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The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is partially attributed to the invasive and metastatic behavior of this disease. Laminin subunit beta-3 (LAMB3) encodes one of the three subunits of LM-332, an extracellular matrix protein secreted by cultured human keratinocytes. In addition, LAMB3 is involved in the invasive and metastatic abilities of some types of cancer, including colon, pancreas, lung, cervix, stomach, and prostate cancer, but the role and mechanism of LAMB3 in PDAC have not been previously determined. Herein, we tentatively investigated the role of LAMB3 in the malignant biological behavior of PDAC. In this study, we demonstrated that LAMB3 is upregulated in PDAC. Inhibition of LAMB3 abrogated the tumorigenic outcomes of PI3K/Akt signaling pathway activation, including those involving cell cycle arrest, cell apoptosis, proliferation, invasion and migration in vitro, and tumor growth and liver metastasis in vivo. Our results showed that LAMB3 could mediate cell cycle arrest and apoptosis in PDAC cells and alter the proliferative, invasive, and metastatic behaviors of PDAC by regulating the PI3K/Akt signaling pathway. LAMB3 may be a novel therapeutic target for the treatment of PDAC in the future.

The existence of a typical triple junction in Colombia is crucial for understanding plate convergence and coupling among the South American Plate, the subducting Nazca Plate, and the Caribbean Plate. However, locating this triple junction is challenging due to complex geodynamic evolution and uncertainty in the slab boundaries. Here, we developed a high‐resolution Lg‐wave attenuation model for Colombia and surrounding areas to constrain crustal magmatic activity, link deep processes with surface volcanism, and identify potential slab boundaries. The area encompassing Central America, western Colombia, and Ecuador exhibits strong Lg attenuation and a concentration of volcanoes, indicating thermal anomalies in the crust. In line with velocity structure, volcanism, seismicity, and isotopic dating, the thermal anomalies caused by the subducting Nazca and Caribbean slabs suggest the presence of three subducting slabs beneath the South American Plate, with a triple junction located at approximately 7.5°N, 77°W.

The compensation behaviors and phase transitions of a new 3D fullerene-like polymer are explored by using Monte Carlo method. The ground-state phase diagrams and magnetization profiles are given, and the conditions for the occurrence of the compensation temperature T comp are obtained. As classified in Néel theory, N-type and P-type magnetization curves are found. To explore the changes in the transition temperature T C and the compensation temperature T comp induced by physical parameters, we also present the phase diagrams. Furthermore, the critical exponents of the system are calculated, and a good agreement can be achieved by comparing our results with others’. Finally, the triple hysteresis loops are discovered.

The Anatolian Plateau, currently experiencing rapid uplift and westward escape, records both the termination of oceanic subduction and the conversion to continental collision. The crustal response to the transition of the subduction environment from eastern to western Anatolia can be inferred by the seismic velocity and attenuation structures. With this study, we construct a broadband Lg‐wave attenuation model for the Anatolian Plateau and use it to constrain lateral crust heterogeneities linked to this transition. Crustal Lg attenuation links late Cenozoic magmatism with asthenospheric upwelling by characterizing the lithospheric thermal structure. The widely distributed strong attenuation observed in eastern Anatolia may be related to the crustal partial melting due to mantle upwelling after the delamination and subsequent break‐off of the Bitlis slab. Lithospheric dripping in central Anatolia likely facilitates the mantle flows through the window between the Cyprus and Aegean slabs, which results in the piecemeal low QLg${Q}_{\\mathit{Lg}}$anomaly in central Anatolia. Plain Language Summary Different parts of the Anatolian Plateau are in different evolution stages between oceanic subduction and continental collision and currently undergoing plateau uplift and tectonic escape. The regional seismic velocity and attenuation can be used to characterize crustal partial melting and lateral heterogeneity, which can further identify the underlying subduction process. In this study, we construct a high‐resolution broadband Lg‐wave attenuation model for the Anatolian Plateau. Strong Lg attenuation in Anatolia correlates well with late Cenozoic magmatism distributions and can be an indicator of high temperature or partial melting in the crust. Combined with previous studies, we suggest that the mantle upwelling induced by the delamination of the Bitlis slab is likely reworking the crust in eastern Anatolia and is the cause of widespread thermal anomalies there. The lithospheric dripping process in central Anatolia may facilitate the mantle flows through the window between the Cyprus and Aegean slabs, and results in a piecemeal low QLg${Q}_{\\mathit{Lg}}$anomaly pattern in central Anatolia. Key Points A high‐resolution broadband Lg‐wave attenuation model is constructed for the Anatolian Plateau Widespread strong attenuation in the eastern Anatolian crust is likely related to slab delamination The circular‐shaped attenuation anomaly may result from slab tearing and lithospheric dripping beneath central Anatolia

This research attempts to reinforce the cultivating expression of radial basis function neural network (RBFnet) through computational intelligence (CI) and swarm intelligence (SI) learning methods. Consequently, the artificial immune system (AIS) and ant colony optimization (ACO) approaches are utilized to cultivate RBFnet for function approximation issue. The proposed hybridization of AIS and ACO approaches optimization (HIAO) algorithm combines the complementarity of exploitation and exploration to realize problem solving. It allows the solution domain having the advantages of intensification and diversification, which further avoids the situation of immature convergence. In addition, the empirical achievements have confirmed that the HIAO algorithm not only obtained the best accurate function approximation for theoretically standard nonlinear problems, it can be further applied on the instance solving for practical crude oil spot price prediction.

The lift generation mechanism of leading-edge vortex (LEV) in the case of a pitching and plunging plate is studied using an experimental approach and the improved discrete vortex method in this research. A formation condition of the secondary structure is introduced into the traditional discrete vortex method to compensate for the shortcomings in the simulation of the viscous effect between LEV and plate. The simulation of the secondary structure helps the improved method perform better in flow-field reconstruction and lift prediction. Accordingly, the lift generation mechanism of the LEV and influence of the secondary structure are studied. The lift contribution of the vortex structure is isolated and linearly decomposed into two parts according to sources of flow field: the quasi-potential flow part and the vortex-induced flow part. The vortex lift is defined as the lift contribution of the vortex structure in vortex-induced flow, which gives a new insight into the production of lift of the LEV. The lift generation mechanism through the discrete vortex method is verified and extended in viscous flow through experimental measurement. In addition, a vortex lift indicator based on the reverse flow of the LEV is proposed to examine the change of vortex lift in experimental measurement. The flow mechanism for the decline of vortex lift for different maximum effective angles of attack is revealed based on the vortex lift indicator. Furthermore, for the LEV-dominating flow, the indicator can also be applied in estimating the maximum value and corresponding critical time of overall lift in experiments.

The diverse physiological functions of tocotrienols have listed them as valuable supplementations to α-tocopherol-dominated Vitamin E products. To make tocotrienols more readily available, tocotrienols-producing S. cerevisiae has been constructed by combining the heterologous genes from photosynthetic organisms with the endogenous shikimate pathway and mevalonate pathway. After identification and elimination of metabolic bottlenecks and enhancement of precursors supply, the engineered yeast can produce tocotrienols at yield of up to 7.6 mg/g dry cell weight (DCW). In particular, proper truncation of the N-terminal transit peptide from the plant-sourced enzymes is crucial. To further solve the conflict between cell growth and tocotrienols accumulation so as to enable high-density fermentation, a cold-shock-triggered temperature control system is designed for efficient control of two-stage fermentation, leading to production of 320 mg/L tocotrienols. The success in high-density fermentation of tocotrienols by engineered yeast sheds light on the potential of fermentative production of vitamin E tocochromanols. Tocotrienols are valuable supplementations to α-tocopherol-dominated Vitamin E products. Here, the authors engineer baker’s yeast by combining the heterologous genes from photosynthetic organisms with the endogenous pathway for the production of tocotrienols under cold-shock-triggered temperature control.

The flow topology and leading-edge vortex (LEV) formation and detachment mechanism of a pitching and plunging flat plate are experimentally investigated in this study. Focus is placed on three novel aspects. First, to examine the differences between start-up and cyclic motions, the flow fields of one-shot experiments are compared to cyclic cases. The results show that the start cycle has very limited effect on the cyclic LEV development and flow topology evolution. Next, the influence of the maximum effective angle of attack on the LEV development in cyclic motion is introduced. Different secondary structures that lead to the detachment of LEV are found with variation of maximum effective angle of attack. Depending on the leading-edge shear-layer angle, three different flow topologies develop on the plate: quasi-steady development, boundary-layer eruption and secondary vortex formation. Which of these three topological scenarios occurs depends entirely on the maximum effective angle of attack. A vortex Reynolds number based on the transition time of the leading-edge shear-layer angle is defined to quantitatively assess which of the flow topologies will appear. Finally, a simplified model to describe the observed LEV growth is proposed, based on the assumptions that the velocity is constant at the outer vortex boundary and that the vortex boundary is a circular arc starting from the leading edge. The LEV circulation growth is found to increase linearly with the combination of the effective inflow velocity and the effective angle of attack.

Background Coronavirus disease 2019 (COVID-19) is a new respiratory and systemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of the present study was to investigate the association between cytokine profiles and lung injury in COVID-19 pneumonia. Methods This retrospective study was conducted in COVID-19 patients. Demographic characteristics, symptoms, signs, underlying diseases, and laboratory data were collected. The patients were divided into COVID-19 with pneumonia and without pneumonia. CT severity score and PaO 2 /FiO 2 ratio were used to assess lung injury. Results 106 patients with 12 COVID-19 without pneumonia and 94 COVID-19 with pneumonia were included. Compared with COVID-19 without pneumonia, COVID-19 with pneumonia had significantly higher serum interleukin (IL)-2R, IL-6, and tumor necrosis factor (TNF)-α. Correlation analysis showed that CT severity score and PaO 2 /FiO 2 were significantly correlated with age, presence of any coexisting disorder, lymphocyte count, procalcitonin, IL-2R, and IL-6. In multivariate analysis, log IL6 was the only independent explanatory variables for CT severity score (β = 0.397, p  < 0.001) and PaO 2 /FiO 2 (β = − 0.434, p  = 0.003). Conclusions Elevation of circulating cytokines was significantly associated with presence of pneumonia in COVID-19 and the severity of lung injury in COVID-19 pneumonia. Circulating IL-6 independently predicted the severity of lung injury in COVID-19 pneumonia.

Since the outbreak in late December 2019 in Wuhan, China, coronavirus disease-2019 (COVID-19) has become a global pandemic. We analyzed and compared the clinical, laboratory, and radiological characteristics between survivors and non-survivors and identify risk factors for mortality. Clinical and laboratory variables, radiological features, treatment approach, and complications were retrospectively collected in two centers of Hubei province, China. Cox regression analysis was conducted to identify the risk factors for mortality. A total of 432 patients were enrolled, and the median patient age was 54 years. The overall mortality rate was 5.09% (22/432). As compared with the survivor group (n = 410), those in the non-survivor group (n = 22) were older, and they had a higher frequency of comorbidities and were more prone to suffer from dyspnea. Several abnormal laboratory variables indicated that acute cardiac injury, hepatic damage, and acute renal insufficiency were detected in the non-survivor group. Non-surviving patients also had a high computed tomography (CT) score and higher rate of consolidation. The most common complication causing death was acute respiratory distress syndrome (ARDS) (18/22, 81.8%). Multivariate Cox regression analysis revealed that hemoglobin (Hb) <90 g/L (hazard ratio, 10.776; 95% confidence interval, 3.075-37.766; p<0.0001), creatine kinase (CK-MB) >8 U/L (9.155; 2.424-34.584; p = 0.001), lactate dehydrogenase (LDH) >245 U/L (5.963; 2.029-17.529; p = 0.001), procalcitonin (PCT) >0.5 ng/ml (7.080; 1.671-29.992; p = 0.008), and CT score >10 (39.503; 12.430-125.539; p<0.0001) were independent risk factors for the mortality of COVID-19. Low Hb, high LDH, PCT, and CT score on admission were the predictors for mortality and could assist clinicians in early identification of poor prognosis among COVID-19 patients.