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Objective. The aim of this study was to evaluate the diagnostic and prognostic value of red blood cell distribution width (RDW) in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods. We retrospectively reviewed 213 CTD-ILD patients and 97 CTD patients without ILD from February 2017 to February 2020. Hospital and office records were used as data sources. CTD-ILD patients were followed up. Results. Patients with CTD-ILD had significantly higher RDW than those with CTD without ILD ( p < 0.001 ). The area under the receiver operating characteristic curve (AUROC) of RDW for discriminating CTD-ILD from CTD without ILD was 0.64 (95% CI: 0.57-0.70, p < 0.001 ). The cutoff value of RDW for discriminating CTD-ILD from CTD without ILD was 13.95% with their corresponding specificity (55.9%) and sensitivity (70.1%). Correlation analyses showed that the increased RDW was significantly correlated with decreased DLCO%predicted ( r = − 0.211 , p = 0.002 ). Cox multiple regression analysis indicated that RDW ( HR = 1.495 , p < 0.001 ) was an independent factor in the survival of CTD-ILD. The best cutoff value of RDW to predict the survival of patients with CTD-ILD was 14.05% ( AUC = 0.78 , 95% CI: 0.72-0.84, p < 0.001 ). The log-rank test showed a significant difference in survival between the two groups ( RDW > 14.05 % and RDW < 14.05 % ). Conclusion. RDW was higher in CTD-ILD patients and had a negative correlation with DLCO%predicted. RDW may be an important serum biomarker for severity and prognosis of patients with CTD-ILD.

Traditional recommendation systems only consider the content of users to predict the rating of items in the recommendation process, and ignore the impact of other factors on the recommendation process except for the user-item rating matrix. Recommendation models that are based on item attributes can portray user preferences and item characteristics from item attribute information, which alleviates the sparseness of rating data to a certain extent. However, they do not consider the potential factors of users and items in the rating matrix. The advantage of deep learning methods in feature representation and feature learning is that they can extract the deep sublinear features of users and items contained in the rating matrix and item attributes. To further improve the quality of recommendation, we proposes the genre rate neural network recommendation (GRNNRec) model, which integrates item attributes based on deep learning. This model integrates the user-item rating matrix and item attributes into a deep neural network to characterize the performance of both in low-dimensional space. First, we use static coding to characterize the properties of the items. Second, we use feature mapping and feature concatenation methods to learn the higher-order features of both continuously. Finally, through the periodic learning rate and the decay rate, we achieve rating prediction. The experiments on different recommendation datasets demonstrate that our model can significantly improve the accuracy of rating prediction in recommendation systems.

A spillway tunnel eroded by high-speed water for a long time is prone to the rebar-exposed defects. Therefore, regular defect detection is very important for the safety of the hydropower station. The images of spillway tunnel are obtained by erecting scaffolding, and then the defects are manually recognized. This traditional method has some disadvantages such as high risk, inefficiently, time consumption and strong subjectivity. To improve the efficiency of defect detection, a real-time method is proposed for spillway tunnel defect detection (STDD) using deep learning. First, images of a spillway tunnel are collected by an Unmanned Aerial Vehicle (UAV) system and raw images are cropped and labeled to create a dataset of rebar-exposed defects. Then, the lightweight STDD network is developed using separable convolution and asymmetric convolution, and the network is trained and tested on the dataset. To evaluate the performance of STDD network, a comparative experiment is conducted with other networks. The results show that the STDD network has better detection performance. For defect segmentation, the recall, precision, F1 and mean intersection over union (mIoU) are 89.92%, 93.48%, 91.59%, and 91.73%, respectively. The STDD network has 1.7 M parameters, and the average inference time is 14.08 ms. In summary, the proposed STDD network achieves accurate and real-time defect detection for spillway tunnel, which can provide reliable support for the structure safety evaluation.

All-solid-state batteries (ASSB) with lithium anode have attracted ever-increasing attention towards developing safer batteries with high energy densities. While great advancement has been achieved in developing solid electrolytes (SE) with superb ionic conductivity rivalling that of the current liquid technology, it has yet been very difficult in their successful application to ASSBs with sustaining rate and cyclic performances. Here in this work, we have realized a stable ASSB using the Li6.25PS5.25Cl0.75 fast ion-conducting electrolyte together with LiNbO3 coated LiCoO2 as cathode and lithium foil as the anode. The effective diffusion coefficient of Li-ions in the battery is higher than 10−12 cm2 s−1, and the significantly enhanced electrochemical matching at the cathode-electrolyte interface was essential to enable long-term stability against high oxidation potential, with the LCO@LNO/Li6.25PS5.25Cl0.75/Li battery to retain 74.12% capacity after 430 cycles at 100 μA cm−2 and 59.7% of capacity after 800 cycles at 50 μA cm−2, at a high charging cut-off voltage of 4.2 V. This demonstrates that the Li6.25PS5.25Cl0.75 can be an excellent electrolyte for the realization of stable ASSBs with high-voltage cathodes and metallic lithium as anode, once the electrochemical compatibility between cathode and electrolyte can be addressed with a suitable buffer coating.

ObjectivesIn the present study, we aimed to assess the clinical significance of cytokeratin 19 fragment (CYFRA21-1) in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM-interstitial lung disease (MDA5-DM-ILD).MethodsA total of 73 MDA5-DM-ILD patients were retrospectively analysed in this work. Their clinical characteristics, including clinical manifestations, laboratory findings, peripheral blood lymphocyte subsets and lung function, were compared between patients with acute/subacute interstitial pneumonia (A/SIP) and chronic interstitial pneumonia (CIP). The level of serum CYFRA21-1 was also compared between the above-mentioned two groups of patients, and its association with the clinical features and mortality of MDA5-DM-ILD was also evaluated.ResultsOf the 73 MDA5-DM-ILD patients, 26 patients exhibited the A/SIP pattern. The level of serum CYFRA21-1 was higher in MDA5-DM patients with A/SIP compared with the CIP group (P = 0.009). Lower oxygenation index (OI), CD3+CD4+ T cell counts and percentage of CD3+CD4+ cells were also observed in MDA5-DM patients with A/SIP compared with the CIP group. Higher serum CYFRA21-1, lower OI, and lower zone consolidation were associated with a higher risk of A/SIP in MDA5-DM-ILD. In addition, 38 decedents with MDA5-DM-ILD exhibited a greater level of CYFRA21-1 compared with 35 survivors (P ConclusionsCYFRA21-1 could be a useful serum indicator associated with occurrence of A/SIP in MDA5-DM-ILD. Moreover, it was associated with a poor survival in MDA5-DM-ILD patients.

It is important to optimize the structure of inlet due to the increasing demand of ram air. In this paper, structural optimization of the submerged inlet is pursued using a hybrid model by integrating least squares support vector machines (LS-SVM) prediction model and improved genetic algorithm-particle swarm optimization (GA-PSO). Inlet shape is controlled by changing three-dimensional geometric parameters. Ramp angle, width to depth ratio and ramp length play significant parts in this optimization process. Ram efficiency and mass flow are the main objectives of the performance evaluation. Results show that the prediction error of the mass flow and ram efficiency is 2.31% and 0.54%, respectively. Comparison with the original geometry is used to prove the optimization capabilities of the proposed optimization method. The mass flow and ram efficiency are increased by 29.2% and 10.0%, respectively. In addition, the characteristics of the optimized submerged inlet geometry are numerically investigated. The numerical results are compared to the optimization results and indicate that this optimization method has high validity. The error of ram efficiency and mass flow is 0.30% and 0.66%, respectively. Consequently, this optimization method can be valuable to aircraft engineers-by providing a novel approach for the design of the submerged inlet.

The scalability processing of all functional layers in perovskite solar cells (PSCs) is one of the critical challenges in the commercialization of perovskite photovoltaic technology. In response to this issue, a large-area and high-quality gallium-doped tin oxide (Ga-SnOx) thin film is deposited by direct current magnetron sputtering and applied in CsPbBr3 all-inorganic PSCs as an electron transport layer (ETL). It is found that oxygen defects of SnOx can be remarkably offset by regulating oxygen flux and acceptor-like Ga doping level, resulting in higher carrier mobility and suitable energy level alignment, which is beneficial in accelerating electron extraction and suppressing charge recombination at the perovskite/ETL interface. At the optimal O2 flux (12 sccm) and Ga doping level (5%), the device based on sputtered Ga-SnOx ETL without any interface modification shows a power conversion efficiency (PCE) of 8.13%, which is significantly higher than that of undoped SnOx prepared by sputtering or spin coating. Furthermore, a PCE of 5.98% for a device with an active area of 1 cm2 is obtained, demonstrating great potential in fabricating efficient and stable large-area PSCs.

X-ray detectors currently employed in dosimetry suffer from a number of drawbacks including the inability to conform to curved surfaces and being limited to smaller dimensions due to available crystal sizes. In this study, a hybrid X-ray detector (HXD) has been developed which offers real-time response with added advantages of being highly sensitive over a broad energy range, mechanically flexible, relatively inexpensive, and able to be fabricated over large areas on the desired surface. The detector comprises an organic matrix embedded with high-atomic-number inorganic nanoparticles which increase the radiation attenuation and within the device allows for simultaneous transfer of electrons and holes. The HXD delivers a peak response of 14 nA cm−2, which corresponds to a sensitivity of $30.8~\mu \text{C}$ Gy−1 cm−2, under the exposure of 6-MV hard X-rays generated by a medical linear accelerator. The angular dependence of the HXD has been studied, which offers a maximum variation of 26% in the posterior versus lateral beam directions. The flexible HXD can be conformed to the human body shape and is expected to eliminate variations due to source-to-skin distance with reduced physical evaluation complexities.

In order to improve the quality of fingerprint with a large noise, this study proposes a fingerprint enhancement method by using a sparse representation of learned multi-scale classification dictionaries with reduced dimensionality. The multi-scale dictionary is used to balance the contradiction between the accuracy and the anti-noise ability, which is an ideal solution to reconcile the demands of enhancement quality and computational performance. The principal component analysis is applied in the authors’ technique for dimension reduction of multi-scale classification dictionaries. Under the quality grading scheme and multi-scale composite windows, the fingerprint patches are enhanced by using a sparse representation of learned multi-scale classification dictionaries with reduced dimensionality according to their priorities. In addition, the multi-scale composite windows help the more high-quality spectra diffuse into the low-quality fingerprint patches and this can greatly improve the spectra quality of them. Experimental results and comparisons on FVC 2000 and FVC 2004 databases are reported. And it shows that the proposed method yields better results in terms of the robustness of fingerprint enhancement as compared with the latest techniques. Moreover, the results show that the proposed algorithm can obtain better identification performance.

To evaluate hospital mortality and associated risk factors for acute exacerbations of idiopathic pulmonary fibrosis (AEIPF). Emphases were put on incidence and impact of extra-pulmonary organ failures. Patients diagnosed with AEIPF from July 2014 to September 2018 were enrolled. Clinical data were collected. Acute physiology and chronic health evaluation II (APACHE II) and simplified acute physiological score II (SAPS II) were calculated. Extra-pulmonary organ failures were diagnosed upon criteria of sequential organ failure assessment (SOFA). Forty-five patients with AEIPF were included. Eighteen patients (40.0%) developed extra-pulmonary organ failures, and 25 patients (55.6%) died during hospitalization. Serum C-reactive protein (CRP) (p = 0.001), SAPS II (p = 0.004), SOFA (p = 0.001) were higher, whereas arterial oxygen pressure (PaO2)/ fractional inspired oxygen (FiO2) (p = 0.001) was lower in non-survivors than survivors. More non-survivors developed extra-pulmonary organ failures than survivors (p = 0.002). After adjustment, elevated serum CRP (OR 1.038, p = 0.049) and extra-pulmonary organ failure (OR 13.126, p = 0.016) were independent predictors of hospital mortality in AEIPF. AEIPF had high hospital mortality and occurrence of extra-pulmonary organ failure was common. Elevated serum CRP and extra-pulmonary organ failure had predictive values for mortality.

Immune checkpoint inhibitors (ICIs) have shown remarkable clinical effects in many cancer types. However, ICIs could also induce severe organ system toxicities, including those of the hematological system. The present study aimed to extensively characterize the hematological toxicities of ICIs immunotherapy. Data were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 1, 2014, to March 31, 2019. Disproportionality analysis, including information component (IC) and reporting odds ratio (ROR), was used to detect potential disproportionality signal. The lower boundary of the 95% confidence interval of IC (IC025 ) exceeding zero or that of ROR (ROR025 ) exceeding one was considered statistically significant for detecting disproportionality signal. A total of 29 294 335 records were extracted from the database, with 132 573 related to ICIs. Overall, hematological adverse events (AEs) were more frequently reported in ICIs (IC025 : 0.81; ROR025 : 1.80). On further analysis, hematological AEs were overreported in female patients (female vs male, ROR025 : 1.04) and anti-CTLA-4 monotherapy groups (anti-CTLA-4 vs anti-PD-1, ROR025 : 1.33) and polytherapy groups (polytherapy vs monotherapy, ROR: 1.20, ROR025 : 1.11). Moreover, class-specific hematological AEs were also detected and differed in unique ICI regimens. Notably, disseminated intravascular coagulation had the highest proportion of death outcomes among the top 10 most frequently reported ICI-associated hematological AEs. Our study shows a high reporting frequency of hematological AEs induced by ICI monotherapy (especially by anti-CTLA-4 therapy) and reinforced by polytherapy. A spectrum of class-specific disproportionality signal was also detected; some were fatal and reported for the first time. The heterogeneous clinical spectrum of hematological toxicities, including the non-negligible proportion of death as reported outcome, are warranted to be reminded by clinicians. Early recognition and management of ICI-related hematological AEs are highly important and further studies are needed to confirm the results of our study.

Serum (1→3)-β-D-glucan (BDG), is an adjunct test in the diagnosis of invasive fungal disease (IFD). Fungitell STAT™, a facile, rapid, single patient option, executable for one or more patient specimens in approximately an hour, has been developed to address a need for rapid in-house testing. This method presents qualitative information concerning serum BDG levels, using an index value that allows the rapid categorization of patients as positive, negative, or indeterminate relative to serum BDG titer. The categorical and analytical performance of Fungitell STAT was evaluated. The categorical agreement between methods was established by testing patient samples which had been previously categorized with Fungitell. Receiver Operating Characteristic curves were used to identify cut-offs using 93 de-identified patient specimens. Subsequently, using these cutoffs, an independent group of 488 patient specimens was analyzed. Positive percent agreement (PPA) with, and without, indeterminate results was 74% and 99%, respectively. Negative percent agreement (NPA) was 91% and 98% with, and without, indeterminate results, respectively. Additionally, commercially available normal off-the-clot sera were spiked with Saccharomyces cerevisiae-derived (1→3)-β-D-glucan to produce analytical samples. Analytical reproducibility using spiked samples was excellent with 94% of the CV (coefficient of variation) values ≤10% among three independent laboratories. Good correlation with the predicate method was demonstrated with correlation coefficients of 0.90 or better with patient samples and 0.99 with spiked samples. The Fungitell STAT index assay provides a rapid and suitable method for serum BDG testing.

Background Increased intestinal barrier permeability and subsequent gut microbial translocation are significant contributors to inflammatory non-AIDS comorbidities in people living with HIV (PLWH). Evidence in animal models have shown that markers of intestinal permeability and microbial translocation vary over the course of the day and are affected by food intake and circadian rhythms. However, daily variations of these markers are not characterized yet in PLWH. Herein, we assessed the variation of these markers over 24 h in PLWH receiving antiretroviral therapy (ART) in a well-controlled environment. Methods As in Canada, PLWH are predominantly men and the majority of them are now over 50 years old, we selected 11 men over 50 receiving ART with undetectable viremia for more than 3 years in this pilot study. Blood samples were collected every 4 h over 24 h before snacks/meals from 8:00 in the morning to 8:00 the next day. All participants consumed similar meals at set times, and had a comparable amount of sleep, physical exercise and light exposure. Plasma levels of bacterial lipopolysaccharide (LPS) and fungal (1→3)-β-D-Glucan (BDG) translocation markers, along with markers of intestinal damage fatty acid binding protein (I-FABP) and regenerating islet-derived protein-3α (REG3α) were assessed by ELISA or the fungitell assay. Results Participants had a median age of 57 years old (range 50 to 63). Plasma levels of BDG and REG3α did not vary significantly over the course of the study. In contrast, a significant increase of LPS was detected between 12:00 and 16:00 (Z-score: − 1.15 ± 0.18 vs 0.16 ± 0.15, p = 0.02), and between 12:00 and 24:00 (− 1.15 ± 0.18 vs 0.89 ± 0.26, p Conclusions Conversely to the fungal translocation marker BDG and the gut damage marker REG3α, time of blood collection matters for the proper evaluation for LPS and I-FABP as markers for the risk of inflammatory non-AIDS co-morbidities. These insights are instrumental for orienting clinical investigations in PLWH.

Aim: We aimed to systematically characterize ear and labyrinth toxicities after immune checkpoint inhibitors (ICIs) initiation. Materials & methods: Data were extracted from the US FDA Adverse Event Reporting System database. Disproportionality analysis including information component and reporting odds ratio (ROR) was performed to access potential signals. Results: In FDA Adverse Event Reporting System database, 284 records for ICIs-associated ear/labyrinth adverse events (AEs) were involved. In general, there was no significant association between total ICIs use and total ear and labyrinth AEs (ROR025: 0.576). However, in ICIs monotherapy and polytherapy groups, signals were detected in several specific ear and labyrinth AEs. Conclusion: Total ear and labyrinth toxicities were not significantly reported with ICI immunotherapy, while class-specific ear toxicities were detected in some strategies.

Numerical calculation and theoretical study on high optical absorption material BaSi2 based np or nip homojunction solar cells were conducted by using AMPS software. The effects of doping concentration and front layer thickness on the performance of n-BaSi2/p-BaSi2 homojunciton solar cell were comprehensive investigated. It was found that the donor concentration and thickness of n-BaSi2 had decisive influence on the light performance of n-BaSi2/p-BaSi2 homojunciton solar cell, since high donor concentration in n-BaSi2 gave rise to extremely high hole trapping concentration in n-BaSi2 and thus reduced the hole current as well as total current density under light illumination. Consequently, the n-BaSi2 layer was suggested to be designed either with low donor concentration or with thin thickness to achieve high power conversion efficiency. Same effect of n-BaSi2 on the performance of nip homojucntion solar cell was also observed. Contrarily, the optimized p-BaSi2 was suggested to possess high acceptor concentration and to be slightly thicker, in order to maintain the high built-in potential as well as Voc of nip homojunciton solar cell. On account of the front and rear contact barrier height between electrode and BaSi2 functional layer, the barrier height between p-BaSi2 and rear contact electrode had comparably more sensitive influence to attenuate the built-in potential and thus the Voc of BaSi2 based nip the solar cell. However, this negative influence caused by high barrier height could be convincingly conquered by employing thick p-BaSi2 layer.

Exposed aggregate is a typical feature of the abrasion erosion in stilling basin slabs concrete surface. Although a variety of underwater robots are designed for inspection, the exposed aggregate detection for identifying abrasion is often done by manual work. The scarcity of image samples, large differences in aggregate size, color and shape are the main difficulties in automatic detection. To address this problem, an improved Attention U-Net deep fully convolutional network-based detection method was proposed. To realize this method, underwater images in site were captured via a self-developed operated underwater robot. Through randomly separating and the cropping of the 128 underwater images, the 512×512 pixels images dataset was built according to the ratio of 8:1:1, including 408 training images, 52 validation images and 52 test images. After the data augmentation, loss function and the optimizer were carefully designed and selected, the proposed Attention U-Net architecture was evaluated on this dataset. For comparative research, the full convolution network (FCN) and U-Net network were trained with the same training and validation dataset. The performance comparison on the test dataset showed that the Attention U-Net architecture has better detection accuracy.

BackgroundImmune cell infiltration in the tumor microenvironment (TME) affects tumor initiation, patients’ prognosis and immunotherapy strategies. However, their roles and interactions with genomics and molecular processes in hepatocellular carcinoma (HCC) still have not been systematically evaluated.MethodsWe performed unsupervised clustering of total 1000 HCC samples including discovery and validation group from available public datasets. Immune heterogeneity of each subtype was explored by multi-dimension analysis. And a support vector machine (SVM) model based on multi-omics signatures was trained and tested. Finally, we performed immunohistochemistry to verify the immune role of signatures.ResultsWe defined three immune subtypes in HCC, with diverse clinical, molecular, and genomic characteristics. Cluster1 had worse prognosis, better anti-tumor characteristics and highest immune scores, but also accompanied by immunosuppression and T cell dysfunction. Meanwhile, a better anti-PD1/CTLA4 immunotherapeutic response was predicted in cluster1. Cluster2 was enriched in TAM-M2 and stromal cells, indicating immunosuppression. Cluster3, with better prognosis, had lowest CD8 T cell but highest immune resting cells. Further, based on genomic signatures, we developed an SVM classifier to identify the patient’s immunological status, which was divided into Type A and Type B, in which Type A had poorer prognosis, higher T cell dysfunction despite higher T cell infiltration, and had better immunotherapeutic response. At the same time, MMP9 may be a potential predictor of the immune characteristics and immunotherapeutic response in HCC.ConclusionsOur work demonstrated 3 immune clusters with different features. More importantly, multi-omics signatures, such as MMP9 was identified based on three clusters to help us recognize patients with different prognosis and responses to immunotherapy in HCC. This study could further reveal the immune status of HCC and provide potential predictors for immune checkpoint treatment response.

Objective To investigate the differences in the proportions of BMPR2 mutations in familial hereditary pulmonary arterial hypertension (HPAH) and idiopathic pulmonary arterial hypertension (IPAH) between males and females and the relationship between BMPR2 mutation and PAH severity. Methods A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and EMBASE databases for clinical trials containing information on the relationship between PAH prognosis and BMPR2 mutations through March 2019. After obtaining the data, a meta-analysis was performed using Review Manager Version 5.3 and Stata. Results A meta-analysis was performed on 17 clinical trials (2198 total patients: 644 male, 1554 female). The results showed that among patients with HPAH and IPAH, the BMPR2 mutation rate is higher in male than in female patients [male group (224/644, 34.78%), female group (457/1554, 29.41%), OR = 1.30, 95% CI: 1.06~1.60, P = 0.01, I2 = 10%]. Furthermore, haemodynamic and functional parameters were more severe in IPAH and HPAH patients with BMPR2 mutations than in those without, and those with BMPR2 mutation were diagnosed at a younger age. The risk of death or transplantation was higher in PAH patients with BMPR2 mutations than in those without (OR = 2.51, 95% CI: 1.29~3.57, P = 0.003, I2 = 24%). Furthermore, the difference was significant only in male patients (OR = 5.58, 95% CI: 2.16~14.39, P = 0.0004, I2 = 0%) and not in female patients (OR = 1.41, 95% CI: 0.75~2.67, P = 0.29, I2 = 0%). Conclusion Among patients with HPAH and IPAH, men are more likely to have BMPR2 mutations, which may predict more severe PAH indications and prognosis.

Background Cystic airspace is an uncommon imaging manifestation involved in non-small lung cancer (NSCLC). Diffuse cystic lesion is even rarer as pulmonary manifestation of NSCLC. In the present study, we reported a rare case of NSCLC associated with progressive diffusion of cystic lesions misdiagnosed as Pulmonary langerhans cell histocytosis (PLCH), finally diagnosed by transbronchial cryobiopsy (TBCB). Case presentation A 52-year-old woman was admitted to our hospital due to cough and dyspnea. High-resolution computed tomography (HRCT) presented diffuse cystic shadow mostly, concomitantly with nodular densities in bilateral lungs. A lung biopsy revealed poorly differentiated adenocarcinoma with vascular tumor emboli. The epidermal growth factor receptor (EGFR) mutation on exon 18 (G719X, G719) was detected by mutation test. The patient received treatment of tyrosine kinase inhibitor (afatinib). Conclusions Diffuse cystic lesion can be a rare manifestation of lung cancer. It was important to improve the recognition of diffuse cystic lung diseases to avoid misdiagnosis.

Survivin is an inhibitor of apoptosis protein that functions to inhibit apoptosis, promote proliferation, and enhance invasion. It is selectively up-regulated in many human tumors and implicated in cellular radiation response through its role in apoptosis, cell division, and DNA damage response. This study aimed to investigate the effect and mechanisms of targeting survivin radiosensitivity in cervical cancer C33A cells. Here, the authors designed a small interfering RNA (siRNA) or plasmid-based small hairpin RNA (shRNA) targeting survivin and tested its effects on radiosensitivity to ionizing radiation (IR) treatment of C33A cells in vitro, as well as on the tumorigenicity of C33A cells in nude mice in vivo. Transient transfection of survivin siRNA into C33A cells suppressed survivin expression, induced cell apoptosis and G2/M arrest and reduced cell proliferation, clone formation ability after IR, followed by p53 upregulated modulator of apoptosis (PUMA) upregulation. But, transient transfection of survivin siRNA alone has no significant effect on cell growth and apoptosis. To confirm that PUMA upregulation is necessary for survivin silencing -induced radiosensitivity to IR treatment, the effect of targeting PUMA in survivin sliencing cells was observed. The results showed that targeting PUMA in survivin sliencing cells rescued C33A cells’ radioresistance. Furthermore, knocking down survivin expression combined with IR treatment significantly slowed tumor growth and promoted tumor cell apoptosis in C33A xenografted tumors. It was concluded that survivin played a role in radiotherapy resistance. Targeting survivin increased the radiosensitivity of C33A cells through induction of PUMA expression., Graphical Abstract

Fuzzy logic controllers are designed for spacecraft hovering flight in a binary asteroid system. The binary asteroid system is modeled as an ellipsoid-sphere system where the spherical harmonics method is adopted to represent the gravitational field of the asteroids. The method to design the fuzzy logic controllers is introduced in detail. Hovering flight about the inner collinear equilibrium point L 1 of binary asteroid Didymos is numerically presented. Detailed steps on roughly estimating the scaling gains of fuzzy logic controllers are also summarized. Numerical simulations are performed to show the effectiveness of the proposed method. Moreover, the aforementioned fuzzy logic controllers can be used for both continuous and impulsive thrusters. The fuzzy controllers with continuous thrust, the fuzzy controllers with fixed thrust, and the other two kinds of sliding-mode controllers are optimized in the same way and compared in the same simulation environment together, to show tremendous advantages of fuzzy logic controllers and continuous thrusters on both control performance and propellant consumption.

Per- and polyfluoroalkyl substances (PFASs) have captured worldwide attention due to their persistent and bioaccumulative characteristics. The bullfrog was a kind of high nutritious and edible aquatic products, nevertheless, its accumulation characteristics of PFAS had not been paid attention. The present study analyzed the PFAS concentrations in different tissues of cultured bullfrogs and relevant water, sediments collected from aquaculture region in the coastal area of South China. The rResults showed that total PFAS concentrations were 50.26 - 364.25 ng/L in water, with a mean of 135.58 ng/L, thereinto, that in effluent water were significantly higher significantly than those in influent water, which means bullfrog farming could increase contaminants into the surroundings. The total PFAS concentrations varied from 2.89 to 162.26 ng/g·dw in sediment. The distribution profile of PFASs in sediment was similar to that of water, with short-chain playing a significant role. The tTotal PFASs in bullfrog tissues were 3.36-84.07 ng/g·dw with the highest values in digestive system (intestines and stomach). As for one novel PFAS alternative, chlorinated polyfluorinated ether sulfonate (F-53B), which was found at high detectable levels in all habitat samples, and higher value of logarithmic bioaccumulation factors. The estimated dietary intake (EDI) for residents in study area was generally higher than that in other regions, however, the hazard ratios (HRs) for most detected PFASs were far below the safety threshold value “1”. These results suggest that frequent consumption of these bullfrogs would basically not cause severe health effects on local residents in terms of PFASs.

Nowadays, people choose to travel in their leisure time more frequently, but fixed predetermined tour routes can barely meet people’s personalized preferences. The needs of tourists are diverse, largely personal, and possibly have multiple constraints. The traditional single-objective route planning algorithm struggles to effectively deal with such problems. In this paper, a novel multi-objective and multi-constraint tour route recommendation method is proposed. Firstly, ArcMap was used to model the actual road network. Then, we created a new interest label matching method and a utility function scoring method based on crowd sensing, and constructed a personalized multi-constraint interest model. We present a variable neighborhood search algorithm and a hybrid particle swarm genetic optimization algorithm for recommending Top-K routes. Finally, we conducted extensive experiments on public datasets. Compared with the ATP route recommendation method based on an improved ant colony algorithm, our proposed method is superior in route score, interest abundance, number of POIs, and running time.

Objective. To explore the mechanism of catechol-O-methyltransferase (COMT) in tooth movement pain. Methods. The experimental groups were randomly allocated into the healthy control, sham operation, model, model+shCOMT experimental, model+shCOMT control, and model+COMT antagonist groups. A tooth movement pain model was established. The pain stimulation and behavior test were performed. The duration of grooming behavior was determined. The appropriate experimental force and duration for application were selected. COMT shRNA vector was constructed and packaged as adenovirus. The shCOMT adenovirus was injected into the left infraorbital foramen. Seven days later, the trigeminal ganglia of all treatment groups were obtained. The COMT and IL-17 expressions were detected by western blot. The appropriate COMT antagonist concentration was selected. The pathological results of each group were detected by HE staining. The tooth movement distance was determined. The COMT gene expression was detected by FISH. The COMT and IL-17 expressions in the right trigeminal ganglion tissue of each group were detected by western blot. Results. The 60 g force and 14-day duration required the lowest stimulus intensity, the duration of grooming behavior was the longest, and the effect on COMT and IL-17 was the most significant. In the model group, formation of digestive cavity was seen in the trigeminal ganglion tissue, with infiltration of inflammatory cells, upregulation of the COMT and IL-17 expressions, and significant increase in the tooth movement distance. Compared with the model group, the shCOMT experimental group and the COMT antagonist group significantly improved the trigeminal ganglion tissue injury, significantly decreased the tooth movement distance, and significantly inhibited the COMT and IL-17 expressions. Conclusion. The efficiency of tooth movement can be influenced by interfering the COMT-related gene expression. This proves that the COMT system can regulate the orthodontic tooth movement pain.

Background and Aims Many previous studies comparing liver resection versus thermal ablation for colorectal cancer liver metastases (CRCLM) are subject to severe selection bias. This study aimed to compare the long-term clinical efficacy of ultrasonography-guided percutaneous microwave ablation (PMWA) with resection for CRCLM using propensity score analysis to reduce confounding by indication. Methods This retrospective study included 184 patients with CRCLM from January 2012 to June 2017. Treatment effect was estimated after propensity score matching, Descriptive, regression and survival statistics were applied. Results A lower American Society of Anesthesiologists classification score and higher performance status were found positively associated with resection (p

Objectives: The prognosis of anti-melanoma differentiation-associated gene (MDA5) antibody-positive dermatomyositis (DM)-interstitial lung disease (ILD) (anti-MDA5 -positive DM-ILD) is often poor, especially in rapidly progressive interstitial lung disease (RPILD). So far there is no established therapy. This study evaluated the efficacy and safety of pharmacological treatments for anti-MDA5-positive DM-ILD. Methods: This retrospective study comprised 87 anti-MDA5-positive DM-ILD patients. We reviewed the clinical characteristics, laboratory findings, lung function treatments, and outcomes of the 87 patients. Cox regression analysis was used to identify predictors of 6-month survival. The association between different combined immunosuppressive regimen and 6-month survival were evaluated.Results: High level of CYFRA21-1 and low PaO2/FiO2 ratio were associated with poor prognosis. Corticosteroid (CS) alone treatment group with higher CYFRA21-1 and lower PaO2/FiO2 ratio showed worse 6-month survival than the combination of CS with immunosuppressants group (pConclusion: Addition of immunosuppressants to CS, were associated with better 6-month survival in anti-MDA5-positive DM-ILD. The triple regimen (CS, tacrolimus/cyclosporine and IVCY) was not superior to duple one (CS, tacrolimus/cyclosporine) in anti-MDA5-positive DM Non-RPILD.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive scarring disease with unknown etiology. The evidence of a pathogenic role for transforming growth factor‐beta (TGF‐β) in the development and progression of IPF is overwhelming. In the present study, we investigated the role of interleukin‐22 (IL‐22) in the pathogenesis of IPF by regulating the TGF‐β pathway. We measured parameters and tissue samples from a clinical cohort of IPF. IL‐22R knock out (IL‐22RA1−/−) and IL‐22 supplementation mouse models were used to determine if IL‐22 is protective in vivo. For the mechanistic study, we tested A549, primary mouse type II alveolar epithelial cell, human embryonic lung fibroblast, and primary fibroblast for their responses to IL‐22 and/or TGF‐β1. In a clinical cohort, the expression level of IL‐22 in the peripheral blood and lung tissues of IPF patients was lower than healthy controls, and the lower IL‐22 expression was associated with poorer pulmonary function. IL‐22R−/− mice demonstrated exacerbated inflammation and fibrosis. Reciprocally, IL‐22 augmentation by intranasal instillation of recombinant IL‐22 repressed inflammation and fibrotic phenotype. In vitro, IL‐22 treatment repressed TGF‐β1 induced gene markers representing epithelial‐mesenchymal‐transition and fibroblast‐myofibroblast‐transition, likely via the inhibition of TGF‐β receptor expression and subsequent Smad2/3 activation. IL‐22 appears to be protective against pulmonary fibrosis by inhibiting TGF‐β1 signaling, and IL‐22 augmentation may be a promising approach to treat IPF., We measured parameters and tissue samples from a clinical cohort of IPF?IL‐22R knock out (IL‐22R−/−) and IL‐22 supplementation mouse models?and A549, human embryonic lung fibroblast and primary fibroblast. We suggested that IL‐22 appears to be protective against pulmonary fibrosis by inhibiting TGF‐?1 signaling, and IL‐22 augmentation may be a promising approach to treat IPF.

BACKGROUND The fungal cell wall constituent 1,3-β-d-glucan (BDG) is a pathogen-associated molecular pattern that can stimulate innate immunity. We hypothesized that BDG from colonizing fungi in critically ill patients may translocate into the systemic circulation and be associated with host inflammation and outcomes. METHODS We enrolled 453 mechanically ventilated patients with acute respiratory failure (ARF) without invasive fungal infection and measured BDG, innate immunity, and epithelial permeability biomarkers in serially collected plasma samples. RESULTS Compared with healthy controls, patients with ARF had significantly higher BDG levels (median [IQR], 26 pg/mL [15–49 pg/mL], P < 0.001), whereas patients with ARF with high BDG levels (≥40 pg/mL, 31%) had higher odds for assignment to the prognostically adverse hyperinflammatory subphenotype (OR [CI], 2.88 [1.83–4.54], P < 0.001). Baseline BDG levels were predictive of fewer ventilator-free days and worse 30-day survival (adjusted P < 0.05). Integrative analyses of fungal colonization and epithelial barrier disruption suggested that BDG may translocate from either the lung or gut compartment. We validated the associations between plasma BDG and host inflammatory responses in 97 hospitalized patients with COVID-19. CONCLUSION BDG measurements offered prognostic information in critically ill patients without fungal infections. Further research in the mechanisms of translocation and innate immunity recognition and stimulation may offer new therapeutic opportunities in critical illness. FUNDING University of Pittsburgh Clinical and Translational Science Institute, COVID-19 Pilot Award and NIH grants (K23 HL139987, U01 HL098962, P01 HL114453, R01 HL097376, K24 HL123342, U01 HL137159, R01 LM012087, K08HK144820, F32 HL142172, K23 GM122069).

P–O–H polycondensation −O–Cu–O– ion-bonded bridges were formed in copper phosphate thermal insulation materials by mixing Al(OH)3 dissolved in H3PO4 with CuO filler and Al2O3, SiC, ZrC, and Cr2O3 as curing accelerators, alone or in combination. The effects of different additive combinations on the curing behavior and thermal stability of the copper phosphate thermal insulation material matrixes were compared using thermogravimetry/differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy. The copper phosphate materials exhibit good thermal stabilities and low thermal conductivities. The thermal weight losses before and after ceramic reinforcement were 4–19.8 and 3.8–9.4%, respectively, and the thermal conductivities of the P–O–H polycondensation −O–Cu–O– ion-bonded bridges formed in the copper phosphate thermal insulation materials were in the range of 0.656–1.824 W/(m·K).

The study aimed to evaluate the clinical and imaging features of critically ill patients with interstitial lung disease (ILD) treated in respiratory intensive care unit (RICU) and assess the prognostic effects of these factors. A total of 160 severe ILD patients admitted to the RICU were finally enrolled in this study. The clinical, imaging and follow-up data of them were studied retrospectively. The in-hospital mortality and total mortality were 43.1% and 63.8% respectively. By multivariate cox regression analysis, shock (OR = 2.39, P = 0.004), pulmonary fibrosis on CT (OR = 2.85, P = 0.002) and non-invasive ventilation (OR = 1.86, P = 0.037) were harmful factors to survivals of critically ill patients with ILD. In contrast, oxygenation index (OR = 0.99, P = 0.028), conventional oxygen therapy (OR = 0.59, P = 0.048) and β-lactam antibiotics use (OR = 0.51, P = 0.004) were protective factors. There is significant difference of survivals between patients with and without fibrosing ILD on CT (Log-rank, p = 0.001). The prognosis of critically ill patients with ILD was poor. Shock, respiratory failure and fibrosing signs on chest CT affected the prognosis. Chest CT was considered as a valuable tool to indicate the prognosis.

Background Immune-checkpoint inhibitors (ICIs) emerged as a novel class of drugs for the treatment of a broad spectrum of malignancies. ICIs can produce durable antitumor responses but they are also associated with immune-related adverse events (irAEs). Endocrinopathies have reported as one of the most common irAEs of ICIs. Methods This study aimed to quantify association of endocrine adverse events (AEs) and ICI therapy and also to characterize the profiles of ICI-related endocrine complications from real-world practice. Data from the first quarter of 2014 to first quarter of 2019 in FDA Adverse Event Reporting System (FAERS) database were gathered to conduct disproportionality analysis. The definition of endocrine AEs relied on the preferred terms (PTs) provided by the Medical Dictionary for Regulatory Activities (MedDRA). Two signal indices based on statistical shrinkage transformation, reporting odds ratios (ROR) and information component (IC), were used to evaluate correlations between ICIs and endocrine events. For ROR, it was defined a signal if the lower limit of the 95% confidence interval (ROR025) more than one, with at least 3 cases. For IC, lower end of the 95% confidence interval of IC (IC025) exceeding zero was deemed statistically significant. Results A total of 29,294,336 records were involved, among these 6260 records related to endocrine AEs after ICIs treatment were identified. In general, male had a slightly lower reporting frequencies for ICIs-related endocrinopathies compared with female but not significant (ROR = 0.98 95%CI: 0.93–1.04) and the difference varied in several common endocrine AEs. Notably, in general, ICI drugs were significantly associated with over-reporting frequencies of endocrine complications, corresponding to IC025 = 2.49 and ROR025 = 5.99. For monotherapy, three strategies (anti-PD-1, anti-PD-L1 and anti-CTLA-4) were all associated with significant increasing endocrine events. Different reporting frequencies emerged when anti-CTLA-4 therapy was compared with anti-PD-1/PD-L1 medications for endocrine toxicities, corresponding to ROR = 1.68 (95%CI 1.55–1.83), ROR = 2.54 (95%CI 2.20–2.93), respectively. Combination therapy was associated with higher risk of endocrinopathies compared with monotherapy (ROR = 2.00, 95%CI 1.89–2.11). When further analysis, the spectrum of endocrine AEs differed in immunotherapy regimens. Hypothyroidism (N = 885,14.14%), adrenal insufficiency(N = 730,11.66%), hypophysitis (N = 688,10.99%) and hyperthyroidism (N = 472,7.54%) were top 4 ranked endocrine events after ICI therapy and their reporting frequency also differed in ICI immunotherapies. Conclusion Our pharmacovigilance analysis shows a high reporting frequency of endocrine AEs provoked by ICI monotherapy (especially anti-CTLA-4 therapy) and further reinforced by combination therapy. In addition, treatment with different ICI immunotherapies may result in a unique and distinct profile of endocrinopathies. Early recognition and management of ICI-related endocrine irAEs is of vital importance in clinical practice.

Background Cytomegalovirus (CMV) seropositivity and anti-CMV immunoglobulin G (IgG) levels are associated with adverse health outcomes in elderly populations. Among people living with human immunodeficiency virus (PLWH), CMV seropositivity has been associated with persistent CD8 T-cell elevation and increased risk of developing non-AIDS comorbidities despite long-term antiretroviral therapy (ART). Herein, we investigated whether CMV seropositivity and elevation of anti-CMV IgG levels were associated with increased epithelial gut damage, microbial translocation, and systemic inflammation. Methods A total of 150 PLWH (79 ART-naive and 71 ART-treated) were compared to 26 without human immunodeficiency virus (HIV) infection (uninfected controls). Plasma markers of HIV disease progression, epithelial gut damage, microbial translocation, nonspecific B-cell activation, anti-CMV and anti–Epstein-Barr virus (EBV) IgG levels, and proinflammatory cytokines were measured. Results CMV seropositivity and elevated anti-CMV IgG levels were associated with markers of epithelial gut damage, microbial translocation, and inflammation in PLWH and participants without HIV infection. In contrast, total nonspecific IgG, immunoglobulin M, immunoglobulin A, and anti-EBV IgG levels were not associated with these markers. CMV seropositivity was associated with markers of epithelial gut damage, microbial translocation, and inflammation independent of sociodemographic and behavioral characteristics of the study population. Conclusions CMV-seropositive people with and without HIV had increased epithelial gut damage, microbial translocation, and inflammation. Furthermore, anti-CMV IgG levels were independently associated with increased epithelial gut damage and microbial translocation. CMV coinfection may partially explain persistent gut damage, microbial translocation, and inflammation in ART-treated PLWH., Cytomegalovirus (CMV) seropositivity and anti-CMV immunoglobulin G levels are associated with increased epithelial gut damage, microbial translocation, and inflammation in antiretroviral therapy (ART)–naive and ART-treated people living with human immunodeficiency virus and uninfected controls.

The asteroid 101955 Bennu is the target asteroid of the ongoing asteroid sample return mission OSIRIS-REx from NASA. In the mission, the spacecraft is scheduled to rendezvous with Bennu in August 2018. Investigating the dynamics of surface motion can offer guidance for further hopping landers or even sample return missions regarding Bennu or similarly irregular-shaped asteroids. This paper presents the free motion of sample particles on and above the surface of Bennu. The concepts and equations that govern the motion of a particle on and above the surface of an asteroid are briefly introduced. Trajectories of a number of particles' free motion are numerically calculated by considering four scenarios with different restitution coefficients. Initial positions of those particles are all randomly given on the surface of Bennu and their initial velocities are set as zero. The distribution of final locations of those sample particles is summarized and analyzed. Both the gravitational potential and its effective potential on the surface of Bennu are calculated to give a possible reason for the distributing characteristics.

Data clustering is a valuable field for extracting effective information and hidden patterns from datasets. In this paper we propose a clustering approach based on density peaks clustering (DPC) and a modified gravitational search algorithm (GSA), called GSA-DPC. To take advantage of the distance measure and nearest neighbor rule among the data points, our method simultaneously combines the distance and density mechanisms. Based on the optimized cluster center set selected by DPC working with density measure, the best clustering distribution is achieved according to the distance criterion of GSA. We compare the performance of GSA-DPC with other well-known clustering approaches, including density-based spatial clustering of applications with noise (DBSCAN), density peaks clustering, K-Means, spectral clustering (SC), grey wolf optimizer for clustering (GWO-C), gravitational search algorithm for clustering (GSA-C) and data clustering algorithm based on GSA and K-Means (GSA-KM). The experimental results indicate that GSA-DPC outperforms these competing approaches.

During the long-term operation of hydro-junction infrastructure, water flow erosion causes concrete surfaces to crack, resulting in seepage, spalling, and rebar exposure. To ensure infrastructure safety, detecting such damage is critical. We propose a highly accurate damage detection method using a deep convolutional neural network with transfer learning. First, we collected images from hydro-junction infrastructure using a high-definition camera. Second, we preprocessed the images using an image expansion method. Finally, we modified the structure of Inception-v3 and trained the network using transfer learning to detect damage. The experiments show that the accuracy of the proposed damage detection method is 96.8%, considerably higher than the accuracy of a support vector machine. The results demonstrate that our damage detection method achieves better damage detection performance.

Background:. The prognosis of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is very poor with a high mortality. The aim of this study was to describe the clinical features and survival of patients with AE-IPF with usual pulmonary fibrosis (UIP) and possible UIP (P-UIP) pattern on chest high resolution computed tomography (HRCT). Methods:. This retrospective study included 107 patients with AE-IPF admitted to Nanjing Drum Tower Hospital from January 2010 to December 2016. The subjects were divided into UIP (n = 86) and P-UIP group (n = 21) based on chest HRCT. Continuous variables were analyzed using Student's t test or Mann-Whitney U test. Categorical variables were analyzed using χ2 test. Log-rank test was used for the survival analysis. Cox proportional models evaluated the risk factors for AE occurrence and survival. Results:. The male, older patients, previous N-acetylcysteine use, elevated white blood cell (WBC) counts, and microbiology infection were more common in the UIP group than the P-UIP group (χ2 = 13.567, P

Software-defined networking (SDN) provides a promising architecture for future networks, and can provide advantages as central control programmability and global view. However, it faces numerous security challenges. Distributed denial of service (DDoS) is a security threat to SDN. Most existing schemes only perform DDoS attack detection and do not address how to defend and recover after detecting DDoS. In this paper, a DDoS attack detection and defense mechanism based on cognitive-inspired computing with dual address entropy is proposed. The flow table characteristics of the switch are extracted, and a DDoS attack model is built by incorporating the support vector machine classification algorithm. This mechanism can realize real-time detection and defense at the preliminary stage of the DDoS attack and can restore normal communication in time. The experiment shows that our mechanism not only detects attacks quickly but also has a high detection rate and low false positive rate. More importantly, it can take appropriate defense and recovery measures in the time after the attack has been identified.

BACKGROUND: Despite antiretroviral therapy (ART), people living with HIV (PLWH) have higher rates of non-AIDS disorders, such as neurocognitive (NC) impairment (NCI) than the general population. (1–3)-b-D-glucan (BDG) is a fungal cell wall component which serves as a biomarker for gut barrier integrity failure and microbial and fungal translocation. The primary objective of this study was to determine whether higher plasma and cerebrospinal fluid (CSF) levels of BDG were associated with NCI in PLWH. METHODS: Paired blood and CSF samples were collected cross-sectionally from 61 male adult PLWH on ART (95% virally suppressed) who underwent a detailed NC assessment as part of the prospective CHARTER study between 2005–2015. BDG and soluble urokinase plasminogen activator receptor (suPAR) were measured in frozen blood and CSF samples while soluble CD14 (sCD14), intestinal fatty acid binding protein (IFABP) and CD4/CD8 ratio were measured in blood only. Spearman’s rho correlation analysis assessed associations between BDG, other biomarkers and NC performance. RESULTS: Median BDG levels were 18 pg/mL in plasma (range: 2–60 pg/mL) and 20 pg/mL in CSF (range: 0–830 pg/mL). Higher levels of plasma BDG were associated with worse NC performance (Spearman’s rho=−0.32; p=0.013) and with presence of NCI (p=0.027). A plasma BDG cut-off of >30pg/mL was 30% sensitive and 100% specific for NCI. After adjusting for age, higher plasma SuPAR levels were also associated with worse NC performance (p

Density peaks clustering is a novel and efficient density-based clustering algorithm. However, the problem of the sensitive information leakage and the associated security risk with the applications of clustering methods is rarely considered. To address the problem, we proposed differential privacy-preserving density peaks' clustering based on the shared near neighbors similarity method in this paper. First, the Euclidean distance and the shared near neighbors similarity were combined to define the local density of a sample, and the Laplace noise was added to the local density and the shortest distance to protect privacy. Second, the process of cluster center selection was optimized to select the initial cluster centers based on the neighborhood information. Finally, each sample was assigned to the cluster as its nearest neighbor with higher local density. The experimental results on both the UCI and synthetic datasets show that compared with other algorithms, our method more effectively protects the data privacy and improves the quality of the clustering results.

As an emerging human-solving paradigm, crowdsourcing has attracted much attention where requesters want to employ reliable workers to complete the specific task. Task assignment is a vital branch in crowdsourcing. Most existing works in crowdsourcing haven't taken self-interested individuals' strategy into account. To guarantee truthfulness, auction has been regarded as a promising form to charge requesters and reward workers. In this paper, we consider an online task assignment scenario, where each worker has a set of experienced skills, whereas specific task is budget-constrained and requires certain skill. Under this scenario, we model the crowdsourcing task assignment as a reverse auction in which requesters are buyers and workers are sellers. Specially, our paper studies simple task case where the requester ask for single skill. We propose TMC-VCG and TMC-ST and prove the related properties for the mechanisms theoretically. Meanwhile, through extensive simulations, we verify the truthfulness and also evaluate other performance.

For a long time, priority has been given to urban development at the expense of agriculture and the rural economy, so widening the gap between urban and rural areas in China. The way rapid urbanization has brought threats to the surrounding environment, and the consequent changes have implications for both rural and urban livelihoods and well-being. Urbanization has increased the pressure on farmers and makes it less economic to farm in a traditional way, while it also provides opportunities for alternative, higher value agricultural enterprises to take advantage of urban market. With more rural people moving into cities, occupational hazards of the working environments，low awareness of health risk, and poor living conditions make them more vulnerable to health risks than other groups. Several strategies particularly relating to agricultural reform and rural-urban migration need to be considered at the national level for sustainable cities. We also suggest ways of handling the delicate rural-urban relationship for smooth social transformation.

Background Hepatocellular carcinoma (HCC) is one of the most common cancers with the highest mortality rate in the world. Receptor tyrosine kinases play an important role in the occurrence and development of cancer. Discoid protein domain receptors 1 (DDR1) are a special type of transmembrane receptor tyrosine kinase. Here, we show DDR1 is significantly increased in Hepatocellular carcinoma(HCC), which is related to poor prognosis of HCC patients. Methods DDR1 expression in HCC cell lines and paired HCC specimens were determined by western blot and immunohistochemistry (IHC). At the same time, the correlation between the DDR1 and SLC1A5 was also studied in HCC specimens. Cell proliferation ability were evaluated by CCK8 and colony formation assays. Knock-down and overexpression experiments, CHX, NH4CL and Mg132 intervention experiments, Immunoprecipitation experiments, and nude mouse xenograft models were used to determine the potential mechanism by which DDR1 promotes tumorigenesis in vitro and in vivo. Results In this study, we find that overexpression of DDR1 promotes the proliferation of HCC cells and accelerates the growth of tumor xenografts, while downregulation of DDR1 has the opposite effect. We also proved that loss or gain of DDR1 could affect the cell cycle progression of liver cancer cells. Mechanistically, DDR1 interacts with the SLC1A5 that belongs to the solute carrier (SLC) family of transporters and regulates its stability, thereby regulating the mTORC1 signaling pathway. In addition, we found that the regulation of SLC1A5 by DDR1 can be restored by lysosome inhibitors. Otherwise, we found that DDR1 was highly expressed in HCC and elevated DDR1 expression predicted shorter overall survival (OS) time for HCC patients. We further revealed that the expression of SLC1A5 was positively correlated with DDR1.In summary, our data shows that DDR1 is a tumor-promoting factor that can control cell proliferation and cell cycle by stabilizing SLC1A5 in a lysosome-dependent pathway, which provides a new treatment target for HCC. Conclusions This study reveals a new mechanism through which DDR1 can play the role of cancer-promoting genes in the progression of liver cancer. We also found that the expression of DDR1 is an independent prognostic indicator of OS, and the expression of DDR1 and SLC1A5 are positively correlated in clinical samples. Our findings provide a new perspective for understanding the development of HCC, which may provide new targets for the treatment and management of this challenging cancer.

During the trough period after the grid-connected power generation of an Hydropower Station, due to the high bus voltage, the generator is in under - excitation operation for a long time, and the guide vane opening of the water turbine unit is small, and operation in the vibration zone will cause some damage to the water turbine unit, which can be solved by installing a high-voltage parallel reactor. The expansion under the full shutdown mode will seriously affect the economic benefits of hydropower stations and the grid structure. Therefore, this research studies the secondary system test scheme for the expansion project of 500kV hydropower station under the partial shutdown mode, and analysis in detail the changes of the protection configuration in the past during the expansion process. According to the analysis results, debugging methods such as the circuit wiring that needs to be removed after the protection configuration changes and the arrangement of secondary safety measures in this mode are put forward to eliminate potential safety hazards during the test. Through the expansion project of an Hydropower Station, the scheme demonstrates a highly secure and reliable solution that could also be referred to the future expansion of the hydropower station.

Osteosarcoma is the most common malignant bone tumor, and although there has been significant progress in its management, metastases often herald incurable disease. Here we defined genes differentially expressed between primary and metastatic osteosarcoma as metastasis-related genes (MRGs) and used them to construct a novel six-MRG prognostic signature for overall survival of patients with osteosarcoma. Validation in internal and external datasets confirmed satisfactory accuracy and generalizability of the prognostic model, and a nomogram based on the signature and clinical variables was constructed to aid clinical decision-making. Of the six MRGs,FHITis a well-documented tumor suppressor gene that is poorly defined in osteosarcoma. Consistent with tumor suppressor function, FHIT was downregulated in osteosarcoma cells and human osteosarcoma samples. FHIT overexpression inhibited osteosarcoma proliferation, migration, and invasion bothin vitroandin vivo. Mechanistically, FHIT overexpression upregulate the epithelial marker E-cadherin while repressing the mesenchymal markers N-cadherin and vimentin. Our six-MRG signature represents a novel and clinically useful prognostic biomarker for patients with osteosarcoma, and FHIT might represent a therapeutic target by reversing epithelial to mesenchymal transition.

In the past decades, the energy consumption of nonrenewable fossil fuels has been increasing, which severely threatens human life. Thus, it is very urgent to develop renewable and reliable energy storage devices with features of environmental harmlessness and low cost. High power density, excellent cycle stability, and a fast charge/discharge process make supercapacitors a promising energy device. However, the energy density of supercapacitors is still less than that of ordinary batteries. As is known to all, the electrochemical performance of supercapacitors is largely dependent on electrode materials. In this review, we firstly introduced six typical transition metal oxides (TMOs) for supercapacitor electrodes, including RuO2, Co3O4, MnO2, ZnO, XCo2O4 (X = Mn, Cu, Ni), and AMoO4 (A = Co, Mn, Ni, Zn). Secondly, the problems of these TMOs in practical application are presented and the corresponding feasible solutions are clarified. Then, we summarize the latest developments of the six TMOs for supercapacitor electrodes. Finally, we discuss the developing trend of supercapacitors and give some recommendations for the future of supercapacitors.

When a metro is constructed by the shield method in the strata containing boulder group, it is prone to some engineering problems such as serious cutter wear, deformation of the cutter holder head, damage of the cutter spindle, which seriously affects the construction efficiency and bring enormous problems to the shield construction. This paper proposes the vibration reduction measures for the boulder deep-hole blasting to meet the construction safety. To achieve this purpose, the field test was applied to investigate the vibration response of adjacent building under five blasting areas. Then, three-dimensional numerical model was employed to discuss the vibration characteristics of the boulder and adjacent buildings under vibration reduction measures. The results show that increasing the damping hole and the isolation hole and changing the charging layout of the blasting areas can blast the boulder under the condition of ensuring effective and safe construction. Damping hole and isolation hole have a positive role in the control and attenuation of blasting stress wave. All of them have good vibration reduction effect, and the vibration reduction efficiency is more than 90%. The double row damping holes with 12.7 cm diameter and 20 cm spacing have good vibration reduction effect and economic benefit. When double row damping holes are used, the maximum particle velocity of the shaft structure under the influence of blasting stress wave is 1.47 cm/s, which is within the reasonable safety range.

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the accumulation of excessive surfactant lipids and proteins in alveolar macrophages and alveoli. Oral statin therapy is a novel treatment for PAP with hypercholesterolemia. However, this treatment has never been described in a patient without hypercholesterolemia. Here, we present a case of successful treatment with atorvastatin for a patient with possibly unclassified PAP without hypercholesterolemia who responded poorly to whole lung lavage therapy and inhaled granulocyte-macrophage colony-stimulating factor. After 18 months of atorvastatin treatment, the patient experienced improvements in dyspnea, radiographic abnormalities and pulmonary function. The present case study supports the feasibility of statin therapy for PAP regardless of the level of cholesterol.