Life on Earth developed under the influence of normal gravity (1g). With evidence from previous studies, scientists have suggested that normal physiological processes, such as the functional integrity of muscles and bone mass, can be affected by microgravity during spaceflight. During the life span, bone not only develops as a structure designed specifically for mechanical tasks but also adapts for efficiency. The lack of weight-bearing forces makes microgravity an ideal physical stimulus to evaluate bone cell responses. One of the most serious problems induced by long-term weightlessness is bone mineral loss. Results from in vitro studies that entailed the use of bone cells in spaceflights showed modification in cell attachment structures and cytoskeletal reorganization, which may be involved in bone loss. Humans exposed to microgravity conditions experience various physiological changes, including loss of bone mass, muscle deterioration, and immunodeficiency. In vitro models can be used to extract valuable information about changes in mechanical stress to ultimately identify the different pathways of mechanotransduction in bone cells. Despite many in vivo and in vitro studies under both real microgravity and simulated conditions, the mechanism of bone loss is still not well defined. The objective of this review is to summarize the recent research on bone cells under microgravity conditions based on advances in the field.

At present, male contraceptive methods are only vasectomy and condoms, so it is necessary to research on male contraceptive techniques. The aim of this study is to observe the effects of scrotal heating (SH) on semen parameters, seminal l-carnitine (LC), epidermal growth factor (EGF), macrophage migration inhibitory factor (MIF), reproductive hormones and sperm chromosome numbers of adult healthy men, and to provide the experimental data for male contraception. The scrotums of 30 healthy male volunteers were exposed to the condition of 40 to 43°C SH belt warming 40 minutes each day for successive 2 days per week. The course of SH was continuous for 3 months. Computer-assisted semen analysis and hypo-osmotic swelling test, sperm DNA integrity, l-carnitine, MIF and EGF, and sperm fluorescence in situ hybridization were performed before, during, and after SH. The serum level of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) were measured by chemiluminescent immunoassay. The mean parameters of sperm concentration, vitality, and normal morphological sperm were significantly decreased in groups with sperms being collected during 1, 2, and 3 months of SH when compared with those in groups of pre-SH (P < 0.01). Statistically significant differences of sperm DNA fragmentation, normal sperm membrane functionality, levels of LC and MIF in semen, and LH, FSH, and T in serum were observed between the groups of before SH and after SH 3 months and the groups of during SH 1, 2, and 3 months (P < 0.001). The total rate of chromosome number for 13, 18, 21, X, and Y in the 3 months of SH was 13.7-fold greater (13.72%/1.69%) than before SH (P < 0.001). The constant SH can impact the semen quality, sperm DNA integrity, sperm chromosome, LC and MIF, and LH, FSH, and T in serum. Transient SH may be a new method for male contraception.

Myostatin (MSTN), associated with the “double muscling” phenotype, affects muscle growth and fat deposition in animals, whereas how MSTN affects adipogenesis remains to be discovered. Here we show that MSTN can act through the MEF2C/miR222/SCD5 cascade to regulate fatty acid metabolism. We generated MSTN-knockout (KO) cloned Meishan pigs, which exhibits typical double muscling trait. We then sequenced transcriptome of subcutaneous fat tissues of wild-type (WT) and MSTN-KO pigs, and intersected the differentially expressed mRNAs and miRNAs to predict that stearoyl-CoA desaturase 5 (SCD5) is targeted by miR222. Transcription factor binding prediction showed that myogenic transcription factor 2C (MEF2C) potentially binds to the miR222 promoter. We hypothesized that MSTN-KO upregulates MEF2C and consequently increases the miR222 expression, which in turn targets SCD5 to suppress its translation. Biochemical, molecular and cellular experiments verified the existence of the cascade. This novel molecular pathway sheds light on new targets for genetic improvements in pigs.

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In mammalian cells, double-strand breaks (DSBs) are repaired predominantly by error-prone non-homologous end joining (NHEJ), but less prevalently by error-free template-dependent homologous recombination (HR). DSB repair pathway selection is the bedrock for genome editing. NHEJ results in random mutations when repairing DSB, while HR induces high-fidelity sequence-specific variations, but with an undesirable low efficiency. In this review, we first discuss the latest insights into the action mode of NHEJ and HR in a panoramic view. We then propose the future direction of genome editing by virtue of these advancements. We suggest that by switching NHEJ to HR, full fidelity genome editing and robust gene knock-in could be enabled. We also envision that RNA molecules could be repurposed by RNA-templated DSB repair to mediate precise genetic editing.

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Oral environment deterioration results from a lack of self-cleaning ability in patients with cognitive dysfunction but is also a risk factor for cognitive dysfunction. Adverse oral conditions can be alleviated and improved through a self-management and medical examination. In this review, the epidemiological evidence of previous studies is integrated to highlight the relationship between periodontitis, tooth loss, oral flora, oral dysfunction and cognitive dysfunction, emphasizing the importance of oral health for cognition. The results show that poor oral condition is associated with cognitive impairment. Although many previous studies have been conducted, there is a lack of higher-level research evidence, different judgment criteria, and conflicting research results. There is a bidirectional relationship between oral health and cognitive dysfunction. A comprehensive analysis of the relationship between oral health and cognitive dysfunction that explores the relationship and takes measures to prevent cognitive dysfunction and control the progression of such diseases is warranted in the future.

BackgroundGenistein, a soy isoflavones, is the most important phytoestrogens in typical oriental diet. Many studies have shown that genistein at lower concentrations promotes breast cancer cells growth through the estrogen receptor pathway. However, recent research has found that long-term consumption of low doses of genistein results in hormone-independent growth phenotypes of MCF-7 tumors, with increased expression of HER2. Overexpression of HER2 has been causally associated with endocrine therapy resistance in human breast cancer. The mechanism by which prolonged exposure to genistein leads to increased HER2 expression is unclear. Whether genistein-induced HER2 expression is the cause of endocrine resistance remains to be determined. MethodsWe selected the MCF-7 and T47D breast cancer cells model with higher ERα and lower HER2. It was investigated whether prolonged exposure to genistein induced TAM-sensitive breast cancer cells to TAM-refractory cells by increasing HER2 expression. Furthermore, it was explored whether HER2 expression and endocrine resistance were associated with EZH2. ResultsWe found that genistein had estrogen-like effect and inhibited HER2 expression during short-term exposure. However, long-term exposure to genistein induced acquire endocrine resistance, because of increased expression of HER2. During long-term exposure to genistein, the continuous activation of ERK1/2 phosphorylated EZH2 at Ser21, resulting in a decrease of lysine 27 trimethylation. As H3K27me3 level decreased, the expression of IL-6 and IL-8 increased, and HER2 level gradually increased, forming a feedback loop of ERK1/2 / EZH2/ IL-6 and IL-8 / HER2. ConclusionsThese findings indicated that high HER2 expression caused by EZH2 phosphorylation was an important mechanism of endocrine resistance. The study also provided a new insight for genistein-induced acquired endocrine resistance. For breast cancer patients, long-term use of soy supplements has potential health risk. Especially, monitoring dietary exposure to genistein is advisable when treated with tamoxifen.