1orf74 in LUAD was analyzed using the LUAD datasets from public databases. The prognostic value of C1orf74 in LUAD was analyzed using Kaplan-Meier Plotter. C1orf74 expression in LUAD cell line A549, H1993 and HCC827 was silenced using small interfering RNA, and then the effects of C1orf74 knockdown on proliferation, migration and invasion of LUAD cells were detected by colony formation assay and Transwell assay, the role of C1orf74 in EGFR/AKT/mTORC1 signaling pathway was examined by Western blot, and the function of C1orf74 in cell cycle was detected by flow cytometry. Results The results of LUAD clinical data showed that C1orf74 was upregulated in LUAD tissues, and its high expression was associated with poor prognosis. The results from cultured LUAD cells demonstrated that C1orf74 knockdown inhibited cell proliferation, migration and invasion, but induced cell cycle arrest and autophagy. Moreover, C1orf74 knockdown suppressed EGFR/AKT/mTORC1 signaling in LUAD cells. In conclusion, the present study revealed that C1orf74 is upregulated in LUAD tissues and plays an oncogenic role in LUAD, and that C1orf74 positively regulates cell proliferation and mobility through the EGFR/AKT/mTORC1 signaling pathway in LUAD cells.
Guo et al. (2022) C1orf74 positively regulates the EGFR/AKT/mTORC1 signaling in lung adenocarcinoma cells. PeerJ 10:e13908 https://doi.org/10.7717/peerj.13908
A survey of researchers’ code sharing and code reuse practices, and assessment of interactive notebook prototypes
This research aimed to understand the needs and habits of researchers in relation to code sharing and reuse; gather feedback on prototype code notebooks created by NeuroLibre; and help determine strategies that publishers could use to increase code sharing. We surveyed 188 researchers in computational biology. Respondents were asked about how often and why they look at code, which methods of accessing code they find useful and why, what aspects of code sharing are important to them, and how satisfied they are with their ability to complete these tasks. Respondents were asked to look at a prototype code notebook and give feedback on its features. Respondents were also asked how much time they spent preparing code and if they would be willing to increase this to use a code sharing tool, such as a notebook. As a reader of research articles the most common reason (70%) for looking at code was to gain a better understanding of the article. The most commonly encountered method for code sharing–linking articles to a code repository–was also the most useful method of accessing code from the reader’s perspective. As authors, the respondents were largely satisfied with their ability to carry out tasks related to code sharing. The most important of these tasks were ensuring that the code was running in the correct environment, and sharing code with good documentation. The average researcher, according to our results, is unwilling to incur additional costs (in time, effort or expenditure) that are currently needed to use code sharing tools alongside a publication. We infer this means we need different models for funding and producing interactive or executable research outputs if they are to reach a large number of researchers. For the purpose of increasing the amount of code shared by authors, PLOS Computational Biology is, as a result, focusing on policy rather than tools.
Cadwallader et al. (2022) A survey of researchers’ code sharing and code reuse practices, and assessment of interactive notebook prototypes. PeerJ 10:e13933 https://doi.org/10.7717/peerj.13933
Recapitulating human ovarian aging using random walks
Mechanism(s) that control whether individual human primordial ovarian follicles (PFs) remain dormant, or begin to grow, are all but unknown. One of our groups has recently shown that activation of the Integrated Stress Response (ISR) pathway can slow follicular granulosa cell proliferation by activating cell cycle checkpoints. Those data suggest that the ISR is active and fluctuates according to local conditions in dormant PFs. Because cell cycle entry of (pre)granulosa cells is required for PF growth activation (PFGA), we propose that rare ISR checkpoint resolution allows individual PFs to begin to grow. Fluctuating ISR activity within individual PFs can be described by a random process. In this article, we model ISR activity of individual PFs by one-dimensional random walks (RWs) and monitor the rate at which simulated checkpoint resolution and thus PFGA threshold crossing occurs. We show that the simultaneous recapitulation of (i) the loss of PFs over time within simulated subjects, and (ii) the timing of PF depletion in populations of simulated subjects equivalent to the distribution of the human age of natural menopause can be produced using this approach. In the RW model, the probability that individual PFs grow is influenced by regionally fluctuating conditions, that over time manifests in the known pattern of PFGA. Considered at the level of the ovary, randomness appears to be a key, purposeful feature of human ovarian aging.
Johnson et al. (2022) Recapitulating human ovarian aging using random walks. PeerJ 10:e13941 https://doi.org/10.7717/peerj.13941
Gas chromatography (GC) fingerprinting and immunomodulatory activity of polysaccharide from the rhizome of Menispermum dauricum DC
This research aimed to establish the gas chromatography (GC) fingerprints and examine the immunomodulatory activity of the rhizome of Menispermum dauricum polysaccharides. In this study, the preparation conditions were optimized by the response surface method (RSM). GC is an effective and sensitive technique employed to measure the composition of monosaccharides; the GC fingerprints of total polysaccharides from 10 batches of the rhizome of M. dauricum (tMDP) were established, and chemometrics methods were adopted to examine the differences and similarities of tMDP from distinct regions. The similarity evaluation illustrated that the polysaccharides derived from the rhizome of M. dauricum from different origins were highly similar. The results of principal components analysis (PCA) illustrated that all the tMDPs may be integrated into one group within the 95% confidence interval, but the rhizome of M. dauricum from different origins could also be distinguished in the plot of PCA scores. Then, the major bioactive fraction MDP was purified and obtained by column chromatography. Our previous study showed that MDP exhibited significant immunomodulatory activity, but the mechanism of the in vitro immunomodulatory activity of MDP is unclear. The macrophage activation induced by MDP was abolished when Toll-like receptor 4 (TLR4) signaling was knocked down by the TLR4 inhibitor. Furthermore, western blot analysis illustrated that MDP activated RAW264.7 cells through MAPKs and NFκB pathways induced by TLR4. This research offers a theoretical foundation for quality control and additional study as a potential immunomodulator of MDP.
Yang et al. (2022) Gas chromatography (GC) fingerprinting and immunomodulatory activity of polysaccharide from the rhizome of Menispermum dauricum DC. PeerJ 10:e13946 https://doi.org/10.7717/peerj.13946
Daylight savings time transition and the incidence of femur fractures in the older population: a nationwide registry-based study
Background Daylight Savings Time (DST) transition is known to cause sleep disruption, and thus may increase the incidence of injuries and accidents during the week following the transition. The aim of this study was to assess the incidence of femur fractures after DST transition. Methods We conducted retrospective population-based register study. All Finnish patients 70 years or older who were admitted to hospital due to femur fracture between 1997 and 2020 were gathered from the Finnish National Hospital Discharge Register. Negative binomial regression with 95% confidence intervals (CI) was used to evaluate the incidence of femur fractures after DST transition. Results The data included a total of 112,658 femur fractures during the study period between 1997 and 2020, with an annual mean (SD) of 4,694 (206) fractures. The incidence of femur fractures decreased at the beginning of the study period from 968 to 688 per 100,000 person-years between 1997 and 2007. The weekly mean of femur fractures remained lower during the summer (from 130 to 150 per 100,000 person-weeks) than in winter (from 160 to 180 per 100,000 person-weeks). Incidence rate ratio for the Monday following DST transition was 1.10 (CI [0.98–1.24]) in spring and 1.10 (CI [0.97–1.24]) in fall, and for the whole week 1.07 (CI [1.01–1.14]) in spring and 0.97 (CI [0.83–1.13]) in fall. Conclusion We found weak evidence that the incidence of femur fractures increases after DST transition in the spring.
Ponkilainen et al. (2022) Daylight savings time transition and the incidence of femur fractures in the older population: a nationwide registry-based study. PeerJ 10:e13672 https://doi.org/10.7717/peerj.13672
Somatization symptoms—prevalence and risk, stress and resilience factors among medical and dental students at a mid-sized German university
Objective Previous studies have shown that an increased prevalence of mental illness can be found among medical and dental students. Among these, somatization symptoms are severely understudied. The present study examined the prevalence of somatization symptoms in a subpopulation of medical and dental students and aimed at finding associated risk and resilience factors. Methods A cross-sectional survey was conducted using a self-reporting questionnaire, including the SOMS-2, the Becks-Depression-Inventory-II (BDI-II), the NEO-Five-Factor-Inventory, and a questionnaire on socio-demographics for possible risk and resilience factors. A total of 271 medical and dental students of a mid-sized German university completed the questionnaire. Results The Somatization index yielded a mean of 9.12 symptoms for the total sample, which is 1.2 SD higher than the reported norm. A total of 50.7% of the medical students and 63.6% of the dental students transcend a critical somatization score. Significant positive associations for eight general risk factors, four university related stress factors, and a significant negative association for seven resilience factors were found. Conclusion Medical and even more dental students at the studied university showed a high burden of somatoform complaints. Also, factors were found that could be of etiological relevance and others that could be used to enhance resilience. Both could present an opportunity for the prevention of somatization disorders but prospective and multicenter studies with an aged-matched comparison group are needed to obtain a more accurate overview.
Feussner et al. (2022) Somatization symptoms—prevalence and risk, stress and resilience factors among medical and dental students at a mid-sized German university. PeerJ 10:e13803 https://doi.org/10.7717/peerj.13803
Users’ needs for a digital smoking cessation application and how to address them: A mixed-methods study
Background Despite their increasing prevalence and potential, eHealth applications for behavior change suffer from a lack of adherence and from dropout. Advances in virtual coach technology provide new opportunities to improve this. However, these applications still do not always offer what people need. We, therefore, need a better understanding of people’s needs and how to address these, based on both actual experiences of users and their reflections on envisioned scenarios. Methods We conducted a longitudinal study in which 671 smokers interacted with a virtual coach in five sessions. The virtual coach assigned them a new preparatory activity for quitting smoking or increasing physical activity in each session. Participants provided feedback on the activity in the next session. After the five sessions, participants were asked to describe barriers and motivators for doing their activities. In addition, they provided their views on videos of scenarios such as receiving motivational messages. To understand users’ needs, we took a mixed-methods approach. This approach triangulated findings from qualitative data, quantitative data, and the literature. Results We identified 14 main themes that describe people’s views of their current and future behaviors concerning an eHealth application. These themes relate to the behaviors themselves, the users, other parties involved in a behavior, and the environment. The most prevalent theme was the perceived usefulness of behaviors, especially whether they were informative, helpful, motivating, or encouraging. The timing and intensity of behaviors also mattered. With regards to the users, their perceived importance of and motivation to change, autonomy, and personal characteristics were major themes. Another important role was played by other parties that may be involved in a behavior, such as general practitioners or virtual coaches. Here, the themes of companionableness, accountability, and nature of the other party (i.e., human vs AI) were relevant. The last set of main themes was related to the environment in which a behavior is performed. Prevalent themes were the availability of sufficient time, the presence of prompts and triggers, support from one’s social environment, and the diversity of other environmental factors. We provide recommendations for addressing each theme. Conclusions The integrated method of experience-based and envisioning-based needs acquisition with a triangulate analysis provided a comprehensive needs classification (empirically and theoretically grounded). We expect that our themes and recommendations for addressing them will be helpful for designing applications for health behavior change that meet people’s needs. Designers should especially focus on the perceived usefulness of application components. To aid future work, we publish our dataset with user characteristics and 5,074 free-text responses from 671 people.
Albers et al. (2022) Users’ needs for a digital smoking cessation application and how to address them: A mixed-methods study. PeerJ 10:e13824 https://doi.org/10.7717/peerj.13824
CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma via the PI3K/AKT signaling pathway
Background CC chemokine receptor 9 (CCR9), an organ-specific chemokine receptor, interacts with its exclusive ligand CCL25 to promote tumor proliferation and metastasis. However, the effect of CCR9 on salivary adenoid cystic carcinoma (SACC) malignant behavior remains unknown. This study aimed to investigate the specific molecular mechanism by which CCR9/CCL25 modulates malignant progression in SACC. Methods Immunohistochemistry staining and RT–qPCR analyses were performed to detect the correlation of CCR9 expression and tumor progression-associated markers in SACC. In vitro, SACC cell proliferation and apoptosis were evaluated using Cell Counting Kit-8 and colon formation, and cell migration and invasion were detected by wound healing and transwell assays. Vercirnon was used as an inhibitor of CCR9, and LY294002 was used as an inhibitor of the PI3K/AKT pathway in this study. Western blot and RT–qPCR assays were carried out to measure the downstream factors of the interaction of CCL25 and CCR9. The effect of CCL25 on the development of SACC in vivo was examined by a xenograft tumor model in nude mice following CCL25, Vercirnon and LY294002 treatment. Results CCR9 was highly expressed in SACC compared with adjacent salivary gland tissues, and its level was associated with tumor proliferation and metastases. CCL25 enhanced cell proliferation, migration, and invasion through its interaction with CCR9 and exerted an antiapoptotic effect on SACC cells. Targeting CCR9 via Vercirnon significantly reduced the phosphorylation level of AKT induced by CCL25. CCL25/CCR9 could activate its downstream factors through the PI3K/AKT signaling pathway, such as cyclin D1, BCL2 and SLUG, thus promoting SACC cell proliferation, antiapoptosis, invasion and metastasis. The in vivo data from the xenograft mouse models further proved that CCL25 administration promoted malignant tumor progression by activating the PI3K/AKT pathway. Conclusion The interaction of CCL25 and CCR9 promotes tumor growth and metastasis in SACC by activating the PI3K/AKT signaling pathway, offering a promising strategy for SACC treatment.
Chai et al. (2022) CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma via the PI3K/AKT signaling pathway. PeerJ 10:e13844 https://doi.org/10.7717/peerj.13844