CUSABIO May Citations Review: 260 High-Impact Citations, Cumulative Impact Factor Exceeds 1200+!

This study reveals that during the endoplasmic reticulum stress response, IRE1α protein forms a membrane phase-separated cluster dynamically connected to stress granules (SGs), a process crucial for the efficient unfolding of protein responses and cell survival mechanisms. The cytoplasmic region of IRE1α contains a disordered domain that is essential for its aggregation with SGs and the splicing function of XBP1 mRNA. Disrupting SG assembly inhibits the formation and function of IRE1α aggregates, indicating that the IRE1α-SG complex plays a key role in enhancing the cell's ability to cope with endoplasmic reticulum stress.

This research uncovers a direct molecular link between self-incompatibility and interspecific incompatibility in the Brassicaceae family. The study finds that the self-incompatibility gene SLR1 plays a pivotal role in recognizing and preventing fertilization by heterospecific pollen, interacting with the S-locus receptor kinase (SRK) and affecting SRK dimerization, thereby activating a common pollen rejection pathway. This discovery suggests that the SLR1-SRK system is critical in distinguishing between self- and cross-pollination as well as pollen from different species, aiding in the understanding of how plant reproductive systems promote speciation.

The study finds that regular exercise during early life stages can persistently enhance the inhibitory effect of male mice on inflammatory responses in adulthood, alleviate lipopolysaccharide-induced sepsis, and promote recovery. Exercise increases the production of pyrrolidine in the liver, affecting the immunometabolic epigenetics, especially by increasing the H3K4me3 modification of the Crym gene (an enzyme catalyzing pyrrolidine production), thereby exerting its long-term immune regulatory benefits. Pyrrolidine reduces inflammatory cytokines by inhibiting the mTORC1 signaling pathway, mitigating inflammatory damage in the liver and lungs. These findings reveal the mechanism by which early exercise confers long-term benefits on immune health, emphasizing the potential role of lifestyle interventions in preventing inflammation and infection.

By studying the enteroendocrine cells (EECs) of the fruit fly gut, this research discovers that they can directly sense amino acids in food and regulate food intake by releasing neuropeptides. Specifically, neuropeptide F (NPF) in EECs can suppress food intake, while L-glutamate acts on EECs through the metabotropic glutamate receptor (mGluR), slowing calcium oscillations and reducing NPF secretion. Additionally, two dopaminergic gut neurons express NPFR to receive EEC-derived NPF and transmit an anorexigenic signal to the brain. These findings reveal how EECs assess food quality and recognize a conserved appetite regulation mechanism.

This study systematically reveals the cellular and molecular characteristics of human ovarian aging through single-cell RNA sequencing and spatial transcriptomics, identifying the spatiotemporal molecular characteristics of ovarian cell types, age-related changes in gene expression (especially the role of DNA damage response pathways in oocyte aging), three subtypes of granulosa cells and five subtypes of stromal cells, as well as their transcriptomic changes during the aging process. FOXP1 is identified as a regulator of ovarian aging, declining with age and inhibiting CDKN1A transcription. Silencing FOXP1 leads to premature ovarian failure in mice. These findings provide a comprehensive insight into the spatiotemporal heterogeneity of human ovarian aging, aiding in the identification of potential diagnostic biomarkers and therapeutic strategies.

The study finds that the ALDH2 rs671 variant (G>A), although associated with increased amyloid-β (Aβ) deposition and Aβ40/42 ratio in Alzheimer's disease (AD) patients, is not an independent risk factor for AD. Reduced ALDH2 activity leads to the accumulation of 4-hydroxy-2-nonenal (4-HNE), affecting the Lys53 residue of C99, promoting the generation of Aβ40 in the Golgi apparatus. Furthermore, decreased ALDH2 activity is also associated with reduced secretion of inflammatory factors, impaired Aβ clearance, and weakened diffusion. Thus, the ALDH2 rs671 variant plays a key role in regulating the generation of Aβ40 or Aβ42.

By analyzing the transcriptomes of different organs in young and middle-aged mice, this article finds that the ovaries exhibit age-related gene expression earlier than other organs and reveals the key role of CD38 in ovarian aging. The study finds that increased CD38 leads to a decline in NAD+ levels, accelerating ovarian aging. Moreover, inhibition of CD38 can enhance the fertility of middle-aged mice. These results provide clues for understanding the mechanisms of ovarian aging and offer potential therapeutic targets for treating related female infertility.

This article primarily investigates how Plet1 expressed by alveolar macrophages drives the repair of lung epithelial cells after viral pneumonia. Through methods such as single-cell transcriptomics, complex lung organ models, in vivo homotypic cell transfer, and BMDM-specific gene targeting, the study finds that transitional ("regenerative") BMDMs and TR-AM highly express Plet1. It is discovered that Plet1 is released from alveolar macrophages and acts as an important mediator during lung repair, inducing the proliferation and re-sealing of the barrier by lung epithelial cells. Early administration of recombinant Plet1 during the disease can alleviate viral lung damage and save mice from otherwise fatal diseases, highlighting its therapeutic potential.

The study reveals a new mechanism by which c-di-GMP (cyclic di-guanosine monophosphate), acting as a second messenger, promotes biofilm formation in mycobacteria by binding to the nucleoid-associated protein Lsr2 and regulating the expression of the lipid synthesis gene hadD. Elevated levels of c-di-GMP enhance the binding of Lsr2 to the hadD promoter, increasing the synthesis of keto-mycolic acid, which in turn facilitates biofilm construction. This finding expands our understanding of the role of the c-di-GMP signaling pathway in mycobacterial biofilm formation and provides a new target for the development of anti-tuberculosis drugs.

This study develops a method for delivering self-amplifying RNA (saRNA) and mRNA to adipose-derived stem cells (ASCs) using lipid nanoparticles (LNPs) to enhance their protein secretion capacity and promote wound healing in diabetes. By optimizing the lipid structure, researchers find that a LNP named DIM1T can effectively deliver mRNA and saRNA, and co-delivery of saRNA with E3 mRNA complex (SEC) can overcome the translational inhibition caused by saRNA and prolong protein expression. In a diabetic mouse model, SEC-ASCs significantly accelerate wound healing, indicating that this LNP platform offers a promising strategy for the genetic engineering of ASCs for the treatment of diabetic ulcers and other diseases.