Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury

Background: Allograft lung ischemia-reperfusion injury (ALIRI) is a major cause of early primary graft dysfunction and poor long-term survival after lung transplantation (LTx); however, its pathogenesis has not been fully elucidated. Cell death is a mechanism underlying ALIRI. Cuproptosis is a recently discovered form of programmed cell death. To date, no studies have been conducted on the mechanisms by which cuproptosis-related genes (CRGs) regulate ALIRI. Therefore, we explored the potential biomarkers related to cuproptosis to provide new insights into the treatment of ALIRI.Materials and methods: Datasets containing pre- and post-LTx lung biopsy samples and CRGs were obtained from the GEO database and previous studies. We identified differentially expressed CRGs (DE-CRGs) and performed functional analyses. Biomarker genes were selected using three machine learning algorithms. The ROC curve and logistic regression model (LRM) of these biomarkers were constructed. CIBERSORT was used to calculate the number of infiltrating immune cells pre- and post-LTx, and the correlation between these biomarkers and immune cells was analyzed. A competing endogenous RNA network was constructed using these biomarkers. Finally, the biomarkers were verified in a validation set and a rat LTx model using qRT-PCR and Western blotting.Results: Fifteen DE-CRGs were identified. GO analysis revealed that DE-CRGs were significantly enriched in the mitochondrial acetyl-CoA biosynthetic process from pyruvate, protein lipoylation, the tricarboxylic acid (TCA) cycle, and copper-transporting ATPase activity. KEGG enrichment analysis showed that the DE-CRGs were mainly enriched in metabolic pathways, carbon metabolism, and the TCA cycle. NFE2L2, NLRP3, LIPT1, and MTF1 were identified as potential biomarker genes. The AUC of the ROC curve for each biomarker was greater than 0.8, and the LRM provided an excellent classifier with an AUC of 0.96. These biomarkers were validated in another dataset and a rat LTx model, which exhibited good performance. In the CIBERSORT analysis, differentially expressed immune cells were identified, and the biomarkers were associated with the immune cells.Conclusion:NFE2L2, NLRP3, LIPT1, and MTF1 may serve as predictors of cuproptosis and play an important role in the pathogenesis of cuproptosis in ALIRI

Dual‐Defect Manipulation Enables Efficient and Spectrally Stable Blue Perovskite Light‐Emitting Diodes

Performance of blue solution‐processed perovskite light‐emitting diodes (LEDs) is limited by availability of blue perovskite materials. Herein, 4‐(trifluoromethyl)benzoyl ammonium bromide (4‐TMBABr) is used with abundant N H and C O groups to passivate the defects and produce highly stable PEAxPA2‐x(CsPbBr3)n‐1PbBr4 perovskites for blue LED applications. The N H group in the 4‐TMBABr suppresses the Br‐ion mismatch through hydrogen bonds (N‐H···Br) and C O group coordinates the unsaturated lead dangling bonds (C O:Pb). The effective defect passivation by 4‐TMBABr reduces the nonradiative recombination in the perovskite films, hence enhancing its optical performance. In the LED structure, the sodium bis(trifluoromethanesulfonyl)imide (SBTI) modified NiOx films are used to improve the hole transport and to inhibit the fluorescence quenching of the perovskite layer. The dual‐defect manipulation strategy is advantageous for producing efficient and spectrally stable blue perovskite LEDs, and the authors demonstrate an LED with maximum luminance of 1094 cd m−2 and external quantum efficiency of 10.3%. This work can inform and underpin future development of blue perovskite LEDs with highly efficient and stabile performance

Tuberous Sclerosis Complex With Multiple Organ Tumors: Case Report and Literature Review

Pancreatic neuroendocrine neoplasms (PNEN) are tumors that originate from neuroendocrine cells. Only about 1% patients are related to mutation of tuberous sclerosis complex gene. Here, we reported a rare case with involvement of multiple organs and space-occupying lesions. Initially, the patient was thought to have metastasis of a pancreatic tumor. However, the patient was diagnosed as pancreatic neuroendocrine tumors, liver perivascular epithelioid tumors, splenic hamartoma, and renal angiomyolipoma by pathological examination after surgery. We performed genetic mutation detection to identify that tuberous sclerosis complex 2 gene presented with a heterozygous variant. Tuberous sclerosis often presents with widespread tumors, but it is less common to present with pancreatic neuroendocrine tumors and liver perivascular tumors as highlighted in the case. So we analyzed the relationship between TSC gene mutations and related tumors. And we also reviewed the current molecular mechanisms and treatments for tuberous sclerosis complex

Response of Nitrogen Losses to Excessive Nitrogen Fertilizer Application in Intensive Greenhouse Vegetable Production

Excessive nitrogen fertilizer application in greenhouse vegetable production (GVP) is of scientific and public concern because of its significance to international environmental sustainability. We conducted a meta-analysis using 1174 paired observations from 69 publications on the effects of nitrogen fertilizer application and reducing nitrogen fertilizer application on the nitrogen losses on a broad scale. We found that the increase in nitrogen loss is much higher than that in production gain caused by excessive application of nitrogen fertilizer: nitrate leaching (+187.5%), ammonium leaching (+28.1%), total nitrogen leaching (+217.0%), nitrous oxide emission (+202.0%), ammonia emission (+176.4%), nitric oxide emission (+543.3%), yield (+35.7%) and nitrogen uptake (+24.5%). Environmental variables respond nonlinearly to nitrogen fertilizer application, with severe nitrate leaching and nitrous oxide emission when the application rate exceeds 570 kg N/ha and 733 kg/N, respectively. The effect of nitrogen fertilizer on yield growth decreases when the application rate exceeds 302 kg N/ha. Appropriate reduction in nitrogen fertilizer application rate substantially mitigates the environmental cost, for example, decreasing nitrate leaching (−32.4%), ammonium leaching (−6.5%), total nitrogen leaching (−37.3%), ammonia emission (−28.4%), nitrous oxide emission (−38.6%) and nitric oxide emission (−8.0%), while it has no significant effect on the nitrogen uptake and yield