Cell-free DNA assay for malignancy classification of high-risk lung nodules.

OBJECTIVE: Although low-dose computed tomography has been proven effective to reduce lung cancer-specific mortality, a considerable proportion of surgically resected high-risk lung nodules were still confirmed pathologically benign. There is an unmet need of a novel method for malignancy classification in lung nodules. METHODS: We recruited 307 patients with high-risk lung nodules who underwent curative surgery, and 247 and 60 cases were pathologically confirmed malignant and benign lung lesions, respectively. Plasma samples from each patient were collected before surgery and performed low-depth (5×) whole-genome sequencing. We extracted cell-free DNA characteristics and determined radiomic features. We built models to classify the malignancy using our data and further validated models with 2 independent lung nodule cohorts. RESULTS: Our models using one type of profile were able to distinguish lung cancer and benign lung nodules at an area under the curve metrics of 0.69 to 0.91 in the study cohort. Integrating all the 5 base models using cell-free DNA profiles, the cell-free DNA-based ensemble model achieved an area under the curve of 0.95 (95% CI, 0.92-0.97) in the study cohort and 0.98 (95% CI, 0.96-1.00) in the validation cohort. At a specificity of 95.0%, the sensitivity reached 80.0% in the study cohort. With the same threshold, the specificity and sensitivity had similar performances in both validation cohorts. Furthermore, the performance of area under the curve reached 0.97 in both the study and validation cohorts when considering the radiomic profile. CONCLUSIONS: The cell-free DNA profiles-based method is an efficient noninvasive tool to distinguish malignancies and high-risk but pathologically benign lung nodules.

Electron-Induced Nonmonotonic Pressure Dependence of the Lattice Thermal Conductivity of θ-TaN.

Recent theoretical and experimental research suggests that θ-TaN is a semimetal with high thermal conductivity (κ), primarily due to the contribution of phonons (κ_{ph}). By using first-principles calculations, we show a nonmonotonic pressure dependence of the κ of θ-TaN. κ_{ph} first increases until it reaches a maximum at around 60 GPa, and then decreases. This anomalous behavior is a consequence of the competing pressure responses of phonon-phonon and phonon-electron interactions, in contrast to the known materials BAs and BP, where the nonmonotonic pressure dependence is caused by the interplay between different phonon-phonon scattering channels. Although TaN has phonon dispersion features similar to BAs at ambient pressure, its response to pressure is different and an overall stiffening of the phonon branches takes place. Consequently, the relevant phonon-phonon scattering weakens as pressure increases. However, the increased electronic density of states near the Fermi level, and specifically the emergence of additional pockets of the Fermi surface at the high-symmetry L point in the Brillouin zone, leads to a substantial increase in phonon-electron scattering at high pressures, driving a decrease in κ_{ph}. At intermediate pressures (∼20-70 GPa), the κ of TaN surpasses that of BAs. Our Letter provides deeper insight into phonon transport in semimetals and metals where phonon-electron scattering is relevant.

Relative Motion Estimation Algorithm for Noncooperative Targets Considering Multiple Solutions of Rotational Parameters.

On-orbit servicing using a space robot is gaining popularity among the space community for both economic and safety aspects. In particular, the estimation of the relative motion of a noncooperative target is a challenging problem. This study presents a relative motion estimation scheme based on stereovision for noncooperative targets considering multiple solutions of rotational parameters. Specifically, the mass distribution of the target is identified based on the least-square method and the principle of conservation of angular momentum. Then, the determination of a unique principal axis coordinate frame of the target is employed to resolve the multiple-solution problem. In addition, an EKF (extended Kalman filter)-based filter with global observability is designed to estimate the full motion states and inertia parameters of the target. The convergence performance of the proposed method is verified by numerical simulation. The results also demonstrate that the method is robust to occlusion.

Synthesis of Pd/Carbon Hollow Spheres by the Microwave Discharge Method for Catalytic Debenzylation.

Pd/C catalysts have been widely applied in the debenzylation process due to their excellent ability of hydrogenolysis. However, they have been suffering from the problems of agglomeration and loss of active components, which lead to decreased and unstable activity. Thus, it is still a challenge to achieve Pd/C catalysts with high activity and stability. Herein, we propose a strategy for preparing Pd/C catalysts on porous carbon hollow spheres by a microwave discharge method. Due to the high-temperature property and reducibility of microwave discharge, Pd precursors can be rapidly reduced, resulting in well-dispersed Pd nanoparticles with a small size on the carbon carrier. Besides, the matched mesopores in the carbon hollow spheres can anchor Pd nanoparticles and effectively reduce the agglomeration and loss of Pd nanoparticles during the catalytic reaction. As a result, the as-prepared Pd/mesoporous carbon hollow spheres exhibit high and stable activity in the debenzylation reaction.

[Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities].

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS: The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.

Enhanced Detection of Landmark Minimal Residual Disease in Lung Cancer Using Cell-free DNA Fragmentomics.

Currently, approximately 30%-55% of the patients with non-small cell lung cancer (NSCLC) develop recurrence due to minimal residual disease (MRD) after receiving surgical resection of the tumor. This study aims to develop an ultrasensitive and affordable fragmentomic assay for MRD detection in patients with NSCLC. A total of 87 patients with NSCLC, who received curative surgical resections (23 patients relapsed during follow-up), enrolled in this study. A total of 163 plasma samples, collected at 7 days and 6 months postsurgical, were used for both whole-genome sequencing (WGS) and targeted sequencing. WGS-based cell-free DNA (cfDNA) fragment profile was used to fit regularized Cox regression models, and leave-one-out cross-validation was further used to evaluate models' performance. The models showed excellent performances in detecting patients with a high risk of recurrence. At 7 days postsurgical, the high-risk patients detected by our model showed an increased risk of 4.6 times, while the risk increased to 8.3 times at 6 months postsurgical. These fragmentomics determined higher risk compared with the targeted sequencing-based circulating mutations both at 7 days and 6 months postsurgical. The overall sensitivity for detecting patients with recurrence reached 78.3% while using both fragmentomics and mutation results from 7 days and 6 months postsurgical, which increased from the 43.5% sensitivity by using only the circulating mutations. The fragmentomics showed great sensitivity in predicting patient recurrence compared with the traditional circulating mutation, especially after the surgery for early-stage NSCLC, therefore exhibiting great potential to guide adjuvant therapeutics. Significance: The circulating tumor DNA mutation-based approach shows limited performance in MRD detection, especially for landmark MRD detection at an early-stage cancer after surgery. Here, we describe a cfDNA fragmentomics-based method in MRD detection of resectable NSCLC using WGS, and the cfDNA fragmentomics showed a great sensitivity in predicting prognosis.

21st anniversary of job embeddedness: A retrospection and future research agenda.

BACKGROUND: Since the previous decade, researchers and academics have paid close attention to studying job embeddedness (JE), but the bibliometric examination of JE has not yet been explored. OBJECTIVE: This study aims to provide general information on the trends of the studies on JE as well as an overall perspective on the development of this topic by utilising a bibliometric analytic approach. METHOD: A bibliometric evaluation was conducted in the JE field since the first publication was documented in the Scopus database. The information retrieved examines 1572 JE papers from a variety of perspectives, including citation and publishing metrics. RESULTS: The research results pinpoint the most productive countries, universities, journals, authors, and JE articles. The study also classified the most important themes and offered some recommendations for further research. CONCLUSION: The study provided a snapshot of JE patterns and trajectories from 1993 to 2020, which can help academics and practitioners figure out the pattern and direction of future research. To the best of our knowledge, no other study examines the bibliographic data on JE and thus this work is one of the first contributions to the literature.

[Correlation between Immune Microenvironment Features and EGFR Mutation Status 
in Lung Adenocarcinoma].

BACKGROUND: The morbidity and mortality rates of lung cancer remain high worldwide, and lung adenocarcinoma is one of the most important tissue subtypes of lung cancer. Epidermal growth factor receptor (EGFR) mutation is an important driver gene mutation for lung adenocarcinoma. In recent years, immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, have achieved remarkable efficacy in some lung cancer patients. Patients with EGFR mutations enjoyed limited benefits from immunotherapy according to recent studies. This study aimed to explore the relationship between EGFR mutation status and the spatial distribution as well as infiltration number of various immune cells in patients with EGFR mutant lung adenocarcinoma. METHODS: This study included 62 lung adenocarcinoma patients who underwent surgery. Through multi-point sampling of surgically removed tumor tissues in different areas, 223 tumor tissue samples were finally obtained. We aquired EGFR mutations status including variant allele frequency (VAF) and mutation subtype in each tumor tissue by genetic test. Afterwards, hematoxylin-eosin (HE) staining, immunohistochemical staining and multiplex fluorescence immunohistochemistry staining have been performed, therefore the infiltration of various immune cells and the distribution of tertiary lymphoid structure (TLS) in tumor tissues were obtained by calculating the immunohistochemical score. RESULTS: Compared with EGFR wild-type patients, patients with EGFR-mutant lung adenocarcinoma had more infiltration of CD68+ macrophages and major histocompatibility complex (MHC) class II antigen-presenting cells and higher spatial distribution heterogeneity of MHC class II antigen presenting cells in tumor tissues, while CD56+ natural killer cells and CD8+ T cells had lower infiltration. Tumor tissues with higher EGFR VAF were associated with lower cell infiltration such as CD3+ T cells, CD20+ B cells, CD56+ natural killer cells, CD68+ macrophages, CD8+ T cells, and only CD3+ T cells showed a lower spatial distribution heterogeneity. For the two common subtypes of EGFR mutations in Chinese population, tumor tissues with EGFR exon 19 deletion mutations have lower immune cell infiltration but higher spatial distribution heterogeneity of CD3+ T cells, CD56+ natural killer cells, CD68+ macrophages, and CD8+ T cells than that in EGFR exon 21 L858R mutant tumor tissues. Prognostic analysis found that patients with EGFR mutations with high degree of CD3+ T cells, CD20+ B cell infiltration and larger numbers of TLS formation and high spatial distribution heterogeneity of CD8+ T cell had longer disease-free survival. CONCLUSIONS: EGFR-mutated lung adenocarcinoma had a unique "non-inflammatory" tumor microenvironment with low infiltration of immune cells, and there was also heterogeneity in the tumor microenvironment among the tumors with different mutation subtypes and mutation abundance. These differences were not only reflected in the number but also the spatial distribution of immune cell infiltration. Hence, further studies on the immune microenvironment of EGFR-mutant lung adenocarcinoma were of great significance for improving the efficacy of immunotherapy in EGFR-mutant lung adenocarcinoma patients in the future.

Integrating the Interpersonal Theory of Suicide Into the Relations Between Cyber-Victimization and Suicidality Among Adolescents: A Short-Term Prospective Study.

The relation between cyber-victimization and suicidality among adolescents has been well documented; however, the mechanisms underlying this association have not been well investigated. Drawing upon the interpersonal theory of suicide, this study aimed to examine the mediating mechanisms (i.e., thwarted belongingness and perceived burdensomeness) underlying longitudinal, bidirectional relations between cyber-victimization and suicidal ideation/attempts among adolescents and explore gender differences in the mechanisms. Participants were 497 Chinese adolescents (46.1% male; Mage = 13.28, SD = .66), who completed the assessment of cyber-victimization, thwarted belongingness, and perceived burdensomeness, suicidal ideation/attempts at three-time points. The time interval between each two assessments is two weeks. Results showed the reciprocal relations between cyber-victimization and thwarted belongingness/perceived burdensomeness, between thwarted belongingness and suicidal ideation/suicide attempts, and between perceived burdensomeness and suicide attempts. Longitudinal mediation analyses indicated that Time 2 thwarted belongingness mediated the relation between Time 1 cyber-victimization and Time 3 suicidal ideation/suicide attempts. Besides, the reverse pathway from Time 1 suicidal ideation to Time 3 cyber-victimization was also mediated by Time 2 thwarted belongingness, but it was only significant in females, as suggested by multiple-group analyses. According to the aforementioned results, the interpersonal theory of suicide provides a useful framework for understanding relations between cyber-victimization and suicidality. Findings suggest that intervention targeted at improving the need to belong may help reduce suicide risk and lower cyber-victimization. Anti-cyber-victimization should be integrated into suicide intervention and prevention programs, and gender differences should be taken into account in order to enhance the program's effectiveness.

Multidimensional Cell-Free DNA Fragmentomic Assay for Detection of Early-Stage Lung Cancer.

Rationale: Cell-free DNA (cfDNA) analysis holds promise for early detection of lung cancer and benefits patients with higher survival. However, the detection sensitivity of previous cfDNA-based studies was still low to suffice for clinical use, especially for early-stage tumors. Objectives: Establish an accurate and affordable approach for early-stage lung cancer detection by integrating cfDNA fragmentomics and machine learning models. Methods: This study included 350 participants without cancer and 432 participants with cancer. The participants' plasma cfDNA samples were profiled by whole-genome sequencing. Multiple cfDNA features and machine learning models were compared in the training cohort to achieve an optimal model. Model performance was evaluated in three validation cohorts. Measurements and Main Results: A stacked ensemble model integrating five cfDNA features and five machine learning algorithms constructed in the training cohort (cancer: 113; healthy: 113) outperformed all the models built on individual feature-algorithm combinations. This integrated model yielded superior sensitivities of 91.4% at 95.7% specificity for cohort validation I (area under the curve [AUC], 0.984), 84.7% at 98.6% specificity for validation II (AUC, 0.987), and 92.5% at 94.2% specificity for additional validation (AUC, 0.974), respectively. The model's high performance remained consistent when sequencing depth was down to 0.5× (AUC, 0.966-0.971). Furthermore, our model is sensitive to identifying early pathological features (83.2% sensitivity for stage I, 85.0% sensitivity for <1 cm tumor at the 0.66 cutoff). Conclusions: We have established a stacked ensemble model using cfDNA fragmentomics features and achieved superior sensitivity for detecting early-stage lung cancer, which could promote early diagnosis and benefit more patients.

Immunotherapy for bilateral multiple ground glass opacities: An exploratory study for synchronous multiple primary lung cancer.

Background: Bilateral multiple ground glass opacities (GGOs) are observed in quite a part of patients with early-stage lung adenocarcinoma. For this so-called synchronous multiple primary lung cancer (sMPLC), targeting immune checkpoint is a favorable option in addition to surgical resection. The purpose of this study is to reveal the safety and efficacy of performing immune checkpoint inhibitors (ICIs) on patients with sMPLC and to explore the biomarkers of the efficacy. Methods: A total of 21 patients with sMPLC were enrolled and all included cases were pathologically confirmed adenocarcinoma after conducting surgical treatment for unilateral GGOs. ICIs of Sintilimab were then used to target programmed death 1 (200mg i.v., Q3W) for up to 10 cycles. Seven patients of them received the other surgery for contralateral GGOs, and multiomics assessments, including neoantigens, somatic mutations, and methylated loci, were further performed to investigate potential biomarkers. Results: Grade 1 or 2 treatment-related adverse events (AEs) occurred in most of the patients (12/21, 57.1%), and one subject withdrawn for grade 3 AEs. For the seven patients underwent twice surgeries, twelve and thirteen GGOs were achieved before and after the use of ICIs separately, and a favorable efficacy was observed among six lesions after immunotherapy (> 50% pathologic tumor regression). Tumor infiltration T-cell and B-cell were further shown to be associated with the biological activity of ICIs. According to mechanism-based multiomics analyses, MUC19- and PCDHB5- mutations were indicated to correlate with a favorable prognosis of sMPLC underwent immunotherapy, and our results suggested that immunogenetic mutation and associated promoter methylation could provide a quantitative explanation for the pathologic response of GGOs. Conclusion: Our study provides evidence that the use of ICIs contributed favorable efficacy and safety to patients with sMPLC. Immune infiltration and immunogenic biomarkers are revealed to be implications of performing ICIs on sMPLC. These preliminary findings exhibit the prospects in performing neoadjuvant or adjuvant immunotherapies on patients with sMPLC. Clinical Trial Registration: https://www.chictr.org.cn/showproj.aspx?proj=36878, identifier ChiCTR1900022159.

Cancer-associated fibroblast-specific lncRNA LINC01614 enhances glutamine uptake in lung adenocarcinoma.

BACKGROUND: Besides featured glucose consumption, recent studies reveal that cancer cells might prefer "addicting" specific energy substrates from the tumor microenvironment (TME); however, the underlying mechanisms remain unclear. METHODS: Fibroblast-specific long noncoding RNAs were screened using RNA-seq data of our NJLCC cohort, TCGA, and CCLE datasets. The expression and package of LINC01614 into exosomes were identified using flow cytometric sorting, fluorescence in situ hybridization (FISH), and quantitative reverse transcription polymerase chain reaction (RT-PCR). The transfer and functional role of LINC01614 in lung adenocarcinoma (LUAD) and CAFs were investigated using 4-thiouracil-labeled RNA transfer and gain- and loss-of-function approaches. RNA pull-down, RNA immunoprecipitation, dual-luciferase assay, gene expression microarray, and bioinformatics analysis were performed to investigate the underlying mechanisms involved. RESULTS: We demonstrate that cancer-associated fibroblasts (CAFs) in LUAD primarily enhance the glutamine metabolism of cancer cells. A CAF-specific long noncoding RNA, LINC01614, packaged by CAF-derived exosomes, mediates the enhancement of glutamine uptake in LUAD cells. Mechanistically, LINC01614 directly interacts with ANXA2 and p65 to facilitate the activation of NF-κB, which leads to the upregulation of the glutamine transporters SLC38A2 and SLC7A5 and eventually enhances the glutamine influx of cancer cells. Reciprocally, tumor-derived proinflammatory cytokines upregulate LINC01614 in CAFs, constituting a feedforward loop between CAFs and cancer cells. Blocking exosome-transmitted LINC01614 inhibits glutamine addiction and LUAD growth in vivo. Clinically, LINC01614 expression in CAFs is associated with the glutamine influx and poor prognosis of patients with LUAD. CONCLUSION: Our study highlights the therapeutic potential of targeting a CAF-specific lncRNA to inhibit glutamine utilization and cancer progression in LUAD.

Whole-Exome Sequencing Reveals the Genomic Features of the Micropapillary Component in Ground-Glass Opacities.

BACKGROUND: Micropapillary components are observed in a considerable proportion of ground-glass opacities (GGOs) and contribute to the poor prognosis of patients with invasive lung adenocarcinoma (LUAD). However, the underlying mutational processes related to the presence of micropapillary components remain obscure, limiting the development of clinical interventions. METHODS: We collected 31 GGOs, which were separated into paired micropapillary and non-micropapillary components using microdissection. Whole-exome sequencing (WES) was performed on the GGO components, and bioinformatics analysis was conducted to reveal the genomic features of the micropapillary component in invasive LUAD. RESULTS: The micropapillary component had more genomic variations, including tumor mutation burden, intratumoral heterogeneity, and copy number variation. We also observed the enrichment of AID/APOBEC mutation signatures and an increased activation of the RTK/Ras, Notch, and Wnt oncogenic pathways within the micropapillary component. A phylogenetic analysis further suggested that ERBB2/3/4, NCOR1/2, TP53, and ZNF469 contributed to the micropapillary component's progression during the early invasion of LUAD, a finding that was validated in the TCGA cohort. CONCLUSIONS: Our results revealed specific mutational characteristics of the micropapillary component of invasive LUAD in an Asian population. These characteristics were associated with the formation of high-grade invasive patterns. These preliminary findings demonstrated the potential of targeting the micropapillary component in patients with early-stage LUAD.

Synthesis of High-Loading Pt/C Electrocatalysts Using a Surfactant-Assisted Microwave Discharge Method for Oxygen Reduction Reactions.

High-loading Pt/C catalysts play an important role in the practical application of metal-air batteries and fuel cells because of their superior activity, high conductivity, and commercial availability. It is well known that high loadings always lead to the agglomeration of Pt nanoparticles, resulting in a loss of catalytic activity and stability; thus, it still remains a challenge to prepare high-loading Pt/C catalysts with high dispersion and small particle sizes. Here, we introduce a surfactant-assisted microwave discharge method to prepare high-loading (>40 wt %) Pt/C electrocatalysts with ultrafine particle sizes (∼3.19 nm) and good dispersion. Benefitting from the high-temperature property and reducibility of carbon-induced-arc, the surfactant and Pt precursors undergo rapid decomposition, reduction, and carbonization, generating the structure of Pt@C on carbon black. The carbon derived from the surfactant can not only inhibit the agglomeration of Pt nanoparticles but also prevent the Pt core from toxication, ensuring high activity and stability of the high-loading Pt/C catalyst. When evaluated in the oxygen reduction reaction, the as-prepared Pt/C catalyst demonstrates a comparable activity and better methanol resistance to commercial Pt/C.

Economic growth, technology, and CO2 emissions in BRICS: Investigating the non-linear impacts of economic complexity.

Upgrading economic structures and producing less pollution-intensive goods are indispensable for achieving Sustainable Development Goals (SDGs) in BRICS (Brazil, Russia, India, China, and South Africa) that produce 41% of global CO2 emissions. Economic complexity (ECC), which measures the sophistication of productivity and economic structure, has important environmental repercussions. Theoretically, the environmental impacts of economic complexity at higher levels and lower levels of complexity vary from each other. However, the majority of previous studies have overlooked these theoretical underpinnings while assessing the environmental repercussions of economic complexity. In addition, technological competencies are necessary to boost the economic complexity levels. Accordingly, this study uncovers the non-linear effects of economic complexity on CO2 emissions including technology, population density, and economic growth in a STIRPAT model. To this end, the panel data from 1992 to 2018 is analyzed using the Continuously Updated Fully Modified method (CuP-FM) in the context of BRICS. The long-run results uncovered that CO2 emissions intensify at a lower level of economic complexity. On the flip side, a higher level of economic complexity is beneficial in mitigating CO2 in BRICS. Hence, the economic complexity and CO2 connections follow an inverted U-shaped curve. The results also disclosed that expanding the level of technology lessens CO2 and stimulates the quality of the environment. Further, population density and economic growth are evidenced to intensify CO2. Moreover, economic complexity and technology Granger cause CO2. Lastly, strategies are directed in the context of Sustainable Development Goals 9 and 13 to control CO2 emissions by upgrading technology and products complexity.

Predicting Tumor Mutation Burden and EGFR Mutation Using Clinical and Radiomic Features in Patients with Malignant Pulmonary Nodules.

Pulmonary nodules (PNs) shown as persistent or growing ground-glass opacities (GGOs) are usually lung adenocarcinomas or their preinvasive lesions. Tumor mutation burden (TMB) and somatic mutations are important determinants for the choice of strategy in patients with lung cancer during therapy. A total of 93 post-operative patients with 108 malignant PNs were enrolled for analysis (75 cases in the training cohort and 33 cases in the validation cohort). Radiomics features were extracted from preoperative non-contrast computed tomography (CT) images of the entire tumor. Using commercial next generation sequencing, we detected TMB status and somatic mutations of all FFPE samples. Here, 870 quantitative radiomics features were extracted from the segmentations of PNs, and pathological and clinical characteristics were collected from medical records. The LASSO (least absolute shrinkage and selection operator) regression and stepwise logistic regressions were performed to establish the predictive model. For the epidermal growth factor receptor (EGFR) mutation, the AUCs of the clinical model and the integrative model validated by the validation set were 0.6726 (0.4755-0.8697) and 0.7421 (0.5698-0.9144). For the TMB status, the ROCs showed that AUCs of the clinical model and the integrative model validated by the validation set were 0.7808 (0.6231-0.9384) and 0.8462 (0.7132-0.9791). The quantitative radiomics signatures showed potential value in predicting the EGFR mutant and TMB status in GGOs. Moreover, the integrative model provided sufficient information for the selection of therapy and deserves further analysis.

Expression and significance of miR-34 with PI3K, AKT and mTOR proteins in colorectal adenocarcinoma tissues.

This research was carried out to investigate the expression of miR-34a, miR-34b and p-PI3K, p-AKT, and mTOR proteins in colorectal adenocarcinoma and corresponding distal cutaneous normal mucosal tissues and their relationship with the clinicopathological parameters of colorectal adenocarcinoma as well as the correlation between miR-34a, miR-34b and PI3K/AKT/mTOR signaling pathway. The expression of p-PI3K, p-AKT, and mTOR proteins in 67 colorectal adenocarcinomas and the corresponding distal cut-off normal mucosa were assayed by immunohistochemistry. Their relationship with clinicopathological parameters and the correlation of the three proteins were evaluated. The expression of miR-34a and miR-34b in colorectal adenocarcinoma and the corresponding distal cutaneous normal mucosa was detected by applying real-time quantitative PCR. The correlation between colorectal adenocarcinoma tissue miR-34a, miR-34b and p-PI3K, p-AKT, and mTOR proteins, respectively, was analyzed. Results showed that the expression of p-PI3K, p-AKT and mTOR proteins in colorectal adenocarcinoma tissues was higher than that in the corresponding distal cutaneous normal mucosa (P=0.000), and there was a positive correlation between the expression of the three proteins in colorectal adenocarcinoma tissues. The expression of p-PI3K and p-AKT protein in colorectal adenocarcinoma tissues were correlated with tumor size, differentiation degree, infiltration degree, lymph node metastasis and TNM stage (P<0.05). The expression of mTOR protein was related to tumor size and differentiation degree (P<0.05). The relative expression of miR-34a and miR-34b in colorectal adenocarcinoma tissues was less than that in the corresponding distal cutaneous normal mucosa (P<0.05), and the expression of miR-34a and miR-34b was positively correlated. The expression of miR-34a and miR-34b in colorectal adenocarcinoma tissues was negatively correlated with the expression of p-PI3K, p-AKT and mTOR proteins. In conclusion, the PI3K/AKT/mTOR signaling pathway may promote colorectal adenocarcinoma and differentially participate in differentiation, infiltration and lymph node metastasis. Also, miR-34a and miR-34b may inhibit colorectal adenocarcinoma. Importantly, miR-34a and miR-34b may affect the development and progression of colorectal adenocarcinoma by regulating PI3K/AKT/mTOR signaling pathway.

Metabolic network-based identification of plasma markers for non-small cell lung cancer.

Metabolic markers, offering sensitive information on biological dysfunction, play important roles in diagnosing and treating cancers. However, the discovery of effective markers is limited by the lack of well-established metabolite selection approaches. Here, we propose a network-based strategy to uncover the metabolic markers with potential clinical availability for non-small cell lung cancer (NSCLC). First, an integrated mass spectrometry-based untargeted metabolomics was used to profile the plasma samples from 43 NSCLC patients and 43 healthy controls. We found that a series of 39 metabolites were altered significantly. Relying on the human metabolic network assembled from Kyoto Encyclopedia of Genes and Genomes (KEGG) database, we mapped these differential metabolites to the network and constructed an NSCLC-related disease module containing 23 putative metabolic markers. By measuring the PageRank centrality of molecules in this module, we computationally evaluated the network-based importance of the 23 metabolites and demonstrated that the metabolism pathways of aromatic amino acids and long-chain fatty acids provided potential molecular targets of NSCLC (i.e., IL4l1 and ACOT2). Combining network-based ranking and support-vector machine modeling, we further found a panel of eight metabolites (i.e., pyruvate, tryptophan, and palmitic acid) that showed a high capability to differentiate patients from controls (accuracy > 97.7%). In summary, we present a meaningful network method for metabolic marker discovery and have identified eight strong candidate metabolites for NSCLC diagnosis.

Risk Signature of Cancer-Associated Fibroblast-Secreted Cytokines Associates With Clinical Outcomes of Breast Cancer.

Cancer-associated fibroblasts (CAFs) are key components in tumor microenvironment (TME). The secreted products of CAFs play important roles in regulating tumor cells and further impacting clinical prognosis. This study aims to reveal the relationship between CAF-secreted cytokines and breast cancer (BC) by constructing the risk signature. We performed three algorithms to reveal CAF-related cytokines in the TCGA BC dataset and identified five prognosis-related cytokines. Then we used single-cell RNA sequencing (ScRNA-Seq) datasets of BC to confirm the expression level of these five cytokines in CAFs. METABRIC and other independent datasets were utilized to validate the findings in further analyses. Based on the identified five-cytokine signature derived from CAFs, BC patients with high-risk score (RS) had shorter overall survival than low-RS cases. Further analysis suggested that the high-RS level correlated with cell proliferation and mast cell infiltration in BCs of the Basal-like subtype. The results also indicated that the level of RS could discriminate the high-risk BC cases harboring driver mutations (i.e., PI3KCA, CDH1, and TP53). Additionally, the status of five-cytokine signature was associated with the frequency and molecular timing of whole genome duplication (WGD) events. Intratumor heterogeneity (ITH) analysis among BC samples indicated that the high-RS level was associated with the increase of tumor subclones. This work demonstrated that the prognostic signature based on CAF-secreted cytokines was associated with clinical outcome, tumor progression, and genetic alteration. Our findings may provide insights to develop novel strategies for early intervention and prognostic prediction of BC.

Modifiers versus Channels: Creating Shape-Selective Catalysis of Metal Nanoparticles/Porous Nanomaterials.

Shape-selective catalysis plays a key role in chemical synthesis. Porous nanomaterials with uniform pore structures are ideal supports for metal nanoparticles (MNPs) to generate efficient shape-selective catalysis. However, many commercial irregular porous nanomaterials face the challenge to realize satisfactory shape selectivity due to the lack of molecular sieving structures. Herein, we report a concept of creating shape selectivity in MNPs/porous nanomaterials through intentionally poisoning certain MNPs using suitable modifiers. The remaining MNPs within the substrates can cooperate with the channels to generate selectivity. Such a strategy not only applies to regular porous nanomaterials (such as MOFs, zeolites) but also extended to irregular porous nanomaterials (such as active carbon, P25). Potentially, the matching among different MNPs, corresponding modifiers, and porous nanomaterials makes our strategy promising in selective catalytic systems.