Identification of immunogenic cell death-related signature on prognosis and immunotherapy in kidney renal clear cell carcinoma

BackgroundImmunogenic cell death (ICD) is considered a particular cell death modality of regulated cell death (RCD) and plays a significant role in various cancers. The connection between kidney renal clear cell carcinoma (KIRC) and ICD remains to be thoroughly explored.MethodsWe conducted a variety of bioinformatics analyses using R software, including cluster analysis, prognostic analysis, enrichment analysis and immune infiltration analysis. In addition, we performed Quantitative Real-time PCR to evaluate RNA levels of specific ICD genes. The proliferation was measured through Cell Counting Kit-8 (CCK-8) assay and colony-formation assay in RCC cell lines. ResultsWe determined two ICD subtypes through consensus clustering analysis. The two subtypes showed significantly different clinical outcomes, genomic alterations and tumor immune microenvironment. Moreover, we constructed the ICD prognostic signature based on TF, FOXP3, LY96, SLC7A11, HSP90AA1, UCN, IFNB1 and TLR3 and calculated the risk score for each patient. Kaplan-Meier survival analysis and ROC curve demonstrated that patients in the high-risk group had significantly poorer prognosis compared with the low-risk group. We then validated the signature through external cohort and further evaluated the relation between the signature and clinical features, tumor immune microenvironment and immunotherapy response. Given its critical role in ICD, we conducted further analysis on LY96. Our results indicated that downregulation of LY96 inhibited the proliferation ability of RCC cells.ConclusionsOur research revealed the underlying function of ICD in KIRC and screened out a potential biomarker, which provided a novel insight into individualized immunotherapy in KIRC

Tailoring the electrocaloric effect of Pb0.78Ba0.2La0.02ZrO3 relaxor thin film by GaN substrates

The electrocaloric (EC) effect in ferroelectric/antiferroelectric thin films has been widely investigated due to its potential applications in solid state cooling devices. It is demonstrated that the EC effect of the Pb0.78Ba0.2La0.02ZrO3 (PBLZ) relaxor thin films prepared by using a sol–gel method strongly depends on the substrates. The maximum ΔT of PBLZ thin films deposited on Pt(111)/TiOx/SiO2/Si(100) (Pt), LaNiO3/Pt(111)/TiOx/SiO2/Si(100) (LaNiO3/Pt), LaNiO3/n-type GaN (LaNiO3/n-GaN) and LaNiO3/p-type GaN (LaNiO3/p-GaN) substrates is ∼13.08 K, 16.46 K, 18.70 K, and 14.64 K, respectively. Moreover, negative EC effects in a broad temperature range (∼340 K to 440 K) could be obtained in the thin films deposited on LaNiO3/n-GaN and LaNiO3/p-GaN substrates, which is ascribed to higher proportions of orthorhombic antiferroelectric phase to rhombohedral ferroelectric phase induced by the GaN substrates. These results indicate that tailoring the EC effects by changing the substrates could provide a new strategy in designing an EC cooling device with high cooling efficiency

Managers as the bridge: how cultural friction influences the integration of cross-border mergers and acquisitions

Despite the abundant research on the effect of cross-border mergers and acquisitions (M&As), very few studies examined the effect of M&As on acquirers’ corporate social responsibility (CSR), especially in the context of emerging economies. We used data of Chinese listed enterprises and the difference-in-differences (DID) approach to examine the effect of cross-border M&As on the CSR of Chinese acquirers. The results show that cross-border M&As have a positive and significant impact on Chinese acquirers’ CSR as well as four detailed dimensions of CSR (Corporate Governance, Employee Relations, Environment Protection, and Product). In addition, we use two indicators, the number of dialects and the proportion of the population using dialects in a particular region, to measure the regional cultural diversity. The results show that the positive relationship between overseas M&As and CSR is strengthened by higher cultural diversity in the region. Moreover, the positive effect of the aforementioned four dimensions of CSR is also stronger when the cultural diversity is more substantial

Cumulative Risk and Subjective Well-Being Among Rural-to-Urban Migrant Adolescents in China: Differential Moderating Roles of Stress Mindset and Resilience

Migrant adolescents are exposed to a variety of risk factors that threaten their well-being. However, previous studies have often focused on one or several factors separately, ignoring the cumulative effect of risks. The current study adopted the cumulative risk (CR) model and examined the deleterious effect of CR on the three indices of subjective well-being (SWB) among early migrant adolescents in China. We further explored the moderating role of resilience and stress mindset on the above associations. A sample of 234 early migrant adolescents (45.7% girls) completed self-reported questionnaires in two waves (2016-2017), and the mean age of valid participants was 11.49 years (SD = 1.16) at T1. The multiple regression results indicated that CR negatively predicted adolescents&#39; life satisfaction one year later. Moreover, high resilience and a more stress-is-enhancing mindset buffered the deleterious effect of CR on the emotional components of SWB. Specifically, the negative effect of CR on positive affect was reduced as resilience increased, whereas the adverse effect of CR on negative affect was attenuated by holding a more stress-is-enhancing mindset. The present findings suggest that CR is a useful predictor for multiple risk factors to which migrant adolescents are exposed and that it has a robust effect on later SWB. These findings also contribute to a better understanding of the moderating roles of resilience and stress mindset to aid future intervention programs.</p

Pre-Archaeological Investigation by Integrating Unmanned Aerial Vehicle Aeromagnetic Surveys and Soil Analyses

Magnetic surveys have been widely used in archaeological field investigations. However, conventional survey methods are often restricted by complicated field conditions and ambiguities in data interpretation. In this study, a novel magnetic survey system was designed for pre-archaeological investigation (preliminary survey prior to the archaeological excavation) based on a modified quadrotor unmanned aerial vehicle (UAV) and was successfully applied to an archaeological area with a complex landform in Huizhou, China. Results show that the target anomaly identified by UAV aeromagnetic survey corresponds well to the location of a potential archaeological site. Subsequent soil analyses further confirm the archaeological value of UAV aeromagnetic results and provide strong constraints on the interpretation of target anomalies. This study demonstrates that the newly proposed UAV aeromagnetic system can adapt to the various field conditions with the advantages of flexibility and efficiency, which has great potential for future archaeological investigations

Diversity and redundancy of the ripening regulatory networks revealed by the fruitENCODE and the new CRISPR/Cas9 CNR and NOR mutants

Tomato is considered as the genetic model for climacteric fruits, in which three major players control the fruit ripening process: ethylene, ripening transcription factors, and DNA methylation. The fruitENCODE project has now shown that there are multiple transcriptional circuits regulating fruit ripening in different species, and H3K27me3, instead of DNA methylation, plays a conserved role in restricting these ripening pathways. In addition, the function of the core tomato ripening transcription factors is now being questioned. We have employed CRISPR/Cas9 genome editing to mutate the SBP-CNR and NAC-NOR transcription factors, both of which are considered as master regulators in the current tomato ripening model. These plants only displayed delayed or partial non-ripening phenotypes, distinct from the original mutant plants, which categorically failed to ripen, suggesting that they might be gain-of-function mutants. Besides increased DNA methylation genome-wide, the original mutants also have hyper-H3K27me3 in ripening gene loci such as ACS2, RIN, and TDR4. It is most likely that multiple genetic and epigenetic factors have contributed to their strong non-ripening phenotypes. Hence, we propose that the field should move beyond these linear and two-dimensional models and embrace the fact that important biological processes such as ripening are often regulated by highly redundant network with inputs from multiple levels

Nuanxinkang (NXK) ameliorates Piezo1-mediated pyroptosis post-myocardial infarction

Aim of the study: This study aims to identify the effects of Nuanxinkang (NXK) on inflammation and pyroptosis post-MI and understand the underlying mechanisms. Materials and methods: Left Anterior Descending (LAD) coronary artery ligation was used to induce MI in mice. NXK or Captopril were orally administered 3 days after surgery for 4 weeks. Cardiac function, as well as infarct size, was detected by echocardiography, 2,3,5-triphenyl-tetrazolium chloride (TTC) staining and Hematoxylin and Eosin (H&E) staining. Inflammatory mediators were measured by flow cytometry, real-time polymerase chain reaction (RT-PCR) and immunofluorescence (IF). Pyroptosis-related protein expressions were determined through Western blot (WB). Intracellular Ca2+ measurements were conducted in bone marrow derived macrophages (BMDM) to detect calcium influx. Molecular docking (MD) was applied to define the candidate ingredients in NXK that regulate Piezo1. Results: NXK increased the ratio of heart or lung and body weight in mice post-MI. TTC and H&E staining infarct size and myocardial damage. The results obtained through echocardiography suggest that NXK remarkably enhanced heart function. Immunofluorescence of F4/80 and flow cytometry results demonstrated that NXK suppressed inflammatory infiltration. Molecular docking showed that Piezo1 had correlation with NXK. Intracellular Ca2+ measurements suggest that NXK inhibit Yoda1-evoked Piezo1 activation. Furthermore, NXK treatment significantly suppressed Piezo1-mediated pyroptosis in vivo and in vitro. Conclusions: The present study indicates that NXK may prevent ventricular remodeling post-MI through regulation of the Piezo1-mediated pyroptosis. Furthermore, the study provides a potential strategy for attenuating NLRP3-inflmmasome activation in the context of ventricular remodeling post-MI using NXK