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As a significant infectious disease in livestock, porcine reproductive and respiratory syndrome (PRRS) imposes substantial economic losses on the swine industry. Identification of diagnostic markers and therapeutic targets has been a focal challenge in PPRS prevention and control. By integrating metabolomic and lipidomic serum analyses of clinical pig cohorts through a machine learning approach with in vivo and in vitro infection models, lysophosphatidic acid (LPA) is discovered as a serum metabolic biomarker for PRRS virus (PRRSV) clinical diagnosis. PRRSV promoted LPA synthesis by upregulating the autotaxin expression, which causes innate immunosuppression by dampening the retinoic acid‐inducible gene I (RIG‐I) and type I interferon responses, leading to enhanced virus replication. Targeting LPA demonstrated protection against virus infection and associated disease outcomes in infected pigs, indicating that LPA is a novel antiviral target against PRRSV. This study lays a foundation for clinical prevention and control of PRRSV infections. [ABSTRACT FROM AUTHOR]

With the development of the regional economy, the metropolitan area has gradually shifted from the rapid development stage of concentrating on the central city to the stage of coordinated and integrated regional development. This trend has brought new development opportunities to the metropolitan fringe area; however, due to the differences in resource endowment and the complex relationship between different levels of government, the metropolitan fringe area inevitably has contradictions and imbalances in economic and social development. There has been extensive research on land use and urban governance in the metropolitan area, but less attention has been paid to the metropolitan fringe area, and it is difficult to quantitatively characterize the complex interactions between various forces in this area. This paper summarizes the spatial pattern and spatiotemporal characteristics of construction land use in the fringe area of Shenzhen metropolitan area based on the 30 m resolution land cover dataset from 2000 to 2020, and analyzes the driving factors affecting the changes of construction land use through logistic regression. The results show that the overall land use in the study area is shifting from cropland and forest land to urban and rural construction land. With different stages of development, the rate of land change varies greatly from one period to another. Three factors, population density, lighting index and distance to highway, have a significant correlation with the changes in built-up land across the region, while the boundary effects of administrative boundaries show some variation in the impact of urban land expansion at different economic levels. Finally, we put forward that reducing the negative impact of administrative divisions on the integration of resources in different cities is important for realizing the synergistic development of the Shenzhen metropolitan area. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea virus (PEDV) has led to significant economic losses in the global porcine industry since the emergence of variant strains in 2010. The high mutability of coronaviruses endows PEDV with the ability to evade the host immune response, which impairs the effectiveness of vaccines. In our previous study, we generated a highly cell-passaged PEDV strain, CT-P120, which showed promise as a live attenuated vaccine candidate by providing satisfactory protection against variant PEDV infection in piglets. However, the mechanism by which the attenuated CT-P120 adapts to cells during passage, resulting in increased replication efficiency, remains unclear. To address this question, we conducted a comparative transcriptomic analysis of Vero E6 cells infected with either the original parental strain (CT-P10) or the cell-attenuated strain (CT-P120) of PEDV at 6, 12, and 24 h post-infection. Compared to CT-P10, CT-P120 infection resulted in a significant decrease in the number of differentially expressed genes (DEGs) at each time point. Functional enrichment analysis of genes revealed the activation of various innate immune-related pathways by CT-P10, notably attenuated during CT-P120 infection. To validate these results, we selected eight genes (TRAF3, IRF3, IFNL1, ISG15, NFKB1, MAP2K3, IL1A, and CCL2) involved in antiviral processes and confirmed their mRNA expression patterns using RT-qPCR, in line with the transcriptomic data. Subsequent protein-level analysis of selected genes via Western blotting and enzyme-linked immunosorbent assay corroborated these results, reinforcing the robustness of our findings. Collectively, our research elucidates the strategies underpinning PEDV attenuation and immune evasion, providing invaluable insights for the development of effective PEDV vaccines. [ABSTRACT FROM AUTHOR]

Lung cancer (LC) is a common cancer with high incidence and mortality rates. In recent years, ginsenoside Rg3 (Rg3), a traditional medicine, is widely used for the treatment of LC. Herein, we concentrate on assessing the effect of Rg3 on LC cell migration and invasion. The effects of Rg3 (0, 25, 50, and 100 μg/ml) on the viability, migration, invasion, angiogenesis, and expressions of epithelial–mesenchymal transition (EMT)‐related proteins, cyclooxygenase‐2 (COX2), and vascular endothelial growth factor (VEGF) of LC cell lines were evaluated by cell counting kit‐8 (CCK‐8), scratch, transwell, tube formation, and western blot assays. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to assess transfection efficiency. COX2 overexpression plasmid and short hairpin RNA for VEGF (shVEGF) were applied to evaluate whether the effect of Rg3 is related to COX2 and VEGF through rescue assay. In this study, Rg3 significantly dose‐dependently suppressed the viability, migration, invasion, angiogenesis, and protein expressions of N‐cadherin, vimentin, COX2, and VEGF in H1299 and A549 cells, while promoting the expression of E‐cadherin protein. COX2 overexpression markedly reversed the effects of Rg3 on the viability, migration, invasion, angiogenesis, and EMT‐related protein expression levels in LC cells; however, such effects of COX2 overexpression were offset by VEGF knockdown. In sum, Rg3 alleviates the migration, invasion, and angiogenesis of LC cells by inhibiting the expressions of COX2 and VEGF. [ABSTRACT FROM AUTHOR]

A recent article in Advanced Science discusses a study on the porcine reproductive and respiratory syndrome virus (PRRSV) and its potential control. The study used multi-omics analysis and machine learning to identify lysophosphatidic acid (LPA) as a biomarker and therapeutic target for PRRSV. The authors suggest that by eliminating LPA, it may be possible to effectively control PRRSV infection. The article provides more details on this antiviral approach. [Extracted from the article]

Online car-hailing services have become an integral part of people's daily travel in China. Considering that young people are the major consumer group in car purchases, it is worth investigating how the experience of online car-hailing services affects their intention to purchase a car. Based on the extended theory of Planned Behavior, this study found that the factors that negatively impact the car purchase intention of the youth are firstly the public transportation service quality, followed by the risks of private cars, and finally the online car-hailing services quality. Elevating the convenience and comfort of public transportation is conducive to reducing car purchasing intention. The indirect effect of online car-hailing services on car purchase intention is greater than its direct effect, and the most important factor is attitude. The car purchase intention is significantly heterogeneous across age and annual household income groups. Improving the convenience of public transportation will reduce the car purchase intention of people in the early youth. For middle and later youth, providing demand-responsive transit for important individuals to meet their diverse needs can reduce car purchase intention. As for online car-hailing services, youth care most about their convenience and comfort and worry most about their safety. Providing better online car-hailing services can reduce the car-purchasing intention of youth. [ABSTRACT FROM AUTHOR]

To address the problems of uneven distribution and low coverage of wireless sensor network (WSN) nodes in random deployment, a node coverage optimization strategy with an improved COOT bird algorithm (COOTCLCO) is proposed. Firstly, the chaotic tent map is used to initialize the population, increase the diversity of the population, and lay the foundation for the global search for the optimal solutions. Secondly, the Lévy flight strategy is used to perturb the individual positions to improve the search range of the population. Thirdly, Cauchy mutation and an opposition-based learning strategy are fused to perturb the optimal solutions to generate new solutions and enhance the ability of the algorithm to jump out of the local optimum. Finally, the COOTCLCO algorithm is applied to WSN coverage optimization problems. Simulation results show that COOTCLCO has a faster convergence speed and better search accuracy than several other typical algorithms on 23 benchmark test functions; meanwhile, the coverage rate of the COOTCLCO algorithm is increased by 9.654%, 13.888%, 6.188%, 5.39%, 1.31%, and 2.012% compared to particle swarm optimization (PSO), butterfly optimization algorithm (BOA), seagull optimization algorithm (SOA), whale optimization algorithm (WOA), Harris hawks optimization (HHO), and bald eagle search (BES), respectively. This means that in terms of coverage optimization effect, COOTCLCO can obtain a higher coverage rate compared to these algorithms. The experimental results demonstrate that COOTCLCO can effectively improve the coverage rate of sensor nodes and improve the distribution of nodes in WSN coverage optimization problems. [ABSTRACT FROM AUTHOR]

Background: The clinical TNM staging system does not differ between the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging manual. A more practical TNM staging system for patients with stage I-III cutaneous melanoma are needed. Methods: Data were accessed from the Surveillance, Epidemiology, and End Results (SEER) open database. We divided the patients into 32 groups based on the T and N categories. The Kaplan-Meier survival curves and treatment guidelines were used to proposed a new TNM staging system. Cox proportional hazards model and 1000-person-years were used to verify accuracy. Results: This retrospective study included 68 861 patients from 2010 to 2015. The new proposed staging system was as follows: stage IA, T1aN0M0; stage IB, T1b/T2aN0M0; stage IIA, T3-4aN0M0 and T2bN0M0; stage IIB, T1-4aN1-2M0 and T3-4bN0M0; and stage III, T1-4aN3M0 and T1-4bN1-3M0. Hazard ratios for the new stages IB, IIA, IIB, and III, with stage IA as reference, were 4.311 (95% confidence interval [CI]: 3.217-5.778), 8.993 (95% CI: 6.637-12.186), 13.179 (95% CI: 9.435-18.407), and 20.693 (95% CI: 13.655-31.356), respectively (all p-values < 0.001). Cancer-specific mortality rates per 1000-person-years were 0.812 (95% CI: 0.674-0.978), 6.612 (95% CI: 5.936-7.364), 22.228 (95% CI: 20.128-24.547), 50.863 (95% CI: 47.472-54.496) and 120.318 (95% CI: 112.596-128.570) for stages IA, IB, IIA, IIB and III, respectively. Conclusion: We developed a more practical and prognosis-relevant staging system than that of the 8th edition AJCC manual for patients with stage I-III cutaneous melanoma. Treatments using this new model would improve the quality of life and survival rates of patients with melanoma. [ABSTRACT FROM AUTHOR]

Current studies on microplastic pollution mainly focus on marine systems. However, few studies have investigated microplastics in an urban lake. This research intends to use an urban lake (Songshan Lake) as an example to explore the pollution characteristics of microplastics and use the principal component as well as the heat map analysis to discuss the relationships between different shapes of microplastics. According to this study, the average abundance of microplastics in the surface water and surface sediments of Songshan Lake were, respectively, 2.29 ± 0.98 items/m3 and 244 ± 121 items/kg; thin films were the major microplastics in both media; transparent this type of color has the most microplastic content. The particle size of microplastics was mainly 0.18–0.6 mm (43.3%) in surface water and 1–2 mm (48.3%) in surface sediments. The composition included five polymers: polyethylene (PE), polypropylene (PP), polypropylene–polyethylene copolymer (PP–PE copolymer), polystyrene (PS), and polyvinyl chloride (PVC), among which PE (47%) and PP (36%) were the main components. Principal component analysis (PCA) showed that there was a positive correlation among the four shapes of microplastics: films, fragments, foams, and fibers. The heat map analysis showed that the same category of shape distribution features may be similar for each sampling site. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) has evolved into a pandemic. We hypothesized that biochemical indicators of liver function may help determine the prognosis of COVID-19 patients. Methods: Patient information was collected from the Wuhan-Leishenshan hospital. Logistic and Cox regression analyses, Kaplan-Meier curves, and Curve fitting were used to determine the correlation between elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT and severity of disease/mortality. Results: Logistic and Cox regression analyses and Kaplan-Meier survival curves showed that COVID-19 progression correlated with elevated levels of AST and AST/ALT. The odds ratios for elevated levels of AST and AST/ALT in patients were 0.818 (95% confidence interval [CI]: 0.274-2.441, P = 0.035) and 2.055 (95% CI: 1.269-3.327, P = 0.003), respectively; the hazard ratios were 4.195 (95% CI: 1.219-14.422, P = 0.023) and 3.348 (95% CI: 1.57-7.139, P = 0.002), respectively. The Kaplan-Meier survival curves demonstrated that patients with elevated AST and AST/ALT levels had a higher risk of developing severe COVID-19. Conclusion: Elevated AST and AST/ALT levels correlated with severity of COVID-19 and mortality. Liver function tests may help clinicians in determining the prognosis of patients undergoing treatment for COVID-19. [ABSTRACT FROM AUTHOR]

Aims: To explore the role of the Sphingosine 1-Phosphate (S1P)/Receptor2 (S1PR2) pathway in thrombin-induced hyperpermeability (TIP) and to test whether bivalirudin can reverse TIP via the S1P-S1PRs pathway. Methods and Results: Using western blot, we demonstrated that Human umbilical vein endothelial cells (HUVECs) that were cultured with 2 U/ml thrombin showed significantly increased S1PR2 expression while S1PR1and three kept unchanged. Such increment was attenuated by JTE-013 pretreatment and by presence of bivalirudin. Exposure of 2 U/ml of thrombin brought a higher level of S1P both intracellularly and extracellularly within the HUVECs by using ELISA detecting. Thrombin induced S1P and S1PR2 increment was restored by usage of PF543 and bivalirudin. Bivalirudin alone did not influenced the level of S1P and S1PR1,2, and S1PR3 compare to control group. As a surrogate of cytoskeleton morphology, phalloidin staining and immunofluorescence imaging were used. Blurry cell edges and intercellular vacuoles or spaces were observed along thrombin-exposed HUVECs. Presence of JTE-013 and bivalirudin attenuated such thrombin-induced permeability morphological change and presence of heparin failed to show the protective effect. Transwell chamber assay and probe assay were used to measure and compare endothelial permeability in vitro. An increased TIP was observed in HUVECs cultured with thrombin, and coculture with bivalirudin, but not heparin, alleviated this increase. JTE-013 treatment yielded to similar TIP alleviating effect. In vivo , an Evans blue assay was used to test subcutaneous and organ microvascular permeability after the treatment of saline only, thrombin + saline, thrombin + bivalirudin, thrombin + heparin or thrombin + JTE-013. Increased subcutaneous and organ tissue permeability after thrombin treatment was observed in thrombin + saline and thrombin + heparin groups while treatment of bivalirudin and JTE-013 absent this effect. Conclusion: S1P/S1PR2 mediates TIP by impairing vascular endothelial barrier function. Unlike heparin, bivalirudin effectively blocked TIP by inhibiting the thrombin-induced S1P increment and S1PR2 expression, suggesting the novel endothelial protective effect of bivalirudin under pathological procoagulant circumstance. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR) spectroscopy, whose time domain data is modeled as the sum of damped exponential signals, has become an indispensable tool in various scenarios, such as biomedicine, biology, and chemistry. NMR spectroscopy signals, however, are usually corrupted by Gaussian noise in practice, raising difficulties in sequential analysis and quantification. The low-rank Hankel property of exponential signals plays an important role in the denoising issue, but selecting an appropriate parameter still remains a problem. In this work, we explore the effect of the regularization parameter of a convex optimization denoising method based on low-rank Hankel matrices for exponential signals corrupted by Gaussian noise. An accurate estimate on the spectral norm of weighted Hankel matrices is provided as a guidance to set the regularization parameter. The bound can be efficiently calculated since it only depends on the standard deviation of the noise and a constant. Aided by the bound, one can easily obtain an auto-setting regularization parameter to produce promising denoised results. Our results on synthetic and realistic NMR spectroscopy data demonstrate a superior denoising performance of the proposed approach over typical Cadzow and the state-of-the-art QR decomposition methods, especially in the low signal-to-noise ratio regime. [ABSTRACT FROM AUTHOR]

Purpose. Parathyroid carcinoma (PC) is an uncommon endocrine disease, and surgery is considered the only potential cure. PC does not have a mature staging system because of the small number of PC patients. Our aim is to further investigate the prognostic factors associated with PC and explore the optimal extent of resection for PC patients. Methods. Univariate and multivariate Cox regression analyses were conducted to explore the influence of relevant factors on cancer-specific survival (CSS) and overall survival (OS). Survival curves were generated using the Kaplan–Meier method and analyzed using the log-rank test. The mortality rates per 1,000 person-years were calculated to evaluate patients' follow-up data. We also performed subgroup analysis based on the extent of resection. Results. The extent of resection was related to both CSS and OS, whereas race and extent of disease had a significant positive correlation with OS (all P < 0.05). Patients who underwent parathyroidectomy had remarkably better CSS and OS than patients who did not undergo definitive treatment. Conclusion. The extent of resection is related to CSS and OS in patients with PC. No significant difference in prognosis was observed between patients who underwent parathyroidectomy and those who underwent en bloc resection, which may provide useful parameters for the treatment of PC. [ABSTRACT FROM AUTHOR]

The nuclear magnetic resonance (NMR) spectroscopy has fruitful applications in chemistry, biology and life sciences, but suffers from long acquisition time. Non‐uniform sampling is a typical fast NMR method by undersampling the time‐domain data of the spectrum but need to restore the fully sampled data with proper constraints. The state‐of‐the‐art method is to model the time‐domain data as the sum of exponential functions and reconstruct these data by enforcing the low rankness of Hankel matrix. However, this method is solved by minimizing the sum of singular values of the Hankel matrix, which leads to the distortion of low‐intensity spectral peaks. Here, a low rank Hankel matrix reconstruction approach with a partial sum of singular values is proposed to protect small singular values, which can faithfully reconstruct all peaks. Results on both synthetic and realistic NMR spectroscopy show that the proposed method can reconstruct a more consistent spectrum to the fully sampled one than other state‐of‐the‐art methods and have particular advantages on preserving low‐intensity peaks. [ABSTRACT FROM AUTHOR]

Purpose: The newest (8th) edition of the TNM staging system published in 2017. In this edition, some significant changes happened from the previous edition. As a result, down-staging appeared in nearly one third of DTC patients. However, we don't know whether the new system predicts the survival of FVPTC patients accurately. Therefore, it is necessary to thoroughly evaluate the correlation between the new system and survival prediction in terms of FVPTC. Methods: We enrolled 17,662 FVPTC patients from the Surveillance, Epidemiology, and End Results database. Factors associated with survival were identified by Cox regression analyses. The mortality rates per 1,000 person-years were calculated and compared. Cox proportional hazards regression quantified the risk of survival, and survival curves were produced by Kaplan-Meier analyses using log-rank tests. Results: Age at diagnosis, race, T-stage at diagnosis, distant metastasis, radiation therapy, and surgery were independent factors associated with cancer-specific survival. Patients aged <55 years with stage T4N1M0 FVPTC had higher mortality rates per 1,000 person-years than patients in the same stage according to the 8th AJCC System. Cox proportional hazards regression reflected that patients aged <55 years with stage T1-3, any N, M0 or T4N0M0 disease (p=0.001) and patients aged ≥55 years with T1-2N0M0 disease (p=0.004) had significantly lower risks of cancer-specific survival (CSS) than those aged <55 years with stage T4N1M0 disease. The CSS curve of patients aged <55 years with stage T4N1M0 disease showed a decline on comparison with others belonging to stage I (p<0.001); and the curve was even not different from patients in stage II and stage III (p>0.05). Conclusion: Patients aged <55 years with stage T4N1M0 FVPTC had worse survival than patients in stage I; no difference was seen on comparison with stage II patients. We recommend this group of patients be upstaged in the 8th AJCC system. [ABSTRACT FROM AUTHOR]

Background: Interleukin-6 (IL-6), a proinflammatory cytokine, has been reported to be associated with disease severity and mortality in patients with coronavirus disease 2019 (COVID-19). Yet, dynamic changes in IL-6 levels and their prognostic value as an indicator of lung injury in COVID-19 patients have not been fully elucidated. Objective: To validate whether IL-6 levels are associated with disease severity and mortality and to investigate whether dynamic changes in IL-6 levels might be a predictive factor for lung injury in COVID-19 patients. Methods: This retrospective, single-center study included 728 adult COVID-19 patients and used data extracted from electronic medical records for analyses. Results: The mortality rate was higher in the elevated IL-6 group than in the normal IL-6 group (0.16 vs 5%). Cox proportional hazards and logistic regression analyses for survival (adjusted hazard ratio, 10.39; 95% confidence interval [CI], 1.09–99.23; p = 0.042) and disease severity (adjusted odds ratio, 3.56; 95% CI, 2.06–6.19; p < 0.001) revealed similar trends. Curve-fitting analyses indicated that patient computed tomography (CT) scores peaked on days 22 and 24. An initial decline in IL-6 levels on day 16 was followed by resurgence to a peak, nearly in tandem with the CT scores. Conclusion: Increased IL-6 level may be an independent risk factor for disease severity and in-hospital mortality and dynamic IL-6 changes may serve as a potential predictor for lung injury in Chinese COVID-19 patients. These findings may guide future treatment of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the clinical courses and outcomes of diabetes mellitus patients with coronavirus disease 2019 (COVID-19) in Wuhan. Methods: This study enrolled 1,880 consecutive patients with confirmed COVID-19 in Leishenshan Hospital. We collected and analyzed their data, including demographic data, history of comorbidity, clinical symptoms, laboratory tests, chest computed tomography (CT) images, treatment options, and survival. Results: The percentages of patients with diabetes among the severe and critical COVID-19 cases were higher than those among the mild or general cases (89.2%, 10.8 vs. 0%, p = 0.001). However, patients with and without diabetes showed no difference in the follow-up period (p = 0.993). The mortality rate in patients with or without diabetes was 2.9% (n = 4) and 1.1% (n = 9), respectively (p = 0.114). Univariate and multivariate Cox regression analyses and the Kaplan-Meier curves did not show any statistically significant differences between patients with and without diabetes (all p > 0.05). Conclusions: Our study results suggested that diabetes had no effect on the prognosis of COVID-19 patients but had a negative association with their clinical courses. These results may be useful for clinicians in the management of diabetic patients with COVID-19. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR) spectroscopy serves as an indispensable tool in chemistry and biology but often suffers from long experimental times. We present a proof‐of‐concept of the application of deep learning and neural networks for high‐quality, reliable, and very fast NMR spectra reconstruction from limited experimental data. We show that the neural network training can be achieved using solely synthetic NMR signals, which lifts the prohibiting demand for a large volume of realistic training data usually required for a deep learning approach. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR) spectroscopy serves as an indispensable tool in chemistry and biology but often suffers from long experimental times. We present a proof‐of‐concept of the application of deep learning and neural networks for high‐quality, reliable, and very fast NMR spectra reconstruction from limited experimental data. We show that the neural network training can be achieved using solely synthetic NMR signals, which lifts the prohibiting demand for a large volume of realistic training data usually required for a deep learning approach. [ABSTRACT FROM AUTHOR]

Differentiated thyroid cancer (DTC) is the most common thyroid cancer with a relatively high survival rate. The association between certain risk factors of distant metastasis (DM) remains uncertain. In order to assess the prognosis of patients with DTC better, the present study aimed to investigate the synergistic effects between histologic subtype, tumor size, lymph node metastasis (LNM) status and extrathyroidal extension (ETE) on the incidence of DM in DTC. Data of 96,788 patients with DTC were obtained from the Surveillance, Epidemiology and End Results database. The association between clinicopathological factors and DM was evaluated by univariate and multivariate analyses. The synergistic effects of relevant factors were determined by measuring the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI). The results demonstrated that tumor size, LNM status, histologic subtype and ETE were independent risk factors for DM [odds ratio (OR)=2.433; P<0.001; OR=3.998; P<0.001; OR=6.266; P<0.001; and OR=3.873; P<0.001, respectively]. In addition, a significant additive synergistic effect on DM was identified between ETE and histologic subtype, ETE and LNM status, as well as between ETE and tumor size (RERI=34.097; AP=0.706; SI=3.585; RERI=6.425; AP=0.410; SI=1.781; and RERI=76.973; AP=0.864; SI=7.930, respectively). Therefore, the results of this study revealed that ETE with follicular thyroid histology, N1 stage or large tumor size may have a synergistic effect on the risk of DM in patients with DTC. These results suggested that individualized treatment may benefit patients with DTC, and when ETE coexists with one of the identified risk factors, radical treatments may be required. [ABSTRACT FROM AUTHOR]

All-inorganic cesium lead halide perovskite (CsPbX3, X = Cl, Br, I) nanocrystals (NCs) have attracted considerable attention due to their tunable optical properties and high optical quantum yield. However, their stability in various environments, such as different solvents, high temperature and UV light, remains to be addressed to enable their exploitation in devices. Here, we report on the synthesis of all inorganic CsPbI3 perovskite nanocrystals capped with didodecyldimethylammonium bromide (DDAB). Monodispersed DDAB-capped CsPbI3 NCs have enhanced stability with respect to their morphological and optical properties compared to conventional oleic acid (OA)/oleylamine (OLA) capped nanocrystals. The DDAB-CsPbI3 NCs retain an optical quantum yield >80% for at least 60 days. The enhanced stability is explained by the binding of branched DDAB ligands to the NC surface, leading to the formation of a halogen-rich surface, as confirmed by X-ray photoelectron spectroscopy, with an iodine to lead atomic ratio of I : Pb = 4 : 1. These perovskites were used in light-emitting diodes (LEDs) and have a maximum external quantum efficiency (EQE) of 1.25% and a luminance of 468 cd m−2, and demonstrated improved operational performance. The enhanced stability of DDAB-CsPbI3 in the environments relevant for device processing and operation is relevant for their exploitation in optoelectronics. [ABSTRACT FROM AUTHOR]

Background: Lung cancer brain metastases are very common and one of the common causes of treatment failure. We aimed to examine the clinical use of chemical exchange saturation transfer (CEST) technology in the evaluation of brain metastases for lung cancer diagnosis and prognosis. Methods: We included26 cases of lung cancer brain metastases, 15 cases of gliomas, and 20 cases with normal tests. The magnetization transfer ratio (MTR;3.5 ppm) image from the GRE-EPI-CEST sequence was analyzed using the ASSET technique and APT technology. The MTR values were measured in the lesion-parenchymal, edema, and non-focus regions, and the MTR image was compared with the conventional MRI. ANOVA and t-test were used for statistical analysis. Results: The lesion-parenchymal, edema, and non-focus areas in the metastatic-tumor-group were red-yellow, yellow-green, and green-blue, and the MTR values were 3.29 ± 1.14%,1.28 ± 0.36%,and 1.26 ± 0.31%, respectively. However, in the glioma-group, the corresponding areas were red, red-yellow, and green-blue, and the MTR values were 6.29 ± 1.58%, 2.87 ± 0.65%, and 1.03 ± 0.30%, respectively. The MTR values of the corresponding areas in the normal-group were 1.07 ± 0.22%,1.04 ± 0.23%, and 1.06 ± 0.24%, respectively. Traditional MR images are in black-white contrast and no metabolic information is displayed. The MTRvalues of the three regions were significantly different among the three groups. The values were also significantly different between the parenchymal and edema areas in the metastatic-tumor-group. There were significant differences in the MTR values between the non-lesion and edema regions, but there was no significant difference between the edema and non-focus areas. In the glioma-group, there were significant differences in the MTR values between the parenchymal and edema areas, between the parenchymal and non-focus areas, and between the edema and non-focus areas. Conclusions: CEST reflects the protein metabolism; therefore, early diagnosis of brain metastases and assessment of the prognosis can be achieved using molecular imaging. [ABSTRACT FROM AUTHOR]

Objectives: Since the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis (AJCC/TNM) cancer staging system introduced some significant changes, we investigated whether patients with stage T1-2N1M1 differentiated thyroid cancer (DTC) should be placed in stage IVB, with the goal of providing suggestions for improved survival prediction. Materials and Methods: We divided 30,234 DTC patients aged ≥55 years enrolled from the Surveillance, Epidemiology, and End Results (SEER) database into different stage groups based on the new stage system but in a more thorough manner. Univariate and multivariate Cox regression analyses were conducted to explore the clinicopathological factors associated with cancer-specific survival. Survival of different stage groups was assessed by mortality rates per 1,000 person-years, Cox proportional hazards regression analyses, and Kaplan-Meier analyses with log-rank tests and the propensity score matching method. Results: Univariate and multivariate analyses demonstrated that age at diagnosis, T stage, lymph node metastasis, distant metastasis, histological types, extrathyroidal extension, and radiation therapy were associated with cancer-specific survival. Patients with stage T1-2N1M1 had a lower cancer-specific mortality rate per 1,000 person-years (28.081, 95% confidence interval [CI]: 12.616–62.505) and all-cause mortality rate per 1,000 person-years (70.203, 95% CI: 42.323–116.448) than those with low-level stages such as stage T4aN1M0, stage IVA, and stage T1-2N0M1. Cox proportional hazards regression analyses suggested that patients with stage T4bN1M0 belonging to stage IVA (hazard ratio: 2.529, 95% CI: 1.018–6.278, p = 0.046) had a significantly higher risk of cancer-specific mortality than those with stage T1-2N1M1. Kaplan-Meier analyses with log-rank tests suggested that the cancer-specific survival curve of patients with stage T1-2N1M1 had a more modest decline than that of stage T4bN1M0 (p = 0.0125), and the cancer-specific survival curve and all-cause survival curve of patients with stage T1-2N1M1 were not different from those of stage T3N1M0, stage T4aN0M0, stage T4aN1M0, stage T4bN0M0, and stage T1-2N0M1 (all, p > 0.05). The analysis yielded similar results after propensity score matching for other clinicopathological characteristics. Conclusion: Patients aged ≥55 years with stage T1-2N1M1 DTC according to the eighth edition AJCC/TNM cancer staging system should be downstaged and those with stage T4bN1M0 upstaged accordingly. [ABSTRACT FROM AUTHOR]

Minimal extrathyroidal extension (ETE) is defined as tumor cells extending to the sternothyroid muscle or perithyroidal soft tissue. However, there is controversy regarding whether the magnitude of ETE (minimal or gross) should be considered in assigning a precise TNM stage to patients with thyroid cancer in the seventh/eighth editions of the AJCC system. The present study evaluated Surveillance, Epidemiology, and End Results data from 107,114 patients with differentiated thyroid cancer (2004–2013) to determine whether the magnitude of ETE (thyroid confinement, minimal, or gross) influenced the ability to predict cancer-specific survival (CSS) and overall survival (OS). Patient mortality was evaluated using Cox proportional hazards regression analyses and Kaplan-Meier analyses with log-rank tests. The cancer-specific mortality rates per 1,000 person-years were 1.407 for the thyroid confinement group (95% CI: 1.288–1.536), 5.133 for the minimal ETE group (95% CI: 4.301–6.124), and 29.735 for the gross ETE group (95% CI: 28.147–31.412). Relative to the thyroid confinement group, patients with minimal ETE and gross ETE had significantly poorer CSS and OS in the univariate and multivariate analyses (both P<0.001). After propensity-score matching according to age, sex, and race, we found that thyroid confinement was associated with better CSS and OS rates than minimal ETE (P<0.001) and gross ETE (P<0.001). These results from a population-based cohort provide a reference for precise personalized treatment and management of patients with minimal ETE. Furthermore, it may be prudent to revisit the magnitude of ETE as advocated by the AJCC and currently used for treatment recommendation by the American Thyroid Association. [ABSTRACT FROM AUTHOR]

It is interesting to compare the residual strength of laminated carbon fiber reinforced polymer under thermal environments with finite heating rate, and laser irradiation with rapid heating rate. In these two conditions, heating rates are varied in two orders of magnitude, and thermally‐induced damage mechanisms are quite different, which may influence the performance of residual strength. Systematic experiments are performed to obtain the tensile failure behavior of laminated carbon fiber reinforced epoxy composites at different temperatures with a heating rate of about 102°C/min. In comparison, composite samples are subjected to laser irradiations of different power densities and then tested for residual strengths, the laser induced heating rate is above 104°C/min. Experimental results indicate that the residual strength decreases with the increase of heating temperatures and laser power densities, however the damage mechanisms for conventional heating are thermal pyrolysis, oxidation and delamination, whereas the main damage mechanisms for laser irradiation are thermal pyrolysis and fiber ablation. The experimentally obtained residual strength and modulus are also compared with those predicted by theoretical model. POLYM. ENG. SCI., 58:2311–2319, 2018. © 2018 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

The pathophysiology and natural history of pelvic organ prolapse (POP) are poorly understood. Consequently, our approaches to treatment of POP are limited. Alterations in the extracellular matrix components of pelvic support ligaments and vaginal tissue, including collagen and elastin, have been associated with the development of POP in animals and women. Prior studies have shown the protease MMP-9, a key player of ECM degradation, is upregulated in vaginal tissues from both mice and women with POP. On the other hand, fibulin-5, an elastogenic organizer, has been found to inhibit MMP-9 in the vaginal wall. Hence, we hypothesized that prolonged release of fibulin-5 may delay progression of POP. To test the hypothesis, oligo (ethylene glycol)-based thermosensitive hydrogels were fabricated, characterized and then used to deliver fibulin-5 to the vaginal wall and inhibit MMP-9 activity. The results indicate that hydrogels are cell and tissue compatible. The hydrogels also prolong the ½ life of fibulin-5 in cultured vaginal fibroblasts and in the vaginal wall in vivo. Finally, fibulin-5-containing hydrogels resulted in incorporation of fibulin-5 into the vaginal matrix and inhibition of MMP-9 for several weeks after injection. These results support the idea of fibulin-5 releasing hydrogel being developed as a new treatment for POP. [ABSTRACT FROM AUTHOR]

ABSTRACT Ischemic osteonecrosis (IO) is caused by disruption of the blood supply to bone. It is a debilitating condition with pathological healing characterized by excessive bone resorption and delayed osteogenesis. Although the majority of research has focused on the role of osteoblasts and osteoclasts in the disease progression, we hypothesize that innate immune cells, macrophages and neutrophils, play a significant role. With the recent development of real-time imaging probes for neutrophils and macrophages, the purpose of this study was to investigate the kinetic immune cell response in a mouse model of IO. Our results show that induction of IO leads to a significant accumulation of activated neutrophils and macrophages at the affected tissue by 48 h after surgery. Additionally, the accumulation of these immune cells remained elevated in comparison to sham controls for up to 6 weeks, indicative of chronic inflammation. Immunohistochemistry confirmed the immune cell infiltration into the necrotic bone marrow and the increased presence of TNFα-positive cells, demonstrating, for the first time, a direct response of these cells to ischemia induced necrotic bone. These new findings support a hypothesis that IO is an osteoimmunologic condition where innate immune cells play a significant role in the chronic inflammation. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:307-313, 2016. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease- (COVID-19-) related renal function abnormality is associated with poor prognosis. However, the clinical significance of dynamic changes in renal function indicators has not been studied, and no studies have evaluated the renal function in COVID-19 patients by cystatin C. Objective: This study aimed to evaluate the effect of abnormal renal function on admission on prognosis of COVID-19 patients and the prognostic value of various renal function indicators. Methods: A total of 1,764 COVID-19 patients without a history of chronic kidney disease were categorized into two groups, an elevated cystatin C group and a normal cystatin C group, based on the results of renal function tests on admission. The clinical characteristics were compared between the two groups, and logistic or Cox regression analyses were performed to explore the associations between elevated cystatin C/serum creatinine levels and disease severity and survival. We also performed receiver operating characteristic (ROC) curve, Kaplan–Meier survival, and curve fitting analyses. Results: When adjusted for several significant clinical variables, elevated cystatin C levels on admission were independent predictors of disease severity (p < 0.001), and elevated creatinine levels were independent predictors of death (p = 0.020). Additionally, the ROC curve analysis shows that elevated cystatin C levels [area under the curve (AUC): 0.656] have a better predictive value for disease severity than elevated creatinine levels (AUC: 0.540). The survival curves of patients with elevated cystatin C/creatinine levels show a sharper decline than those of patients with normal cystatin C/creatinine levels (p < 0.001). The curve fitting analysis revealed that, compared to the flat curves of cystatin C and creatinine levels for patients who survived, the curves for patients who died kept rising, and cystatin C levels rose above the normal range earlier than creatinine. Conclusions: Elevated cystatin C, which occurs earlier than serum creatinine, is useful for the early detection of renal function abnormality and might have better predictive value for disease severity in COVID-19 patients, while elevated serum creatinine may have a better predictive value for risks of death. [ABSTRACT FROM AUTHOR]

In the present research, an iterative numerical model is proposed to investigate the nanosecond pulsed laser ablation (PLA) mechanism of the DD6 single-crystal superalloy. In the numerical model, two subroutines are introduced to trace the moving boundary and update the thermal load. The iteration between the main governing equation and the two subroutines enables the PLA numerical simulation to consider material moving front and effect of comprehensive heat dissipation including thermal convection and radiation. The basic experimental results exhibit a good agreement with simulation results which indicates the good accuracy of the simulation model. Therefore, the PLA mechanism of the DD6 single-crystal superalloy is studied base on the improved iterative model, which indicates the evolution of temperature field, ablation zone morphology, formation of recast layer and heat-affected zone are closely related with time. The temperature of the laser spot center increases sharply at the first stage, reaching a maximum value of 5252 K, and then decreases gradually. The thermal dissipation postpones the ablation rate but promotes the formation of a recast layer and heat-affected zone. Due to the evaporation and thermal dissipation, the depth of the molten layer exhibits two rapid increasing stages. The comprehensive analysis of the PLA processing by the improved simulation model helps the understanding of the intrinsic mechanism, which would contribute to the further optimizing parameters of PLA fabrication of the DD6 single-crystal superalloy. [ABSTRACT FROM AUTHOR]

Lymph node (LN) metastasis causes poor prognosis for patients with prostate cancer (PCa). Although LN‐cells and cellular responses play a pivotal role in cancer metastasis, the interplay between LN‐cells and PCa cells is undetermined due to the small size and widespread distribution of LNs. To identify factors responsible for LN metastasis, a 3D cell culture biosystem is fabricated to simulate LN responses during metastasis. First, it is determined that LN explants previously exposed to high metastatic PCa release substantially more chemotactic factors to promote metastatic PCa migration than those exposed to low‐metastatic PCa. Furthermore, T‐lymphocytes are found to produce chemotactic factors in LNs, among which, CXCL12, CCL21, and IL‐10 are identified to have the most chemotactic effect. To mimic the LN microenvironment, Cytodex beads are seeded with T cells to produce a LN‐mimetic biosystem in both static and flow conditions. As expected, the flow condition permits prolonged cellular responses. Interestingly, when PCa cells with varying metastatic potentials are introduced into the system, it produces PCa‐specific chemokines accordingly. These results support that the LN mimetic helps in analyzing the processes underlying metastasized LNs and for testing various treatments to reduce cancer LN metastasis. [ABSTRACT FROM AUTHOR]

Gelsenicine is an indole alkaloid isolated from Gelsemium elegans Benth. In recent years, the role of G. elegans Benth preparations in anti‐tumor, analgesic, dilatation and dermatological treatment has attracted attention, and it has been applied clinically, but it is easy to cause poisoning with its use. An UPLC–MS/MS method was established to determine the gelsenicine in mouse blood, and the pharmacokinetics of gelsenicine after intravenous (0.1 mg/kg) and intragastric (0.5 and 1 mg/kg) administration was studied. Deltalin was used as internal standard; a UPLC BEH C18 column was used for chromatographic separation. The mobile phase consisted of acetonitrile and 10 mmol/L ammonium acetate (0.1% formic acid) with a gradient elution flow rate of 0.4 mL/min. Multiple reaction monitoring mode was used for quantitative analysis of gelsenicine in electrospray ionization positive interface. Proteins from mouse blood were removed by acetonitrile precipitation. A validation of this method was performed in accordance with the US Food and Drug Administration guidelines. In the concentration range of 0.05–100 ng/mL, the gelsenicine in the mouse blood was linear (r > 0.995), and the lower limit of quantification was 0.05 ng/mL. In the mouse blood, the intra‐day precision RSD was <12%, the inter‐day precision RSD was <15%, the accuracy ranged from 89.8 to 112.3%, the average recovery was >76.8%, and the matrix effect was between 103.7 and 108.4%, which meet the pharmacokinetic research requirements of gelsenicine. The UPLC–MS/MS method is sensitive, rapid and selective, and has been successfully applied to the pharmacokinetic study of gelsenicine in mice. The absolute bioavailability of gelsenicine is 1.13%. [ABSTRACT FROM AUTHOR]

Summary In Huntington disease (HD), the analysis of tissue-specific CAG repeat length effects has been challenging, given the difficulty in obtaining relevant patient tissues with a broad range of CAG repeat lengths. We used genome editing to generate an allelic panel of isogenic HD (IsoHD) human embryonic stem cell (hESC) lines carrying varying CAG repeat lengths in the first exon of HTT. Functional analyses in differentiated neural cells revealed CAG repeat length-related abnormalities in mitochondrial respiration and oxidative stress and enhanced susceptibility to DNA damage. To explore tissue-specific effects in HD, we differentiated the IsoHD panel into neural progenitor cells, neurons, hepatocytes, and muscle cells. Transcriptomic and proteomic analyses of the resultant cell types identified CAG repeat length-dependent and cell-type-specific molecular phenotypes. We anticipate that the IsoHD panel and transcriptomic and proteomic data will serve as a versatile, open-access platform to dissect the molecular factors contributing to HD pathogenesis. Graphical Abstract Highlights • Generation of isogenic HD (IsoHD) hESCs to enable the study of CAG length effects • IsoHD hESCs and neural cells exhibit CAG-dependent phenotypic abnormalities • CNS and peripheral cell types of interest can be differentiated from IsoHD hESCs • Large-scale, unbiased -omics analyses reveal cell-type-specific, CAG-dependent effects Ooi et al. use genome engineering to establish an allelic panel of isogenic Huntington disease (IsoHD) hESCs. Using unbiased analyses on neural progenitors, neurons, hepatocytes, and skeletal myotubes derived from the IsoHD hESCs, the authors illustrate how this approach can identify cell-type-specific, CAG-dependent effects of relevance to HD etiology. [ABSTRACT FROM AUTHOR]