Immunogenic cell death (ICD) genes predict immunotherapy response and therapeutic targets in acute myeloid leukemia (AML).

Introduction: Numerous studies have demonstrated acute myeloid leukemia (AML) is one of the malignancies with high mortality worldwide. Immunogenic cell death (ICD) is a form of cell death that is specialised in that it triggers the body's immune response, particularly the adaptive immune response. Recent evidence has confirmed that pseudogenes are implicated in multiple human tumorigenesis and progression although lacking the function of coding protein. However, the roles of ICD-associated genes in AML remain largely unascertained. Methods: TCGA-AML and GSE71014 cohorts were picked out and we combined them into a merged dataset by removing the batch effect using the sva package in the R project. A consensus clustering analysis of the ICD genes in AML was performed to define subgroups. Based on the expression of 15 prognostic-related pseudogenes, we developed a prognostic model and categorized AML samples into low and high-risk groups. Results: AML was differentiated into two subgroups (C1 and C2 clusters). Most ICD-related genes were significantly up-regulated in the C2 cluster. The single sample gene set enrichment analysis (ssGSEA) revealed that the immune cell infiltration and immune checkpoint gene expression of the C2 cluster was strongly high, suggesting that the C2 population responded well to immune checkpoint blockade (ICB) therapy and had better survival. The C1 group was sensitive to chemotherapy, including Cytarabine, Midostaurin, and Doxorubicin. On the other hand, 15 ICD-related pseudogenes were identified to be associated with AML prognosis. The receiver operator curve (ROC) analysis and nomogram manifested that our prognostic model had high accuracy in predicting survival. However, the high-risk group was sensitive to ICB therapy and chemotherapy such as Methotrexate, Cytarabine, and Axitinib while the low-risk group benefited from 5-Fluorouracil, Talazoparib, and Navitoclax therapy. Discussion: In summary, we defined two subgroups relying on 33 ICD-related genes and this classification exerted a decisive role in assessing immunotherapy and chemotherapy benefit. Significantly, a prognostic signature identified by critical ICD-related pseudogene was created. The pseudogene prognostic signature had a powerful performance in predicting prognosis and therapeutic efficacy, including immunotherapy and chemotherapy to AML. Our research points out novel implications of ICD in cancer prognosis and treatment approach choice.

Catalytic Growth of High-Performance Graphite-like Carbon Films on a Nitrided Substrate: Experimental Study and First-Principles Calculations.

This study reports a novel process for the fabrication of high-performance graphite-like carbon (GLC) films on nitrided substrates through successive steps in a plasma nitriding system. Unlike films fabricated via conventional dual treatments (nitriding + film deposition), here-fabricated GLC films were grown on the surface of nitrided steel via a catalytic reaction. A transition zone having a nanocrystalline and amorphous structure was observed at the interface between the nitrided substrate and GLC films, which increased the durability of GLC films because this structure enhanced the adhesion of GLC films on the nitrided substrate, improving resistance to spallation and wear. Experimental study and first-principles calculations showed that the Fe3N phase had a stronger catalytic effect on GLC films than the Fe4N phase, and GLC films grown on the nitrided layer dominated by Fe3N were thicker with stronger adhesion and excellent frictional and wear properties compared with GLC films grown on the nitrided layer dominated by Fe4N because of the beneficial structure formed at the interface. This study reports a simple and inexpensive method to fabricate a dual layer containing high-performance GLC films via a catalytic growth and interface matching mechanism.

Gold-Catalyzed Cascade Reaction of 2-Alkynyl Aryl Azides with Enecarbamates for Direct Synthesis of α-(3-Indolyl)ketones.

α-(3-Indolyl)ketones are essential building blocks for the generation of biologically active molecules. We described a new method for the direct assembly of α-(3-indolyl)ketones through the cascade reaction of 2-alkynyl aryl azides with enecarbamates, in which the in situ generated α-imino gold carbene intermediate was trapped by enecarbamate to achieve umpolung reactivity of indole at the 3-position.

Access to 3-Sulfonamidoquinolines by Gold-Catalyzed Cyclization of 1-(2'-Azidoaryl)propargylsulfonamides through 1,2-N Migration.

We describe a gold-catalyzed cyclization of 1-(2'-azidoaryl)propargylsulfonamides for the synthesis of 3-sulfonamidoquinolines, featuring a rare and highly selective 1,2-N migration. The key α-imino gold carbene intermediate is generated through an intramolecular nucleophilic attack of the azide group to the Au-activated triple bonds in a 6-endo-dig manner.

[Color Doppler and contrast-enhanced ultrasonography for assessment of vascular perfusion in porcine liver allografts with acute graft rejection].

OBJECTIVE: To investigate the feasibility of evaluating hepatic blood perfusion after liver transplantation using color Doppler and contrast-enhanced ultrasonography and the diagnostic value of hepatic blood perfusion for acute graft rejection. METHOD: In this before-after study with quantitative analysis, contrast-enhanced sonography was performed with simultaneous liver function monitoring in porcine models of allograft liver transplantation before and after the operation. RESULTS: In pigs with acute graft rejection, the AUC decreased significantly after transplantation as compared with that of non-rejection transplant group (F=11.069, P=0.011), but the parameters including A, Alpha, C, t(0), DPI, or TTP showed no significant differences between the two groups. CONCLUSIONS: Pulse-inversion contrast harmonic imaging combined with acoustic quantitative technology can be an efficient means for evaluating blood perfusion in the liver allograft, and the TIC obtained using this method possesses high values for quantitative evaluation of liver allograft rejection.

[Treatment of distal radius fracture by combination of external fixator and volar approach fixation].

OBJECTIVE: To investigate the operative indication and clinical efficacy of combination of external fixator and volar approach fixation in treating distal radius fracture. METHODS: From March 2000 to March 2005, 28 patients with distal radius fracture were treated with combination of external fixator and volar approach fixation. Dorsal external fixator was used to maintain wrist in functional position, combinated volar plate or Kirschner wire fixation after reduction was achieved. Bone graft was necessary if there were severe comminuted cortical bone or compress of cancellous bone. Of 28 patients, there were 21 males and 7 females, aging from 18-54 years with a median age of 41 years. The locations were the left side in 4 cases and the right side in 24 cases. According to typing criterion for AO, 18 cases were classified as C2 and 10 cases as C3. One case was accompanied with dislocation of lunate bone. RESULTS: Among 28 patients, 24 were followed up for an average of 8.5 months. The anatomical relationship of their wrist joint were re-established and retained. Overall good to excellent results were achieved in 87%, excellent in 16 cases, good in 5 cases and fair in 3 cases. CONCLUSION: A combination of external fixator and volar approach fixation is an effective method of treating fractures of the distal radius, because distal radius fracture is unstable or difficult to close reduction. Volar fixation can avoid operative complication, and external fixator can obtain satisfactory reduction and function.

[Protective effect of donator liver ischemic preconditioning on posttransplant liver graft function in Chinese miniature pigs].

OBJECTIVE: To investigate the protective effect of the ischemia preconditioning of the donor liver on posttransplant liver graft function in Chinese miniature pigs. METHODS: Twenty-five partially inbred Chinese miniature pigs were randomized into three groups, namely the normal control group, the ischemia-reperfusion group and ischemic preconditioning group. Biopsies of the liver graft were performed to analyze HSP70 expression by means of immunoblotting, and the changes of serum AST/ALT levels were assayed using an automated biochemical analyzer. Histopathological assessment was carried out to identify the hepatocyte injury using optical and transmission electron microscopy. RESULTS: Ischemia preconditioning resulted in a notable increase in HSP70 expression and milder injury of the hepatocyte microstructure, whereas ischemia-reperfusion caused a significant increase of serum transaminases level (P<0.01) with declined HSP70 expression and obvious microstructural changes of the liver tissue. CONCLUSION: Ischemic preconditioning can produce obvious protective effects on the donor liver, and positively regulates the expression of shock protein.