Identification of a novel glioblastoma multiforme molecular subtype with poor prognosis and high immune infiltration based on oxidative stress-related genes.

Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor with a poor prognosis. Reactive oxygen species that accumulate during tumorigenesis can cause oxidative stress (OS), which plays a crucial role in cancer cell survival. Clinical and transcriptome data of TCGA-GBM dataset from UCSC Xena database were analyzed. Consensus clustering analysis was conducted to identify OS-related molecular subtypes for GBM. The immune infiltrate level between subtypes were characterized by ESTIMATE algorithm. Differentially expressed genes (DEGs) between subtypes were screened by DESeq2 package. Two OS-related molecular subtypes of GBM were identified, and cluster 2 had poorer overall survival and higher immune infiltration levels than cluster 1. Enrichment analysis showed that 54 DEGs in cluster 2 were significantly enriched in cytokine/chemokine-related functions or pathways. Ten hub genes (CSF2, CSF3, CCL7, LCN2, CXCL6, MMP8, CCR8, TNFSF11, IL22RA2, and ORM1) were identified in GBM subtype 2 through protein-protein interaction network, most of which were positively correlated with immune factors and immune checkpoints. A total of 55 small molecule drugs obtained from drug gene interaction database (DGIdb) may have potential therapeutic effects in GBM subtype 2 patients. Our study identified 10 hub genes as potential therapeutic targets in GBM subtype 2 patients, who have poorer overall survival and higher immune infiltration levels. These findings could pave the way for new treatments for this aggressive form of brain cancer.

Gas-phase formation of the resonantly stabilized 1-indenyl (C9H7•) radical in the interstellar medium.

The 1-indenyl (C9H7•) radical, a prototype aromatic and resonantly stabilized free radical carrying a six- and a five-membered ring, has emerged as a fundamental molecular building block of nonplanar polycyclic aromatic hydrocarbons (PAHs) and carbonaceous nanostructures in deep space and combustion systems. However, the underlying formation mechanisms have remained elusive. Here, we reveal an unconventional low-temperature gas-phase formation of 1-indenyl via barrierless ring annulation involving reactions of atomic carbon [C(3P)] with styrene (C6H5C2H3) and propargyl (C3H3•) with phenyl (C6H5•). Macroscopic environments like molecular clouds act as natural low-temperature laboratories, where rapid molecular mass growth to 1-indenyl and subsequently complex PAHs involving vinyl side-chained aromatics and aryl radicals can occur. These reactions may account for the formation of PAHs and their derivatives in the interstellar medium and carbonaceous chondrites and could close the gap of timescales of their production and destruction in our carbonaceous universe.

N-methyl-d-aspartate receptor 1 activation mediates cadmium-induced epithelial-mesenchymal transition in proximal tubular cells.

Cadmium (Cd) is a commonly found environmental pollutant and is known to damage multiple organs with kidneys being the most common one. N-methyl-d-aspartate receptor 1 (NMDAR1) is a ligand-gated ion channel that is highly permeable to calcium ion (Ca2+). Because Cd2+ and Ca2+ have structural and physicochemical similarities, whether and how Cd could interfere NMDAR1 function to cause renal epithelial cells dysfunction remains unknown. In this study, we investigated the role of NMDAR1 in Cd-induced renal damage and found that Cd treatment upregulated NMDAR1 expression and promoted epithelial-mesenchymal transition (EMT) in mouse kidneys in vivo and human proximal tubular epithelial HK-2 cells in vitro, which were accompanied with activation of the inositol-requiring enzyme 1 (IRE-1α) / spliced X box binding protein-1 (XBP-1s) pathway, an indicative of endoplasmic reticulum (ER) stress. Mechanistically, NMDAR1 upregulation by Cd promoted Ca2+ channel opening and Ca2+ influx, resulting in ER stress and subsequently EMT in HK-2 cells. Inhibition of NMDAR1 by pharmacological antagonist MK-801 significantly attenuated Cd-induced Ca2+ influx, ER stress, and EMT. Pretreatment with the IRE-1α/XBP-1s pathway inhibitor STF-083010 also restored the epithelial phenotype of Cd-treated HK-2 cells. Therefore, our findings suggest that NMDAR1 activation mediates Cd-induced EMT in proximal epithelial cells likely through the IRE-1α/XBP-1s pathway, supporting the idea that NMDAR1 could be a potential therapeutic target for Cd-induced renal damage.

Multifunctional Au@AgBiS2 Nanoparticles as High-Efficiency Radiosensitizers to Induce Pyroptosis for Cancer Radioimmunotherapy.

Radiotherapy (RT), a widely used clinical treatment modality for cancer, uses high-energy irradiation for reactive oxygen species (ROS) production and DNA damage. However, its therapeutic effect is primarily limited owing to insufficient DNA damage to tumors and harmful effects on normal tissues. Herein, a core-shell structure of metal-semiconductors (Au@AgBiS2 nanoparticles) that can function as pyroptosis inducers to both kill cancer cells directly and trigger a robust anti-tumor immune against 4T1 triple-negative murine breast cancer and metastasis is rationally designed. Metal-semiconductor composites can enhance the generation of considerable ROS and simultaneously DNA damage for RT sensitization. Moreover, Au@AgBiS2 , a pyroptosis inducer, induces caspase-3 protein activation, gasdermin E cleavage, and the release of damage-associated molecular patterns. In vivo studies in BALB/c mice reveal that Au@AgBiS2 nanoparticles combined with RT exhibit remarkable antitumor immune activity, preventing tumor growth, and lung metastasis. Therefore, this core-shell structure is an alternative for designing highly effective radiosensitizers for radioimmunotherapy.

Efficient photocatalytic hydrogen production over ZnIn2S4 by producing sulfur vacancies and coupling with nickel-based polyoxometalate.

A composite catalytic system using sulfur-vacancy-containing ZnIn2S4-Sv as a light-harvesting material and nickel-based polyoxometalate Na6K4[Ni4(H2O)2(PW9O34)2] (Ni4POM) as a co-catalyst was developed. The Ni4POM/ZnIn2S4-Sv composite gave a good hydrogen production rate of 337.5 µmol h-1, a value 11.8 times higher than that of ZnIn2S4-Sv. The direction of electron transfer, from ZnIn2S4-Sv to Ni4POM, was verified using surface photovoltage spectra.

Bi2-xMnxO3 Nanospheres Engaged Radiotherapy with Amplifying DNA Damage.

Radiotherapy efficacy was greatly limited by hypoxia and overexpression of glutathione (GSH) in the tumor microenvironment (TME), which maintained the immunosuppressive microenvironment and promoted DNA repair. In this work, 4T1 cell membrane-coated Bi2-xMnxO3 nanospheres have been achieved via a facile protocol, which showed enhanced therapeutic efficacy for a combination of radiotherapy and immunotherapy. Bi2-xMnxO3 nanospheres showed appreciable performance in generating O2 in situ and depleting GSH to amplify DNA damage and remodel the tumor immunosuppressive microenvironment, thus enhancing radiotherapy efficacy. Cancer cell membrane-coated Bi2-xMnxO3 nanospheres (T@BM) prolonged blood circulation time and enriched the accumulation of the materials in the tumor. Meanwhile, the released Mn2+ could activate STING pathway-induced immunotherapy, resulting in the immune infiltration of CD8+ T cells on in situ mammary tumors and the inhibition of pulmonary nodules. As a result, approximately 1.9-fold recruitment of CD8+ T cells and 4.0-fold transformation of mature DC cells were observed compared with the phosphate-buffered saline (PBS) group on mammary tumors (in situ). In particular, the number of pulmonary nodules significantly decreased and the proliferation of pulmonary metastatic lesions was substantially inhibited, which provided a longer survival period. Therefore, T@BM exhibited great potential for the treatment of 4T1 tumors in situ and lung metastasis.

[Automatic modeling of the knee joint based on artificial intelligence].

Objective: To investigate an artificial intelligence (AI) automatic segmentation and modeling method for knee joints, aiming to improve the efficiency of knee joint modeling. Methods: Knee CT images of 3 volunteers were randomly selected. AI automatic segmentation and manual segmentation of images and modeling were performed in Mimics software. The AI-automated modeling time was recorded. The anatomical landmarks of the distal femur and proximal tibia were selected with reference to previous literature, and the indexes related to the surgical design were calculated. Pearson correlation coefficient ( r) was used to judge the correlation of the modeling results of the two methods; the consistency of the modeling results of the two methods were analyzed by DICE coefficient. Results: The three-dimensional model of the knee joint was successfully constructed by both automatic modeling and manual modeling. The time required for AI to reconstruct each knee model was 10.45, 9.50, and 10.20 minutes, respectively, which was shorter than the manual modeling [(64.73±17.07) minutes] in the previous literature. Pearson correlation analysis showed that there was a strong correlation between the models generated by manual and automatic segmentation ( r=0.999, P<0.001). The DICE coefficients of the 3 knee models were 0.990, 0.996, and 0.944 for the femur and 0.943, 0.978, and 0.981 for the tibia, respectively, verifying a high degree of consistency between automatic modeling and manual modeling. Conclusion: The AI segmentation method in Mimics software can be used to quickly reconstruct a valid knee model.

Left Atrial and Ventricular Strain Differentiates Cardiac Amyloidosis and Hypertensive Heart Disease: A Cardiac MR Feature Tracking Study.

RATIONALE AND OBJECTIVES: Strain measured by feature tracking technique represents the degree of deformation and reflects the systolic and diastolic function of the heart. Our purpose was to evaluate the differential diagnostic value and correlations of left atrial (LA) strain (LAS) and left ventricular (LV) strain (LVS) in cardiac amyloidosis (CA) and hypertensive heart disease (HHD) patients. MATERIALS AND METHODS: We recruited 25 CA patients, 30 sex- and age-matched HHD patients and 20 healthy subjects totally. LAS and LVS were analyzed by CVI42 post-processing software. The efficiency of LAS and LVS in differentiating CA from HHD was compared by receiver operating characteristic curves analysis. Pearson or Spearman's analysis were used to assess the correlation between LAS and LV parameters. RESULTS: Both HHD and CA patients had impaired LVS, the gradient of increasing absolute values of longitudinal strain (LS) and radial strain (RS) from the basal to the apical myocardium was most pronounced in the CA group, its relative apical sparing of LS (RASLS) ratio reached 0.91 ± 0.02, significantly higher than other two groups (HHD: 0.72 ± 0.02; controls: 0.56 ± 0.01, all p <0.001). Additionally, except for the booster strain in the HHD group was preserved, all other LAS were reduced in patients' groups. The RASLS had the best differential diagnostic efficacy with an area under the curve (AUC) of 0.930 (p <0.001); The AUCs of LAS all greater than 0.850, above global LS (GLS) (AUC = 0.770, p = 0.001). LAS was notably correlated with LV ejection fraction (LVEF) and GLS, with reservoir strain having the greatest correlation with GLS (r = -0.828, p <0.001). CONCLUSION: The RASLS has high efficiency in guiding the differential diagnosis of CA and HHD with similar degree and presentation of LVH. Moreover, LAS values can also provide some useful information and they are closely linked with LV function, CMR feature tracking may provide assistance in the evaluation of LA-LV coupling.

Replacing the tropolonic methoxyl group of colchicine with methylamino increases tubulin binding affinity with improved therapeutic index and overcomes paclitaxel cross-resistance.

AIMS: Microtubule inhibitors are widely used in first line cancer therapy, though drug resistance often develops and causes treatment failure. Colchicine binds to tubulins and inhibits tumor growth, but is not approved for cancer therapy due to systemic toxicity. In this study, we aim to improve the therapeutic index of colchicine through structural modification. METHODS: The methoxyl group of the tropolonic ring in colchicine was replaced with amino groups. The cross-resistance of the derivatives with paclitaxel and vincristine was tested. Antitumor effects of target compounds were tested in vivo in A549 and paclitaxel-resistant A549/T xenografts. The interaction of target compounds with tubulins was measured using biological and chemical methods. RESULTS: Methylamino replacement of the tropolonic methoxyl group of colchicine increases, while demethylation loses, selective tubulin binding affinity, G2/M arrest and antiproliferation activity. Methylaminocolchicine is more potent than paclitaxel and vincristine to inhibit tumor growth in vitro and in vivo without showing cross-resistance to paclitaxel. Methylaminocolchicine binds to tubulins in unique patterns and inhibits P-gp with a stable pharmacokinetic profile. CONCLUSION: Methylanimo replacement of the tropolonic methoxyl group of colchicine increases antitumor activity with improved therapeutic index. Methylaminocolchicine represents a new type of mitotic inhibitor with the ability of overcoming paclitaxel and vincristine resistance.

Gas-phase synthesis of racemic helicenes and their potential role in the enantiomeric enrichment of sugars and amino acids in meteorites.

The molecular origins of homochirality on Earth is not understood well, particularly how enantiomerically enriched molecules of astrobiological significance like sugars and amino acids might have been synthesized on icy grains in space preceding their delivery to Earth. Polycyclic aromatic hydrocarbons (PAHs) identified in carbonaceous chondrites could have been processed in molecular clouds by circularly polarized light prior to the depletion of enantiomerically enriched helicenes onto carbonaceous grains resulting in chiral islands. However, the fundamental low temperature reaction mechanisms leading to racemic helicenes are still unknown. Here, by exploiting synchrotron based molecular beam photoionization mass spectrometry combined with electronic structure calculations, we provide compelling testimony on barrierless, low temperature pathways leading to racemates of [5] and [6]helicene. Astrochemical modeling advocates that gas-phase reactions in molecular clouds lead to racemates of helicenes suggesting a pathway for future astronomical observation and providing a fundamental understanding for the origin of homochirality on early Earth.

A CT-based nomogram for predicting the risk of adenocarcinomas in patients with subsolid nodule according to the 2021 WHO classification.

PURPOSE: To establish a nomogram for predicting the risk of adenocarcinomas in patients with subsolid nodules (SSNs) according to the 2021 WHO classification. METHODS: A total of 656 patients who underwent SSNs resection were retrospectively enrolled. Among them, 407 patients were assigned to the derivation cohort and 249 patients were assigned to the validation cohort. Univariate and multi-variate logistic regression algorithms were utilized to identity independent risk factors of adenocarcinomas. A nomogram based on the risk factors was generated to predict the risk of adenocarcinomas. The discrimination ability of the nomogram was evaluated using the concordance index (C-index), its performance was calibrated using a calibration curve, and its clinical significance was evaluated using decision curves and clinical impact curves. RESULTS: Lesion size, mean CT value, vascular change and lobulation were identified as independent risk factors for adenocarcinomas. The C-index of the nomogram was 0.867 (95% CI, 0.833-0.901) in derivation cohort and 0.877 (95% CI, 0.836-0.917) in validation cohort. The calibration curve showed good agreement between the predicted and actual risks. Analysis of the decision curves and clinical impact curves revealed that the nomogram had a high standardized net benefit. CONCLUSIONS: A nomogram for predicting the risk of adenocarcinomas in patients with SSNs was established in light of the 2021 WHO classification. The developed model can be adopted as a pre-operation tool to improve the surgical management of patients.

Sirtuin-1 attenuates cadmium-induced renal cell senescence through p53 deacetylation.

Cadmium (Cd), the common environmental pollutant, primarily targets at renal proximal tubules and induces nephrotoxicity. Cellular senescence, a phenomenon of cell growth arrest and a characteristics of maladaptive cell self-repair, is associated with renal disease progression. However, whether and how Cd induces renal tubular cells premature senescence is unknown. In our study, we found that Cd induced kidney damage and dysfunctions, which correlated with exacerbated tubular cell senescence, evidenced by increased senescence-associated ß-galactosidase activity, the upregulated protein expression of p53 and p21Waf1/Cip1 proteins, and elevated expression and secretion of cytokines in human proximal tubular epithelial HK-2 cells in vitro and in Cd-treated mice in vivo. Moreover, a S-phase arrest and decrease in Edu positive rate were found in Cd-treated HK-2 cells. Mechanistically, Cd suppressed the expression and activity of Sirtuin-1 (SIRT1), an anti-senescence deacetylase, resulting in the accumulation of acetylated p53 and upregulation of p21Waf1/Cip1. Activation of SIRT1 significantly abolished Cd-induced premature senescence and S-phase arrest. Finally, silencing p21Waf1/Cip1 efficiently delayed premature senescence and recovered cell cycle progression. These findings indicate that Cd promotes tubular cells senescence and impairs tubular cells regeneration, resulting in kidney dysfunctions, which could be ameliorated by SIRT1 activation.

Dual-layer dual-energy CT for improving differential diagnosis of squamous cell carcinoma from adenocarcinoma at gastroesophageal junction.

Objective: To examine the clinical values of dual-energy CT parameters derived from dual-layer spectral detector CT (SDCT) in the differential diagnosis of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the gastroesophageal junction (GEJ). Methods: Totally 66 patients with SCC and AC of the GEJ confirmed by pathological analysis were retrospectively enrolled, and underwent dual-phase contrast-enhancement chest CT with SDCT. Plain CT value, CT attenuation enhancement (△CT), iodine concentration (IC), spectral slope (λHU), effective atomic number (Zeff) and 40keV CT value (CT40keV) of the lesion in the arterial phase (AP) and venous phase (VP) were assessed. Multivariate logistic regression analysis was performed to evaluate the diagnostic efficacies of different combinations of dual-energy CT parameters. Receiver operating characteristic (ROC) curves were used to analyze the accuracy of dual-energy CT parameters and Delong test was used to compare AUCs. Results: IC, λHU, Zeff and CT40keV in AP and VP and △CT in VP were significantly higher in the AC group than those in the SCC group (all P<0.05). ROC curve analysis showed that IC, λHU, Zeff and CT40keV in VP had high diagnostic performances, with AUCs of 0.74, 0.74, 0.79 and 0.78, respectively. Logistic regression showed the combination of ICVP, λHU VP, CT40keV VP and Zeff VP had the highest AUC (0.84), with a threshold of 0.40, sensitivity and specificity in distinguishing SCC and AC were 93.1% and 73.0%, respectively. Delong test showed that the AUC of △CTVP was lower than other AUCs of dual-energy CT parameters. Conclusion: Dual-energy CT parameters derived from SDCT provide added value in the differential diagnosis of SCC and AC of the GEJ, especially the combination of IC, λHU, CT40keV and Zeff in VP. Advances in knowledge: Dual-energy CT parameters derived from dual-layer spectral detector CT provide added value to differentiate AC from SCC at the GEJ, especially the combination of effective atomic number, spectral slope, iodine concentration and 40keV CT value in VP.

Manganese Dioxide-Based Nanocarrier Delivers Paclitaxel to Enhance Chemotherapy against Orthotopic Glioma through Hypoxia Relief.

Chemotherapy plays an important role in treating cancers in clinic. Hypoxia-mediated chemoresistance remains a major hurdle for effective tumor chemotherapy. Herein, a new class of tLyP-1-modified dopamine (DOPA)-ß-cyclodextrin (CD)-coated paclitaxel (PTX)- and manganese dioxide (MnO2 )-loaded nanoparticles (tLyP-1-CD-DOPA-MnO2 @PTX) is developed to enhance glioma chemotherapy. The nanomedicine delivered to the tumor site decomposes in response to the weak acidity and high hydrogen peroxide in the tumor microenvironment (TME), resulting in collapse of the system to release PTX and generates Mn2+ and O2 . In a rat model of intracranial glioma, tLyP-1-CD-DOPA-MnO2 @PTX can efficiently pass through the blood-brain-barrier to accumulate in tumor sites. The hypoxia in TME can be relieved via O2 generated by MnO2 and the reactive oxygen species produced by Mn2+ can kill tumor cells. The tLyP-1-CD-DOPA-MnO2 @PTX nanoparticles exert a remarkable antitumor effect by promoting apoptosis and inhibiting proliferation of tumor cells in addition to enabling real-time tumor monitoring with magnetic resonance imaging. This MnO2 -based theranostic medicine will offer a novel strategy to simultaneously enhance chemotherapy and achieve real-time imaging of therapeutic process in glioma treatment.

Enhanced refractory organics removal by •OH and 1O2 generated in an electro-oxidation system with cathodic Fenton-like reaction.

Recently, carbon nanotubes coated carbon black and polytetrafluoroethylene (CNTs-C/PTFE) gas diffusion electrode was used as an air-cathode in an electro-oxidation (EO) system for effectively generating hydrogen peroxide (H2O2) through a 2-electron oxygen reduction reaction (ORR). This ORR-EO system not only lowered applied voltage and conserved energy, but the synergistic peroxone (O3/H2O2) reaction could increase hydroxyl radicals (•OH) generation for organics elimination. However, a significant proportion of H2O2 was left in the effluent of ORR-EO, which was a loss of resources and energy. In this study, a Fenton-like reaction for in-situ H2O2 decomposition to generate active oxidation species was inserted by introducing MnO2 into the cathodic catalyst layer, and the sole MnO2/CNTs-C/PTFE air-cathode could accomplish 90% of phenol degradation. When MnO2/CNTs-C/PTFE air-cathode combined with Ti/NATO anode in an ORR-EO system, all anodic oxidation, Fenton-like reaction, and peroxone took place to successfully generate •OH and singlet oxygen (1O2). Over 95% of TOC in phenol and landfill leachate bio-effluent was effectively eliminated, with 20% energy savings compared to the ORR-EO with CNTs-C/PTFE air cathode.

Multimodal Imaging and Synergetic Chemodynamic/Photodynamic Therapy Achieved Using an NaGdF4 ,Yb,Er@ NaGdF4 ,Yb,Tm@NaYF4 @Fe-MOFs Nanocomposite.

Here, NaGdF4 ,Yb,Er@NaGdF4 ,Yb,Tm@NaYF4 core@shell@shell three-layer structure of upconversion nanoparticles (UCNPs) coated with Fe-Tetrakis (4-carboxyphenyl) porphine (TCPP) metal-organic frameworks (Fe-MOFs) nanocomposite (UCNPs@MOFs) was designed and constructed for multimodal imaging and synergetic chemodynamic therapy (CDT)/photodynamic therapy (PDT) of tumors. The UCNPs@MOFs were successfully applied for tumor cells imaging in vitro and in vivo in near-infrared (NIR) region. The doped Gd was used as contrast agent for the magnetic resonance imaging (MRI) of mouse tumors. The luminescence in the UV-vis region was absorbed by the Fe-MOFs to produce singlet oxygen (1 O2 ) for PDT. The Fe3+ doped in the MOFs can catalyze H2 O2 to produce oxygen and hydroxyl radical (⋅OH). Hydroxyl radical is used in CDT and cooperates with the 1 O2 of PDT. Based on the CDT/PDT synergistic effects, the UCNPs@MOFs nanocomposite had obviously enhanced tumor inhibitory efficiency in vivo. These results described that the asprared UCNPs@MOFs nanocomposite have great potential in the effective multimodal imaging and treatment of tumors.

Mining whole-lung information by artificial intelligence for predicting EGFR genotype and targeted therapy response in lung cancer: a multicohort study.

BACKGROUND: Epidermal growth factor receptor (EGFR) genotype is crucial for treatment decision making in lung cancer, but it can be affected by tumour heterogeneity and invasive biopsy during gene sequencing. Importantly, not all patients with an EGFR mutation have good prognosis with EGFR-tyrosine kinase inhibitors (TKIs), indicating the necessity of stratifying for EGFR-mutant genotype. In this study, we proposed a fully automated artificial intelligence system (FAIS) that mines whole-lung information from CT images to predict EGFR genotype and prognosis with EGFR-TKI treatment. METHODS: We included 18 232 patients with lung cancer with CT imaging and EGFR gene sequencing from nine cohorts in China and the USA, including a prospective cohort in an Asian population (n=891) and The Cancer Imaging Archive cohort in a White population. These cohorts were divided into thick CT group and thin CT group. The FAIS was built for predicting EGFR genotype and progression-free survival of patients receiving EGFR-TKIs, and it was evaluated by area under the curve (AUC) and Kaplan-Meier analysis. We further built two tumour-based deep learning models as comparison with the FAIS, and we explored the value of combining FAIS and clinical factors (the FAIS-C model). Additionally, we included 891 patients with 56-panel next-generation sequencing and 87 patients with RNA sequencing data to explore the biological mechanisms of FAIS. FINDINGS: FAIS achieved AUCs ranging from 0·748 to 0·813 in the six retrospective and prospective testing cohorts, outperforming the commonly used tumour-based deep learning model. Genotype predicted by the FAIS-C model was significantly associated with prognosis to EGFR-TKIs treatment (log-rank p<0·05), an important complement to gene sequencing. Moreover, we found 29 prognostic deep learning features in FAIS that were able to identify patients with an EGFR mutation at high risk of TKI resistance. These features showed strong associations with multiple genotypes (p<0·05, t test or Wilcoxon test) and gene pathways linked to drug resistance and cancer progression mechanisms. INTERPRETATION: FAIS provides a non-invasive method to detect EGFR genotype and identify patients with an EGFR mutation at high risk of TKI resistance. The superior performance of FAIS over tumour-based deep learning methods suggests that genotype and prognostic information could be obtained from the whole lung instead of only tumour tissues. FUNDING: National Natural Science Foundation of China.

Neutrophils as emerging immunotherapeutic targets: Indirect treatment of tumors by regulating the tumor immune environment based on a sialic acid derivative-modified nanocomplex platform.

Tumor cells are dependent on their microenvironment; thus, targeting the non-cancerous components surrounding the tumor may be beneficial. Neutrophils are important inflammatory cells in the tumor microenvironment that significantly affect tumor cell proliferation, metastasis, and immune regulation. Targeted regulation of tumor-associated neutrophil-related pathways is expected to become a new therapeutic approach. Colchicine compounds are powerful anti-inflammatory drugs that strongly inhibit the chemotaxis of neutrophils to the inflammatory site. We attempted to achieve anticancer effects by utilizing its ability to inhibit neutrophil recruitment rather than killing tumor cells. As such drugs are likely to cause non-specific damages due to the lack of selectivity, we synthesized and used sialic acid and cholesterol derivatives (SA-CH) for surface modification of the newly synthesized low-toxic colchicine derivative (BCS) nanocomposite to improve neutrophil targeting. In vivo and in vitro experiments have shown that SA-CH-modified BCS preparations are effectively absorbed by neutrophils, inhibit cell migration, reduce infiltration of tumor-associated neutrophils, enhance T lymphocyte function, and exhibit good anti-S180 early tumor effect. In addition, in a triple-negative breast cancer model, the agent could strongly inhibit tumor metastasis to the lungs.

AHU-MultiNet: Adaptive loss balancing based on homoscedastic uncertainty in multi-task medical image segmentation network.

Medical image segmentation is an important field in medical image analysis and a vital part of computer-aided diagnosis. Due to the challenges in acquiring image annotations, semi-supervised learning has attracted high attention in medical image segmentation. Despite their impressive performance, most existing semi-supervised approaches lack attention to ambiguous regions (e.g., some edges or corners around the organs). To achieve better performance, we propose a novel semi-supervised method called Adaptive Loss Balancing based on Homoscedastic Uncertainty in Multi-task Medical Image Segmentation Network (AHU-MultiNet). This model contains the main task for segmentation, one auxiliary task for signed distance, and another auxiliary task for contour detection. Our multi-task approach can effectively and sufficiently extract the semantic information of medical images by auxiliary tasks. Simultaneously, we introduce an inter-task consistency to explore the underlying information of the images and regularize the predictions in the right direction. More importantly, we notice and analyze that searching an optimal weighting manually to balance each task is a difficult and time-consuming process. Therefore, we introduce an adaptive loss balancing strategy based on homoscedastic uncertainty. Experimental results show that the two auxiliary tasks explicitly enforce shape-priors on the segmentation output to further generate more accurate masks under the adaptive loss balancing strategy. On several standard benchmarks, the 2018 Atrial Segmentation Challenge and the 2017 Liver Tumor Segmentation Challenge, our proposed method achieves improvements and outperforms the new state-of-the-art in semi-supervised learning.

A coordinate positioning puncture method under robot-assisted CT-guidance: phantom and animal experiments.

PURPOSE: To evaluate the accuracy of the robot-assisted computed tomography (CT)-guided coordinate positioning puncture method by phantom and animal experiments. MATERIAL AND METHODS: In the phantom experiment, seven robot-assisted punctures were made to evaluate the accuracy of the method. In the animal experiment, 18 punctures (nine robotic and nine manual) were made in the livers of nine rabbits. The indicators, such as needle-tract length, angle deviation, puncture accuracy, number of scans required, and radiation exposure dose were compared between manual and robotic punctures. The paired-samples t-test was used for analysis. RESULTS: In the phantom experiment, the mean accuracy of seven punctures was 2.67 mm. In the animal experiment, there was no significant difference in needle-tract length (32.58 mm vs. 34.04 mm, p = .606), angle deviation (17.21° vs. 21.23° p = .557) and puncture accuracy (8.42 vs. 8.77 mm, p = .851) between the two groups. However, the number CT scans required (2.44 vs. 3.33, p = .002), and the radiation exposure dose (772.98 vs. 1077.89 mGy/cm, p = .003) were lower in the robot group than in the manual group. CONCLUSIONS: The coordinate positioning puncture method under robot-assisted CT-guidance can reach an accuracy that is comparable to that of the traditional manual CT-guided puncture method and with fewer CT scanning times accompanied with a lower radiation dosage.