title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=523 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Association of ApoE gene polymorphisms with serum lipid levels and the risk of type 2 diabetes mellitus in the Chinese Han population of central China link: https://peerj.com/articles/15226 last-modified: 2023-04-24 description: BackgroundApolipoprotein E (ApoE) is involved in lipid transformation and metabolism. Although some studies have examined the association between ApoE polymorphisms and the risk of type 2 diabetes mellitus (T2DM), the findings differ depending on the location and population.MethodsA total of 1,738 participants, including 743 patients with T2DM and 995 controls without T2DM, were enrolled from central China, and ApoE polymorphisms, 388T > C (rs429358) and 526C > T (rs7412), were genotyped. The association between ApoE alleles and T2DM and blood lipid levels was analyzed. Logistic regression analysis was performed to evaluate the interactions between ApoE polymorphisms and various factors, such as age, sex, and prevalence of hypertension in patients with T2DM.ResultsThe genotype ɛ3/ɛ4 and ɛ4 alleles of ApoE were associated with T2DM risk in the Chinese Han population in central China. Moreover, in patients with T2DM, participants in the E4 (ɛ3/ɛ4, ɛ4/ɛ4) group had significantly higher lipid profiles than those in the E3 (ɛ3/ɛ3) group, whereas participants in the E2 group (ɛ2/ɛ2, ɛ2/ɛ3) showed lower total cholesterol, low-density lipoprotein cholesterol, and ApoE-A1 levels than those in the E3 (ɛ3/ɛ3) group. The results from the current study may help in understanding ApoE polymorphisms and lipid profiles in the Chinese Han population. creator: Yali Zeng creator: Shuang Wen creator: Lijun Huan creator: Liang Xiong creator: Botao Zhong creator: Pengyun Wang uri: https://doi.org/10.7717/peerj.15226 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Zeng et al. title: Sex differences in gene expression and alternative splicing in the Chinese horseshoe bat link: https://peerj.com/articles/15231 last-modified: 2023-04-24 description: Sexually dimorphic traits are common in sexually reproducing organisms and can be encoded by differential gene regulation between males and females. Although alternative splicing is common mechanism in generating transcriptional diversity, its role in generating sex differences relative to differential gene expression is less clear. Here, we investigate the relative roles of differential gene expression and alternative splicing between male and female the horseshoe bat species, Rhinolophus sinicus. Horseshoe bats are an excellent model to study acoustic differences between sexes. Using RNA-seq analyses of two somatic tissues (brain and liver) from males and females of the same population, we identified 3,471 and 2,208 differentially expressed genes between the sexes (DEGs) in the brain and liver, respectively. DEGs were enriched with functional categories associated with physiological difference of the sexes (e.g.,gamete generation and energy production for reproduction in females). In addition, we also detected many differentially spliced genes between the sexes (DSGs, 2,231 and 1,027 in the brain and liver, respectively) which were mainly involved in regulation of RNA splicing and mRNA metabolic process. Interestingly, we found a significant enrichment of DEGs on the X chromosome, but not for DSGs. As for the extent of overlap between the two sets of genes, more than expected overlap of DEGs and DSGs was observed in the brain but not in the liver. This suggests that more complex tissues, such as the brain, may require the intricate and simultaneous interplay of both differential gene expression and splicing of genes to govern sex-specific functions. Overall, our results support that variation in gene expression and alternative splicing are important and complementary mechanisms governing sex differences. creator: Wenli Chen creator: Weiwei Zhou creator: Qianqian Li creator: Xiuguang Mao uri: https://doi.org/10.7717/peerj.15231 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Chen et al. title: Uncovering the potential functions of lymph node metastasis-associated aberrant methylation differentially expressed genes and their association with the immune infiltration and prognosis in bladder urothelial carcinoma link: https://peerj.com/articles/15284 last-modified: 2023-04-24 description: BackgroundBladder urothelial carcinoma (BLCA) is a malignant tumor of the urinary system. This study aimed to explore the potential role of lymph node metastasis-associated aberrant methylation differentially expressed genes (DEGs) in BLCA.MethodsCHAMP and limma packages were used to identify lymph node metastasis-associated aberrant methylation DEGs. Univariate Cox analysis and Lasso analysis were performed to identify the signature genes, and multivariate Cox analysis was used to construct the risk score. Subsequently, the molecular characteristics of the signature genes and the relationship between risk score and prognosis, clinical characteristics and immune cell infiltration were analyzed. The signature gene AKAP7 was selected for functional verification.ResultsA novel risk score model was constructed based on 12 signature genes. The risk score had a good ability to predict overall survival (OS). The nomogram constructed based on age, N stage and risk score had a higher value in predicting the prognosis of patients. It was also found that stromal activation in TIME may inhibit the antitumor effects of immune cells. Functional enrichment analysis revealed that ECM receptor interaction and focal adhesion were two important pathways involved in the regulation of BLCA. Immunohistochemistry showed that AKAP7 may be associated with the occurrence, clinical stages and grades, and lymph node metastasis of BLCA. In vitro cell experiments showed that the migration and invasion ability of EJ cells was significantly inhibited after AKAP7 overexpression, while the migration and invasion ability of T24 cells was significantly promoted after AKAP7 knockdown.ConclusionThe risk score model based on lymph node metastasis-associated aberrant methylation DEGs has a good ability to predict OS and is an independent prognostic factor for BLCA. It was also found that stromal activation in TIME may inhibit the antitumor effects of immune cells. This implicates aberrant methylation modifications as an important factor contributing to the heterogeneity and complexity of individual tumor microenvironments. Functional enrichment analysis revealed that ECM receptor interaction and focal adhesion were two important pathways involved in the regulation of BLCA, which contributed to the exploration of the pathological mechanism of BLCA. In addition, immunohistochemistry showed that AKAP7 may be associated with the occurrence, progression and lymph node metastasis of BLCA. In vitro cell experiments showed that AKAP7 could also inhibit the migration and invasion of cancer cells. creator: Wenzhi Gao creator: Jiafeng Zhang creator: Tai Tian creator: Zhixin Fu creator: Liangliang Bai creator: Yifei Yang creator: Qiangqiang Wu creator: Wei Wang creator: Yuexian Guo uri: https://doi.org/10.7717/peerj.15284 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Gao et al. title: Effects of two different dual-task training protocols on gait, balance, and cognitive function in community-dwelling older adults: a 24-week randomized controlled trial link: https://peerj.com/articles/15030 last-modified: 2023-04-21 description: BackgroundAlthough alternating dual-task (ADT) training is functionally easier for older adults, a large part of the motor and cognitive tasks is simultaneously performed, especially during activities of daily living that require maintaining body balance.ObjectiveTo evaluate the effects of mixed dual-task training on mobility, cognitive function, and balance in community-dwelling older adults.MethodsSixty participants were randomly allocated at a 1:1 ratio into the experimental group—single motor task (SMT) and simultaneous dual task (SDT) interchangeably in stage 1 (for 12 weeks) and after strictly with SDT in stage 2 (the last 12 weeks)—or into the control group—only SMT and SDT interchangeably in stages 1 and 2. Gait parameters were acquired by two inertial sensors. Physical and cognitive performance were acquired by specific questionnaires. Generalized linear mixed models were used for analyzing interaction and main effects.ResultsNo between-group difference was observed for gait performance. Both protocols improved mobility (mean change ((MC) = 0.74)), dual-task effect (MC = −13.50), lower limb function (MC = 4.44), static (MC = −0.61), and dynamic balance (MC = −0.23), body sway (MC = 4.80), and cognitive function (MC = 41.69).ConclusionBoth dual-task training protocols improved these outcomes. creator: Francis Trombini-Souza creator: Vitória Thaysa Gomes de Moura creator: Lucas Willian Nunes da Silva creator: Iara dos Santos Leal creator: Cleber Anderson Nascimento creator: Paloma Sthefane Teles Silva creator: Monica Rodrigues Perracini creator: Isabel CN Sacco creator: Rodrigo Cappato de Araújo creator: Marcelo de Maio Nascimento uri: https://doi.org/10.7717/peerj.15030 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2023 Trombini-Souza et al. title: PAIP1 regulates expression of immune and inflammatory response associated genes at transcript level in liver cancer cell link: https://peerj.com/articles/15070 last-modified: 2023-04-21 description: Poly(A) binding protein interacting protein 1 (PAIP1) is a translation regulator and also regulate the decay of mRNA. PAIP1 has also been reported to be a marker of increased invasive potential of liver cancer. However, the roles and underlying molecular mechanism of PAIP1 in liver cancer is still unclear. Here, cell viability and the gene expression profile of liver cancer line HepG2 transfected with PAIP1 siRNA was compared with cells transfected with non-targeting control siRNA. The results showed that PAIP1 knockdown inhibited cell viability, and extensively affects expression of 893 genes at transcriptional level in HepG2 cells. Gene function analysis showed that a large number of PAIP1 up-regulated genes were enriched in term of DNA-dependent transcription and the down-regulated genes were enriched in some pathways including immune response and inflammatory response. qPCR confirmed that PAIP1 knockdown positively regulated the expression of selected immune and inflammatory factor genes in HepG2 cells. Expression analysis of TCGA revealed that PAIP1 had positive correlations with two immune associated genes IL1R2 and PTAFR in liver tumor tissue. Taken together, our results demonstrated that PAIP1 was not only a translation regulator, but also a transcription regulator in liver cancer. Moreover, PAIP1 could function as a regulatory factor of immune and inflammatory genes in liver cancer. Thus, our study provides important cues for further study on the regulatory mechanism of PAIP1 in liver cancer. creator: Jianfeng Zheng creator: Weiwei Fan creator: Xiaoyu Zhang creator: Weili Quan creator: Yunfei Wu creator: Mengni Shu creator: Moyang Chen creator: Ming Liang uri: https://doi.org/10.7717/peerj.15070 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Zheng et al. title: Metabolic shift and the effect of mitochondrial respiration on the osteogenic differentiation of dental pulp stem cells link: https://peerj.com/articles/15164 last-modified: 2023-04-21 description: BackgroundMetabolism shifts from glycolysis to mitochondrial oxidative phosphorylation are vital during the differentiation of stem cells. Mitochondria have a direct function in differentiation. However, the metabolic shift and the effect of mitochondria in regulating the osteogenic differentiation of human dental pulp stem cells (hDPSCs) remain unclear.MethodsHuman dental pulp stem cells were collected from five healthy donors. Osteogenic differentiation was induced by osteogenic induction medium. The activities of alkaline phosphatase, hexokinase, pyruvate kinase, and lactate dehydrogenase were analyzed by enzymatic activity kits. The extracellular acidification rate and the mitochondrial oxygen consumption rate were measured. The mRNA levels of COL-1, ALP, TFAM, and NRF1 were analyzed. The protein levels of p-AMPK and AMPK were detected by western blotting.ResultsGlycolysis decreased after a slight increase, while mitochondrial oxidative phosphorylation continued to increase when cells grew in osteogenic induction medium. Therefore, the metabolism of differentiating cells switched to mitochondrial respiration. Next, inhibiting mitochondrial respiration with carbonyl cyanide-chlorophenylhydrazone, a mitochondrial uncoupler inhibited hDPSCs differentiation with less ALP activity and decreased ALP and COL-1 mRNA expression. Furthermore, mitochondrial uncoupling led to AMPK activation. 5-Aminoimidazole-4-carboxamide ribonucleotide, an AMPK activator, simulated the effect of mitochondrial uncoupling by inhibiting osteogenic differentiation, mitochondrial biogenesis, and mitochondrial morphology. Mitochondrial uncoupling and activation of AMPK depressed mitochondrial oxidative phosphorylation and inhibited differentiation, suggesting that they may serve as regulators to halt osteogenic differentiation from impaired mitochondrial oxidative phosphorylation. creator: Lingyun Wan creator: Linyan Wang creator: Ran Cheng creator: Li Cheng creator: Tao Hu uri: https://doi.org/10.7717/peerj.15164 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Wan et al. title: Evaluation of waterlogging tolerance and responses of protective enzymes to waterlogging stress in pumpkin link: https://peerj.com/articles/15177 last-modified: 2023-04-21 description: Waterlogging caused by short and severe, or prolonged precipitation can be attributed to global warming. Pumpkin plants are drought-tolerant but not tolerate to waterlogging stress. Under frequent rain and waterlogging conditions, the production of pumpkins is of lower quality, sometimes rotten, and harvest failure occurs in severe cases. Therefore, it is of great significance to assess the waterlogging tolerance mechanism of pumpkin plants. In this study, 10 novel pumpkin varieties from Baimi series were used. The waterlogging tolerance level of pumpkin plants was evaluated by measuring waterlogging tolerance coefficient of biomass and physiological indices using waterlogging stress simulation method. The criteria to evaluate the waterlogging tolerance capacities of pumpkin plants were also explored. Using principal component and membership function analysis, waterlogging tolerance levels of the pumpkin varieties were ranked as follows: Baimi No. 10>; Baimi No. 5>; Baimi No. 1>; Baimi No. 2>; Baimi No. 3>; Baimi No. 7>; Baimi No. 9>; Baimi No. 6>; Baimi No. 4>; Baimi No. 8. Based on the results, Baimi No. 10 was identified with strong waterlogging tolerance and Baimi No. 8 with weak waterlogging tolerance. The responses of malondialdehyde (MDA), proline, key enzymes responsible for anaerobic respiration, and antioxidant enzymes to waterlogging stress were studied in pumpkin plants. The relative expression levels of related genes were determined using real-time fluorescence quantitative PCR technique. The aim of our study was to assess the waterlogging tolerance mechanism of pumpkin plants, thus laying a theoretical foundation for breeding waterlogging-tolerant varieties in the future. After flooding stress treatment, the antioxidant enzyme activities, contents of proline and alcohol dehydrogenases of Baimi No. 10 and Baimi No. 8 displayed an increase followed by a decrease. All indices of Baimi No. 10 were higher than Baimi No. 8. MDA contents gradually increased, with the content being higher in Baimi No. 8 than Baimi No. 10. The activities of pyruvate decarboxylases (PDCs) in Baimi No. 8 and Baimi No. 10 exhibited a decrease initially, followed by an increase, and then a decrease again. The PDC activity in Baimi No. 8 was generally higher than Baimi No. 10. The relative expression levels of genes encoding superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase were consistent with their corresponding enzyme activities. During the early stage of flooding stress, pumpkin plants waterlogging tolerance was improved by enhancing the expression levels of antioxidant enzyme encoding genes and increasing the antioxidant enzyme activities. creator: Zhenwei Liu creator: Dandan Qiao creator: Zhenyu Liu creator: Pengwei Wang creator: Li Sun creator: Xinzheng Li uri: https://doi.org/10.7717/peerj.15177 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Liu et al. title: Captive breeding in the endangered alpine tree frog, Litoria verreauxii alpina link: https://peerj.com/articles/15179 last-modified: 2023-04-21 description: Amphibians are experiencing dramatic worldwide declines and many species are reliant on captive breeding programs to ensure continued survival. However, captive breeding in amphibians is not always successful because many species, especially ones in decline, have particular and specific breeding needs. The endangered alpine tree frog, Litoria verreauxii alpina, has never been bred in captivity before. Due to its dramatic declines across the Australian Alps caused by the global pandemic chytridiomycosis, the species is a potential candidate for captive assurance colonies, which rely on captive breeding. For this study we tested hormone induction using two hormones that have had some success in other amphibian species, to no avail. We then tried outdoor breeding mesocosms during the winter/spring at temperatures similar to their natural breeding season, which was successful. Sixty-five percent of the egg masses laid successfully hatched tadpoles. Females laid more than one clutch over the experiment indicating either a shorter than annual ovulation cycle, or that females are capable of partial ovulation during breeding events. Outdoor breeding mesocosms are a possibility outside the native climate of a species, provided that temperatures overlap with their natural environment. Here, we highlight that troubleshooting is essential before embarking on a captive breeding program of a species that has not been bred before. Hormonal induction of breeding is not always successful; therefore, outdoor mesocosms might be required to achieve healthy tadpoles. creator: Laura A. Brannelly creator: Preeti Sharma creator: Danielle K. Wallace uri: https://doi.org/10.7717/peerj.15179 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Brannelly et al. title: Exploratory and confirmatory factor analyses identify three structural dimensions for measuring physical function in community-dwelling older adults link: https://peerj.com/articles/15182 last-modified: 2023-04-21 description: BackgroundPhysical function is a strong indicator of biological age and quality of life among older adults. However, the results from studies exploring the structural dimensions of physical function are inconsistent, and the measures assessed vary greatly, leading to a lack of comparability among them. This study aimed to construct a model to identify structural dimensions that are suitable and best assess physical function among community-dwelling adults 60–74 years of age in China.MethodThis study was conducted in 11 communities in Shanghai, China, from May to July 2021. A total of 381 adults 60–74 years of age were included in the study. Measured physical function data were used in factor analyses. Data collected from individuals were randomly assigned to either exploratory factor analysis (EFA) (n = 190) or confirmatory factor analysis (CFA) (n = 191). The statistical software used in the study was SPSS for EFA and AMOS for CFA. To test the properties of the structural dimension model of physical function, various fit indices, convergent validity, and discriminant validity were calculated.ResultsThe EFA results derived seven indicators in three factors, with 58.548% of the total variance explained. The three factors were mobility function (three indicators), which explained 26.380% of the variance, handgrip strength and pulmonary function (two indicators), which explained 19.117% of the variance, and muscle strength (two indicators) which explained 13.050% of the variance. The CFA indicated that this model had an acceptable fit (χ2/df ratio, 2.102; GFI, 0.967; IFI, 0.960; CFI, 0.959; and RMSEA, 0.076), and the criteria for convergent validity and discriminability were also met by the model.ConclusionThe constructed structural dimension model of physical function appeared to be a suitable and reliable tool to measure physical function in community-dwelling adults aged 60–74 years in China. The structural dimension indicators identified by this model may help sports medicine experts and healthcare providers offer more targeted interventions for older adults to reverse or slow the decline of physical function and to offer actionable targets for healthy aging in this population. creator: Guiping Jiang creator: Xiaohuan Tan creator: Hailong Wang creator: Min Xu creator: Xueping Wu uri: https://doi.org/10.7717/peerj.15182 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Jiang et al. title: The influence of climate warming on flowering phenology in relation to historical annual and seasonal temperatures and plant functional traits link: https://peerj.com/articles/15188 last-modified: 2023-04-21 description: Climate warming has the potential to influence plant flowering phenology which in turn can have broader ecological consequences. Herbarium collections offer a source of historical plant data that makes possible the ability to document and better understand how warming climate can influence long-term shifts in flowering phenology. We examined the influence of annual, winter, and spring temperatures on the flowering phenology of herbarium specimens for 36 species collected from 1884–2015. We then compared the response to warming between native and non-native, woody and herbaceous, dry and fleshy fruit, and spring vs summer blooming species. Across all species, plants flowered 2.26 days earlier per 1 °C increase in annual average temperatures and 2.93 days earlier per 1 °C increase in spring onset average temperatures. Winter temperatures did not significantly influence flowering phenology. The relationship of temperature and flowering phenology was not significantly different between native and non-native species. Woody species flowered earlier than herbaceous species only in response to increasing annual temperatures. There was no difference in the phenological response between species with dry fruits and those fleshy fruits for any of the temperature periods. Spring blooming species exhibited a significantly greater phenological response to warming yearly average temperatures than summer blooming species. Although herbarium specimens can reveal climate change impacts on phenology, it is also evident that the phenological responses to warming vary greatly among species due to differences in functional traits such as those considered here, as well as other factors. creator: Cole Geissler creator: Allison Davidson creator: Richard A. Niesenbaum uri: https://doi.org/10.7717/peerj.15188 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2023 Geissler et al.