iScience最新文献

In patients with polycystic ovary syndrome (PCOS), the concentration of homocysteine (Hcy) in follicular fluid is inversely correlated with oocyte and embryo quality. Nevertheless, other metabolic abnormalities associated with PCOS may also impact oocyte and early embryo quality. Therefore, it remains uncertain whether reproductive function is affected in patients without PCOS with hyperhomocysteinemia (HHcy). Here, we observed reduced fertility, increased ovarian atretic follicles, and reduced oocyte maturation rates in HHcy mice. Proteomic analyses revealed that HHcy causes mitochondrial dysfunction and reduced expression of zona pellucida proteins (ZP1, ZP2, and ZP3) in oocytes. Transmission electron microscopy confirmed abnormal formation of the zona pellucida and microvilli in oocytes from HHcy mice. Additionally, in vitro fertilization (IVF) demonstrated a reduction in the rate of 2-cell embryo formation in HHcy mice. These findings reveal that HHcy reduces female reproductive longevity by affecting follicular development and oocyte quality.

Group 2 innate lymphoid cells (ILC2s) are key players in type 2 immunity, but whether they can be directly activated by microbial ligands remain uncertain. In this study, we observed a positive correlation between blood endotoxin (LPS) levels and circulating ILC2s in allergic patients. In vitro, LPS robustly induced ILC2 proliferation and production of type 2 effector cytokines. RNA-seq revealed a type 2 immune-responsive profile in LPS-stimulated ILC2s. Notably, ILC2s lost their LPS-mediated growth and activation capacity when treated with TLR4 receptor antagonists and inhibitors of the NF-κB and JAK pathways, though this effect was not observed with IL-33 receptor blocking antibodies. Genetically, ILC2s from TLR4 knockout (KO) mice, but not from ST2 KO mice, were unresponsive to LPS. Collectively, these findings suggest a direct, non-canonical activation mechanism of ILC2s via the LPS-TLR4-NF-κB/JAK signaling axis.

The prophylactic implantation of biological mesh can effectively prevent the occurrence of stoma-site incisional hernia (SSIH) in patients undergoing stoma retraction. Therefore, our study prospectively established and validated a mixed model, which combined radiomics, stepwise regression, and deep learning for the prediction of SSIH in patients with temporary ileostomy. The mixed model showed good discrimination of the SSIH patients on all cohorts, which outperformed deep learning, radiomics, and clinical models alone (overall area under the curve [AUC]: 0.947 in the primary cohort, 0.876 in the external validation cohort 1, and 0.776 in the external validation cohort 2). Moreover, the sensitivity, specificity, and precision for predicting SSIH were improved in the mixed model. Thus, the mixed model can provide more information for SSIH precaution and clinical decision-making.

Why aggressive traits evolve in some species but not in others is poorly understood. We modeled the population dynamics of the extinct Mauritius dodo and Rodrigues solitaire to examine divergent pathways in the evolution of aggression. Whereas the dodo conformed to island syndrome predictions of tameness, its sister-taxon the solitaire evolved strong sexual dimorphism and aggressive traits. We computed rates of change in island size from sea level modeling and connected island size change to population dynamics by integrating a Hawk-Dove game theory model for territory competition with a population model. We find that the rapid rate of decrease in island size likely was an important trigger for the onset of aggressive behavior and that aggressive behavior becomes fixed if a tipping point is reached where island size falls below a critical threshold.

Physical/chemical crosslinking and surface-modifications of hydrogels have been extensively endorsed to enhance their biomaterial functionalities. The latter approaches involve using toxic crosslinkers or chemical modifications of the biopolymers, limiting the clinical translation of hydrogels beyond short-term promising results. The current study aims to tailor the polymer's structure to obtain customized applications using the same FDA-approved ingredients. PEGs of different molecular weights have been used to tune the van der Waal's forces, NaCl has been used to alter the electrostatic interactions of the charged polymers, and glycerol has been used to tweak the H-bonding. Same crosslinker-free sodium alginate/gelatin hydrogel formulation unfolds multiple properties: controlled-release, self-healing, mesh size, storage modulus, degradation rate. The hydrogels, lacking in one aspect, displayed superior performance in another. This study, including experiments and molecular simulations, illustrates that developing new materials may not always be necessary, as the same polymeric matrix can generate immense variations in different aspects.

Gene knockout disrupts cellular homeostasis, altering gene expression, and phenotypes. We investigated whether cells return to their pre-knockout transcriptomic state through adaptive evolution experiments on hap4Δ and ade1Δ yeast strains. Analysis revealed that genes with higher expression levels and more physical interaction partners in wild-type strains were more likely to be restored, suggesting that genes of significant functional importance have increased resilience to genetic perturbations. However, as the experiment progressed, most initially restored genes became unrestored. Over 60% of differentially expressed genes in knockout strains remained unrestored in evolved strains. Evolved strains exhibited distinct transcriptomic states, diverging from the original strain over time. Ribosome biogenesis components exhibited systematic sequential changes during the evolution. Our findings suggest the knockout strain transcriptomes struggle to return to the original state even after 28 days of culture. Instead, compensatory mechanisms lead to distinct suboptimal states, highlighting the complex transcriptomic dynamics following genetic perturbations.

HIV-1 reservoirs display a heterogeneous nature, lodging both intact and defective proviruses. To deepen our understanding of such heterogeneous HIV-1 reservoirs and their functional implications, we integrated basic concepts of graph theory to characterize the composition of HIV-1 reservoirs. Our analysis revealed noticeable topological properties in networks, featuring immunologic signatures enriched by genes harboring intact and defective proviruses, when comparing antiretroviral therapy (ART)-treated HIV-1-infected individuals and elite controllers. The key variable, the rich factor, played a pivotal role in classifying distinct topological properties in networks. The host gene expression strengthened the accuracy of classification between elite controllers and ART-treated patients. Markov chain modeling for the simulation of different graph networks demonstrated the presence of an intrinsic barrier between elite controllers and non-elite controllers. Overall, our work provides a prime example of leveraging genomic approaches alongside mathematical tools to unravel the complexities of HIV-1 reservoirs.