Machine learning-based integration develops an immunogenic cell death-derived lncRNA signature for predicting prognosis and immunotherapy response in lung adenocarcinoma.

Accumulating evidence demonstrates that lncRNAs are involved in the regulation of the immune microenvironment and early tumor development. Immunogenic cell death occurs mainly through the release or increase of tumor-associated antigen and tumor-specific antigen, exposing "danger signals" to stimulate the body's immune response. Given the recent development of immunotherapy in lung adenocarcinoma, we explored the role of tumor immunogenic cell death-related lncRNAs in lung adenocarcinoma for prognosis and immunotherapy benefit, which has never been uncovered yet. Based on the lung adenocarcinoma cohorts from the TCGA database and GEO database, the study developed the immunogenic cell death index signature by several machine learning algorithms and then validated the signature for prognosis and immunotherapy benefit of lung adenocarcinoma patients, which had a more stable performance compared with published signatures in predicting the prognosis, and demonstrated predictive value for benefiting from immunotherapy in multiple cohorts of multiple cancers, and also guided the utilization of chemotherapy drugs.

Deciphering the heterogeneity dominated by tumor-associated macrophages for survival prognostication and prediction of immunotherapy response in lung adenocarcinoma.

Tumor-associated macrophages (TAMs) are a specific subset of macrophages that reside inside the tumor microenvironment. The dynamic interplay between TAMs and tumor cells plays a crucial role in the treatment response and prognosis of lung adenocarcinoma (LUAD). The study aimed to examine the association between TAMs and LUAD to advance the development of targeted strategies and immunotherapeutic approaches for treating this type of lung cancer. The study employed single-cell mRNA sequencing data to characterize the immune cell composition of LUAD and delineate distinct subpopulations of TAMs. The "BayesPrism" and "Seurat" R packages were employed to examine the association between these subgroups and immunotherapy and clinical features to identify novel immunotherapy biomarkers. Furthermore, a predictive signature was generated to forecast patient prognosis by examining the gene expression profile of immunotherapy-associated TAMs subsets and using 104 machine-learning techniques. A comprehensive investigation has shown the existence of a hitherto unidentified subgroup of TAMs known as RGS1 + TAMs, which has been found to have a strong correlation with the efficacy of immunotherapy and the occurrence of tumor metastasis in LUAD patients. CD83 was identified CD83 as a distinct biomarker for the expression of RGS1 + TAMs, showcasing its potential utility as an indicator for immunotherapeutic interventions. Furthermore, the prognostic capacity of the RTMscore signature, encompassing three specific mRNA (NR4A2, MMP14, and NPC2), demonstrated enhanced robustness when contrasted against the comprehensive collection of 104 features outlined in the published study. CD83 has potential as an immunotherapeutic biomarker. Meanwhile, The RTMscore signature established in the present study might be beneficial for survival prognostication.

ScCBF1 plays a stronger role in cold, salt and drought tolerance than StCBF1 in potato (Solanum tuberosum).

Solanum tuberosum (St) and Solanum commersonii (Sc) are two potato varieties with different freezing tolerance. Among them, St is a freezing-sensitive variety and. Sc is a cold-resistant wild potato. CBF/DREB family members mainly function in response to freezing stress. In order to explore the different roles of St C-Repeat Binding Factor1 (StCBF1) and Sc C-Repeat Binding Factor1 (ScCBF1) in potato plants (Solanum tuberosum) under stress conditions, two kinds of potato lines were obtained with ScCBF1 and StCBF1 overexpressing respectively. Phenotypes analysis showed that both overexpressing ScCBF1 and StCBF1 caused smaller leaves, and reduced tuber yield. While the limited phenotypes of StCBF1 lines were more severe than that of ScCBF lines. After freezing treatment, StCBF1 over expression plants grown better than WT plants and worse than ScCBF1 over expression plants. Specifically, compared with wild-type lines, overexpressing ScCBF1 could up-regulate fatty acid desaturase genes, key enzyme of Calvin cycle genes, and antioxidant enzyme genes. Both ScCBF1 and StCBF1 lines showed higher PSII activity, thus maintaining a higher photosynthetic rate under cold stress. In addition, we also found that overexpression ScCBF1 and StCBF1 could also enhance the drought and salt tolerance in potato. In summary, ScCBF1 plays a stronger role in cold, salt, and drought tolerance than StCBF1 in potato (Solanum tuberosum).

Functional Characterization of Peptide Transporters in Bovine Mammary Epithelial Cells.

The objective of this study was to characterize the expression profile, transport kinetics, and regulation of peptide transporters in bovine mammary epithelial cells (BMECs). Quantitative reverse-transcription real-time PCR, Western blotting, and immunofluorescence staining were used to investigate the expression of peptide transporters in bovine mammary tissues. The effects of time, pH, concentration, and specific inhibitors on ß-alanyl-l-lysyl- Nε-7-amino-4-methyl-coumarin-3-acetic acid (ß-Ala-Lys-AMCA) uptake in BMECs were also studied. The results showed that the peptide transporters PepT2 and PhT1 are both expressed in bovine mammary glands. The optimal pH for the uptake of ß-Ala-Lys-AMCA in BMECs was 6.5. The transport-kinetics study suggested that the uptake of ß-Ala-Lys-AMCA in BMECs is saturable over the tested concentration, with a Km value of 82 ± 18 µM and a Vmax of 124 ± 11 pmol/min per milligram of protein. Other dipeptides, including Gly-Sar, Met-Gly, and Met-Met, competitively inhibited ß-Ala-Lys-AMCA uptake in BMECs. However, histidine had no effect on ß-Ala-Lys-AMCA uptake. Furthermore, knocking down PepT2 could significantly reduce ß-Ala-Lys-AMCA uptake, but PhT1 interference had no effect on peptide uptake in BMECs. The inhibition of PI3K and Akt decreased the uptake of ß-Ala-Lys-AMCA. The above results revealed functional characteristics of peptide transporters and demonstrated that PepT2 may play a major role in ß-Ala-Lys-AMCA uptake in BMECs. Moreover, the PI3K-Akt signaling pathway may regulate the uptake of ß-Ala-Lys-AMCA in BMECs.

Methionine Partially Replaced by Methionyl-Methionine Dipeptide Improves Reproductive Performance over Methionine Alone in Methionine-Deficient Mice.

Decreased protein breakdown in pregnant women results in lower concentration of methionine (Met) in plasma, causing pregnancy-related metabolic disturbance. Its dipeptide methionyl-methionine (Met-Met) may exert positive influence in fetal development. This study mainly investigated whether Met-Met can be used as part of free Met to promote reproductive outcomes in mice and the underlying mechanisms. Met-deficient pregnant mice were treated with Met alone or with Met-Met during pregnancy. Daily intraperitoneal injection of 35% dietary Met in pregnant mice was the best dose among the 15⁻45% doses. Embryo development and newborn birth weight were enhanced when 25% of the Met in the 35% Met group was replaced with Met-Met. Met-Met replacement had higher plasma insulin, glucose, and free amino acids (AA) concentrations. Besides, in the placenta, the AA transporter mRNA abundances and peptide transporters (PhT1 and PepT1) protein levels were higher in Met-Met treatment group. Moreover, Met-Met increased 4E-BP1, S6K1 and AKT/mTOR phosphorylation. These results suggest that Met-Met could be used as a partial source of Met to promote reproductive outcomes in Met-restricted pregnant mice, which might be mediated by promoting nutrient availability and activating AKT/mTOR-mediated signaling pathway.

Stag3 regulates microtubule stability to maintain euploidy during mouse oocyte meiotic maturation.

Stag3, a meiosis-specific subunit of cohesin complex, has been demonstrated to function in both male and female reproductive systems in mammals. However, its roles during oocyte meiotic maturation have not been fully defined. In the present study, we report that Stag3 uniquely accumulates on the spindle apparatus and colocalizes with microtubule fibers during mouse oocyte meiotic maturation. Depletion of Stag3 by gene-targeting morpholino disrupts normal spindle assembly and chromosome alignment in oocytes. We also find that depletion of Stag3 reduces the acetylated level of tubulin and microtubule resistance to microtubule depolymerizing drug, suggesting that Stag3 is required for microtubule stability. Consistent with these observations, kinetochore-microtubule attachment, an important mechanism controlling chromosome alignment, is severely impaired in Stag3-depleted oocytes, resultantly causing the significantly increased incidence of aneuploid eggs. Collectively, our data reveal that Stag3 is a novel regulator of microtubule dynamics to ensure euploidy during moue oocyte meiotic maturation.