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Inspired by the multilayer structure of the shellfish, a novel two-dimensional (2D) composite structure consisting of graphene oxide, MoS2 and graphene oxide (G/M/G) was integrated to the flexible pressure sensing. The composite structure was prepared by the vacuum suction filtration in order to imitate the high toughness of shellfish. Based on the strategy of strain engineering, a comprehensive experimental bench capable of meeting different strain conditions was connected to a push–pull meter and an LCR digital bridge, and then a computer was used to record the changes in transducer capacitance when an external load was applied to the meter. Graphene oxide (GO) and G/M/G supercells were constructed, and density functional theory (DFT) simulations of the initial energy band structure under strain-free conditions were carried out to determine the relationship between the band gap, conductivity, capacitance, and sensitivity of the G/M/G structure based on band gap theory, and to easily understand the mechanism of the shellfish heterostructure leading to enhanced sensitivity of the sensors. Using two-point bending and axial tensile tests, a flexible pressure sensing device was designed to realize positive strains in the ranges of 0%–5 % and 5%–50 %. The results show that the sensitivity of both GO and G/M/G capacitive pressure sensors decreased with increased strain, and the sensitivity of the G/M/G sensors was significantly improved by 75%–102 % compared to the GO sensors at the same strain. The parallel-plate capacitor model and crack growth theory well explain the experimental results at small and large strains. Our results provide new concepts for the design of novel flexible sonar with high sensitivity and large strain operating range by a simple vacuum filtration method, which can be extended to the design of other high-performance 2D flexible electronic devices. Inspired by the multilayer structures of shellfish in nature, we constructed a GO/MoS2/GO heterojunction pressure sensor. The working range under strain and the pressure sensitivity of this new bio-inspired sensor were respectively improved by 25% and 102% compared to the traditional GO sensor structure. [ABSTRACT FROM AUTHOR]

Channel fracturing technology is designed to form fractures supported by non-uniform pillar proppants. Non-cured adhesive resin-coated proppant gradually becomes viscous after immersion and agglomerates during transportation. The pillars are stable after the fracture is closed. They not only maintain a certain compressive strength but also maintain long-term conductivity. Currently, there are few evaluations of coated proppant migration. Based on CFD-DEM method, a two-phase flow coupling model considering the adhesive contact force of coated proppant particles is established to study the cementation characteristics of coated proppant during transportation. The transportation mechanism of coated proppant are revealed by numerical calculation analysis. The results show that different from the conventional proppant, the migration process of the coated proppant is divided into four stages (1) the softening of the proppant contact; (2) the paving of the proppant agglomeration; (3) proppant pillars growth along fracture height; and (4) proppant pillars growth along fracture length. We have completed a preliminary geometric characteristics evaluation of sand bank formed by coated proppant by evaluating the pore volume ratio (the ratio of void volume between pillars to the sand bank volume) under various parameters. This evaluation offers some theoretical guidance for the optimization of channel fracturing proppant injection parameters. [ABSTRACT FROM AUTHOR]

Vertical drains have been widely used in soil improvement projects to accelerate consolidation and improve the strength of soft soil. Previous consolidation models are mainly based on instantaneous loading, which cannot reflect the actual time-variable loading condition. This paper presents a set of analytical solutions for consolidation with vertical drains under depth and time-dependent loading, involving one-step loading, multi-step loading, and cyclic loading. A four-element model, which is a combination of the Merchant model and Maxwell model, is introduced to consider the rheological characteristics of the soil. By simulating the results of a consolidation test, it is found that the four-element model is more accurate than the Merchant model in predicting the changes in pore pressure and settlement during the clay consolidation process. Based on the solutions obtained, several factors affecting consolidation behavior are investigated. It has been shown that the rheological behavior becomes more and more obvious at the later stage of consolidation with the decrease both in the modulus of the spring in the Kelvin body and the viscosity coefficient of the independent dashpot. With the increase in the viscosity coefficient of the dashpot in the Kelvin body, the rate of consolidation becomes faster at an initial stage but slower at a later stage. For cyclic loading, the consolidation degree in each cycle reaches a maximum at the end of unloading and reaches a minimum at the beginning of the loading. [ABSTRACT FROM AUTHOR]

Clogging of the landfill drainage layer leads to a high leachate head developing over the bottom liner, which increases the risk of leachate leakage. Estimation of the maximum leachate head in the landfill drainage layer is of great significance to the pollution control of bottom liners. In this study, a simplified model considering the development of clogging is established through assuming the spatial and temporal distributions of clogging in a drainage layer of landfill. The calculation results are compared with a previous study to verify the proposed model. Through parameter analysis, it is discovered that the larger the initial hydraulic conductivity, the less the influence of clogging on the leachate head at the beginning, but it will increase over time. Meanwhile, a longer drainage distance, a larger inflow rate, or a higher ion concentration will lead to a greater influence of clogging on the leachate head. The completion time of clogging is more sensitive to the variation of inflow rate and ion concentration. In order to effectively control the maximum leachate head, it is suggested that the drainage material with large hydraulic conductivity such as pebbles or gravel should be used, the drainage slope should be greater than 4%, the drainage distance should be controlled at 20 m, and calcium products should be removed from leachate through adsorption, precipitation, or waste reuse. [ABSTRACT FROM AUTHOR]

Aims: Paroxysmal atrial fibrillation (PAF) commonly recurs after radiofrequency catheter ablation (RFCA). This study aimed to assess left atrial appendage (LAA) volume and function by transesophageal echocardiography (TEE) and to explore its value in predicting PAF recurrence after RFCA. Methods: Eighty patients with PAF were recruited. The left atrial (LA) and LAA volume and function were measured by transthoracic echocardiography (TTE) and TEE before ablation. Patients were followed up for 12 months after RFCA, and recurrence was recorded. Odds ratios of candidate risk indicators were determined by logistic regression analysis. Prediction model was constructed using logistic regression with backward selection. Receiver operating characteristic (ROC) curve with area under curve (AUC) was performed to evaluate the prediction efficiency. Results: Twenty‐four (30%) PAF patients had recurrence (R group), and 56 (70%) patients had no recurrence (NR group). Compared to NR group, LA dimension (LAD), LA volume index (LAVI), LAA maximum volume (LAAVmax), and LAA minimum volume (LAAVmin) were significantly higher in R group, while LAA peak emptying flow velocity (LAAeV), LAA peak filling flow velocity (LAAfV), and LAA ejection fraction (LAAEF) significantly declined in R group. According to multivariate analysis and backward selection, LAVI, LAAEF, and LAAeV were significant risk factors for PAF recurrence. The LAVI + LAAEF + LAAeV joint model could effectively predict PAF recurrence with AUC of 0.893 (95% confidence interval = 0.816, 0.970), sensitivity of 0.75, and specificity of 0.929. Conclusions: This study demonstrated that LAVI, LAAEF, and LAAeV were significant predictors of PAF recurrence after RFCA. [ABSTRACT FROM AUTHOR]

Background: There is ongoing debate about surgery of primary site in nasopharyngeal carcinoma patients.Methods: 3919 patients with nasopharyngeal carcinoma identified in the SEER registry between 2004 and 2013. The benefit of surgery of primary nasopharynx tumor site on overall and cancer-specific survival was assessed by risk-adjusted multivariate Cox proportional hazard regression and propensity score matching modeling.Results: Surgery was marginally associated with better overall survival (hazard ratio (HR) = 0.816, 95% CI 0.656-1.015, p = 0.07) and cancer-specific survival (HR = 0.749, 95% CI 0.552-1.018, p = 0.06) in the propensity score model. Among 398 cases who underwent primary site surgery, 282 (70.85%) received local tumor excision and 79 (20.31%) received pharyngectomy. Local tumor excision and pharyngectomy had almost the same effect on survival in propensity score matching analysis. The benefit was significant in subgroups of white, age <60 year, and patients with T3, N1, M0, AJCC stage III, or moderately differentiated tumors. Further survival analysis showed surgery to promote survival in both radiotherapy and non-radiotherapy patients.Conclusion: This is the first population-based analysis using propensity score model to provide evidence of a positive impact of surgery on survival in nasopharyngeal carcinoma. Moreover, surgery demonstrated the significant benefit in subgroups of patients with specific clinical characteristics. [ABSTRACT FROM AUTHOR]

Background: Long intergenic noncoding RNAs (lincRNAs) are a series of novel transcribed regions expressed in cancers that may represent candidate biomarkers for lung squamous cell carcinoma (LSqCC) treatment. In this study, we evaluated the lincRNA profile in LSqCC patients and screened valuable lincRNAs for diagnosis and prognosis. Methods: Transcriptome profiling of 549 samples derived from 501 LSqCC patients were identified in TCGA database. 48 patients had paired primary tumor (PT) and solid normal (SN) tissue samples, while 453 patients had only PT samples. 1,771 lincRNA candidates were evaluated. Paired test (Wilcoxon two‐sample paired signed rank tests) was performed in paired PT and SN samples. Logistic regression analysis were performed in independent 453 PT samples and 48 SN samples to screen the significant lincRNAs candidates for malignances. Independent 501 PT samples were further used to screen the significant lincRNAs candidates for prognosis. Results: Among 1,771 lincRNAs, 10 lincRNAs were significant highly‐expressed risk candidates in PT samples, and 10 protective lincRNAs candidates were significant lowly‐expressed in PT samples. Among 10 highly‐expressed risk lincRNAs, a small panel of LINC00487, LINC01927, and C10orf143 (LINC00959) could effectively predict malignancies in paired samples (AUC = 0.7274, 95%CI = (0.6264, 0.8285)). When combined with protective lincRNA candidates LINC02315, LINC00491, and LINC01697, the predictive efficiency was greatly improved in both paired samples (AUC = 0.8030, 95%CI = (0.7250, 0.8810)) and independent samples (AUC = 0.7481, 95%CI= (0.6642, 0.8320)). Additionally, three highly‐expressed risk lincRNAs, LINC01031, LINC01088, and LINC01931, were significantly associated with poor prognosis in PT samples, suggesting potential targets for anti‐LSqCC treatment. Conclusion: Therefore, lincRNAs could be promising biomarkers for predicting malignancies and potential anti‐LSqCC targets for drug development. [ABSTRACT FROM AUTHOR]

Lung squamous cell carcinoma (LUSC) accounts for approximately 25% to 30% of lung cancers, but largely no targeted therapy is available against it, calling for identification of new oncogenes in LUSC growth for new therapeutic targets. In this study, REL was identified through a screening for oncogenes that are highly amplified in human LUSC. Its expression was associated with poor prognosis in LUSC patients. Furthermore, knockdown of c-Rel in LUSC cell lines lead to significant decrease in cell proliferation and migration. Mechanistically, c-Rel knockdown suppressed NFκB pathway by blocking phosphorylation of IκB. Consistently, pharmaceutic inhibition of c-Rel also. In orthotopic xenograft lung cancer mouse model, c-Rel knockdown inhibited the tumor growth. Cancer cell proliferation and epithelial-mesenchymal-transition (EMT) of the tumors were impaired by c-Rel knockdown. Finally, it's confirmed in precision-cut tumor slices of LUSC that deletion of c-Rel inhibits the NFκB pathway and cancer cell growth. Accordingly, we hypothesize that c-Rel promotes the activation of the NFκB pathway by promoting the phosphorylation of IκB in LUSC. Our study reveals REL as a novel LUSC oncogene and provides new insights into the molecular regulation of LUSC, which will provide new therapeutic targets for the treatment of squamous lung cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: Recent research indicates a potential association between workplace violence and an increased risk of cardiovascular disease (CVD) in the working-age population. However, the relevant evidence in the United States is sparse. Thus, this study was conducted to explore the possible relationship between workplace violence and CVD among United States workers., Methods: We utilized cross-sectional data from the 2015 National Health Interview Survey, which included a representative sample of 18 380 workers, to investigate the associations between workplace violence and the prevalence of CVD using logistic regression. Workplace violence was determined based on self-reported threats, bullying, or harassment at work over the past 12 months, supplemented with additional information regarding frequency. CVD included all forms of heart disease and stroke., Results: A total of 1334 workers reported experiences of workplace violence, and 1336 workers were diagnosed with CVD. After adjustment for covariates, participants who reported any instance of workplace violence had significantly higher odds of having CVD (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.35 to 2.30) than those who reported no such violence. Furthermore, the highest odds of CVD (OR, 1.80; 95% CI, 1.23 to 2.63) were observed among those frequently exposed to workplace violence. Even occasional exposure to workplace violence was associated with 74% excess odds of CVD., Conclusions: Our study indicates an association between workplace violence and CVD in United States workers, exhibiting a dose-response pattern.

There is a positive association between air pollution and lung cancer burden. This study aims to identify and examine lung cancer risks and mortality burdens associated with air pollutants, including PM 10 , NO 2 and SO 2 , in seven eastern metropolises of China. The study population comprised a population from seven eastern metropolises of China. The yearly average values (YAV, μg/m 3 ) of the PM 10 , NO 2 and SO 2 levels were extracted from China Statistical Yearbook (CSYB) for each selected city from 2006 to 2014. Data collected in the China Cancer Registry Annual Report (CCRAR) provide lung cancer incidence and mortality information. A two-level normal random intercept regression model was adopted to analyze the association between the lung cancer rates and individual air pollutant concentration within a five-year moving window of past exposure. The yearly average values of PM10, SO2 and NO2 significantly decreased from 2006 to 2014. Consistently, the male age-adjusted incidence rate (MAIR) and male age-adjusted mortality rate (MAMR) decreased significantly from 2006 to 2014.Air pollutants have a lag effect on lung cancer incidence and mortality for 2-3 years. NO2 has the significant association with MAIR (RR=1.57, 95% CI: 1.19-2.05, p=0.002), MAMR (RR=1.70, 95% CI: 1.32-2.18, p=0.0002) and female age-adjusted mortality rate (FAMR) (RR=1.27, 95% CI: 1.08-1.49, p=0.003). Our findings suggested that air pollutants may be related to the occurrence and mortality of lung cancer. NO2 was significantly associated with the risk of lung cancer, followed by SO2. Air pollutants have the strongest lag effect on the incidence and mortality of lung cancer within 2-3 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Meng, Hu, Yuan, Zeng, Li, Luo, Tang, Zhou, Tian, Luo, He and Yang.)

Approximately 15-20% of breast cancer patients are epidermal growth factor receptor 2 (HER2)-positive, and about half of these are also hormone receptor (HR)-positive. The mainstay treatment for HER2-positive/HR-positive patients is anti-HER2 treatment combined with chemotherapy. However, many patients are not suitable for this treatment regimen due to their poor physical health and inability to tolerate chemotherapy. Pyrotinib is a novel, irreversible tyrosine kinase inhibitor (TKI) with activity against EGFR/HER1, HER2, and HER4. Several studies have shown pyrotinib's anti-tumor activity and safety profile in treating HER-2 positive breast cancer patients, but its effect on metastatic breast cancer (MBC) when combined with letrozole as a first-line treatment remains to be verified. Here, we present a case of a 50-year-old postmenopausal HER2-positive/HR-positive breast cancer patient who received pyrotinib plus letrozole as a first-line treatment following a diagnosis of left axillary lymph node and double lung metastases after modified radical mastectomy for left breast cancer. Two months after administration of combined pyrotinib and letrozole, a complete response (CR) was confirmed by CT scan. The patient experienced only mild and tolerable adverse events. At the time of writing, the patient was still alive without any recurrence. Our case indicates that the combined therapy of pyrotinib plus letrozole may/can be a promising treatment option for patients with HER2-positive/HR-positive MBC. Nevertheless, further evidence is needed to verify this conclusion., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-3978). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), and is highly contagious and pathogenic. TMPRSS2 and Neuropilin-1, the key components that facilitate SARS-CoV-2 infection, are potential targets for treatment of COVID-19. Here we performed a comprehensive analysis on NRP1 and TMPRSS2 in lung to provide information for treating comorbidity of COVID-19 with lung cancer. NRP1 is widely expressed across all the human tissues while TMPRSS2 is expressed in a restricted pattern. High level of NRP1 associates with worse prognosis in multiple cancers, while high level of TMPRSS2 is associated with better survival of Lung Adenocarcinoma (LUAD). Moreover, NRP1 positively correlates with the oncogenic Cancer Associated Fibroblast (CAF), macrophage and endothelial cells infiltration, negatively correlates with infiltration of CD8 + T cell, the tumor killer cell in Lung Squamous cell carcinoma (LUSC). TMPRSS2 shows negative correlation with the oncogenic events in LUAD. RNA-seq data show that NRP1 level is slightly decreased in peripheral blood of ICU admitted COVID-19 patients, unaltered in lung, while TMPRSS2 level is significantly decreased in lung of COVID-19 patients. Our analysis suggests NRP1 as a potential therapeutic target, while sets an alert on targeting TMPRSS2 for treating comorbidity of COVID-19 and lung cancers.

Background: The overexpression of integrin α V β 3 in hepatocarcinoma (HCC) promotes tumor progression, metastasis, and clinical staging. Thus, the inhibition of integrin α V β 3 might be potentially effective as an anti-cancer agent in HCC., Methods: In this study, we aimed to investigate the antitumor effect of integrin α V β 3 antibody conjugated cationic microbubbles (CMBs) in HCC model. By conjugating with integrin α V β 3 antibody with non-targeting CMBs, CMBs αvβ3 was constructed. The antitumor effect of CMBs αvβ3 was evaluated in HepG2 cells in vitro and in HepG2 xenograft mice models. Bcl-2, p53 and CD31 mRNA level, and caspase-3 activity were examined in xenograft tumors. Cell proliferation assay and scratch test were performed to evaluate the anti-migrant effect of CMBs αvβ3 in vitro ., Results: CMBs αvβ3 could specifically target to HCC HepG2 cells and improve pEGFP-KDRP-CD/TK plasmid transfection efficiency. In HepG2 xenograft mice models, CMBs αvβ3 treatment significantly suppressed tumor weights and volumes. CMBs αvβ3 treatment suppressed Bcl-2 and p53 mRNA level in tumors. In HepG2 cells, CMBs αvβ3 significantly impaired wound healing and inhibited cell proliferation. Moreover, when combined with CD/TK double suicide gene transfection and 5-FC/GCV treatment, caspase-3 was activated and the cell proliferation was tremendously inhibited., Conclusions: CMBs αvβ3 not only suppresses cell migration and proliferation, but also facilitates 5-FC/GCV plus CD/TK double suicide gene-induced apoptotic cell death. CMBs αvβ3 is a promising gene delivery agent with potential anti-tumor activity itself., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.05.29). The authors have no conflicts of interest to declare., (2019 Translational Cancer Research. All rights reserved.)

Bronchoscopy inspection, as a follow-up procedure next to the radiological imaging, plays a key role in the diagnosis and treatment design for lung disease patients. When performing bronchoscopy, doctors have to make a decision immediately whether to perform a biopsy. Because biopsies may cause uncontrollable and life-threatening bleeding of the lung tissue, thus doctors need to be selective with biopsies. In this paper, to help doctors to be more selective on biopsies and provide a second opinion on diagnosis, we propose a computer-aided diagnosis (CAD) system for lung diseases, including cancers and tuberculosis (TB). Based on transfer learning (TL), we propose a novel TL method on the top of DenseNet: sequential fine-tuning (SFT). Compared with traditional fine-tuning (FT) methods, our method achieves the best performance. In a data set of recruited 81 normal cases, 76 TB cases and 277 lung cancer cases, SFT provided an overall accuracy of 82% while other traditional TL methods achieved an accuracy from 70% to 74%. The detection accuracy of SFT for cancers, TB, and normal cases are 87%, 54%, and 91%, respectively. This indicates that the CAD system has the potential to improve lung disease diagnosis accuracy in bronchoscopy and it may be used to be more selective with biopsies.

Thyroid cancer is a common malignant disease with high survival rate (98.1%, 2006-2012, Surveillance Epidemiology and End Results (SEER) program). In this study, we investigated the treatment paradoxes in thyroid T0 and micro-carcinoma patients. 48,234 thyroid carcinoma patients were identified from 2010 to 2013 in SEER*Stat database (version 8.2.1) released in 2016. Survival analysis showed a significantly lower thyroid carcinoma-specific survival in T0 patients compared with T1-T3 patients. In propensity score analysis, T0 patients had a similar survival curve with T1-T3 patients when lymph node and distant metastasis stages were matched. When all variables, including radiation and surgery treatment, were matched, T0 patients had significantly higher survival compared to T3 patients. These findings suggested that more metastasis and less treatment led to poorer prognosis in T0 patients. Another paradox is about thyroid micro-carcinoma. The survival rate of micro-carcinoma patients was high (4 years survival rate was 99.92%), and more than 99% micro-carcinoma patients received surgery. Interestingly, all the patients who died because of thyroid carcinoma received surgery. Survival analysis showed no difference in survival when patients stratified by surgery or radiation. In conclusion, we suggested paradoxes in thyroid carcinoma treatment: over-treated in micro-carcinoma patients and less-treated in T0 patients.

microRNAs (miRNAs) are involved in the various processes of DNA damage repair and play crucial roles in regulating response of tumors to radiation therapy. Here, we used nasopharyngeal carcinoma (NPC) radio-resistant cell lines as models and found that the expression of miR-504 was significantly up-regulated. In contrast, the expression of nuclear respiratory factor 1 (NRF1) and other mitochondrial metabolism factors, including mitochondrial transcription factor A (TFAM) and oxidative phosphorylation (OXPHOS) complex III were down-regulated in these cell lines. At the same time, the Seahorse cell mitochondrial stress test results indicated that the mitochondrial respiratory capacity was impaired in NPC radio-resistant cell lines and in a miR-504 over-expressing cell line. We also conducted dual luciferase reporter assays and verified that miR-504 could directly target NRF1. Additionally, miR-504 could down-regulate the expression of TFAM and OXPHOS complexes I, III, and IV and impaired the mitochondrial respiratory function of NPC cells. Furthermore, serum from NPC patients showed that miR-504 was up-regulated during different weeks of radiotherapy and correlated with tumor, lymph nodes and metastasis (TNM) stages and total tumor volume. The radio-therapeutic effect at three months after radiotherapy was evaluated. Results indicated that patients with high expression of miR-504 exhibited a relatively lower therapeutic effect ratio of complete response (CR), but a higher ratio of partial response (PR), compared to patients with low expression of miR-504. Taken together, these results demonstrated that miR-504 affected the radio-resistance of NPC by down-regulating the expression of NRF1 and disturbing mitochondrial respiratory function. Thus, miR-504 might become a promising biomarker of NPC radio-resistance and targeting miR-504 might improve tumor radiation response.