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PURPOSE Bladder urothelial carcinoma (BLCA), the most common urinary tract malignancy, has a high recurrence rate and poor survival at late stages. Necroptosis, a form of programmed cell death, is involved in cancer development and progression, but its function in BLCA prognosis remains unclear. This study sought to investigate the role of necroptosis in the development and prognosis of BLCA. METHODS Clinical information and RNA expression matrix data were obtained from the databases. Survival analysis was performed to obtain survival- and necroptosis-related genes and identify any that overlapped. Consensus clustering analysis was used to create different subgroups by combining the overlapping gene expression matrix and clinical information. The tumor immune microenvironment and immune status of the different subgroups were determined using ESTIMATE, MCPcounter, and ssGSEA analysis. We performed differential analysis on the gene expression matrix of molecular subpopulations to find and screen out differentially expressed genes (DEGs). GO, KEGG, GSVA, and GSEA analyses were used to elucidate the underlying mechanisms of the DEGs. Lasso Cox regression analysis was used to build a prognostic risk model and perform a pan-cancer analysis of the screened genes. The results were used to define potential roles for these genes in other cancers and assess the efficacy of the risk model. RESULTS Cluster analysis identified two subgroups, C1 and C2, with significantly different survival rates. ESTIMATE, MCPcounter, and ssGSEA analyses showed that high immune scores, tumor purity, and immune status were associated with poorer prognoses. GO and KEGG functional enrichment analyses indicated that DEGs were mainly focused on tumor proliferation, invasion, and immunity and GSEA analysis suggested that necroptosis may affect Toll-like receptor signaling pathways, MAPK cascade regulation of leukocyte trafficking, and cytokine-cytokine receptor interaction pathways. Lasso Cox regression analysis was used to model the prognostic risk while screening for representative necroptosis-associated genes, ANXA1, ATAD3A, and TRPC6, with high potential for survival prediction in BLCA patients. The pan-cancer analysis indicated that the three representative genes were also differentially expressed in other cancer types. CONCLUSION Expression of necroptosis-related genes such as ANXA1, ATAD3A, and TRPC6 correlate with the immune microenvironment of BLCA patients and have the potential for use in disease prognostics.

The precise control of cardiomyocyte viability is imperative to combat myocardial ischemia-reperfusion injury (I/R), in which apoptosis and pyroptosis putatively contribute to the process. Recent researches indicated that GSDMD is involved in I/R as an executive protein of pyroptosis. However, its effect on other forms of cell death is unclear. We identified that GSDMD and GSDMD-N levels were significantly upregulated in the I/R myocardium of mice. Knockout of GSDMD conferred the resistance of the hearts to reperfusion injury in the acute phase of I/R but aggravated reperfusion injury in the chronic phase of I/R. Mechanistically, GSDMD deficiency induced the activation of PARylation and the consumption of NAD+ and ATP, leading to cardiomyocyte apoptosis. Moreover, PJ34, a putative PARP-1 inhibitor, reduced the myocardial injury caused by GSDMD deficiency. Our results reveal a novel action modality of GSDMD in the regulation of cardiomyocyte death; inhibition of GSDMD activates PARylation, suggesting the multidirectional role of GSDMD in I/R and providing a new theory for clinical treatment.

Objective: To investigate the genetic characteristics and transcriptional regulation of the SCN5A gene of Brugada syndrome (BrS) patients in China.Methods: Using PubMed, Medline, China National Knowledge Internet (CNKI), and Wanfang Database, Chinese patients with BrS who underwent SCN5A gene testing were studied.Results: A total of 27 suitable studies involving Chinese BrS patients who underwent the SCN5A gene test were included. A total of 55 SCN5A gene mutations/variations were reported in Chinese BrS patients, including 10 from southern China and 45 from northern China. Mutations/variations of BrS patients from southern China mostly occurred in the regions of the α-subunit of Nav1.5, including DIII (Domain III), DIV, DIII-DIV, C-terminus regions, and the 3'UTR region. Furthermore, we analyzed the post-transcriptional modifications (PTMs) throughout the Nav1.5 protein encoded by SCN5A and found that the PTM changes happened in 72.7% of BrS patients from southern China and 26.7% from northern China.Conclusions: SCN5A mutations/variations of BrS patients in southern China mostly occurred in the DIII-DIV to C-terminus region and the 3'-UTR region of the SCN5A gene, different from northern China. PTM changes were consistent with the mutation/variation distribution of SCN5A, which might be involved in the regulation of the pathogenesis of BrS patients.

Loganin is an iridoid glycoside extracted from Cornus officinalis, which is a traditional oriental medicine, and many biological properties of loganin have been reported. Nevertheless, it is not clear whether loganin has therapeutic effect on cardiovascular diseases. Hence, the aim of the present study was to investigate the effect of loganin on Ang II–induced cardiac hypertrophy. In the present study, we reported for the first time that loganin inhibits Ang II–provoked cardiac hypertrophy and cardiac damages in H9C2 cells and in mice. Furthermore, loganin can achieve cardioprotective effects through attenuating cardiac fibrosis, decreasing pro-inflammatory cytokine secretion, and suppressing the phosphorylation of critical proteins such as JAK2, STAT3, p65, and IκBα. Besides, the outstanding findings of the present study were to prove that loganin has no significant toxicity or side effects on normal cells and organs. Based on these results, we conclude that loganin mitigates Ang II–induced cardiac hypertrophy at least partially through inhibiting the JAK2/STAT3 and NF-κB signaling pathways. Accordingly, the natural product, loganin, might be a novel effective agent for the treatment of cardiac hypertrophy and heart failure.

Supplemental material, sj-docx-1-cnr-10.1177_10547738211051881 for Factors Associated With Informational Support in Transitional Care for Older Adults With Chronic Diseases: A Cross-Sectional Study by Gui-Ling Geng, Wen-Wen Yang, Xiao-Liu Shi, Jia-Ning Hua, Min Cui, Cheng-Feng-Yi Yang, Zi-Han Geng and Xiang-Yun Qian in Clinical Nursing Research

Supplemental material, sj-docx-2-cnr-10.1177_10547738211051881 for Factors Associated With Informational Support in Transitional Care for Older Adults With Chronic Diseases: A Cross-Sectional Study by Gui-Ling Geng, Wen-Wen Yang, Xiao-Liu Shi, Jia-Ning Hua, Min Cui, Cheng-Feng-Yi Yang, Zi-Han Geng and Xiang-Yun Qian in Clinical Nursing Research

Hirota et al. [6] found that the magneto-Archimedes force could be used to levitate biological materials at different heights in pressurized oxygen, providing the possibility to separate them. However the magnetic levitation of mineral particles has not been widely explored. With this in mind some preliminary experiments were performed by levitating pure mineral materials in a paramagnetic solution manganese (II) chloride. Besides the report of levitation heights of various mineral particles in manganese (II) chloride solution, the lines obtained from the basic formula provided by previous researchers were compared with experimental data. The act of cryogenic paramagnetic fluid in the magneto-Archimedes levitation was also demonstrated. The obtained results are compared with the same particle levitation heights in manganese (II) chloride solution.

This paper describes the horizontal deflection behaviour of the streams of particles in paramagnetic fluids under a high-gradient superconducting magnetic field, which is the continued work on the exploration of particle magneto-Archimedes levitation. Based on the previous work on the horizontal deflection of a single particle, a glass box and collector had been designed to observe the movement of particle group in paramagnetic fluids. To get the exact separation efficiency, the method of "sink-float" involved the high density fluid polytungstate (dense medium separation) and MLA (Mineral Liberation Analyser) was performed. It was found that the particles were deflected and settled at certain positions on the container floor due to the combined forces of gravity and magneto-Archimedes forces as well as a lateral buoyancy (displacement) force. Mineral particles with different densities and susceptibilities could be deflected to different positions, thus producing groups of similar types of particles. The work described here, although in its infancy, could form the basis of new approach of separating particles based on a combination of susceptibility and density.

This paper describes the horizontal deflection behaviour of a single particle in paramagnetic fluids under a high-gradient superconducting magnetic field. A glass box was designed to carry out experiments and test assumptions. It was found that the particles were deflected away from the magnet bore centre and particles with different density and/or susceptibility settled at a certain position on the container floor due to the combined forces of gravity and magneto-Archimedes as well as lateral buoyant (displacement) force. Matlab was chosen to simulate the movement of the particle in the magnetic fluid, the simulation results were in good accordance with experimental data. The results presented here, though, are still very much in their infancy, which could potentially form the basis of a new approach to separating materials based on a combination of density and susceptibility. Graphical abstract: [Figure not available: see fulltext.]