In conclusion, HOXB8 promotes cell proliferation, migration and invasion through modulating Wnt/β-catenin and STAT3 signaling pathways in ovarian cancer, suggesting that HOXB8 may provide a promising target for the therapy of ovarian cancer.Mechanical strain regulated osteoclastic differentiation and angiogenesis are crucial for bone modeling and remodeling, and previous data indicate that high-magnitude strain within physiological load regulates osteoclastic differentiation. However, the underlying mechanisms are still not fully understood. In the present study, the RAW264.7 mouse monocyte/macrophage was used as an osteoclast precursor, and the bone marrow-derived macrophages (BMMs) were isolated and cultured in vitro. The above cells were subjected to macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL) for the induction of osteoclast differentiation. Subsequently, the above cells were stretched by differential strain magnitudes to simulate the mechanical stimuli in the physiological conditions, and we found that low-magnitude strain (100 με) increased the expression levels of Acp5, Clcn7, MMP9 and Ctsk to promote osteoclastogenesis, while high-magnitude strain (3000 με) had opposite effects. In addition, we noticed that high-magnitude strain upregulated PTEN to inactivate the PI3K/Akt signaling pathway, and silencing of PTEN abrogated the suppressing effects of high-magnitude strain on osteoclastic differentiation. Next, we screened out that high-magnitude strain downregulated miR-21 to promote PTEN expressions in a competing endogenous RNA (ceRNA)-dependent manner. Finally, upregulation of miR-21 recovered osteoclastic differentiation in RAW264.7 and BMMs cells stimulated with high-magnitude strain. Collectively, our findings suggested that high-magnitude mechanical strain affected osteoclastic differentiation through modulating the miR-21/PTEN/PI3K/Akt signaling cascade, which provided potential strategies for the treatment of bone-related diseases.

The online version contains supplementary material available at 10.1007/s10616-021-00507-x.

The online version contains supplementary material available at 10.1007/s10616-021-00507-x.Accumulating evidence supports that exosomal RNAs are crucial in tumor microenvironment and may be used as diagnostic biomarkers for cancers. This study aimed to determine the role of exosomal circular RNA_protein tyrosine phosphatase receptor type A (circ_PTPRA) in colorectal cancer (CRC). The morphology of exosomes was identified by transmission electron microscopy (TEM), and several exosome-specific proteins were quantified by western blot. The expression of circ_PTPRA, miR-671-5p and SMAD family member 4 (SMAD4) was detected using quantitative polymerase chain reaction (qPCR). Cell cycle was assessed using flow cytometry assay. Cell proliferation was assessed by MTT assay. Radiosensitivity was observed according to colony growth and cell apoptosis rate by colony formation assay and flow cytometry assay. The protein levels of proliferation- and apoptosis-related markers and SMAD4 were measured by western blot. The predicted relationship between miR-671-5p and circ_PTPRA or SMAD4 was verified by dual-lucifeed as a potential predicted and therapeutic target for CRC.To date, the production of antibodies (mAbs) usually faces the risks of transgene expression reduction and instability, especially after long-time culture. The inclusion of ubiquitous chromatin opening element (UCOE) into expression vectors was reported to enhance protein production and maintain transgene expression stability in CHO cell lines. Thus, we investigate the effects of UCOE on recombinant monoclonal anti-TNFα antibody (mAbTNFα) production and expression stability in CHO-DG44 cells. In our study, non-UCOE and UCOE-based vectors encoding mAbTNFα were constructed and introduced into the CHO-DG44 cells. Cell pools and single-cell clones were obtained by selecting transfected cells with G418, amplifying them by treatment with methotrexate (MTX), and isolating them by limiting dilution. The effects of UCOE on mAb production and stable transgene expression in transfected cells were analyzed via the correlation between mAb yields and mRNA expression level variations, and gene copy number changes. The UCOE pool exhibited higher mAb yield compared to non-UCOE pool. The UCOE was associated with higher transgene transcriptional activity, leading to improvement of mAb production after MTX-mediated gene amplification. The incorporation of UCOE generated cells allowed isolation of greater numbers of positive clones with higher expression. Despite the slightly decreased mAb yield, UCOE clones still retain stable long-term expression in the absence of selective pressure, which was explained by the loss of transgene copies rather than due to the decline of transcriptional activity. In addition, the purified mAb had primary chemical and biological characteristics similar to those of adalimumab. The results showed that the incorporation of UCOE within vectors provides significant advantages in the generation of high-producing clones, enhancement of mAb production, and improvement of gene expression stability.Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are present in human umbilical connective tissue and can differentiate into various cell types. Our previous studies have proved that hUC-MSCs do not lead to allergies and tumorigenesis. In the present study, the acute and long-term toxicity of hUC-MSCs in mice and rats was evaluated. The acute toxicity of hUC-MSCs was assessed in 8-week-old mice receiving two caudal intravenous (i.v.) injections of hUC-MSCs at the maximum tolerated dose of 1.5 × 107 cells/kg with an interval of 8 h and the observation period sustained for 14 days. For the long-term toxicity evaluation, rats were randomly divided into control, low-dose (3.0 × 105 cells/kg), mid-dose (1.5 × 106 cells/kg), and high-dose (7.5 × 106 cells/kg) groups, which were treated with hUC-MSCs via a caudal i.v. injection every 3 days for 90 days. Weight and food intake evaluation was performed for all rats for 2 weeks after the hUC-MSC administration. The animals were then sacrificed for hematological, blood biochemical, and pathological analyses, as well as organ index determination. We observed no obvious acute toxicity of hUC-MSCs in mice at the maximum tolerated dose. Long-term toxicity tests in rats showed no significant differences between HUC-MSC-treated and control groups in the following parameters body weight, hematological and blood biochemical parameters, and histopathologic changes in the heart, liver, kidneys, and lungs. This study provides evidence of the safety of i.v. hUC-MSCs infusion for future clinical therapies.Cryopreservation and transplantation of ovarian tissue is the only fertility preservation option used for prepubertal girls and women who don’t have a chance for embryo or oocyte vitrification. For women with aggressive cancer, hormone-responsive malignancies, autoimmune diseases, etc. ovary transplantation cannot be performed so an alternative technology called in-vitro follicle activation is thinkable. In this method, dormant primordial follicles are activated from the resting primordial pool by in-vitro culture and enter their growth phase. Different in-vitro culture media and supplements in addition to various culturing methods have been conducted for activating these dormant follicles. Furthermore, several signaling pathways such as Hippo, phosphatidylinositol-3-kinase, and mTOR influence follicle activation. Therefore, the addition of different activators of these signaling pathways can beneficially regulate this culture system. This review summarizes the findings on different aspects of human ovarian tissue culture strategies for in-vitro follicular activation, their medium, and different factors involved in this activation. Afterward, signaling pathways important for follicle activation and their clinical applications towards improving activation in culture are also reviewed.Social insects have high levels of cooperation and division of labor. In bumble bees this is partly size-based, with larger bees performing tasks outside the nest and smaller bees remaining inside, although bumble bees still display considerable behavioral plasticity. The level of specialization in tasks outside the colony, including foraging, guarding and drifting (entering a foreign colony), is currently unknown for bumble bees. This study aimed to assess division of labor between outside tasks and the degree of specialization in foraging, guarding, and switching colonies in commercially reared bumble bees placed in the field. Nine factory-bought Bombus terrestris colonies were placed on three farms in Sussex, UK, between June and August 2015. Forty workers from each colony were radio-tagged and a reader on the colony entrance recorded the date, time and bee ID as they passed. The length and frequency of foraging trips and guarding behavior were calculated, and drifting recorded. The mean (±SD) length of foraging trips was 45 ± 36 min, and the mean number of foraging trips per day was 7.75 ± 7.71. Low levels of specialization in guarding or foraging behavior were found; however, some bees appeared to guard more frequently than others, and twenty bees were categorized as guards. Five bees appeared to exhibit repeated “stealing” behavior, which may have been a specialist task. The division of labor between tasks was not size-based. It is concluded that commercial bumble bees are flexible in performing outside nest tasks and may have diverse foraging strategies including intra-specific nest robbing.

The online version contains supplementary material available at 10.1007/s10905-021-09790-0.

The online version contains supplementary material available at 10.1007/s10905-021-09790-0.Gender scholars have addressed a variety of gender gaps between men and women, including a gender gap in orgasms. In this mixed-methods study of heterosexual Canadians, we examine how men and women engage in gender labor that limits women’s orgasms relative to men. Etomoxir With representative survey data, we test existing hypotheses that sexual behaviors and relationship contexts contribute to the gender gap in orgasms. We confirm previous research that sexual practices focusing on clitoral stimulation are associated with women’s orgasms. With in-depth interview data from a subsample of 40 survey participants, we extend this research to show that both men and women engage in gender labor to explain and justify the gender gap in orgasms. Relying on an essentialist view of gender, a narrow understanding of what counts as sex, and moralistic language that recalls the sexual double standard, our participants craft a narrative of women’s orgasms as work and men’s orgasms as natural. The work to produce this gendered narrative of sexuality mirrors the gender labor that takes place in the bedroom, where both women and men engage in sexual behaviors that emphasize men’s pleasure to a greater extent than women’s.Given that real-world infection-spread scenarios pose many uncertainties, and predictions and simulations may differ from reality, this study explores factors essential for more realistically describing an infection situation. It furnishes three approaches to the argument that human mobility can create an acceleration of the spread of COVID-19 infection and its cyclicality under the simultaneous relationship. First, the study presents a dynamic model comprising the infection-mobility trade-off and mobility demand, where an increase in human mobility can cause infection explosion and where, conversely, an increase in new infections can be made temporary by suppressing mobility. Second, using time-series data for Japan, it presents empirical evidence for a stochastic trend and cycle in new infection cases. Third, it employs macroeconometrics to ascertain the feasibility of our model’s predictions. Accordingly, from March 2020 to May 2021, the sources of COVID-19 infection spread in Japan varied significantly over time, and each change in the trend and cycle of new infection cases explained approximately half the respective variation.