Multi-omic validation of the cuproptosis-sphingolipid metabolism network: modulating the immune landscape in osteosarcoma.

Background: The current understanding of the mechanisms by which metal ion metabolism promotes the progression and drug resistance of osteosarcoma remains incomplete. This study aims to elucidate the key roles and mechanisms of genes involved in cuproptosis-related sphingolipid metabolism (cuproptosis-SPGs) in regulating the immune landscape, tumor metastasis, and drug resistance in osteosarcoma cells. Methods: This study employed multi-omics approaches to assess the impact of cuproptosis-SPGs on the prognosis of osteosarcoma patients. Lasso regression analysis was utilized to construct a prognostic model, while multivariate regression analysis was applied to identify key core genes and generate risk coefficients for these genes, thereby calculating a risk score for each osteosarcoma patient. Patients were then stratified into high-risk and low-risk groups based on their risk scores. The ESTIMATE and CIBERSORT algorithms were used to analyze the level of immune cell infiltration within these risk groups to construct the immune landscape. Single-cell analysis was conducted to provide a more precise depiction of the expression patterns of cuproptosis-SPGs among immune cell subtypes. Finally, experiments on osteosarcoma cells were performed to validate the role of the cuproptosis-sphingolipid signaling network in regulating cell migration and apoptosis. Results: In this study, seven cuproptosis-SPGs were identified and used to construct a prognostic model for osteosarcoma patients. In addition to predicting survival, the model also demonstrated reliability in forecasting the response to chemotherapy drugs. The results showed that a high cuproptosis-sphingolipid metabolism score was closely associated with reduced CD8 T cell infiltration and indicated poor prognosis in osteosarcoma patients. Cellular functional assays revealed that cuproptosis-SPGs regulated the LC3B/ERK signaling pathway, thereby triggering cell death and impairing migration capabilities in osteosarcoma cells. Conclusion: The impact of cuproptosis-related sphingolipid metabolism on the survival and migration of osteosarcoma cells, as well as on CD8 T cell infiltration, highlights the potential of targeting copper ion metabolism as a promising strategy for osteosarcoma patients.

Heterogeneous Network Switching Strategy Based on Communication Blind Area Dwell Time.

The limitation of indoor visible light coverage and the attenuation of its signal when propagating in line-of-sight has seriously affected the stable communication of receiving devices when users move randomly and also aggravated the power consumption of visible light networking systems. According to the above situation, on the basis of the heterogeneous networking of visible light communication (VLC) and RF communication integration, this article proposes a horizontal-vertical collaborative handover strategy based on the communication blind area dwell time (CBD-HVHO). Combining asymmetrically clipped optical orthogonal frequency division multiplexing (ACO-OFDM) technology with networking handover technology, ACO-OFDM is used to determine the indoor communication blind area by calculating the bit error rate (BER) value at the signal receiver while reducing the multipath interference generated by visible light signals during channel transmission. To achieve this, set the communication blind channel interruption time as the threshold time, compare the communication blind area dwell time with the threshold time, and finally combine the horizontal and vertical collaborative handover strategies based on the communication blind area dwell time. The simulation results show that the handover probability is 0.009, the average number of handovers is 1.006, and the average network throughput is 195.2826 Mbps. Compared with the previously proposed immediate vertical handover (I-VHO) scheme and the dwell vertical handover (D-VHO) scheme, the communication stability is significantly improved, and the power consumption of the network system is reduced to a certain extent.

PBS3: a versatile player in and beyond salicylic acid biosynthesis in Arabidopsis.

AVRPPHB SUSCEPTIBLE 3 (PBS3) belongs to the GH3 family of acyl acid amido synthetases, which conjugates amino acids to diverse acyl acid substrates. Recent studies demonstrate that PBS3 in Arabidopsis plays a key role in the biosynthesis of plant defense hormone salicylic acid (SA) by catalyzing the conjugation of glutamate to isochorismate to form isochorismate-9-glutamate, which is then used to produce SA through spontaneous decay or ENHANCED PSEUDOMONAS SUSCEPTIBILITY (EPS1) catalysis. Consistent with its function as an essential enzyme for SA biosynthesis, PBS3 is well known to be a positive regulator of plant immunity in Arabidopsis. Additionally, PBS3 is also involved in the trade-off between abiotic and biotic stress responses in Arabidopsis by suppressing the inhibitory effect of abscisic acid on SA-mediated plant immunity. Besides stress responses, PBS3 also plays a role in plant development. Under long-day conditions, PBS3 influences Arabidopsis flowering time by regulating the expression of flowering regulators FLOWERING LOCUS C and FLOWERING LOCUS T. Taken together, PBS3 functions in the signaling network of plant development and responses to biotic and/or abiotic stresses, but the molecular mechanisms underlying its diverse roles remain obscure.