Expression Changes in Programmed Death Ligand 1 from Precancerous Lesions to Invasive Adenocarcinoma in Subcentimeter Pulmonary Nodules: A Large Study of 2022 Cases in China.

PURPOSE: This large-scale, multicenter, retrospective observational study aimed to evaluate the clinicopathological and molecular profiles associated with programmed death-ligand 1 (PD-L1) expression in precancerous lesions and invasive adenocarcinoma in subcentimeter pulmonary nodules. PATIENTS AND METHODS: Patients with histologically confirmed atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (ADC) were included. PD-L1 expression was evaluated at each center using a PD-L1 immunohistochemistry 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). The tumor proportion score (TPS) cutoff values were set at ≥ 1% and ≥ 50%. RESULTS: A total of 2022 nodules from 1844 patients were analyzed. Of these, 9 (0.45%) nodules had PD-L1 TPS ≥ 50%, 187 (9.25%) had PD-L1 TPS 1-49%, and 1826 (90.30%) had PD-L1 TPS < 1%. A total of 378 (18.69%), 1016 (50.25%), and 628 (31.06%) nodules were diagnosed as AAH/AIS, MIA, and ADC, respectively, by pathology. A total of 1377 (68.10%), 591 (25.67%), and 54 (2.67%) nodules were diagnosed as pure ground-glass opacity (GGO), mixed GGO, and solid nodules, respectively, by computed tomography. There was a significant difference between PD-L1 expression and anaplastic lymphoma kinase (ALK) mutation status (P < 0.001). PD-L1 expression levels were significantly different from those determined using the International Association for the Study of Lung Cancer (IASLC) grading system (P < 0.001). CONCLUSIONS: PD-L1 expression was significantly associated with radiological and pathological invasiveness and driver mutation status in subcentimeter pulmonary nodules. The significance of PD-L1 expression in the evolution of early-stage lung adenocarcinoma requires further investigation.

A Conformal Carbon Nanolayer Coated Fe2 O3 Cocatalyst for the Promoted Activity of Plasma-Sputtered BiVO4 Photoanode.

To simultaneously improve the hole extraction ability of the BiVO4 photoanode and accelerate the surface reaction kinetics, herein, a carbon nanolayer conformally coated Fe2 O3 (C-Fe2 O3 ) as oxygen evolution catalyst (OEC) is loaded on the H2 plasma treated nanoporous BiVO4 (BVO(H2 )) surface by a hydrothermal reaction. It is found that the H2 plasma induced vacancies in BVO remarkably increases the conductivity, and the C-Fe2 O3 enables hole extraction from the bulk to the surface as well as efficient hole injection to the electrolyte. As a result, the C-Fe2 O3 /BVO(H2 ) photoanode achieves a photocurrent density of 4.4 mA/cm2 at 1.23 V vs. reversible hydrogen electrode (RHE) and an ABPE value of 1.5 % at 0.68 V vs. RHE, which are 4.8-fold and 13-fold higher than that of BVO photoanode, respectively.

ITHscore: comprehensive quantification of intra-tumor heterogeneity in NSCLC by multi-scale radiomic features.

OBJECTIVES: To quantify intra-tumor heterogeneity (ITH) in non-small cell lung cancer (NSCLC) from computed tomography (CT) images. METHODS: We developed a quantitative ITH measurement-ITHscore-by integrating local radiomic features and global pixel distribution patterns. The associations of ITHscore with tumor phenotypes, genotypes, and patient's prognosis were examined on six patient cohorts (n = 1399) to validate its effectiveness in characterizing ITH. RESULTS: For stage I NSCLC, ITHscore was consistent with tumor progression from stage IA1 to IA3 (p < 0.001) and captured key pathological change in terms of malignancy (p < 0.001). ITHscore distinguished the presence of lymphovascular invasion (p = 0.003) and pleural invasion (p = 0.001) in tumors. ITHscore also separated patient groups with different overall survival (p = 0.004) and disease-free survival conditions (p = 0.005). Radiogenomic analysis showed that the level of ITHscore in stage I and stage II NSCLC is correlated with heterogeneity-related pathways. In addition, ITHscore was proved to be a stable measurement and can be applied to ITH quantification in head-and-neck cancer (HNC). CONCLUSIONS: ITH in NSCLC can be quantified from CT images by ITHscore, which is an indicator for tumor phenotypes and patient's prognosis. KEY POINTS: • ITHscore provides a radiomic quantification of intra-tumor heterogeneity in NSCLC. • ITHscore is an indicator for tumor phenotypes and patient's prognosis. • ITHscore has the potential to be generalized to other cancer types such as HNC.

A MOF-derived Bimetallic Co-catalyst for Promoting Visible-light Photocatalytic Hydrogen Evolution on NH2 -MIL-125.

In order to construct noble metal-free co-catalysts to facilitate the transport and separation of photocatalyst carriers, herein, a MOF-based derived bimetallic NiCu0.2 co-catalyst was loaded on NH2 -MIL-125(Ti). The obtained NiCu0.2 /NH2 -MIL-125 exhibited a photocatalytic activity of 161.4 µmol g-1 h-1 for hydrogen evolution, 12.6 times higher than that of the Ni/NH2 -MIL-125 and even slightly better than Pt/NH2 -MIL-125. The work expands the development pathway of cost-effective and highly active bimetallic co-catalysts for photocatalytic H2 evolution.

A Novel Radiopathological Grading System to Tailor Recurrence Risk for Pathologic Stage IA Lung Adenocarcinoma.

To validate the efficiency of pathologic grading system in pathologic stage IA lung adenocarcinoma (LUAD), and explore whether integrating preoperative radiological features would enhance the performance of recurrence discrimination. We retrospectively collected 510 patients with resected stage IA LUAD between January 2012 and December 2019 from Guangdong Provincial People's Hospital (GDPH). Pathologic grade classification of each case was based on the International Association for the Study of Lung Cancer (IASLC) pathologic staging system. Kaplan-Meier curves was used to assess the power of recurrence stratification. Concordance index (C-Index) and receiver operating characteristic curves (ROC) were used for evaluating the clinical utility of different grading systems for recurrence discrimination. Patients of lower IASLC grade showed improved recurrence-free survival (RFS) (P < 0.0001) where numerically difference was found between grade II and grade III (P = 0.119). By integrating the IASLC grading system and radiological feature, we found the RFS rate decreased as the novel radiopathological (RP) grading system increased (P < 0.0001). The difference of RFS curves between any 2 groups as per the RP grading system was statisticallysignificant (RP grade I vs RP grade II, p = 0.007; RP grade I vs RP grade III, P < 0.0001; RP grade II vs RP grade III, P = 0.0003). Compared with the IASLC grading system, the RP grading system remarkably improved recurrence survival discrimination (C-index: 0.822; area under the curve, 0.845). Integrating imaging features into pathologic grading system enhanced the efficiency of recurrence discrimination for resected stage IA LUAD and might help conduct subsequent management.

Construction of a ruthenium-doped CoFe-layered double hydroxide as a bifunctional electrocatalyst for overall water splitting.

In this study, ruthenium-doped CoFe-based layered double hydroxides on Ni foam (CoFe-ZLDH/Ru@NF) were fabricated via an etching-precipitation strategy. The resultant CoFe-ZLDH/Ru@NF exhibited excellent activity, showing low overpotentials of 219.8 mV and 60.9 mV to reach the current density of 10 mA cm-2 for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), respectively. As a bifunctional electrocatalyst, it was assembled in an anion exchange membrane water electrolyser (AEMWE) unit, performing as an anode and cathode simultaneously, which only required a cell voltage of 2.33 V to accomplish the industrial level current density of 1 A cm-2 and operated steadily for over 12 h, making it promising for utilization in hydrogen production.

Spatial downregulation of CD74 signatures may drive invasive component development in part-solid lung adenocarcinoma.

Pulmonary nodules with part-solid imaging features manifest during the progression from preinvasive to invasive lung adenocarcinoma. To define the spatial composition and evolutionary trajectories of early-stage lung adenocarcinoma, we combined spatial transcriptomics (ST) and pathological annotations from 20 part-solid nodules (PSNs), four of which were matched with single-cell RNA sequencing. Two malignant cell populations (MC1 and MC2) were identified, and a linear evolutionary relationship was observed. Compared to MC2, the pre-existing malignant MC1 exhibited a lower metastatic signature, corresponding to the preinvasive component (lepidic) on pathology and the ground glass component on PSN imaging. Higher immune infiltration was observed among MC1 regions in ST profiles, and further analysis revealed that macrophages may be involved in this process through the CD74 axis. This work provides deeper insights into the evolutionary process and spatial immune cell composition behind PSNs and highlights the mechanisms of immune escape behind this adenocarcinoma trajectory.

Lack of incremental value of three-dimensional measurement in assessing invasiveness for lung cancer.

OBJECTIVES: The aim of this study was to evaluate the performance of consolidation-to-tumour ratio (CTR) and the radiomic models in two- and three-dimensional modalities for assessing radiological invasiveness in early-stage lung adenocarcinoma. METHODS: A retrospective analysis was conducted on patients with early-stage lung adenocarcinoma from Guangdong Provincial People's Hospital and Shenzhen People's Hospital. Manual delineation of pulmonary nodules along the boundary was performed on cross-sectional images to extract radiomic features. Clinicopathological characteristics and radiomic signatures were identified in both cohorts. CTR and radiomic score for every patient were calculated. The performance of CTR and radiomic models were tested and validated in the respective cohorts. RESULTS: A total of 818 patients from Guangdong Provincial People's Hospital were included in the primary cohort, while 474 patients from Shenzhen People's Hospital constituted an independent validation cohort. Both CTR and radiomic score were identified as independent factors for predicting pathological invasiveness. CTR in two- and three-dimensional modalities exhibited comparable results with areas under the receiver operating characteristic curves and were demonstrated in the validation cohort (area under the curve: 0.807 vs 0.826, P = 0.059) Furthermore, both CTR in two- and three-dimensional modalities was able to stratify patients with significant relapse-free survival (P < 0.000 vs P < 0.000) and overall survival (P = 0.003 vs P = 0.001). The radiomic models in two- and three-dimensional modalities demonstrated favourable discrimination and calibration in independent cohorts (P = 0.189). CONCLUSIONS: Three-dimensional measurement provides no additional clinical benefit compared to two-dimensional.