To investigate the influences of sperm quality on the zygotes and embryos development, as the role of the paternal factor in early human embryogenesis is gaining more attention because of the application of techniques such as intracytoplasmic sperm injection (ICSI) for the treatment of men infertility. 136 infertility couples with men factors (Group I ) were included from May 2002 to January 2001. One hundred and seventy-two infertility couples with tube factors (Group II) served as controls. The sperm parameters, gemmates and embryos quality, implantation rate and pregnant rate in both groups were analyzed. It was found that there was no significant differences in the number of oocytes retrieved, the fertilization rate and number of embryos transferred between two groups. Sperm concentration, percentage of motile sperm and percentage of sperm with normal morphology were significantly lower in group I than in group II (P < 0.01). The proportion of good quality zygotes and good quality embryos were significantly lower in the male infertility group than in the tubal disease group (P < 0.05). Implantation rate and pregnancy rate were similar in two groups. It was concluded that spermatozoa is involved in the embryo quality, even in the early stages of development, which limited the treatment potency of IVF procedure.
Embryo Transfer ; Embryonic Development ; Fertilization in Vitro ; Infertility, Male ; Sperm Count ; Sperm Injections, Intracytoplasmic ; Sperm Motility/*physiology ; *Spermatozoa/cytology ; *Spermatozoa/physiology

To investigate the influences of sperm quality on the zygotes and embryos development,as the role of the paternal factor in early human embryogenesis is gaining more attention because of the application of techniques such as intracytoplasmic sperm injection (ICSI) for the treatment of men infertility, 136 infertility couples with men factors (Group Ⅰ ) were included from May 2002 to January 2004. One hundred and seventy two infertility couples with tube factors (Group Ⅱ ) served as controls. The sperm parameters, gemmates and embryos quality, implantation rate and pregnant rate in both groups were analyzed. It was found that there was no significant differences in the number of oocytes retrieved, the fertilization rate and number of embryos transferred between two groups. Sperm concentration, percentage of motile sperm and percentage of sperm with normal morphology were significantly lower in group Ⅰ than in group Ⅱ (P＜0.01). The proportion of good quality zygotes and good quality embryos were significantly lower in the male infertility group than in the tubal disease group (P＜0.05). Implantation rate and pregnancy rate were similar in two groups. It was concluded that spermatozoa is involved in the embryo quality, even in the early stages of development, which limited the treatment potency of IVF procedure.

TANK-binding kinase 1 (TBK1) is an important enzyme in the regulation of cellular antiviral effects. TBK1 regulates the activity of the interferon regulatory factors IRF3 and IRF7, thereby playing a key role in type I interferon (IFN) signaling pathways. The structure of TBK1 consists of an N-terminal kinase domain, a middle ubiquitin-like domain (ULD), and a C-terminal elongated helical domain. It has been reported that the ULD of TBK1 regulates kinase activity, playing an important role in signaling and mediating interactions with other molecules in the IFN pathway. In this study, we present the crystal structure of the ULD of human TBK1 and identify several conserved residues by multiple sequence alignment. We found that a hydrophobic patch in TBK1, containing residues Leu316, Ile353, and Val382, corresponding to the "Ile44 hydrophobic patch" observed in ubiquitin, was conserved in TBK1, IκB kinase epsilon (IKKɛ/IKKi), IκB kinase alpha (IKKα), and IκB kinase beta (IKKβ). In comparison with the structure of the IKKβ ULD domain of Xenopus laevis, we speculate that the Ile44 hydrophobic patch of TBK1 is present in an intramolecular binding surface between ULD and the C-terminal elongated helices. The varying surface charge distributions in the ULD domains of IKK and IKK-related kinases may be relevant to their specificity for specific partners.
Amino Acid Sequence ; Conserved Sequence ; Crystallography, X-Ray ; Humans ; Hydrophobic and Hydrophilic Interactions ; I-kappa B Kinase ; chemistry ; metabolism ; Isoleucine ; chemistry ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Multimerization ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases ; chemistry ; Sequence Alignment ; Static Electricity ; Ubiquitin ; chemistry

Amino Acid Motifs ; DEAD-box RNA Helicases ; chemistry ; Humans ; Protein Domains ; Structure-Activity Relationship

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.