Obesity is increasingly recognized as a major factor contributing to female reproductive dysfunction and declining fertility. Excessive lipid accumulation and oxidative stress under obese conditions can disrupt mitochondrial homeostasis in oocytes, leading to impaired meiotic maturation, abnormal cytoskeletal organization, DNA damage, and reduced embryonic developmental competence. However, effective interventions targeting obesity-associated oocyte deterioration remain limited.

A recent study published in Protein & Cell by researchers from the Southern University of Science and Technology (SUSTech) provides critical structural and functional insights into the UBR4-KCMF1-Calmodulin (UKC) complex, revealing its pivotal role in protein quality control, cancer cell survival, and stress adaptation. The work, led by Professors Renhong Yan and Baotong Zhang, elucidates how this complex assembles and functions as an E4 ubiquitin ligase, extending ubiquitin chains on pre-tagged substrates to regulate protein degradation.

This work was funded by Key Research and Development Program, Ministry of Science and Technology of China (2022YFA1103103), National Natural Science Foundation of China (32488101, 32330030, 32370870, and 32170801), Fundamental Research Funds for the Central Universities (22120250336), and Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China (JYB2025XDXM508). The authors thank the Peak Disciplines (Type IV) of Institutions of Higher Learning in Shanghai, and the Frontier Science Research Center for Stem Cells, Ministry of Education for their support.; 4) Method of Research: experimental study; 5) Subject of Research: cell.

Neurons face an exceptional proteostasis challenge because their extreme polarization requires rapid proteome remodeling at distal axons and synapses. Rather than acting as separate systems, ribonucleoprotein granules and membranous organelles cooperate to form mobile translation platforms.

T-cell engagers (TCEs) are an emerging class of immunotherapeutics that have demonstrated considerable clinical efficacy across a range of tumor types. However, their clinical application remains constrained by the challenge of balancing antitumor activity with acceptable safety, which is particularly prominent in solid malignancies. Multiple strategies have been explored to address this trade-off, including molecular engineering, dosing regimens, and patient selection. Nonetheless, within molecular design efforts, activity and toxicity are still largely optimized in isolation.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a non-canonical neurotrophic factor broadly expressed throughout the brain. Previous work has shown that MANF modulates neuronal functions in various disease contexts; however, its cell-type-specific roles within the brain remain incompletely understood. Notably, clinical data link MANF deficiency to microcephaly in humans, yet traditional rodent models fail to replicate this pathology.