The vertebrate- and testis- specific transmembrane protein C11ORF94 plays a critical role in sperm-oocyte membrane binding.

Sperm-oocyte membrane fusion is necessary for mammalian fertilization. The factors that determine the fusion of sperm with oocytes are largely unknown. So far, spermatozoon factor IZUMO1 and the IZUMO1 counter-receptor JUNO on the oocyte membrane has been identified as a protein requiring fusion. Some sperm membrane proteins such as FIMP, SPACA6 and TEME95, have been proved not to directly regulate fusion, but their knockout will affect the fusion process of sperm and oocytes. Here, we identified a novel gene C11orf94 encoding a testicular-specific small transmembrane protein that emerges in vertebrates likely acquired via horizontal gene transfer from bacteria and plays an indispensable role in sperm-oocyte binding. We demonstrated that the deletion of C11orf94 dramatically decreased male fertility in mice. Sperm from C11orf94-deficient mice could pass through the zona pellucida, but failed to bind to the oocyte membrane, thus accumulating in the perivitelline space. In consistence, when the sperm of C11orf94-deficient mice were microinjected into the oocyte cytoplasm, fertilized oocytes were obtained and developed normally to blastocysts. Proteomics analysis revealed that C11orf94 influenced the expression of multiple gene products known to be indispensable for sperm-oocyte binding and fusion, including IZUMO1, EQTN and CRISP1. Thus, our study indicated that C11ORF94 is a vertebrate- and testis-specific small transmembrane protein that plays a critical role in sperm binding to the oolemma.

Molecular fingerprints of polar narcotic chemicals based on heterozygous essential gene knockout library in Saccharomyces cerevisiae.

Cytotoxicity of non-polar narcotic chemicals can be predicted by quantitative structure activity relationship (QSAR) models, but the polar narcotic chemicals' actual cytotoxicity exceeds the predicted values by their chemical structures. This discrepancy indicates that the molecular mechanism by which polar narcotic chemicals exert their toxicity is unclear. Taking advantage of Saccharomyces cerevisiae (yeast) functional genome-wide heterozygous essential gene knockout mutants, we here have identified the specific molecular fingerprints of two main chemical structure groups (phenols and anilines) of polar narcotic chemicals (dichlorophen (DCP), 4-chlorophenol (4-CP), 2, 4, 6-trichlorophenol (TCP), 3, 4-dichloroaniline (DCA) and N-methylaniline (NMA)) and one non-polar narcotic chemical 2, 2, 2-trichloroethanol (TCE). Especially, we identify 33, 57, 54, 46, 59 and 53 responsive strains through exposure to TCE, DCP, 4-CP, TCP, DCA and NMA with three test concentrations, respectively, revealing that these polar narcotic chemicals have more responsive strains than the non-polar narcotic chemical. Remarkably, we find that the molecular fingerprints of polar narcotic chemicals in different chemical structure groups are obviously varied, particularly phenols and anilines have their own specific molecular fingerprints. Interestingly, our results demonstrate that the molecular toxicity mechanisms of anilines are associated with DNA replication, but phenols are related with pathway of RNA degradation. Additionally, we find that the two knockout strains (SME1 and DIS3) and the three knockout strains (TSC11, RSP5 and HSF1) can specifically respond to exposure to phenols and anilines, respectively. Thus, they may be served as potential biomarkers to distinguish phenols from anilines. Collectively, our works demonstrate that the functional genomic platform of yeast essential gene mutants can not only act as an effective tool to identify key specific molecular fingerprints for polar narcotic chemicals, but also help to understand the molecular mechanisms of polar narcotic chemicals.

A Systematic Review and Meta-Analysis of Low-Residue Diet Versus Clear Liquid Diet: Which Is Better for Bowel Preparation Before Colonoscopy?

The goal of this systematic review was to compare the clear liquid diet and the low-residue diet to determine which is better for bowel preparation before colonoscopy. A literature search for randomized controlled trials on the effects of employing the clear liquid diet and low-residue diets before colonoscopy was conducted in major online English databases (PubMed, Web of Science, and Ovid EMBASE). After the systematic review of all 16 studies, the outcomes including quality of bowel preparation, tolerance, willingness to repeat, and adverse effects were analyzed through meta-analysis. The statistical analysis was performed by using RevMan 5.3 software. No statistically significant difference was observed between the low-residue diet and clear liquid diet groups (odds ratio [95% confidence interval] = 1.19 [0.79, 1.81]; p = .41). There was no statistically significant difference between the Boston Bowel Preparation Scale (standard mean difference [95% confidence interval] =-0.04 [-0.21, -0.14]; p = .68) Ottawa Bowel Preparation Scale (standard mean difference [95% confidence interval] =-0.04 [-0.19, 0.11]; p = .59) scores of the two groups. The quality indicators for colonoscopy of the two groups were not statistically significant. However, patient tolerance to the low-residue diet was higher (odds ratio [95% confidence interval] = 1.86 [1.47, 2.36]; p < .01). More patients in the low-residue diet group were willing to repeat the low-residue diet for bowel preparation (odds ratio [95% confidence interval] = 2.34 [1.72, 3.17]; p < .01). More patients in the clear liquid diet group experienced hunger, nausea, and vomiting. People who employed the low-residue diet before colonoscopy had the same quality of bowel preparation as those with clear liquid diet. Meanwhile, the tolerance of people with low-residue diet was better than people with clear liquid diet, and these people were more willing to repeat the colonoscopy with less adverse events.