A novel glycolysis-related gene signature for predicting the prognosis of multiple myeloma

Background: Metabolic reprogramming is an important hallmark of cancer. Glycolysis provides the conditions on which multiple myeloma (MM) thrives. Due to MM’s great heterogeneity and incurability, risk assessment and treatment choices are still difficult.Method: We constructed a glycolysis-related prognostic model by Least absolute shrinkage and selection operator (LASSO) Cox regression analysis. It was validated in two independent external cohorts, cell lines, and our clinical specimens. The model was also explored for its biological properties, immune microenvironment, and therapeutic response including immunotherapy. Finally, multiple metrics were combined to construct a nomogram to assist in personalized prediction of survival outcomes.Results: A wide range of variants and heterogeneous expression profiles of glycolysis-related genes were observed in MM. The prognostic model behaved well in differentiating between populations with various prognoses and proved to be an independent prognostic factor. This prognostic signature closely coordinated with multiple malignant features such as high-risk clinical features, immune dysfunction, stem cell-like features, cancer-related pathways, which was associated with the survival outcomes of MM. In terms of treatment, the high-risk group showed resistance to conventional drugs such as bortezomib, doxorubicin and immunotherapy. The joint scores generated by the nomogram showed higher clinical benefit than other clinical indicators. The in vitro experiments with cell lines and clinical subjects further provided convincing evidence for our study.Conclusion: We developed and validated the utility of the MM glycolysis-related prognostic model, which provides a new direction for prognosis assessment, treatment options for MM patients

Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma

Background: Cuproptosis is a newly identified unique copper-triggered modality of mitochondrial cell death, distinct from known death mechanisms such as necroptosis, pyroptosis, and ferroptosis. Multiple myeloma (MM) is a hematologic neoplasm characterized by the malignant proliferation of plasma cells. In the development of MM, almost all patients undergo a relatively benign course from monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM), which further progresses to active myeloma. However, the prognostic value of cuproptosis in MM remains unknown.Method: In this study, we systematically investigated the genetic variants, expression patterns, and prognostic value of cuproptosis-related genes (CRGs) in MM. CRG scores derived from the prognostic model were used to perform the risk stratification of MM patients. We then explored their differences in clinical characteristics and immune patterns and assessed their value in prognosis prediction and treatment response. Nomograms were also developed to improve predictive accuracy and clinical applicability. Finally, we collected MM cell lines and patient samples to validate marker gene expression by quantitative real-time PCR (qRT-PCR).Results: The evolution from MGUS and SMM to MM was also accompanied by differences in the CRG expression profile. Then, a well-performing cuproptosis-related risk model was developed to predict prognosis in MM and was validated in two external cohorts. The high-risk group exhibited higher clinical risk indicators. Cox regression analyses showed that the model was an independent prognostic predictor in MM. Patients in the high-risk group had significantly lower survival rates than those in the low-risk group (p < 0.001). Meanwhile, CRG scores were significantly correlated with immune infiltration, stemness index and immunotherapy sensitivity. We further revealed the close association between CRG scores and mitochondrial metabolism. Subsequently, the prediction nomogram showed good predictive power and calibration. Finally, the prognostic CRGs were further validated by qRT-PCR in vitro.Conclusion: CRGs were closely related to the immune pattern and self-renewal biology of cancer cells in MM. This prognostic model provided a new perspective for the risk stratification and treatment response prediction of MM patients

Study on Residual Stress and Optimization of Welding Parameters in Linear Friction Welding of TC17 Titanium Alloy

Linear friction welding (LFW) is a kind of advanced manufacturing technology and used mainly in the manufacturing of aircraft engine bladed disks (blisks) currently. However, the residual stress evolution of TC17 titanium alloy during LFW is complex and its distribution is difficult to characterize. In this study, the residual stress of welding was studied using numerical simulation and experimental methods. The results showed that the maximum temperature on the welded surface was up to 1000 °C and the cooling rates in the lengthwise, widthwise, and normal direction with the same distance from the center of the weld were 456 °C/s, 448 °C/s, and 232 °C/s, respectively. The lengthwise stress on the welding surface was the largest, followed by the widthwise stress and normal stress. Among the three factors affecting welding stress, the upsetting force played a leading role, followed by the vibration amplitude and frequency of the welded parts. By optimizing the process parameters: upsetting force 18.2 kN, vibration amplitude 2.5 mm, vibration frequency 40 Hz, a 30% decrease of the maximum residual stress could be achieved compared to that without optimization. The residual stress before and after welding parameter optimization was measured by the contour method, and the measured results were in good agreement with the simulation results, which verified the effectiveness of parameter optimization on residual stress controlling

How to generate popular post headlines on social media?

Posts, as important containers of user-generated-content on social media, are of tremendous social influence and commercial value. As an integral component of post, headline has decisive influence on post’s popularity. However, the current mainstream method for headline generation is still manually writing, which is unstable and requires extensive human effort. This drives us to explore a novel research question: Can we automate the generation of popular headlines on social media? We collect more than 1 million posts of 42,447 thousand celebrities from public data of Xiaohongshu, which is a well-known social media platform in China. We then conduct careful observations on the headlines of these posts. Observation results demonstrate that trends and personal styles are widespread in headlines on social medias and have significant contribution to posts’ popularity. Motivated by these insights, we present MEBART, which combines Multiple preference-Extractors with Bidirectional and Auto-Regressive Transformers (BART), capturing trends and personal styles to generate popular headlines on social medias. We perform extensive experiments on real-world datasets and achieve SOTA performance compared with advanced baselines. In addition, ablation and case studies demonstrate that MEBART advances in capturing trends and personal styles

Image1_Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma.JPEG

Background: Cuproptosis is a newly identified unique copper-triggered modality of mitochondrial cell death, distinct from known death mechanisms such as necroptosis, pyroptosis, and ferroptosis. Multiple myeloma (MM) is a hematologic neoplasm characterized by the malignant proliferation of plasma cells. In the development of MM, almost all patients undergo a relatively benign course from monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM), which further progresses to active myeloma. However, the prognostic value of cuproptosis in MM remains unknown.Method: In this study, we systematically investigated the genetic variants, expression patterns, and prognostic value of cuproptosis-related genes (CRGs) in MM. CRG scores derived from the prognostic model were used to perform the risk stratification of MM patients. We then explored their differences in clinical characteristics and immune patterns and assessed their value in prognosis prediction and treatment response. Nomograms were also developed to improve predictive accuracy and clinical applicability. Finally, we collected MM cell lines and patient samples to validate marker gene expression by quantitative real-time PCR (qRT-PCR).Results: The evolution from MGUS and SMM to MM was also accompanied by differences in the CRG expression profile. Then, a well-performing cuproptosis-related risk model was developed to predict prognosis in MM and was validated in two external cohorts. The high-risk group exhibited higher clinical risk indicators. Cox regression analyses showed that the model was an independent prognostic predictor in MM. Patients in the high-risk group had significantly lower survival rates than those in the low-risk group (p Conclusion: CRGs were closely related to the immune pattern and self-renewal biology of cancer cells in MM. This prognostic model provided a new perspective for the risk stratification and treatment response prediction of MM patients.</p

Sport, Nationalism and the Building of the Modern Chinese Nation State (1912–49)

This article will examine the relationship between sport, Chinese nationalism and the building of the Republic. It will highlight the role of sport in constructing the modern Chinese nation state in a historical and political context. The Republic of China Era (1912–49) saw the transformation of the modern Chinese nation state from its infancy to maturity. Sport played an important part in this process of change, supporting and facilitating the rise of a Republic from the ashes of the Qing Empire. During this period, sport contributed to the shaping of national conscious among the Chinese people and greatly consolidated the unity of the newly established nation state. It became an essential part of Chinese nationalists, politicians and educationalists’strategy to achieve national salvation and revival