N6-methyladenosine demethyltransferase FTO mediated m6A modification of estrogen receptor alpha in non-small cell lung cancer tumorigenesis.

Fat mass and obesity-associated protein (FTO), which is closely linked with obesity and dietary intake, plays an important role in diet-related metabolic diseases. However, the underlying mechanism of the N6-methyladenosine (m6A) demethyltransferase FTO in tumor development and progression remains largely unexplored. Here, we demonstrated that FTO expression was largely lower in non-small cell lung cancer (NSCLC) samples than in adjacent healthy tissues, and its expression negatively correlated with poor prognosis. Gain- and loss-of-function assays revealed that FTO inhibited NSCLC tumor cell growth and metastasis in vitro and in vivo. Mechanistically, estrogen receptor alpha (ESR1) is a target of FTO, and increased FTO expression significantly impaired the m6A levels of ESR1 mRNA. There were two clear m6A modification sites (5247A and 5409A) in the 3' untranslated region (3'UTR) of ESR1, and FTO could decrease their methylation. Moreover, the m6A readers YTHDF1 and IGF2BP3 recognized and bound the m6A sites in ESR1 mRNA, thereby enhancing its stability and facilitating tumor growth. We also showed that ESR1 has good diagnostic value for NSCLC. In conclusion, we uncovered an important mechanism of epitranscriptomic regulation by the FTO-YTHDF1-IGF2BP3-ESR1 axis and identified the potential of m6A-dependent therapeutic strategies for NSCLC.

Zwitterion Dual-Modification Strategy for High-Quality NiOx and Perovskite Films for Solar Cells.

Nickel oxide (NiOx ) has been limited in use as a hole transport layer for its low conduction, surface defects, and redox reactions with the perovskite layer. To address these issues, the incorporation of zwitterion L-tryptophan (Trp) is proposed at the NiOx /Trp interface. The carboxyl group of Trp effectively passivates the surface positive defects of NiOx , thereby improving its optical and electrical properties. The ammonium group of Trp not only passivates negative defects but modulates the growth of the perovskite layer, resulting in an improved perovskite film quality. Furthermore, the Trp layer acts as a buffer layer, suppressing adverse interfacial reactions between the perovskite and NiOx . Consequently, perovskite solar cells with 1.56 and 1.68 eV absorbers achieve the champion power conversion efficiency (PCE) of 23.79% and 20.41%, respectively. Moreover, the unencapsulated devices demonstrate excellent long-term stability, retaining above 80% of the initial PCE value after 1600 h of storage in the air with a humidity of 50-60%.

Liquid biopsy in lung cancer.

Lung cancer is a highly prevalent malignancy worldwide and the primary cause of mortality. The absence of systematic and standardized diagnostic approaches for identifying potential pulmonary nodules, early-stage cancers, and indeterminate tumors has led clinicians to consider tissue biopsy and pathological sections as the preferred method for clinical diagnosis, often regarded as the gold standard. The conventional tissue biopsy is an invasive procedure that does not adequately capture the diverse characteristics and evolving nature of tumors. Recently, the concept of 'liquid biopsy' has gained considerable attention as a promising solution. Liquid biopsy is a non-invasive approach that facilitates repeated analysis, enabling real-time monitoring of tumor recurrence, metastasis, and response to treatment. Currently, liquid biopsy includes circulating tumor cells, circulating cell-free DNA, circulating tumor DNA, circulating cell-free RNA, extracellular vesicles, and other proteins and metabolites. With rapid progress in molecular technology, liquid biopsy has emerged as a highly promising and intriguing approach, yielding compelling results. This article critically examines the significant role and potential clinical implications of liquid biopsy in the diagnosis, treatment, and prognosis of lung cancer.

Enhanced Quasi-Fermi Level Splitting of Perovskite Solar Cells by Universal Dual-Functional Polymer.

Perovskite solar cells (PSCs) have attracted extensive attention due to their higher power conversion efficiency (PCE) and simple fabrication process. However, the open-circuit voltage (VOC) loss remains a significant impediment to enhance device performance. Here, a facile strategy to boost the VOC to 95.5% of the Shockley-Queisser (S-Q) limit through the introduction of a universal multifunctional polymer additive is demonstrated. This additive effectively passivates the cation and anion defects simultaneously, thereby leading to the transformation from the strong n-type to weak n-type of perovskite films. Benefitting from the energy level alignment and the suppression of bulk non-radiative recombination, the quasi-Fermi level splitting (QFLS) is enhanced.  Consequently, the champion devices with 1.59 eV-based perovskite reach the highest VOC value of 1.24 V and a PCE of 23.86%. Furthermore, this strategy boosts the VOC by at least 0.07 V across five different perovskite systems, a PCE of 25.04% is achieved for 1.57 eV-based PSCs, and the corresponding module (14 cm2) also obtained a high PCE of 21.95%. This work provides an effective and universal strategy to promote the VOC approach to the detailed balance theoretical limit.

Differences in serum cytokine levels distinguish between clinically noninvasive lung adenocarcinoma and invasive lung adenocarcinoma: A cross-sectional study.

Background: Lung cancer incidence and mortality remain high and are now the leading cause of cancer-related death. Lung adenocarcinoma (LUAD) is one of the main histological subtypes of lung cancer. Previous studies have shown the role of inflammation in the development of lung cancer, but the relationship between cytokines and LUAD is still unclear. To further differentiate and explore the association of cytokines with the risk of non-invasive and invasive LUAD, we studied and assessed serum cytokine levels in patients with two types of LUAD. Methods: A cohort study of 90 non-invasive LUAD and 90 invasive LUAD was retrospectively included, and the clinical characteristics were recorded in detail. The differences in the levels of 12 serum cytokines (IFN-α, IFN-γ, IL-10, IL-12P70, IL-17A, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, and TNF-α) between the two groups of patients with LUAD were analyzed and evaluated. And we evaluated the clinical value of cytokine differential diagnosis of invasive LUAD based on receiver operating characteristics (ROC) curves. Results: The mean age of the patients was 56.6 years, and the proportions of males and females were 38.9% and 61.1%, respectively. IFN-α, IL-1ß, IL-2, IL-6, TNF-α, IL-4, and IL-8 were significantly increased in patients with invasive LUAD compared with the non-invasive LUAD group. Further research found that smoking is an important factor, with changes in the four cytokines IL-1ß, IL-6, IL-8, and TNF-α being significantly higher in the smoking group of patients with invasive LUAD. It can be seen from the area under the curve that IL-1ß and IL-2 have a significant differential diagnosis. Conclusions: We observed differences in preoperative serum cytokine levels between patients with invasive and non-invasive LUAD, which may serve as potential serum biomarkers for clinical differential diagnosis and disease progression assessment.

Polymerization Strategies to Construct a 3D Polymer Passivation Network toward High Performance Perovskite Solar Cells.

The spontaneously formed uncoordinated Pb2+ defects usually make the perovskite films demonstrate strong n-type with relatively lower carrier diffusion length and serious non-radiative recombination energy loss. In this work, we adopt different polymerization strategies to construct three-dimensional passivation frameworks in the perovskite layer. Thanks to the strong C≡N⋅⋅⋅Pb coordination bonding and the penetrating passivation structure, the defect state density is obviously reduced, accompanied by a significant increase in the carrier diffusion length. Additionally, the reduction of iodine vacancies also changed the Fermi level of the perovskite layer from strong n-type to weak n-type, which substantially promotes the energy level alignment and carrier injection efficiency. As a result, the optimized device achieved an efficiency exceeded 24 % (the certified efficiency is 24.16 %) with a high open-circuit voltage of 1.194 V, and the corresponding module achieved an efficiency of 21.55 %.

A Multifunctional Polymer as an Interfacial Layer for Efficient and Stable Perovskite Solar Cells.

Metal-cation defects and halogen-anion defects in perovskite films are critical to the efficiency and stability of perovskite solar cells (PSCs). In this work, a random polymer, poly(methyl methacrylate-co-acrylamide) (PMMA-AM), was synthesized to serve as an interfacial passivation layer for synergistically passivating the under-coordinated Pb2+ and anchor the I- of the [PbI6 ]4- octahedron. Additionally, the interfacial PMMA-AM passivation layer cannot be destroyed during the hole transport layer deposition because of its low solubility in chlorobenzene. This passivation leads to an enhancement in the open-circuit voltage from 1.12 to 1.22 V and improved stability in solar cell devices, with the device maintaining 95 % of the initial power conversion efficiency (PCE) over 1000 h of maximum power point tracking. Additionally, a large-area solar cell module was fabricated using this approach, achieving a PCE of 20.64 %.

Bivalirudin plus a high-dose infusion versus heparin monotherapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomised trial.

BACKGROUND: Previous randomised trials of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) have reported conflicting results, in part because of treatment with different pharmacological regimens. We designed a large-scale trial examining bivalirudin with a post-PCI high-dose infusion compared with heparin alone, the regimens that previous studies have shown to have the best balance of safety and efficacy. METHODS: BRIGHT-4 was an investigator-initiated, open-label, randomised controlled trial conducted at 87 clinical centres in 63 cities in China. Patients with STEMI undergoing primary PCI with radial artery access within 48 h of symptom onset who had not received previous fibrinolytic therapy, anticoagulants, or glycoprotein IIb/IIIa inhibitors were randomly assigned (1:1) to receive bivalirudin with a post-PCI high-dose infusion for 2-4 h or unfractionated heparin monotherapy. There was no masking. Glycoprotein IIb/IIIa inhibitor use was reserved for procedural thrombotic complications in both groups. The primary endpoint was a composite of all-cause mortality or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days. This trial is registered with ClinicalTrials.gov (NCT03822975), and is ongoing. FINDINGS: Between Feb 14, 2019, and April 7, 2022, a total of 6016 patients with STEMI undergoing primary PCI were randomly assigned to receive either bivalirudin plus a high-dose infusion after PCI (n=3009) or unfractionated heparin monotherapy (n=3007). Radial artery access was used in 5593 (93·1%) of 6008 patients. Compared with heparin monotherapy, bivalirudin reduced the 30-day rate of the primary endpoint (132 events [4·39%] in the heparin group vs 92 events [3·06%] in the bivalirudin group; difference, 1·33%, 95% CI 0·38-2·29%; hazard ratio [HR] 0·69, 95% CI 0·53-0·91; p=0·0070). All-cause mortality within 30 days occurred in 118 (3·92%) heparin-assigned patients and in 89 (2·96%) bivalirudin-assigned patients (HR 0·75; 95% CI 0·57-0·99; p=0·0420), and BARC types 3-5 bleeding occurred in 24 (0·80%) heparin-assigned patients and five (0·17%) bivalirudin-assigned patients (HR 0·21; 95% CI 0·08-0·54; p=0·0014). There were no significant differences in the 30-day rates of reinfarction, stroke, or ischaemia-driven target vessel revascularisation between the groups. Within 30 days, stent thrombosis occurred in 11 (0·37%) of bivalirudin-assigned patients and 33 (1·10%) of heparin-assigned patients (p=0·0015). INTERPRETATION: In patients with STEMI undergoing primary PCI predominantly with radial artery access, anticoagulation with bivalirudin plus a post-PCI high-dose infusion for 2-4 h significantly reduced the 30-day composite rate of all-cause mortality or BARC types 3-5 major bleeding compared with heparin monotherapy. FUNDING: Chinese Society of Cardiology Foundation (CSCF2019A01), and a research grant from Jiangsu Hengrui Pharmaceuticals.

Ammonia for post-healing of formamidinium-based Perovskite films.

Solvents employed for perovskite film fabrication not only play important roles in dissolving the precursors but also participate in crystallization process. High boiling point aprotic solvents with O-donor ligands have been extensively studied, but the formation of a highly uniform halide perovskite film still requires the participation of additives or an additional step to accelerate the nucleation rate. The volatile aliphatic methylamine with both coordinating ligands and hydrogen protons as solvent or post-healing gas facilitates the process of methylamine-based perovskite films with high crystallinity, few defects, and easy large-scale fabrication as well. However, the attempt in formamidinium-containing perovskites is challenged heretofore. Here, we reveal that the degradation of formamidinium-containing perovskites in aliphatic amines environment results from the transimination reaction of formamidinium cation and aliphatic amines along with the formation of ammonia. Based on this mechanism, ammonia is selected as a post-healing gas for a highly uniform, compact formamidinium-based perovskite films. In particular, low temperature is proved to be crucial to enable formamidinium-based perovskite materials to absorb enough ammonia molecules and form a liquid intermediate state which is the key to eliminating voids in raw films. As a result, the champion perovskite solar cell based on ammonia post-healing achieves a power conversion efficiency of 23.21% with excellent reproducibility. Especially the module power conversion efficiency with 14 cm2 active area is over 20%. This ammonia post-healing treatment potentially makes it easier to upscale fabrication of highly efficient formamidinium-based devices.

Integrated Clinical and Prognostic Analysis of the m6A RNA Methylation Regulator YTHDF3 in Pan-Cancer and its Correlation with Cancer Cell Proliferation.

Background: N6-methyladenosine (m6A) is the most abundant and extensive chemical modification of mammalian RNA molecules. Although numerous studies have investigated m6A methylation-related genes, to the best of our knowledge, none have examined the expression patterns of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) across cancers. Methods: Using various publicly available datasets, we searched for a potential carcinogenic role of YTHDF3 in 33 tumor types. Furthermore, the clinicopathological parameters, clinical prognostic value, enrichment analysis, mutations, microsatellite instability (MSI), tumor mutation burden (TMB), levels of infiltrating cells, and related immune checkpoint genes were included. Finally, we performed a validation analysis using existing clinical samples and proliferation-related functional experiments. Results: YTHDF3 is highly expressed in most cancer types and associated with patient prognosis in certain tumors. The ROC analysis suggested that YTHDF3 has high diagnostic value in 13 types of cancer. Furthermore, we found that the genes associated with YTHDF3 were enriched for translation initiation and mRNA metabolic processes. The results of the GSEA enrichment suggest that YTHDF3 may be associated with different pathways in cells in various tumor types. We further analyzed the correlations between YTHDF3 expression and MSI, TMB, and immune checkpoint genes. YTHDF3 also possibly exerts important antitumor immunotherapy effects. Additionally, the results of the immune analysis using TIMER showed that high YTHDF3 expression levels in pan-cancer tissues were related to an immunosuppressive microenvironment. Finally, we experimentally demonstrated that both overexpression and downregulation of YTHDF3 can affect cancer cell proliferation rates. Conclusion: YTHDF3 is a promising biomarker for cancer diagnosis. This study provides the first comprehensive pan-cancer report on YTHDF3 and increases our understanding of its oncogenic role in different tumors.