RNA splicing analysis deciphers developmental hierarchies and reveals therapeutic targets in adult glioma.

Widespread alterations in RNA alternative splicing (AS) have been identified in adult gliomas. However, their regulatory mechanism, biological significance, and therapeutic potential remain largely elusive. Here, using a computational approach with both bulk and single-cell RNA-Seq, we uncover a prognostic AS signature linked with neural developmental hierarchies. Using advanced iPSC glioma models driven by glioma driver mutations, we show that this AS signature could be enhanced by EGFRvIII and inhibited by in situ IDH1 mutation. Functional validations of 2 isoform switching events in CERS5 and MPZL1 show regulations of sphingolipid metabolism and SHP2 signaling, respectively. Analysis of upstream RNA binding proteins reveals PTBP1 as a key regulator of the AS signature where targeting of PTBP1 suppresses tumor growth and promotes the expression of a neuron marker TUJ1 in glioma stem-like cells. Overall, our data highlights the role of AS in affecting glioma malignancy and heterogeneity and its potential as a therapeutic vulnerability for treating adult gliomas.

Synthesis and Structural Optimization of ATG4B Inhibitors for the Attenuation of Autophagy in Glioblastoma.

Glioblastoma, a prevalent malignant CNS tumor, presents a therapeutic challenge because of resistance to standard treatments, including radiation therapy and temozolomide. Both modalities induce autophagy, thereby paradoxically promoting tumor survival. The cysteine protease ATG4B is implicated in this cellular process, which highlights the enzyme as a viable therapeutic target for glioblastoma. We have developed streamlined syntheses for ATG4B inhibitor NSC185058, its derivatives, and fluorogenic ATG4B substrate pim-FG-PABA-AMC. We leveraged these findings to rapidly identify novel compound MJO445, which demonstrates markedly greater potency biochemically and in cells.

Markers of insulin resistance associated with non-alcoholic fatty liver disease in non-diabetic population.

Insulin resistance (IR) plays an important role in the development of non-alcoholic fatty liver disease (NAFLD). IR markers are divided into two types: (1) insulin-based IR marker, homeostatic model assessment of IR (HOMA-IR); and (2) non-insulin-based IR markers, such as triglyceride-glucose (TyG) index, TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-c), and metabolic score for IR (METS-IR). The non-insulin-based IR markers are often associated with lipids. The aim of this study was to analyse the association between IR markers and NAFLD in non-diabetic population. Baseline data of NAFLD and non-NAFLD groups were compared. Logistic regression was used to evaluate the relationship between five IR markers and NAFLD risk. The odds ratios (ORs) and 95% confidence intervals (CIs) of IR markers were calculated. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to evaluate the ability of different IR markers to detect NAFLD. Subgroup analyses were performed in obese and non-obese subgroups. This study found a positive correlation between NAFLD risk and elevation in five IR markers (HOMA-IR, TyG, TyG-BMI, TG/HDL-c, and METS-IR). In non-obese subjects, the AUC of TyG-BMI was larger than that of the other four IR markers to detect NAFLD. The AUC of HOMA-IR was larger than that of the other four IR markers to detect NAFLD in obese subjects. In non-diabetic population, the five IR markers are associated with the risk of NAFLD, including non-obese and obese NAFLD. TyG-BMI and HOMA-IR can be used to detect non-obese and obese NAFLD, respectively, with better detection ability compared with the other IR markers.

HOMA-IR is an effective biomarker of non-alcoholic fatty liver disease in non-diabetic population.

OBJECTIVES: This study aimed to investigate the correlation between homeostasis model assessment of insulin resistance (HOMA-IR) and non-alcoholic fatty liver disease (NAFLD) in the non-diabetic population and establish its diagnostic efficacy. METHODS: This observational study involved participants divided into NAFLD and non-NAFLD groups, and baseline data were analyzed. Univariate and multivariate logistic regression analyses were used to correlate HOMA-IR with the risk of NAFLD. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of HOMA-IR for NAFLD. Subgroup analyses of non-obese individuals were performed. RESULTS: Overall, 2234 non-diabetic participants were included. The HOMA-IR was significantly higher in the NAFLD group than in the non-NAFLD group. Multivariate logistic regression analysis showed that HOMA-IR was a strong and independent risk factor for NAFLD after correcting for confounding factors. The area under the ROC curve (AUC) value of HOMA-IR for predicting NAFLD was 0.792. In the non-obese non-diabetic population, HOMA-IR was an independent risk factor for increased risk of lean NAFLD after correcting for confounding factors. The AUC value of HOMA-IR for predicting lean NAFLD was 0.770. CONCLUSIONS: HOMA-IR is independently associated with the risk of NAFLD in the non-diabetic and non-obese non-diabetic populations and has good diagnostic value.

CD73, a Promising Therapeutic Target of Diclofenac, Promotes Metastasis of Pancreatic Cancer through a Nucleotidase Independent Mechanism.

CD73, a cell surface-bound nucleotidase, facilitates extracellular adenosine formation by hydrolyzing 5'-AMP to adenosine. Several studies have shown that CD73 plays an essential role in immune escape, cell proliferation and tumor angiogenesis, making it an attractive target for cancer therapies. However, there are limited clinical benefits associated with the mainstream enzymatic inhibitors of CD73, suggesting that the mechanism underlying the role of CD73 in tumor progression is more complex than anticipated, and further investigation is necessary. In this study, CD73 is found to overexpress in the cytoplasm of pancreatic ductal adenocarcinoma (PDAC) cells and promotes metastasis in a nucleotidase-independent manner, which cannot be restrained by the CD73 monoclonal antibodies or small-molecule enzymatic inhibitors. Furthermore, CD73 promotes the metastasis of PDAC by binding to the E3 ligase TRIM21, competing with the Snail for its binding site. Additionally, a CD73 transcriptional inhibitor, diclofenac, a non-steroidal anti-inflammatory drug, is more effective than the CD73 blocking antibody for the treatment of PDAC metastasis. Diclofenac also enhances the therapeutic efficacy of gemcitabine in the spontaneous KPC (LSL-KrasG12D/+ , LSL-Trp53R172H/+ , and Pdx-1-Cre) pancreatic cancer model. Therefore, diclofenac may be an effective anti-CD73 therapy, when used alone or in combination with gemcitabine-based chemotherapy regimen, for metastatic PDAC.

The Predictive Role of Immune Related Subgroup Classification in Immune Checkpoint Blockade Therapy for Lung Adenocarcinoma.

Background: In lung adenocarcinoma (LUAD), the predictive role of immune-related subgroup classification in immune checkpoint blockade (ICB) therapy remains largely incomplete. Methods: Transcriptomics analysis was performed to evaluate the association between immune landscape and ICB therapy in lung adenocarcinoma and the associated underlying mechanism. First, the least absolute shrinkage and selection operator (LASSO) algorithm and K-means algorithm were used to identify immune related subgroups for LUAD cohort from the Cancer Genome Atlas (TCGA) database (n = 572). Second, the immune associated signatures of the identified subgroups were characterized by evaluating the status of immune checkpoint associated genes and the immune cell infiltration. Then, potential responses to ICB therapy based on the aforementioned immune related subgroup classification were evaluated via tumor immune dysfunction and exclusion (TIDE) algorithm analysis, and survival analysis and further Cox proportional hazards regression analysis were also performed for LUAD. In the end, gene set enrichment analysis (GSEA) was performed to explore the metabolic mechanism potentially responsible for immune related subgroup clustering. Additionally, two LUAD cohorts from the Gene Expression Omnibus (GEO) database were used as validation cohort. Results: A total of three immune related subgroups with different immune-associated signatures were identified for LUAD. Among them, subgroup 1 with higher infiltration scores for effector immune cells and immune checkpoint associated genes exhibited a potential response to IBC therapy and a better survival, whereas subgroup 3 with lower scores for immune checkpoint associated genes but higher infiltration scores for suppressive immune cells tended to be insensitive to ICB therapy and have an unfavorable prognosis. GSEA revealed that the status of glucometabolic reprogramming in LUAD was potentially responsible for the immune-related subgroup classification. Conclusion: In summary, immune related subgroup clustering based on distinct immune associated signatures will enable us to screen potentially responsive LUAD patients for ICB therapy before treatment, and the discovery of metabolism associated mechanism is beneficial to comprehensive therapeutic strategies making involving ICB therapy in combination with metabolism intervention for LUAD.

CD73 induces gemcitabine resistance in pancreatic ductal adenocarcinoma: A promising target with non-canonical mechanisms.

CD73, a cell surface-localized ecto-5'-nucleotidase, is the major enzymatic source of extracellular adenosine. Canonically, it plays multiple roles in cancer-related processes via its metabolite. As a druggable target, clinical trials targeting CD73 in various malignant diseases are currently ongoing. Here, we report the ecto-5'-nucleotidase-independent functions of CD73 in pancreatic ductal adenocarcinoma (PDAC). Our findings support that the elevated expression of CD73 in PDAC cells promotes gemcitabine (GEM) resistance by activating AKT. We discovered that a large amount of intracellular CD73 are localized in the endoplasmic reticulum membrane. Intracellular CD73 physically interacts with major vault protein to activate the SRC-AKT circuit. Troglitazone (TGZ) is a peroxisome proliferator-activated receptor gamma agonist that could inhibit the expression of CD73. The administration of TGZ markedly enhances sensitivity to GEM via downregulating CD73 in PDAC. Our findings support that CD73 could be targeted to overcome chemoresistance in PDAC.

Identification of Ferroptosis-Related Genes Signature Predicting the Efficiency of Invasion and Metastasis Ability in Colon Adenocarcinoma.

Background: Colon adenocarcinoma (COAD) is one of the most prevalent cancers worldwide and has become a leading cause of cancer death. Although many potential biomarkers of COAD have been screened with the bioinformatics method, it is necessary to explore novel markers for the diagnosis and appropriate individual treatments for COAD patients due to the high heterogeneity of this disease. Epithelial-to-mesenchymal transition (EMT)-mediated tumor metastasis suggests poor prognosis of cancers. Ferroptosis is involved in tumor development. EMT signaling can increase the cellular sensitivity to ferroptosis in tumors. The aim of our study is finding novel prognostic biomarkers to determine COAD patients for predicting efficiency of metastasis status and targeting precise ferroptosis-related therapy. Methods: A novel gene signature related to metastasis and ferroptosis was identified combing with risk model and WGCNA analysis with R software. The biological functions and predictive ability of the signature in COAD were explored through bioinformatics analysis. Results: We established a four-gene prognostic signature (MMP7, YAP1, PCOLCE, and HOXC11) based on EMT and ferroptosis related genes and validated the reliability and effectiveness of this model in COAD. This four-gene prognostic signature was closely connected with metastasis and ferroptosis sensitivity of COAD. Moreover, WGCNA analysis further confirmed the correlation between PCOLCE, HOXC11, and liver and lymphatic invasion of COAD. Conclusion: The four genes may become potential prognostic biomarkers to identify COAD patients with metastasis. Moreover, this four-gene signature may be able to determine the COAD suitable with ferroptosis induction therapy. Finally, PCOLCE2 and HOXC11 were selected individually because of their novelties and precise prediction ability. Overall, this signature provided novel possibilities for better prognostic evaluation of COAD patients and may be of great guiding significance for individualized treatment and clinical decision.

Stable and Catalytically Active Shape-Engineered Cerium Oxide Nanorods by Controlled Doping of Aluminum Cations.

Shape-engineered nanocrystals (SENs) promise a better selectivity and a higher activity in catalytic reactions than the corresponding non-shape-engineered ones because of their larger specific surface areas and desirable crystal facets. However, often, it is challenging to apply SENs in practical catalytic applications at high reaction temperatures, where SENs deforms into more stable, less active nanoparticles. In this paper, we show that atomic layer deposition (ALD) of Al2O3 at 200 °C can controllably dope Al cations into the shape-engineered CeO2 nanorods (NRs) to not only increase their shape transition temperature from 400 °C to beyond 700 °C but also greatly increase their specific reversible oxygen storage capacity (srOSC). The substituted Al3+ ions impede the surface diffusion of Ce ions and therefore improve the thermal stability of CeO2 NRs. These Al3+ dopants form -Al-O-Ce-O- clusters, which are new Ce species and can be reversibly reduced and oxidized at 500-700 °C. This low-temperature chemical doping method decouples the synthesis process of SENs from the doping process and maintains the shape of the SENs during the activation of dopants. This concept could be adopted to enable the applications of other SENs in challenging high-temperature environments.

Enhanced glucose metabolism mediated by CD147 is associated with 18 F-FDG PET/CT imaging in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most deadly thoracic tumors. Reprogrammed glycolytic metabolism is a hallmark of cancer cells and significantly affects several cellular functions. In the current study, we aimed to investigate cluster of differentiation 147 (CD147)-mediated glucose metabolic regulation in LUAD and its association with 18 F-FDG PET/CT imaging. METHODS: The expression profile and prognostic potential of CD147 in LUAD were analyzed using UALCAN and a Kaplan-Meier plotter. Tissue immunohistochemical analyses and PET metabolic parameters were used to identify the relationship between CD147 expression and reprogrammed glycolysis. The role of CD147 in glucose metabolic reprogramming was assessed by radioactive uptake of 18 F-FDG through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo. Western blotting assays were used to determine the expression level of monocarboxylate transporter 1 (MCT1) and MCT4 in established human LUAD cell lines (ie, HCC827 and H1975) with different CD147 expression levels via lentiviral transduction. RESULTS: CD147 was highly expressed in LUAD. A significant positive correlation existed between CD147 expression and PET metabolic parameters(SUVmax,SUVmean, SUVpeak). CD147 could promote radioactive uptake of 18 F-FDG in vitro and in vivo, suggesting the ability of CD147 to enhance glycolytic metabolism. Furthermore, as an obligate chaperone for MCT1 and MCT4, CD147 positively correlated with MCT1 and MCT4 expression in LUAD tissues and established cell lines with different CD147 expression. CONCLUSIONS: Our study revealed that CD147 is a promising novel target for LUAD treatment and CD147-mediated glucose metabolism demonstrated its contribution to the predictive role of 18 F-FDG PET/CT imaging for targeted therapeutic efficacy.

Enhanced glucose metabolism mediated by CD147 contributes to immunosuppression in hepatocellular carcinoma.

From a metabolic perspective, cancer may be considered as a metabolic disease characterized by reprogrammed glycolytic metabolism. The aim of the present study was to investigate CD147-mediated glucose metabolic regulation in hepatocellular carcinoma (HCC) and its contribution to altered immune responses in the tumor microenvironment. Several HCC cell lines and corresponding nude mice xenografts models differing in CD147 expressions were established to directly investigate the role of CD147 in the reprogramming of glucose metabolism, and to determine the underlying molecular mechanisms. Immunohistochemistry (IHC) analyses and flow cytometry were used to identify the relationship between reprogrammed glycolysis and immunosuppression in HCC. Upregulated CD147 expressions were found to be associated with enhanced expressions of GLUT1, MCT1 in HCC tumorous tissues. CD147 promoted the glycolytic metabolism in HCC cell lines in vitro via the PI3K/Akt/mTOR signaling pathway. A positive correlation existed between a profile of immunosuppressive lymphocytes infiltration and CD147 expression in HCC tissues. Accumulation of FOXP3-expressing regulatory T cells was induced under a stimulation with lactate in vitro. In conclusion, CD147 promoted glycolytic metabolism in HCC via the PI3K/Akt/mTOR signaling pathway, and was related to immunosuppression in HCC.

Reaction Temperature and Partial Pressure Induced Etching of Methylammonium Lead Iodide Perovskite by Trimethylaluminum.

Al2O3 atomic layer deposition (ALD), which uses trimethylaluminum (TMA) as the metal precursor, shows promise in improving the environmental stability of hybrid halide perovskites. However, it is not yet entirely clear how TMA, a strong Lewis acid, reacts with fresh perovskites and how the reaction affects the nucleation of ALD Al2O3. Here, the effects of reaction temperature and partial pressure of TMA on the mechanisms of TMA/CH3NH3PbI3 reactions are investigated. Our real time mass gain data and in situ mass spectrometry data show that the TMA/CH3NH3PbI3 reaction can either remove mass or accumulate mass onto CH3NH3PbI3 substrates, depending strongly on the reaction temperature and partial pressure of TMA. The TMA/CH3NH3PbI3 reaction probably generates TMA-CH3NHx adduct compounds, which protects CH3NH3PbI3 from TMA by forming a shell at 25 °C in the vacuum process. However, these adduct compounds decompose at higher temperatures (e.g., 75 °C). This product layer is much thicker than a monolayer, suggesting the interface formed between Al2O3 coating and CH3NH3PbI3 is blurring and messy. These results have not yet, but should be, carefully considered to correctly interpret the effect of ALD Al2O3 treatment on optoelectronic properties of CH3NH3PbI3.

MicroRNA-520c-3p functions as a novel tumor suppressor in lung adenocarcinoma.

Lung cancer is a malignancy with one of the highest incidence rates, and it is the leading cause of cancer-related death. To gain further insights into the underlying mechanisms of tumor growth and metastasis, we investigated the role and expression of microRNAs in lung adenocarcinoma (LUAD). We discovered a significantly lower expression level of microRNA-520c-3p (miR-520c-3p) in LUAD tissues than in nontumor tissues. miR-520c-3p is known to regulate multiple biological functions and cellular behaviors. In this study, we show that AKT1 and AKT2 are key direct targets of miR-520c-3p, which are required for its biological roles in LUAD. Mechanistically, downregulation of miR-520c-3p in LUAD is due to DNA methylation of the miR-520c-3p promoter region. Conversely, the activity of the transcription factor Yin Yang 1 (YY1) results in the upregulation of miR-520c-3p. Taken together, our results reveal methylation/YY1/miR-520c-3p/AKT1/AKT2 as a molecular axis with a potent biological function and highlight miR-520c-3p as a novel potent tumor suppressor in LUAD.

18 Fluorodeoxyglucose-positron emission tomography/computed tomography features of suspected solitary pulmonary lesions in breast cancer patients following previous curative treatment.

BACKGROUND: Differentiating pulmonary metastasis from primary lung cancer can be challenging in patients with breast malignancy. This study aimed to characterize the imaging features of 18 fluorodeoxyglucose-positron emission tomography/computed tomography (18 F-FDG-PET/CT) for distinguishing between these diseases. METHODS: We enrolled 52 patients who received curative treatment for breast cancer but later presented with suspected solitary pulmonary lesions (SPLs) and subsequently underwent 18 F-FDG-PET/CT to investigate. RESULTS: Subsolid lesions, ill-defined borders, lung lesions with negative maximum standardized uptake value, and lesions without 18 F-FDG-PET/CT-diagnosed hilar and/or mediastinal lymph nodes and pleural metastases were more likely to be associated with primary lung cancer. CONCLUSIONS: CT border, FDG uptake, hilar and/or mediastinal lymph node metastasis, and pleural metastasis are potential markers for diagnosis.

Correlation between EGFR mutation status and F18 -fluorodeoxyglucose positron emission tomography-computed tomography image features in lung adenocarcinoma.

BACKGROUND: The purpose of this study was to investigate an association between EGFR mutation status and 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET-CT) image features in lung adenocarcinoma. METHODS: Retrospective analysis of the data of 139 patients with lung adenocarcinoma confirmed by surgical pathology who underwent preoperative 18 F-FDG PET-CT was conducted. Correlations between EGFR mutation status, clinical characteristics, and PET-CT parameters, including the maximum standardized uptake value (SUVmax), the mean of the SUV (SUVmean), the peak of the SUV (SUVpeak) of the primary tumor, and the ratio of SUVmax between the primary tumor and the mediastinal blood pool (SUVratio), were statistically analyzed. Multivariate logistic regression analysis was performed to identify predictors of EGFR mutation. Receiver operating characteristic curves of statistical quantitative parameters were compared. RESULTS: EGFR mutations were detected in 74 (53.2%) of the 139 lung adenocarcinomas and were more frequent in non-smoking patients. Univariate analysis showed that the SUVmax, SUVmean, SUVpeak, and SUVratio were lower in EGFR-mutated than in wild-type tumors. The receiver operating characteristic curves showed no significant differences between their diagnostic efficiencies. Multivariate logistic regression analysis showed that being a never smoker was an independent predictor of EGFR mutation. CONCLUSION: Quantitative parameters based on 18 F-FDG PET-CT have modest power to predict the presence of EGFR mutation in lung adenocarcinoma; however, when compared to smoking history, they are not good or significant predictive factors.

CD147-mediated glucose metabolic regulation contributes to the predictive role of 18 F-FDG PET/CT imaging for EGFR-TKI treatment sensitivity in NSCLC.

The aim of this study is to investigate the role of CD147 in glucose metabolic regulation and its association with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment sensitivity prediction using 18 F-fluorodeoxyglucose (18 F-FDG) PET/CT imaging in non-small cell lung cancer (NSCLC). In this study, four human NSCLC cell lines with different EGFR-TKI responses were used to detect p-EGFR/EGFR and CD147 expression via Western blotting and flow cytometric analyses. Radioactive uptake of 18 F-FDG by established stable NSCLC cell lines (HCC827, H1975) with different levels of CD147 expression and the corresponding xenografts was assessed through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo to study the role of CD147 in glucose metabolic reprogramming. Correlation analyses were performed to investigate the association between CD147 expression and PD-L1 expression in stable NSCLC cell lines. Higher CD147 expression was found in EGFR-TKI-sensitive NSCLC cell lines than in relatively resistant NSCLC cell lines (HCC827>PC9>A549>H1975). CD147 could promote 18 F-FDG uptake by HCC827 and H1975 cells in vitro and in vivo through an EGFR-initiated Akt/mTOR-dependent signaling pathway. Programmed cell death-ligand 1 (PD-L1) expression was positively correlated with CD147 expression in human NSCLC cell lines. EGFR-TKI treatment sensitivity prediction in NSCLC using 18 F-FDG PET/CT imaging significantly correlated with CD147-mediated glucose metabolic regulation via the Akt/mTOR-dependent pathway. Moreover, PD-L1 expression in NSCLC cell lines could be regulated by CD147, suggesting a potential immunosuppression induced by the upregulation of tumor glucose metabolism.

Quantitative assessment of metabolic tumor burden in molecular subtypes of primary breast cancer with FDG PET/CT.

PURPOSE: We aimed to quantitatively evaluate volumetric metabolic tumor burden including metabolic tumor volume and total lesion glycolysis in different molecular subtypes of breast cancer using 18F-fluorodeoxyglucose (FDG) positron emission tomography/ computed tomography (PET/CT). METHODS: This study involved 99 female patients with pathologic diagnosis of primary breast cancer, who underwent 18F-FDG PET/CT before any therapy. Patients were divided into subtypes of luminal A, luminal B, ERBB2+, and basal-like based on the immunohistochemistry results. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) before and after correction for lean body mass were achieved and compared. Correlations between metabolic tumor burden and Ki-67 were analyzed and diagnostic performances of volumetric metabolic parameters were evaluated. RESULTS: TLG values were significantly different between each molecular subtype, while MTV values were not. Values of TLG were significantly reduced after normalizing for lean body mass in each subtype. Both of them showed correlations with Ki-67 and presented high diagnostic ability in identifying patients with basal-like breast cancer from the rest. TLGs before and after normalizing for the lean body mass had similar diagnostic performances in differentiating patients of basal-like subtype from the rest. CONCLUSION: Metabolic tumor burden could comprehensively reflect tumor metabolic differences of molecular subtypes of breast cancer, and it can serve to help differentiate patients with basal-like breast cancer.

Improve the Stability of Hybrid Halide Perovskite via Atomic Layer Deposition on Activated Phenyl-C61 Butyric Acid Methyl Ester.

Atomic layer deposition (ALD) of oxide film on [6,6]-phenyl-C61 butyric acid methyl ester (PCBM) shows a great promise to dramatically improve the ambient stability of hybrid halide perovskite. The nucleation of an ALD oxide on PCBM is critical to reliably apply this strategy. In this paper, we present the first study of the nucleation behavior of ALD oxides, including Al2O3 and ZnO, on PCBM. We find that PCBM film acts a gas diffusion barrier blocking the ALD reactants (diethyl zinc) from etching the underlying CH3NH3PbI3. However, ZnO is not able to nucleate on PCBM. We further identify that trimethyl aluminum, a strongly Lewis acid, reacts readily with C═O on PCBM to generate a seeding layer for nucleating ZnO ALD. This new chemical route is highly reliable and can be used to synthesize ALD ZnO coatings over PCBM. The synthesized PCBM/Al2O3-ZnO dramatically improves the stability of CH3NH3PbI3 against the ambience and even against liquid water. The result signifies the importance of understanding of nucleation of ALD in enabling reliable barrier coatings for hybrid halide perovskites.

Reaction between Pyridine and CH3NH3PbI3: Surface-Confined Reaction or Bulk Transformation?

Pyridine molecules have been used to passivate surface Pb2+ sites of CH3NH3PbI3, to recrystallize CH3NH3PbI3, and to bleach CH3NH3PbI3. However, these results contradict each other, as recrystallization and optical-bleach require transformation of bulk CH3NH3PbI3, but surface passivation demands the confinement of the reaction at the surface region. The underlying mechanism for these seemly contradicting results is not yet understood. In this paper, we show, at 25 °C, partial pressure of pyridine vapor is a determining factor for its reaction behaviors with CH3NH3PbI3: one can modify the surface region of CH3NH3PbI3 by using pyridine vapor of pressure 1.15 torr or lower but can transform the whole bulk CH3NH3PbI3 film with a pyridine vapor of 1.3 torr or higher. Our result is the first demonstration that the reaction modes, i.e., surface-confined reaction and bulk transformation, are very sensitive to the partial pressure of under-saturated pyridine vapor. Despite the different reaction behaviors, it is interesting that in all pressure ranges, pyridinium ion is a main product from the reaction between pyridine and CH3NH3PbI3. The bulk transformation is due to the formation of a liquid-like film, which increases the mobility of species to catalyze the reaction between pyridine and CH3NH3PbI3. It is important to note 1.3 torr is much smaller than the saturated vapor pressure of pyridine (20 torr at 25 °C). These findings provide a guidance in applying pyridine and other amines to functionalize and transform CH3NH3PbI3 and other hybrid halide perovskites. It also highlights the critical role of fundamental studies in controllably modifying CH3NH3PbI3.

Role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Newly Found Suspected Malignant Solitary Pulmonary Lesions in Patients Who Have Received Curative Treatment for Colorectal Cancer.

Background. Positron emission tomography/computed tomography (PET/CT) is recommended for colorectal cancer (CRC) patients with suspected malignant pulmonary lesions. This study aims to systematically discuss the 18F-FDG-PET/CT diagnosis of solitary pulmonary lesions that are strongly suspected to be malignant in CRC patients who have previously undergone curative therapy. Methods. This retrospective study involved 49 consecutive CRC patients who had previously undergone curative therapy and then underwent PET/CT for the investigation of solitary pulmonary lesions that were strongly suspected to be malignant. Results. Pathological examination confirmed the presence of pulmonary metastases (29 patients, 59.2%), primary lung cancer (15 patients, 30.6%), and benign pulmonary disease (5 patients, 10.2%). Small lung lesions, advanced pathological stage, adjuvant chemotherapy after CRC surgery, solitary pulmonary lesions with lower border irregularity, higher carcinoembryonic antigen level, and the lack of concomitant mediastinal lymph node metastasis were more likely to be associated with pulmonary metastasis than with primary lung cancer. None of these factors was independently significant in the multivariate analysis. Conclusion. Clinicopathological characteristics help to differentiate metastasis and primary lung cancer to some extent during the diagnosis of solitary pulmonary lesions suspected to be malignant in this group of patients. This may provide valuable information to clinicians.