Evaluating Virtual Contrast-enhanced MRI (VCE-MRI) in Nasopharyngeal Carcinoma Radiotherapy: A Retrospective Analysis for Primary Gross Tumor Delineation.

PURPOSE: To investigate the potential of virtual contrast-enhanced MRI (VCE-MRI) for gross-tumor-volume (GTV) delineation of nasopharyngeal carcinoma (NPC) using multi-institutional data. METHODS AND MATERIALS: This study retrospectively retrieved T1-weighted (T1w), T2-weighted (T2w) MRI, gadolinium-based contrast-enhanced MRI (CE-MRI) and planning CT of 348 biopsy-proven NPC patients from three oncology centers. A multimodality-guided synergistic neural network (MMgSN-Net) was trained using 288 patients to leverage complementary features in T1w and T2w MRI for VCE-MRI synthesis, which was independently evaluated using 60 patients. Three board-certified radiation oncologists and two medical physicists participated in clinical evaluations in three aspects: image quality assessment of the synthetic VCE-MRI, VCE-MRI in assisting target volume delineation, and effectiveness of VCE-MRI-based contours in treatment planning. The image quality assessment includes distinguishability between VCE-MRI and CE-MRI, clarity of tumor-to-normal tissue interface and veracity of contrast enhancement in tumor invasion risk areas. Primary tumor delineation and treatment planning were manually performed by radiation oncologists and medical physicists, respectively. RESULTS: The mean accuracy to distinguish VCE-MRI from CE-MRI was 31.67%; no significant difference was observed in the clarity of tumor-to-normal tissue interface between VCE-MRI and CE-MRI; for the veracity of contrast enhancement in tumor invasion risk areas, an accuracy of 85.8% was obtained. The image quality assessment results suggest that the image quality of VCE-MRI is highly similar to real CE-MRI. The mean dosimetric difference of planning target volumes were less than 1Gy. CONCLUSIONS: The VCE-MRI is highly promising to replace the use of gadolinium-based CE-MRI in tumor delineation of NPC patients.

BDTX-189, a novel tyrosine kinase inhibitor, inhibits cell activity via ERK and AKT pathways in the EGFR C797S triple mutant cells.

The tertiary mutation C797S in the structural domain of the EGFR kinase is a common cause of resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs). In this study, we used a potent, selective and irreversible inhibitor, BDTX-189, to target EGFR C797S triple mutant cells for cell activity. The study constructed the H1975-C797S (EGFR L858R/T790 M/C797S) cell line using the CRISPR/Cas9 method and investigated its potential as a fourth-generation tyrosine kinase inhibitor via chemosensitivity approach. The results demonstrated its ability to induce cytotoxic effects, and inhibit EGFR L858R/T790 M/C797S cell growth and proliferation in a dose-dependent manner. Meanwhile, BDTX-189 reduces the protein phosphorylation levels of EGFR, ERK, and AKT, promoting apoptosis. Furthermore, BDTX-189 not only inhibits common EGFR triple mutations but also effectively inhibits EGFR L858R mutation and EGFR L858R/T790 M mutation. These findings support the cytotoxic effect of BDTX-189 and its inhibitory effect on cell division and proliferation with the EGFR C797S triple mutation.

Almonertinib and alflutinib show novel inhibition on rare EGFR S768I mutant cells.

PURPOSE: EGFR classical mutations respond well to EGFR tyrosine kinase inhibitors. However, it is uncertain whether currently available EGFR-TKIs are effective against rare EGFR mutations and compound mutations. Herein, the effectiveness of almonertinib and alflutinib, the third-generation tyrosine kinase inhibitors developed in China, on rare EGFR S768I mutations and compound mutations is identified. METHODS: In this study, using CRISPR method, four EGFR S768I mutation cell lines were constructed, and the sensitivity of EGFR to almonertinib and alflutinib was tested, with positive controls being the 1st (gefitinib), 2nd (afatinib), and 3rd (osimertinib) generation drugs. RESULTS: The present results indicate that almonertinib and alflutinib can effectively inhibit cell viability and proliferation in rare EGFR S768I mutations through the ERK or AKT pathways in a time-dependent manner, by blocking the cell cycle and inhibiting apoptosis. CONCLUSIONS: These findings suggest that almonertinib and alflutinib may be potential therapeutic options for non-small cell lung cancer patients with the EGFR S768I mutation.

First Report of Colletotrichum gloeosporioides Causing Anthracnose on Euphorbia lathyris in China.

Euphorbia lathyris L. is a biennial herb in the Euphorbiaceae that has been used as a medicinal plant. It is distributed or cultivated worldwide, and the seeds of E. lathyris are the main source of ingenol, which is the precursor of Picato, the first medicine approved by USFDA for the treatment of solar keratosis (Abramovits et al. 2013). However, the production of E. lathyris can be severely hampered by the occurrence of plant diseases. Between 2020-2022 (specifically in October-November of each year), anthracnose-like symptoms were observed on E. lathyris in fields (E 118°49'50″, N 32°3'33″) in Nanjing, Jiangsu Province, China. The incidence of E. lathyris with disease symptoms was between 25%-30% (n = 100). The lesions on the leaves were evident initially as dark brown spots, which expanded into larger necrotic spots, finally resulting in leaves withering and dropping off. In severe cases, stem wilting was also observed. To determine the causal agent, we collected diseased leaf samples (n = 20) from different E. lathyris plants in the field (~ 1800 m2). After cleaning, the junctions of the diseased and healthy parts were excised and sterilized in 75% ethanol for 20-25 seconds, and rinsed with sterile water. After that, they were transferred onto potato sucrose agar (PSA) plates and placed at 25℃ for 3-4 days, until fungal growth was evident. The fungus was purified by recovering single conidia and growing them on PSA (Hu et al. 2015). A consistent fungal colony, based on morphological characteristics, was recovered from 17 samples. The colony color was initially white, green in the middle, and gradually changed into gray green as the colony matured. Conidia were transparent and cylindrical (22-28 µm × 7-9 µm, n = 50). Five loci informative (ITS, TUB, ACT, GAPDH, and CHS-1) (Weir et al. 2012) for Colletotrichum spp. identification were sequenced from two isolates ELC-1 and ELC-2 obtained from different plant individuals. Compared with a reference isolate (Colletotrichum gloeosporioides ZH3), the GAPDH, CHS-1, and TUB2 sequences of ELC-1 and ELC-2 showed 95% (263 bp out of 275 bp), 98% (295 bp out of 299 bp), and 99% (711 bp out of 712 bp and 717 bp out of 719 bp) similarity, respectively. The ITS sequence identities were 100% (577 bp out of 577 bp) and 99% (594 bp out of 597 bp), while the ACT sequence identities were 100% (281 bp out of 281 bp) and 98% (279 bp out of 284 bp). All sequences have been deposited in Genbank database (OR865865-OR865866 and OR873625-OR873632). After performing phylogenetic analysis with Mega 11, the pathogen was confirmed as C. gloeosporioides. To fulfil Koch's postulates, we sprayed six-week-old healthy plants with a conidia suspension of C. gloeosporioides (106 spores/mL) or sterile water (serve as control). The inoculated plants were placed at 25℃, 100% relative humidity, and 12-h photoperiod (Zhang et al. 2021). Six plants were inoculated for each treatment, and the experiment was repeated three times. After 6-8 days, the plants inoculated with C. gloeosporioides showed similar symptoms to those observed on diseased plants in the field, while the control plants remained healthy and free of disease. The pathogens were then re-isolated and identified as C. gloeosporioides. To our knowledge, this is the first report of C. gloeosporioides causing anthracnose on E. lathyris. Anthracnose may cause significant yield losses in E. lathyris production, and our results will provide experimental and theoretical basis for the management of the disease.

Diagnosis of pulmonary Scedosporium apiospermum infection from bronchoalveolar lavage fluid by metagenomic next-generation sequencing in an immunocompetent female patient with normal lung structure: a case report and literature review.

BACKGROUND: Scedosporium apiospermum (S. apiospermum) belongs to the asexual form of Pseudallescheria boydii and is widely distributed in various environments. S. apiospermum is the most common cause of pulmonary infection; however, invasive diseases are usually limited to patients with immunodeficiency. CASE PRESENTATION: A 54-year-old Chinese non-smoker female patient with normal lung structure and function was diagnosed with pulmonary S. apiospermum infection by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF). The patient was admitted to the hospital after experiencing intermittent right chest pain for 8 months. Chest computed tomography revealed a thick-walled cavity in the upper lobe of the right lung with mild soft tissue enhancement. S. apiospermum was detected by the mNGS of BALF, and DNA sequencing reads were 426. Following treatment with voriconazole (300 mg q12h d1; 200 mg q12h d2-d20), there was no improvement in chest imaging, and a thoracoscopic right upper lobectomy was performed. Postoperative pathological results observed silver staining and PAS-positive oval spores in the alveolar septum, bronchiolar wall, and alveolar cavity, and fungal infection was considered. The patient's symptoms improved; the patient continued voriconazole for 2 months after surgery. No signs of radiological progression or recurrence were observed at the 10-month postoperative follow-up. CONCLUSION: This case report indicates that S. apiospermum infection can occur in immunocompetent individuals and that the mNGS of BALF can assist in its diagnosis and treatment. Additionally, the combined therapy of antifungal drugs and surgery exhibits a potent effect on the disease.

Reconstruction of multi-phase parametric maps in 4D-magnetic resonance fingerprinting (4D-MRF) by optimization of local T1 and T2 sensitivities.

BACKGROUND: Time-resolved magnetic resonance fingerprinting (MRF), or 4D-MRF, has been demonstrated its feasibility in motion management in radiotherapy (RT). However, the prohibitive long acquisition time is one of challenges of the clinical implementation of 4D-MRF. The shortening of acquisition time causes data insufficiency in each respiratory phase, leading to poor accuracies and consistencies of the predicted tissues' properties of each phase. PURPOSE: To develop a technique for the reconstruction of multi-phase parametric maps in four-dimensional magnetic resonance fingerprinting (4D-MRF) through the optimization of local T1 and T2 sensitivities. METHODS: The proposed technique employed an iterative optimization to tailor the data arrangement of each phase by manipulation of inter-phase frames, such that the T1 and T2 sensitivities, which were quantified by the modified Minkowski distance, of the truncated signal evolution curve was maximized. The multi-phase signal evolution curves were modified by sliding window reconstruction and inter-phase frame sharing (SWIFS). Motion correction (MC) and dot product matching were sequentially performed on the modified signal evolution and dictionary to reconstruct the multi-parametric maps. The proposed technique was evaluated by numerical simulations using the extended cardiac-torso (XCAT) phantom with regular and irregular breathing patterns, and by in vivo MRF data of three health volunteers and six liver cancer patients acquired at a 3.0 T scanner. RESULTS: In simulation study, the proposed SWIFS approach achieved the overall mean absolute percentage error (MAPE) of 8.62% ± 1.59% and 16.2% ± 3.88% for the eight-phases T1 and T2 maps, respectively, in the sagittal view with irregular breathing patterns. In contrast, the overall MAPE of T1 and T2 maps generated by the conventional approach with multiple MRF repetitions were 22.1% ± 11.0% and 30.8% ± 14.9%, respectively. For in-vivo study, the predicted mean T1 and T2 of liver by the proposed SWIFS approach were 795 ms ± 38.9 ms and 58.3 ms ± 11.7 ms, respectively. CONCLUSIONS: Both simulation and in vivo results showed that the approach empowered by T1 and T2 sensitivities optimization and sliding window under the shortened acquisition of MRF had superior performance in the estimation of multi-phase T1 and T2 maps as compared to the conventional approach with oversampling of MRF data.

Protein tyrosine phosphatase PTPRO represses lung adenocarcinoma progression by inducing mitochondria-dependent apoptosis and restraining tumor metastasis.

Emerging evidence indicates that protein activities regulated by receptor protein tyrosine phosphatases (RPTPs) are crucial for a variety of cellular processes, such as proliferation, apoptosis, and immunological response. Protein tyrosine phosphatase receptor type O (PTPRO), an RPTP, has been revealed as a putative suppressor in the development of particular tumors. However, the function and the underlying mechanisms of PTPRO in regulating of lung adenocarcinoma (LUAD) are not well understood. In this view, the present work investigated the role of PTPRO in LUAD. Analysis of 90 pairs of clinical LUAD specimens revealed significantly lower PTPRO levels in LUAD compared with adjacent non-tumor tissue, as well as a negative correlation of PTPRO expression with tumor size and TNM stage. Survival analyses demonstrated that PTPRO level can help stratify the prognosis of LUAD patients. Furthermore, PTPRO overexpression was found to suppress the progression of LUAD both in vitro and in vivo by inducing cell death via mitochondria-dependent apoptosis, downregulating protein expression of molecules (Bcl-2, Bax, caspase 3, cleaved-caspase 3/9, cleaved-PARP and Bid) essential in cell survival. Additionally, PTPRO decreased LUAD migration and invasion by regulating proteins involved in the epithelial-to-mesenchymal transition (E-cadherin, N-cadherin, and Snail). Moreover, PTPRO was shown to restrain JAK2/STAT3 signaling pathways. Expression of PTPRO was negatively correlated with p-JAK2, p-STAT3, Bcl-2, and Snail levels in LUAD tumor samples. Furthermore, the anti-tumor effect of PTPRO in LUAD was significant but compromised in STAT3-deficient cells. These data support the remarkable suppressive role of PTPRO in LUAD, which may represent a viable therapeutic target for LUAD patients.

DPP-4 exacerbates LPS-induced endothelial cells inflammation via integrin-α5ß1/FAK/AKT signaling.

Endothelial dysfunction plays a pivotal role in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Dipeptidyl peptidase IV (DPP-4), a cell surface glycoprotein, has been implicated in endothelial inflammation and barrier dysfunction. In this study, the role of DPP-4 on lipopolysaccharide (LPS)-induced pulmonary microvascular endothelial cells (HPMECs) dysfunction and the underlying mechanism were investigated by siRNA-mediated knockdown of DPP-4. Our results indicated that LPS (1 µg/ml) challenge resulted in either the production and releasing of DPP-4, as well as the secretion of IL-6 and IL-8 in HPMECs. DPP-4 knockdown inhibited chemokine releasing and monolayer hyper-permeability in LPS challenged HPMECs. When cocultured with human polymorphonuclear neutrophils (PMNs), DPP4 knockdown suppressed LPS-induced neutrophil-endothelial adhesion, PMN chemotaxis and trans-endothelial migration. Western blotting showed that DPP-4 knockdown attenuated LPS-induced activation of TLR4/NF-κB pathway. Immunoprecipitation and liquid chromatography-tandem mass spectrometry revealed that DPP-4 mediated LPS-induced endothelial inflammation by interacting with integrin-α5ß1. Moreover, exogenous soluble DPP-4 treatment sufficiently activated integrin-α5ß1 downstream FAK/AKT/NF-κB signaling, thereafter inducing ICAM-1 upregulation in HPMECs. Collectively, our results suggest that endothelia synthesis and release DPP-4 under the stress of endotoxin, which interact with integrin-α5ß1 complex in an autocrine or paracrine manner to exacerbate endothelial inflammation and enhance endothelial cell permeability. Therefore, blocking DDP-4 could be a potential therapeutic strategy to prevent endothelial dysfunction in ALI/ARDS.

NLRP3 inflammasome mediates abnormal epithelial regeneration and distal lung remodeling in silica­induced lung fibrosis.

NOD-like receptor protein 3 (NLRP3) inflammasome is closely related to silica particle­induced chronic lung inflammation but its role in epithelial remodeling, repair and regeneration in the distal lung during development of silicosis remains to be elucidated. The present study aimed to determine the effects of the NLRP3 inflammasome on epithelial remodeling and cellular regeneration and potential mechanisms in the distal lung of silica­treated mice at three time points. Pulmonary function assessment, inflammatory cell counting, enzyme­linked immunosorbent assay, histological and immunological analyses, hydroxyproline assay and western blotting were used in the study. Single intratracheal instillation of a silica suspension caused sustained NLRP3 inflammasome activation in the distal lung. Moreover, a time­dependent increase in airway resistance and a decrease in lung compliance accompanied progression of pulmonary fibrosis. In the terminal bronchiole, lung remodeling including pyroptosis (membrane­distributed GSDMD+), excessive proliferation (Ki67+), mucus overproduction (mucin 5 subtype AC and B) and epithelial­mesenchymal transition (decreased E­Cadherin+ and increased Vimentin+), was observed by immunofluorescence analysis. Notably, aberrant spatiotemporal expression of the embryonic lung stem/progenitor cell markers SOX2 and SOX9 and ectopic distribution of bronchioalveolar stem cells were observed in the distal lung only on the 7th day after silica instillation (the early inflammatory phase of silicosis). Western blotting revealed that the Sonic hedgehog/Glioma­associated oncogene (Shh/Gli) and Wnt/ß­catenin pathways were involved in NLRP3 inflammasome activation­mediated epithelial remodeling and dysregulated regeneration during the inflammatory and fibrotic phases. Overall, sustained NLRP3 inflammasome activation led to epithelial remodeling in the distal lung of mice. Moreover, understanding the spatiotemporal profile of dysregulated epithelial repair and regeneration may provide a novel therapeutic strategy for inhalable particle­related chronic inflammatory and fibrotic lung disease.

Model Generalizability Investigation for GFCE-MRI Synthesis in NPC Radiotherapy Using Multi-Institutional Patient-Based Data Normalization.

Recently, deep learning has been demonstrated to be feasible in eliminating the use of gadoliniumbased contrast agents (GBCAs) through synthesizing gadolinium-free contrast-enhanced MRI (GFCE-MRI) from contrast-free MRI sequences, providing the community with an alternative to get rid of GBCAs-associated safety issues in patients. Nevertheless, generalizability assessment of the GFCE-MRI model has been largely challenged by the high inter-institutional heterogeneity of MRI data, on top of the scarcity of multi-institutional data itself. Although various data normalization methods have been adopted to address the heterogeneity issue, it has been limited to single-institutional investigation and there is no standard normalization approach presently. In this study, we aimed at investigating generalizability of GFCE-MRI model using data from seven institutions by manipulating heterogeneity of MRI data under five popular normalization approaches. Three state-of-the-art neural networks were applied to map from T1-weighted and T2-weighted MRI to contrast-enhanced MRI (CE-MRI) for GFCE-MRI synthesis in patients with nasopharyngeal carcinoma. MRI data from three institutions were used separately to generate three uni-institution models and jointly for a tri-institution model. The five normalization methods were applied to normalize the data of each model. MRI data from the remaining four institutions served as external cohorts for model generalizability assessment. Quality of GFCE-MRI was quantitatively evaluated against ground-truth CE-MRI using mean absolute error (MAE) and peak signal-to-noise ratio(PSNR). Results showed that performance of all uni-institution models remarkably dropped on the external cohorts. By contrast, model trained using multi-institutional data with Z-Score normalization yielded the best model generalizability improvement.

Coarse-Super-Resolution-Fine Network (CoSF-Net): A Unified End-to-End Neural Network for 4D-MRI With Simultaneous Motion Estimation and Super-Resolution.

Four-dimensional magnetic resonance imaging (4D-MRI) is an emerging technique for tumor motion management in image-guided radiation therapy (IGRT). However, current 4D-MRI suffers from low spatial resolution and strong motion artifacts owing to the long acquisition time and patients' respiratory variations. If not managed properly, these limitations can adversely affect treatment planning and delivery in IGRT. In this study, we developed a novel deep learning framework called the coarse-super-resolution-fine network (CoSF-Net) to achieve simultaneous motion estimation and super-resolution within a unified model. We designed CoSF-Net by fully excavating the inherent properties of 4D-MRI, with consideration of limited and imperfectly matched training datasets. We conducted extensive experiments on multiple real patient datasets to assess the feasibility and robustness of the developed network. Compared with existing networks and three state-of-the-art conventional algorithms, CoSF-Net not only accurately estimated the deformable vector fields between the respiratory phases of 4D-MRI but also simultaneously improved the spatial resolution of 4D-MRI, enhancing anatomical features and producing 4D-MR images with high spatiotemporal resolution.

Ultra-fast multi-parametric 4D-MRI image reconstruction for real-time applications using a downsampling-invariant deformable registration (D2R) model.

BACKGROUND AND PURPOSE: Motion estimation from severely downsampled 4D-MRI is essential for real-time imaging and tumor tracking. This simulation study developed a novel deep learning model for simultaneous MR image reconstruction and motion estimation, named the Downsampling-Invariant Deformable Registration (D2R) model. MATERIALS AND METHODS: Forty-three patients undergoing radiotherapy for liver tumors were recruited for model training and internal validation. Five prospective patients from another center were recruited for external validation. Patients received 4D-MRI scans and 3D MRI scans. The 4D-MRI was retrospectively down-sampled to simulate real-time acquisition. Motion estimation was performed using the proposed D2R model. The accuracy and robustness of the proposed D2R model and baseline methods, including Demons, Elastix, the parametric total variation (pTV) algorithm, and VoxelMorph, were compared. High-quality (HQ) 4D-MR images were also constructed using the D2R model for real-time imaging feasibility verification. The image quality and motion accuracy of the constructed HQ 4D-MRI were evaluated. RESULTS: The D2R model showed significantly superior and robust registration performance than all the baseline methods at downsampling factors up to 500. HQ T1-weighted and T2-weighted 4D-MR images were also successfully constructed with significantly improved image quality, sub-voxel level motion error, and real-time efficiency. External validation demonstrated the robustness and generalizability of the technique. CONCLUSION: In this study, we developed a novel D2R model for deformation estimation of downsampled 4D-MR images. HQ 4D-MR images were successfully constructed using the D2R model. This model may expand the clinical implementation of 4D-MRI for real-time motion management during liver cancer treatment.

Eschar dissolution and the immunoregulator effect of keratinase on burn wounds.

At present, enzyme debridement preparation has shown a good curative effect on eschar removal of burn wounds. Keratinase has shown great potential in enzymatic debridement because of its good fibrin-degrading ability. In this study, the debridement of keratinase was examined by using a third degree burn wound model in rats. We observed the wound, and keratinase shortened the time of eschar dissolution after debridement. Histopathology and immunofluorescence staining showed that the eschar in the keratinase group became thinner, inflammatory cell infiltration in the wound increased, the fluorescence intensity of the macrophage surface marker CD68 increased, and the CD163/CD86 ratio increased. In bone marrow-derived macrophages (BMDMs), there was no significant difference in the activity of CCK-8 in cells in the keratinase group compared with the control group. The fluorescence intensity of the keratinase group was higher than that of the control group. At 12 h, the cell scratches were obviously closed. The number of migrated Transwell cells increased. Flow cytometry and immunofluorescence analysis showed increased expression of CD206 and Arg-1 and decreased expression of CD86 and iNOS. The gene expression of the Arg-1, iNOS and IL-10 was increased, as shown by qPCR. The secretion of IL-10 was increased and TNF-α was decreased, as shown by ELISA. We concluded that keratinase dissolution of eschar not only has a hydrolytic effect on eschar but may also affect immune regulation to enhance the migration and phagocytosis of macrophages, promote the polarization of macrophages, and further enhance the effect of eschar dissolution. Therefore, keratinase may have good prospects for the debridement of burn wounds.

Gender differences in cigarette smoking cessation attempts among adults who smoke and drink alcohol at high levels: Findings from the 2018-2020 International Tobacco Control Four Country Smoking and Vaping Surveys.

BACKGROUND: This study examined the association between alcohol consumption and smoking cessation behaviour of adults who smoke in four countries. METHODS: Data came from 4275 adults (≥18 years) who smoked tobacco ≥ monthly and participated in the 2018 and 2020 International Tobacco Control Four Country Smoking and Vaping Surveys (Australia: n = 720; Canada: n = 1250; US: n = 1011; England: n = 1294). The 2018 Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) survey data coded into three levels ('never/low', 'moderate' or 'heavy' consumption) were analysed using multivariable logistic regression models to predict any smoking cessation attempts and successful cessation by 2020 survey, and whether this differed by gender and country. RESULTS: Compared to never/low alcohol consumers, only those who drink heavily were less likely to have made a quit smoking attempt (40.4 % vs. 43.8 %; AOR = 0.69, 95 % CI = 0.57-0.83, p < .001). The association differed by gender and country (3-way interaction, p < .001), with females who drink heavily being less likely to attempt to quit smoking in England (AOR = 0.27, 95 % CI = 0.15-0.49, p < .001) and Australia (AOR = 0.38, 95 % CI = 0.19-0.77, p = .008), but for males, those who drink moderately (AOR = 2.18, 95 % CI = 1.17-4.06, p = .014) or heavily (AOR = 2.61, 95 % CI = 1.45-4.68, p = .001) were more likely to make a quit attempt in England only. Alcohol consumption did not predict quit success. CONCLUSION: Heavy alcohol use among adults who smoke appears to only undermine the likelihood of trying to quit smoking with some variation by gender and country of residence, but not their chances of succeeding if they tried.

[Progress in the relationship between head and neck squamous cell carcinom and the microbial community].

Microorganisms are one of the important factors which maintain the homeostasis of human health. Despite recent advances, the relationship between microorganisms and head and neck squamous cell carcinoma （HNSCC） is still unclear, and the impact of microorganisms on the incidence and prognosis of HNSCC cannot be neglected. Therefore, this article provides a systematic and comprehensive review summarizing the epidemiological evidence of microbial dysbiosis related to HNSCC and discusses the associations between them.

Respiratory-Correlated 4-Dimensional Magnetic Resonance Fingerprinting for Liver Cancer Radiation Therapy Motion Management.

PURPOSE: The objective of this study was to develop a respiratory-correlated (RC) 4-dimensional (4D) imaging technique based on magnetic resonance fingerprinting (MRF) (RC-4DMRF) for liver tumor motion management in radiation therapy. METHODS AND MATERIALS: Thirteen patients with liver cancer were prospectively enrolled in this study. k-space MRF signals of the liver were acquired during free-breathing using the fast acquisition with steady-state precession sequence on a 3T scanner. The signals were binned into 8 respiratory phases based on respiratory surrogates, and interphase displacement vector fields were estimated using a phase-specific low-rank optimization method. Hereafter, the tissue property maps, including T1 and T2 relaxation times, and proton density, were reconstructed using a pyramid motion-compensated method that alternatively optimized interphase displacement vector fields and subspace images. To evaluate the efficacy of RC-4DMRF, amplitude motion differences and Pearson correlation coefficients were determined to assess measurement agreement in tumor motion between RC-4DMRF and cine magnetic resonance imaging (MRI); mean absolute percentage errors of the RC-4DMRF-derived tissue maps were calculated to reveal tissue quantification accuracy using digital human phantom; and tumor-to-liver contrast-to-noise ratio of RC-4DMRF images was compared with that of planning CT and contrast-enhanced MRI (CE-MRI) images. A paired Student t test was used for statistical significance analysis with a P value threshold of .05. RESULTS: RC-4DMRF achieved excellent agreement in motion measurement with cine MRI, yielding the mean (± standard deviation) Pearson correlation coefficients of 0.95 ± 0.05 and 0.93 ± 0.09 and amplitude motion differences of 1.48 ± 1.06 mm and 0.81 ± 0.64 mm in the superior-inferior and anterior-posterior directions, respectively. Moreover, RC-4DMRF achieved high accuracy in tissue property quantification, with mean absolute percentage errors of 8.8%, 9.6%, and 5.0% for T1, T2, and proton density, respectively. Notably, the tumor contrast-to-noise ratio in RC-4DMRI-derived T1 maps (6.41 ± 3.37) was found to be the highest among all tissue property maps, approximately equal to that of CE-MRI (6.96 ± 1.01, P = .862), and substantially higher than that of planning CT (2.91 ± 1.97, P = .048). CONCLUSIONS: RC-4DMRF demonstrated high accuracy in respiratory motion measurement and tissue properties quantification, potentially facilitating tumor motion management in liver radiation therapy.

Downregulation of circ_PLXND1 inhibits tumorigenesis of non-small cell lung carcinoma via miR-1287-5p/ERBB3 axis.

BACKGROUND: Circular RNAs (circRNAs) have been reported to play vital roles in the progression of diverse human cancers, including non-small cell lung cancer (NSCLC). The purpose of this study was to explore the exact role and underlying mechanism of circ_PLXND1 in NSCLC progression. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to determine the expression levels of circ_PLXND1, microRNA (miR)-1287-5p and human epidermal growth factor receptor 3 (ERBB3). The localization of circ_PLXND1 in NSCLC cells was tested by subcellular fractionation and localization assay. Cell angiogenesis, proliferation, apoptosis, migration and invasion were evaluated by tube formation assay, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and transwell assay. Dual-luciferase reporter assay was utilized to confirm the interaction between miR-1287-5p and circ_PLXND1 or ERBB3. Western blot assay was exploited to examine the expression of proteins. RESULTS: Circ_PLXND1 and ERBB3 were upregulated while miR-1287-5p was downregulated in NSCLC tissues and cells. Circ_PLXND1 was a stable circRNA and mainly located in cytoplasm. Circ_PLXND1 silencing suppressed the proliferation, angiogenesis, migration and invasion of NSCLC cells in vitro. For mechanism analysis, circ_PLXND1 could positively regulate ERBB3 expression via sponging miR-1287-5p. The inhibitory impacts of circ_PLXND1 knockdown on the malignant behaviors of NSCLC cells were overturned by miR-1287-5p inhibitor. Overexpression of miR-1287-5p repressed the malignant phenotypes of NSCLC cells by targeting ERBB3. Furthermore, circ_PLXND1 interference inhibited tumor growth in vivo. CONCLUSIONS: Circ_PLXND1 knockdown impeded NSCLC progression through modulating the miR-1287-5p/ERBB3 axis, indicating a promising molecular target for NSCLC treatment.

[The application progress on diagnostic scales of laryngopharyngeal reflux disease].

At present, objective methods for diagnosing laryngopharyngeal reflux disease(LPRD) are not minimally invasive, effective, and economical. Diagnostic scales are widely used worldwide due to the advantages of inexpensive, noninvasive, and easy to operate. The reflux symptom index(RSI) and the reflux finding score(RFS) are preferred to use in clinical diagnosis. However, many controversies have appeared in the application of RSI and RFS in recent years, causing many troubles to clinical diagnosis. Therefore, this review briefly discusses the problems of RSI and RFS in clinical applications to provide reference for diagnosing LPRD accurately.

PU.1-CD23 signaling mediates pulmonary innate immunity against Aspergillus fumigatus infection by driving inflammatory response.

BACKGROUND: Aspergillosis is a common cause of morbidity and mortality in immunocompromised populations. PU.1 is critical for innate immunity against Aspergillus fumigatus (AF) in macrophages. However, the molecular mechanism underlying PU.1 mediating immunity against AF infection in human alveolar macrophages (AMs) is still unclear. METHODS: In this study, we detected the expressions of PU.1, CD23, p-ERK, CCL20 and IL-8 and key inflammatory markers IL-1ß, IL-6, TNF-α and IL-12 in human THP-1-derived macrophages (HTMs) or PU.1/CD23-overexpressed immunodeficient mice with AF infection. Moreover, we examined these expressions in PU.1-overexpressed/interfered HTMs. Additionally, we detected the phagocytosis of macrophages against AF infection with altered PU.1 expression. Dual luciferase, ChIP and EMSAs were performed to detect the interaction of PU.1 and CD23. And we invested the histological changes in mouse lung tissues transfected with PU.1/CD23-expressing adenoviruses in AF infection. RESULTS: The results showed that the expressions of PU.1, CD23, p-ERK, CCL20, IL-8, IL-1ß, IL-6, TNF-α and IL-12 increased significantly with AF infection, and PU.1 regulated the later 8 gene expressions in HTMs. Moreover, CD23 was directly activated by PU.1, and overexpression of CD23 in PU.1-interfered HTMs upregulated IL-1ß, IL-6, TNF-α and IL-12 levels which were downregulated by PU.1 interference. PU.1 overexpression strengthened the phagocytosis of the HTMs against AF. And injection of PU.1/CD23-expressing adenoviruses attenuated pathological defects in immunodeficient mouse lung tissues with AF infection. Adenovirus (Ad)-PU.1 increased the CD23, p-ERK, CCL20, IL-8 levels. CONCLUSIONS: Our study concluded that PU.1-CD23 signaling mediates innate immunity against AF in lungs through regulating inflammatory response. Therefore, PU.1-CD23 may be a new anti-aspergillosis therapeutic for the treatment of invasive aspergillosis with the deepening of gene therapy and its wide application in the clinic.

Superelastic 3D Assembled Clay/Graphene Aerogels for Continuous Solar Desalination and Oil/Organic Solvent Absorption.

Superelastic, arbitrary-shaped, and 3D assembled clay/graphene aerogels (CGAs) are fabricated using commercial foam as sacrificial skeleton. The CGAs possess superelasticity under compressive strain of 95% and compressive stress of 0.09-0.23 MPa. The use of clay as skeletal support significantly reduces the use of graphene by 50%. The hydrophobic CGAs show high solvent absorption capacity of 186-519 times its own weight. Moreover, both the compression and combustion methods can be adopted for reusing the CGAs. In particular, it is demonstrated a design of 3D assembled hydrophilic CGA equipped with salt collection system for continuous solar desalination. Due to energy recovery and brine transport management promoted by this design, the 3D assembled CGA system exhibits an extremely high evaporation rate of 4.11 kg m-2  h-1 and excellent salt-resistant property without salt precipitation even in 20 wt% brine for continuous 36 h illumination (1 kW m-2 ), which is the best reported result from the solar desalination devices. More importantly, salts can be collected conveniently by squeezing and drying the solution out of the salt collection system. The work provides new insights into the design of 3D assembled CGAs and advances their applications in continuous solar desalination and efficient oil/organic solvent adsorption.