Zygotic Splicing Activation of the Transcriptome is a Crucial Aspect of Maternal-to-Zygotic Transition and Required for the Conversion from Totipotency to Pluripotency.

During maternal-to-zygotic transition (MZT) in the embryo, mRNA undergoes complex post-transcriptional regulatory processes. However, it is unclear whether and how alternative splicing plays a functional role in MZT. By analyzing transcriptome changes in mouse and human early embryos, dynamic changes in alternative splicing during MZT are observed and a previously unnoticed process of zygotic splicing activation (ZSA) following embryonic transcriptional activation is described. As the underlying mechanism of RNA splicing, splicing factors undergo dramatic maternal-to-zygotic conversion. This conversion relies on the key maternal factors BTG4 and PABPN1L and is zygotic-transcription-dependent. CDK11-dependent phosphorylation of the key splicing factor, SF3B1, and its aggregation with SRSF2 in the subnuclear domains of 2-cell embryos are prerequisites for ZSA. Isoforms generated by erroneous splicing, such as full-length Dppa4, hinder normal embryonic development. Moreover, alternative splicing regulates the conversion of early embryonic blastomeres from totipotency to pluripotency, thereby affecting embryonic lineage differentiation. ZSA is an essential post-transcriptional process of MZT and has physiological significance in generating new life. In addition to transcriptional activation, appropriate expression of transcript isoforms is also necessary for preimplantation embryonic development.

The RNA ligase RNA terminal phosphate cyclase B regulates mRNA alternative splicing and is required for mouse oocyte development and maintenance.

Recent large-scale mRNA sequencing has shown that introns are retained in 5-10% of mRNA, and these events are named intron retention (IR). IR has been recognized as a key mechanism in the regulation of gene expression. However, the role of this mechanism in female reproduction in mammals remains unclear. RNA terminal phosphate cyclase B (RTCB) is a RNA ligase; we found that RTCB conditional knockout mice have premature ovarian failure and that RTCB plays a crucial role in follicular development. RTCB regulated the splicing of transcripts related to DNA methylation and DNA damage repair. In addition, it regulated the resumption of oocyte meiosis by affecting CDK1 activation. Moreover, the loss of RTCB suppressed zygotic genome activation (ZGA) and decreased translation at the global level. In addition, Rtcb deletion resulted in the accumulation of maternal mRNAs containing unspliced introns and in a decline in the overall level of transcripts. As a result, the Rtcb-/- females were sterile. Our study highlights the important role of RTCB-regulated noncanonical alternative splicing in female reproduction.

Access to benzene-modified 2nd generation strigolactams and GR24 by merging C-H olefination with decarboxylative Giese cyclization.

Herein, we reported an efficient and general synthetic route to assemble benzene-modified 2nd generation strigolactams and GR24. The key features of this synthesis include a palladium-catalyzed ortho-selective olefination of the commercially available substituted N-Boc phenylalanine and a decarboxylative Giese radical cyclization. The bioactivities of these compounds to stimulate the seed germination of Orobanche aegyptiaca parasitic weed were also analysed. 2nd generation strigolactam 15f derived from para-OMe phenylalanine showed superior bioactivity to the original unsubstituted 15b.

Biomimetic Total Syntheses of Ergot Alkaloids via Decarboxylative Giese Coupling.

Biomimetic total syntheses of Festuclavine and Pyroclavine were achieved by a sequential radical coupling. The key steps include intramolecular decarboxylative Giese reaction to form the central C ring and 4-nitrobenzenesulfonyl (Ns)-directed indole C4-H olefination to introduce the indole C4 component. In addition, D-ring formation was completed by decarboxylative alkenylation and intramolecular SN2 reaction.

Equine infectious anemia virus in China.

Equine infectious anemia is an equine disease caused by equine infectious anemia virus, which was first reported in 1840. Equine infectious anemia virus research in China started in the 1960s, focusing on etiology, pathology, diagnosis, and immunology. Notably, in 1978 an attenuated vaccine was successfully developed for equine infectious anemia virus, effectively preventing equine infectious anemia virus in China. This article will review equine infectious anemia virus in China, including past and recent research, and commemorate scientists who have made great contributions to equine infectious anemia virus prevention.

Synthesis and Characterization of a Rosmarinic Acid Derivative that Targets Mitochondria and Protects against Radiation-Induced Damage In Vitro.

Mitochondrial dysfunction plays an important role in gamma-radiation-induced mediating oxidative stress. Scavenging radiation-induced reactive oxygen species (ROS) can help mitochondria to maintain their physiological function. Rosmarinic acid is a polyphenol antioxidant that can scavenge radiation-induced ROS, but the structure prevents it from accumulating in mitochondria. In this study, we designed and synthesized a novel rosmarinic acid derivative (Mito-RA) that could use the mitochondrial membrane potential to enter the organelle and scavenge ROS. The DCFH-DA assay revealed that Mito-RA was more effective than rosmarinic acid at scavenging ROS. DNA double-strand breaks, chromosomal aberration, micronucleus and comet assays demonstrated the ability of Mito-RA to protect against radiation-induced oxidative stress in vitro. These findings demonstrate the potential of Mito-RA as an antioxidant, which can penetrate mitochondria, scavenge ROS and protect cells against radiation-induced oxidative damage.

[Cross-sectional Study on the Relationship among Syndrome of TCM, BODE Index and Qulity of Life, in Patients with COPD at Stable Phase].

OBJECTIVE: To study the syndrome of traditional Chinese medicine (TCM) and relevant indexes of conventional Western medicine for patients with chronic obstructive pulmonary disease (COPD) at stable phase, and further explore the trend of change of the deficiency syndrome of TCM, and the correlation of each syndrome with the BODE index (body mass index, airflow obstruction, dyspnea, and exercise capacity index) and quality of life. METHODS: 300 cases with COPD which were in line with the standard were differentiated to 5 groups (60 cases for each group) by the symptoms. which were Lung Qi deficiency (Group A), Lung and Spleen Qi deficiency (Group B), Lung and Kidney Qi deficiency (Group C), Lung, Spleen and Kidney Qi deficiency (Group D), and deficiency of both Qi and Yin (Group E). Some basic details about the patients were recorded, such as body mass and height. Also BODE index and COPD assessment test were conducted. And then the differences of the indexes among groups, the relationship between the BODE index and the COPD assessment test (CAT) score were analyzed. RESULTS: Comparison in 5 groups, the body mass index (BMD and forced expiratory volume in 1 s to forced vital capacity ratio (FEV1%) of Group A was the highest, the 6-min walk distance (6MWD) of Group A was the longest, but the degree of dyspnea, BODE index and CAT score of patients in Group A were the lowest (P < 0.05) No statistical significance of above index and score between Group D and E was observed (P > 0.05). In Group D and E, the BMI and FEV1% was the lowest, 6MWD was the shortest, and the degree of dyspnea of patients was the highest (P < 0.05). A positive correlation between BODE index and CAT score observed (r = 0.883, P < 0.05). CONCLUSION: With the progress of COPD, disease from single viscera gradually accumulated to multiple viscera, from Group A --> Group B/Group C --> Group D, with the gradually increasing of BODE index and CAT score.