Construction of a conjugated covalent organic framework for iodine capture.

Radioactive iodine in the nuclear field is considered very dangerous nuclear waste because of its chemical toxicity, high mobility and long radioactive half-life. Herein, a conjugated two-dimensional covalent organic framework, TPB-TMPD-COF, has been designed and synthesized for iodine capture. TPB-TMPD-COF has been well characterized by several techniques and showed long order structure and a large surface area (1090 m2 g-1). Moreover, TPB-TMPD-COF shows a high iodine capture value at 4.75 g g-1 under 350 K and normal pressure conditions, benefitting from the increased density of adsorption sites. By using multiple techniques, the iodine vapor adsorbed into the pores may readily generate the electron transfer species (I3- and I5-) due to the strong interactions between imine groups and iodine molecules, which contributes to the high iodine uptake for TPB-TMPD-COF. Our study will stimulate the design and synthesis of COFs as a solid-phase adsorbent for iodine uptake.

Allelic Context of EGFR C797X-Mutant Lung Cancer Defines Four Subtypes With Heterogeneous Genomic Landscape and Distinct Clinical Outcomes.

INTRODUCTION: EGFR C797X (C797S or C797G) mutation is the most frequent on-target mechanism of resistance to osimertinib. The hypothesis that the allelic context of C797X/T790M has implications for treatment is on the basis of sporadic reports and needs validation with larger cohorts. METHODS: We identified patients with EGFR C797X-mutant NSCLC from nine centers who progressed on osimertinib, all analyzed in a single laboratory through next-generation sequencing. We analyzed genomic profiles and assessed associations between clinical outcomes and C797X status. RESULTS: A total of 365 EGFR C797X-mutant cases were categorized into four subtypes on the basis of allelic context: in cis (75.3%), in trans (6.4%), cis&trans (10.4%), and C797X-only (7.9%). Genomically, the cis&trans subtype displayed the highest frequency of concurrent alterations at osimertinib resistance sites (21.1%), while the in cis subtype had the lowest (8.4%). Clinically, cis&trans patients exhibited the worst progression-free survival (PFS) on both previous (median 7.7 mo) and subsequent treatment (median 1.0 mo) and overall survival (median 3.9 mo). In subsequent treatments, in cis patients exhibited superior PFS with combined brigatinib and cetuximab (median 11.0 mo) compared with other regimens (p = 0.005), while in trans patients exhibited variable outcomes with combined first or second- and third-generation EGFR inhibitor (PFS range: 0.7-8.1 mo, median 2.6 mo). Notably, subtype switching was observed after subsequent treatments, predominantly toward the in cis subtype. CONCLUSIONS: Allelic context could define four EGFR C797X-mutant NSCLC subtypes with heterogeneous genetic landscapes and distinct clinical outcomes. Subsequent treatments further complicate the scenario through subtype switching.

Enhancing the Iodine Adsorption Capacity of Pyrene-Based Covalent Organic Frameworks by Regulating the Pore Environment.

Regulating of pore environment is an efficient way to improve the performance of covalent organic frameworks (COFs) for specific application requirements. Herein, the design and synthesis of two pyrene-based 2D COFs with -H or -Me substituents, TFFPy-PPD-COF and TFFPy-TMPD-COF are reported. Both of them show long order structure and high porosity, in which TFFPy-PPD-COF displays a larger pore volume and bigger BET surface area (2587 m2 g-1 , 1.17 cm3 g-1 ). Interestingly, TFPPy-TMPD-COF exhibits a much higher vapor iodine capacity (4.8 g g-1 ) than TFPPy-PPD-COF (2.9 g g-1 ), in contrast to their pore volume size. By using multiple techniques, the better performance of TFPPy-TMPD-COF in iodine capture is ascribed to the altered pore environment by introducing methyl groups, which contributes to the formation of polyiodide anions and enhances the interactions between the frameworks and iodine. These results will be helpful for understanding the effect of pore environment in COFs for iodine uptake and constructing novel structure with high iodine capture performance.

The predictive value of YAP-1 and POU2F3 for the efficacy of immuno-chemotherapy in extensive-stage SCLC patients.

INTRODUCTION: Recently, several clinical trials of immunotherapy for extensive-stage small-cell lung cancer (ES-SCLC) have shown limited benefits because of unselected patients. Thus, we aimed to explore whether YES-associated protein 1 (YAP-1) and POU domain class 2 transcription factor 3 (POU2F3) could identify SCLC patients with durable benefits from immunotherapy as potential biomarkers. METHODS: We performed IHC of YAP-1 and POU2F3, and RNA-seq on tissues of ES- SCLC patients. An open-source plugin based on IHC-profiler was conducted to calculate the expression levels of YAP-1 and POU2F3. RESULTS: Patients with ES-SCLC were retrospectively investigated in the Guangdong Provincial People's Hospital from January 2018 to July 2021, and 21 patients whoever received atezolizumab plus etoposide/carboplatin (ECT) regimen also had tissue samples reachable. The median IHC-score of YAP-1 in responders (CR/PR patients) was significantly lower than in nonresponders (SD/PD patients) at 13.97 (95% CI: 8.97-16.30) versus 23.72 (95% CI: 8.13-75.40). The IHC-score of YAP-1 and PFS showed a negative correlation by Spearman (r=-0.496). However, POU2F3 did not show a correlation with efficacy. Besides, patients with YAP-1 high expression had IL6, MYCN, and MYCT1 upregulated, while analysis of immune cell infiltration only showed that M0 macrophages were significantly higher. CONCLUSIONS: The expression of YAP-1 negatively correlated with the efficacy of ECT in ES-SCLC patients while POU2F3 did not reveal the predictive value. However, prospective investigations with a large sample size are needed.

N6-Methyladenosine (m6A)-Related lncRNAs Are Potential Signatures for Predicting Prognosis and Immune Response in Lung Squamous Cell Carcinoma.

Background: Despite increasing understanding of m6A-related lncRNAs in lung cancer, the role of m6A-related lncRNAs in the prognosis and treatment of lung squamous cell carcinoma is poorly understood to date. Thus, the current study aims to elucidate its role and build a model to predict the prognosis of LUSC patients. Materials and Methods: The data of the current study were accessed from the TCGA database. Pearson correlation analysis was performed to identify lncRNAs correlated to m6A. Next, an m6A-related lncRNAs risk model was built using a single factor, least absolute association, selection operator, and multivariate Cox regression analysis. Results: The relevance between 23 m6A genes and 14,056 lncRNAs is shown by Pearson correlation analysis by Sankey diagram. Multivariate Cox regression analysis determined that 11 m6A-lncRNAs show predictive potential in prognosis, which is confirmed by the consistency index, Kaplan-Meier analysis, principal component analysis, and ROC curve. Additionally, the immune analysis showed that the enrichment of immune cells, major histocompatibility complex molecules, and immune checkpoints in the high and low-risk subgroups were markedly disparate, with the high-risk group showing a stronger immune escape ability and a worse response to immunotherapy. Conclusion: In conclusion, the risk model based on m6A-related lncRNAs showed great promise in predicting the prognosis and the efficacy of immunotherapy.

Clinical outcomes of EGFR+/METamp+ vs. EGFR+/METamp- untreated patients with advanced non-small cell lung cancer.

BACKGROUND: MET dysregulation has been implicated in the development of primary and secondary resistance to EGFR tyrosine kinase inhibitor (TKI) therapy. However, the clinicopathological characteristics and outcomes of patients harboring EGFR-sensitive mutations and de novo MET amplifications still need to be explored. METHODS: A total of 54 patients from our hospital with non-small cell lung cancer harboring EGFR-sensitive mutations and/or de novo MET amplifications were included in this study. Survival rates were estimated by the Kaplan-Meier method with log-rank statistics. Lung cancer organoids (LCOs) were generated from patient-derived malignant pleural effusion to perform drug sensitivity assays. RESULTS: Fifty-four patients with the appropriate clinicopathological characteristics were enrolled. MET FISH was performed in 40 patients who were stratified accordingly into two groups: EGFR+/METamp- (n = 22) and EGFR+/METamp + (n = 18). Survival rates for EGFR+/METamp- and EGFR+/METamp + patients respectively, were as follows: the median progression-free survival (PFS) was 12.1 and 1.9 months (p<0.001); the median post-progression overall survival (pOS) was 25.6 and 11.6 months (p = 0.023); the median overall survival (OS) was 33.2 and 12.7 months (p = 0.013). Drug testing conducted in LCOs derived from malignant pleural effusion from EGFR+/METamp + patients showed that dual targeted therapy was more effective than TKI monotherapy. CONCLUSION: EGFR+/METamp + patients treated with first-line TKI monotherapy had poor clinical outcomes. Dual targeted therapy showed potent anticancer activity in the LCO drug testing assay, suggesting that it is a promising first-line treatment for EGFR+/METamp + patients. Randomized controlled trials are needed to further validate these results.

[Assessment on dietary iodine intake in three areas of Zhejiang province, 2009].

OBJECTIVE: To assess the level of dietary iodine intake in three areas of Zhejiang and the related policy on universal salt iodization in the province. METHODS: The study involved 497 residents from 180 families living in Hangzhou, Taizhou, Zhoushan cities, representing coastal and inland areas in Zhejiang province in 2009. A total diet study was applied to obtain the typical diet samples at three study areas through food consumption, aggregation, sampling and preparation processes. The contents of iodine in diet samples were determined by tetramethylammonium hydroxide extraction-inductively coupled plasma-mass spectrometry. The amount of dietary iodine intake was calculated by timing the food consumption data and the iodine content in different dietary samples. The safety of dietary iodine intake was evaluated according to the recommended nutrient intake (RNI) and tolerable upper intake level (UL) published by the Chinese Nutrition Society in 2001. RESULTS: The dietary iodine intake of reference person in three areas of Zhejiang province was 421.0 µg/d. The levels of P5, P25, median, P75, P90, P95 dietary iodine intake were 145.7 µg/d, 267.6 µg/d, 358.5 µg/d, 495.6 µg/d, 774.1 µg/d and 1273.0 µg/d respectively. Daily dietary iodine intake at UL accounted for 5.2%, 87.5% and 7.2% of all the participants respectively. Without considering the loss through cooking, salt iodine provided 81.6% of the dietary iodine source. The resources of dietary iodine would include vegetables, cereals and marine food, proportionally, as 57.2%, 13.0% and 8.5%, respectively. Participants whose daily dietary iodine intake exceeded the UL level would consume more marine algae products than those whose dietary iodine intakes were lower than RNI or between RNI-UL. CONCLUSION: Dietary iodine intake among most residents and their average level were among reasonable ranges. Meanwhile, deficiency and excess of iodine intake coexisted. Salt iodine was the main resource of dietary iodine. Participants whose dietary iodine intakes exceeding the UL level, would prefer consume more marine algae products.