Exposure to prescribed medication in early life and impacts on gut microbiota and disease development.

The gut microbiota during early life plays a crucial role in infant development. This microbial-host interaction is also essential for metabolism, immunity, and overall human health in later life. Early-life pharmaceutical exposure, mainly referring to exposure during pregnancy, childbirth, and infancy, may change the structure and function of gut microbiota and affect later human health. In this Review, we describe how healthy gut microbiota is established in early life. We summarise the commonly prescribed medications during early life, including antibiotics, acid suppressant medications and other medications such as antidepressants, analgesics and steroid hormones, and discuss how these medication-induced changes in gut microbiota are involved in the pathological process of diseases, including infections, inflammatory bowel disease, metabolic diseases, allergic diseases and neurodevelopmental disorders. Finally, we review some critical methods such as dietary therapy, probiotics, prebiotics, faecal microbiota transplantation, genetically engineered phages, and vagus nerve stimulation in early life, aiming to provide a new strategy for the prevention of adverse health outcomes caused by prescribed medications exposure in early life.

Regulation of Miwi-mediated mRNA stabilization by Ck137956/Tssa is essential for male fertility.

BACKGROUND: Sperm is formed through spermiogenesis, a highly complex process involving chromatin condensation that results in cessation of transcription. mRNAs required for spermiogenesis are transcribed at earlier stages and translated in a delayed fashion during spermatid formation. However, it remains unknown that how these repressed mRNAs are stabilized. RESULTS: Here we report a Miwi-interacting testis-specific and spermiogenic arrest protein, Ck137956, which we rename Tssa. Deletion of Tssa led to male sterility and absence of sperm formation. The spermiogenesis arrested at the round spermatid stage and numerous spermiogenic mRNAs were down-regulated in Tssa-/- mice. Deletion of Tssa disrupted the localization of Miwi to chromatoid body, a specialized assembly of cytoplasmic messenger ribonucleoproteins (mRNPs) foci present in germ cells. We found that Tssa interacted with Miwi in repressed mRNPs and stabilized Miwi-interacting spermiogenesis-essential mRNAs. CONCLUSIONS: Our findings indicate that Tssa is indispensable in male fertility and has critical roles in post-transcriptional regulations by interacting with Miwi during spermiogenesis.

Online Teaching Self-efficacy of Group Counseling Instructors during the COVID-19 Pandemic.

Due to the COVID-19 pandemic, many counseling-related programs switched to online teaching modalities. Group counseling instructors may face various challenges in teaching group counseling courses online. With a mixed-method design, this study explored group counseling instructors' online teaching self-efficacy by collecting survey responses from 39 group counseling instructors and interviewing eight instructors from the programs accredited by the Council for Accreditation of Counseling and Related Educational Programs (CACREP). The instructors demonstrated a general high teaching self-efficacy with concerns about students' engagement. Facilitating and hindering factors related to online teaching self-efficacy are identified. Implications and recommendations for instructors, counseling-related programs, and the counseling profession are also discussed.

Proteomic Analysis of Dpy19l2-Deficient Human Globozoospermia Reveals Multiple Molecular Defects.

PURPOSE: To investigate the differences in protein expression between Dpy19l2-deficient human globozoospermia and normozoospermia. EXPERIMENTAL DESIGN: Human sperm samples from three globozoospermic donors with Dpy19l2 deletion and three normal controls are subjected to TMT quantitative technology. SPESP1, HIST1H4A, and LYZL1 are randomly selected for western blotting analysis. GO annotations are performed using the Database for Annotation, Visualization, and Integrated Discovery. RESULTS: A total of 2567 proteins are identified, of which 2510 proteins are quantified, and 491 are differentially expressed (fold-change > 2), with 370 upregulated and 121 downregulated in globozoospermic patients. The levels of several important proteins, including SPACA 1, IZUMO1, ZPBP1, and PLCZ1, are decreased in globozoospermic sperm. Bioinformatics analysis indicates the Dpy19l2-deficient sperm presented molecular defects in acrosome, chromatin, sperm-egg interaction, and fertilization. CONCLUSIONS AND CLINICAL RELEVANCE: The present study is the first to analyze total globozoospermia with Dpy19l2 deletion using high-throughput proteomics. This study may provide insights into the mechanism of globozoospermia.

RSBP15 interacts with and stabilizes dRSPH3 during sperm axoneme assembly in Drosophila.

Flagellum in sperm is composed of over 200 different proteins and is essential for sperm motility. In particular, defects in the assembly of the radial spoke in the flagellum result in male infertility due to loss of sperm motility. However, mechanisms regulating radial spoke assembly remain unclear in metazoans. Here, we identified a novel Drosophila protein radial spoke binding protein 15 (RSBP15) which plays an important role in regulating radial spoke assembly. Loss of RSBP15 results in complete lack of mature sperms in seminal vesicles (SVs), asynchronous individualization complex (IC) and defective "9 + 2" structure in flagella. RSBP15 is colocalized with dRSPH3 in sperm flagella, and interacts with dRSPH3 through its DD_R_PKA superfamily domain which is important for the stabilization of dRSPH3. Moreover, loss of dRSPH3, as well as dRSPH1, dRSPH4a and dRSPH9, showed similar phenotypes to rsbp15KO mutant. Together, our results suggest that RSBP15 acts in stabilizing the radial spoke protein complex to anchor and strengthen the radial spoke structures in sperm flagella.

Nuclear export signal-interacting protein forms complexes with lamin A/C-Nups to mediate the CRM1-independent nuclear export of large hepatitis delta antigen.

Nuclear export is an important process that not only regulates the functions of cellular factors but also facilitates the assembly of viral nucleoprotein complexes. Chromosome region maintenance 1 (CRM1) that mediates the transport of proteins bearing the classical leucine-rich nuclear export signal (NES) is the best-characterized nuclear export receptor. Recently, several CRM1-independent nuclear export pathways were also identified. The nuclear export of the large form of hepatitis delta antigen (HDAg-L), a nucleocapsid protein of hepatitis delta virus (HDV), which contains a CRM1-independent proline-rich NES, is mediated by the host NES-interacting protein (NESI). The mechanism of the NESI protein in mediating nuclear export is still unknown. In this study, NESI was characterized as a highly glycosylated membrane protein. It interacted and colocalized well in the nuclear envelope with lamin A/C and nucleoporins. Importantly, HDAg-L could be coimmunoprecipitated with lamin A/C and nucleoporins. In addition, binding of the cargo HDAg-L to the C terminus of NESI was detected for the wild-type protein but not for the nuclear export-defective HDAg-L carrying a P205A mutation [HDAg-L(P205A)]. Knockdown of lamin A/C effectively reduced the nuclear export of HDAg-L and the assembly of HDV. These data indicate that by forming complexes with lamin A/C and nucleoporins, NESI facilitates the CRM1-independent nuclear export of HDAg-L.