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Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The objective of this study is to investigate the effects of varying amounts of cinnamon extract (CE) on chitosan (CS) films in order to enhance their food packaging properties and antioxidant abilities. The findings revealed that all fillers, including citric acid, glycerol, and CE, were thoroughly mixed and uniformly dispersed within the CS-polymer substrate, resulting in a homogeneous composite film material through electrostatic interactions and hydrogen bonding. Multiple data analyses demonstrated that compared to the CS film alone, the CS film with 2.0% CE exhibited superior plasticity, light barrier properties, and antioxidant capabilities (a light transmittance of 74.7%, a DPPH scavenging rate of 47.33%, and a ferric reducing antioxidant power value of 0.465). Additionally, the content of total volatile base nitrogen (TVB-N) and the thiobarbituric acid value (TBARS) in the CS film containing 2.0% CE decreased by 30.86% and 59.44%, respectively, compared to the control CS film. These results suggest that the developed CS-CE composite films could effectively delay chicken meat spoilage and lipid oxidation, demonstrating significant potential for food-related applications. [ABSTRACT FROM AUTHOR]

Synthetic dyes pose a significant environmental threat due to their complex structures and resistance to microbial degradation. S. commune 15R-5-F01 exhibited over 96% degradation efficiency of Methyl Red in a medium with 100 mg L−1 Methyl Red within 3 h. The fungus demonstrated adaptability to various environmental conditions, including different pH levels, temperatures, oxygen concentrations, salinity, and heavy metals. S. commune 15R-5-F01 is capable of achieving repeated cycles of Methyl Red reduction with sustained degradation duration minimum of 6 cycles. It showed a maximum Methyl Red biodegradation capacity of at least 558 mg g−1 dry mycelia and a bioadsorption capacity of 57 mg g−1. Gas chromatography–mass spectrometry analysis confirmed the azo reduction of Methyl Red into N,N-dimethyl-p-phenylenediamine and 2-aminobenzoic acid. Enzymatic activity assays indicated the involvement of lignin peroxidases, laccases, and manganese peroxidase in the biodegradation process. Phytotoxicity tests on Triticum eastivum, Oryza sativa, and Vigna umbellata seeds revealed reduced toxicity of the degradation products compared to Methyl Red. This study identifies S. commune 15R-5-F01 as a viable candidate for the sustainable degradation of synthetic dyes in industrial wastewater. [ABSTRACT FROM AUTHOR]

The exploitation of new green polymerization avenues for the effective synthesis of polymers by reversible-deactivation radical polymerization plays a critical role in pursuing the development of polymeric materials. In this work, serials of deep eutectic solvents (DES) with intermolecular-hydrogen-bonding interaction were constructed as catalysts and medium for actuating reversible complexation-mediated polymerization (RCMP) for the first time, yielding methacrylate polymers with high monomer conversion and narrow dispersion molecular weight in both water and oil systems. The mechanism and elementary reaction of RCMP were explored deeply, revealing that the complexation of initiator with DES to generate radicals was a ratecontrolling step and intermolecular-hydrogen-bond was primary factor to influence polymerization rate. Moreover, the insights of density functional theory calculations revealed that negative electrostatic potential ensured nucleophilic capacity. This investigation demonstrated the considerable potential of DES for RCMP, which is anticipated for other polymerization applications as a novel medium mode. [ABSTRACT FROM AUTHOR]

The WWE domain is a relatively under-researched domain found in twelve human proteins and characterized by a conserved tryptophan-tryptophan-glutamate (WWE) sequence motif. Six of these WWE domain-containing proteins also contain domains with E3 ubiquitin ligase activity. The general recognition of poly-ADP-ribosylated substrates by WWE domains suggests a potential avenue for development of Proteolysis-Targeting Chimeras (PROTACs). Here, we present novel crystal structures of the HUWE1, TRIP12, and DTX1 WWE domains in complex with PAR building blocks and their analogs, thus enabling a comprehensive analysis of the PAR binding site structural diversity. Furthermore, we introduce a versatile toolbox of biophysical and biochemical assays for the discovery and characterization of novel WWE domain binders, including fluorescence polarization-based PAR binding and displacement assays, 15N-NMR-based binding affinity assays and 19F-NMR-based competition assays. Through these assays, we have characterized the binding of monomeric iso-ADP-ribose (iso-ADPr) and its nucleotide analogs with the aforementioned WWE proteins. Finally, we have utilized the assay toolbox to screen a small molecule fragment library leading to the successful discovery of novel ligands targeting the HUWE1 WWE domain. Six WWE domain-containing proteins also contain domains with E3 ubiquitin ligase activity. We report structures, biophysical and biochemical assays for the discovery of novel WWE domain binders and their respective application. [ABSTRACT FROM AUTHOR]

This paper proposes the double-endplates replaceable beam-column joint (DEBJ) based on the seismic design concept of replaceable beam. Compared to the common extended endplate bolted joint (CEBJ), the DEBJ is easy to be connected and replaced after earthquakes, and it can achieve plastic hinge outward movement in steel frame. Due to double endplates and different failure modes, the current moment-rotation models for CEBJ cannot be used for DEBJ. Therefore, based on the classical model used for traditional endplate joints, a theoretical moment-rotation model for DEBJ is developed, and the calculation methods on ultimate bending moment and initial rotational stiffness are deduced. A parametric study is performed for DEBJ based on a test-validated finite element (FE) model developed in this paper. The predicted moment-rotation curves calculated from proposed theoretical model is validated by the experimental results on endplate joints and FE results on DEBJ. The results show that the established theoretical model proposed in this paper can predict the moment-rotation relation curves of DEBJ and the common extended endplate bolted joint (CEBJ) accurately, the predicted results by established theoretical model are in good agreement with experimental and FE results according to the comparison. It is revealed that the established model has universality to some extent. [ABSTRACT FROM AUTHOR]

Liquidity index is used to measure the relative consistency of natural soils, making it possible to evaluate the stiffness degree and strength of clays. However, a systematic understanding of the relationship between the undrained shear strength and the liquidity index remains unclear. While some studies are being conducted on this putative relationship, the theoretical foundation is still lacking. This study proposes a new undrained shear strength prediction model based on the Mohr–Coulomb failure criterion and the critical state theory. A database of 103 soil samples from 18 research is utilised to validate the model's applicability. The results reflect a consistent level of accuracy. The proposed model has an obvious advantage and has potential for predicting the undrained shear strength of clays. [ABSTRACT FROM AUTHOR]

Background: The role of minimally invasive surgery using robotics versus laparoscopy in resectable gastric cancer patients with a high body mass index (BMI) remains controversial. Methods: A total of 482 gastric adenocarcinoma patients with BMI ≥ 25 kg/m2 who underwent minimally invasive radical gastrectomy between August 2016 and December 2019 were retrospectively analyzed, including 109 cases in the robotic gastrectomy (RG) group and 321 cases in the laparoscopic gastrectomy (LG) group. Propensity score matching (PSM) with a 1:1 ratio was performed, and the perioperative outcomes, lymph node dissection, and 3-year overall survival (OS) and disease-free survival (DFS) rates were compared. Results: After PSM, 109 patients were included in each of the RG and LG groups, with balanced baseline characteristics. Compared with the LG group, the RG group had similar intraoperative estimated blood loss [median (IQR) 30 (20–50) vs. 35 (30–59) mL, median difference (95%CI) − 5 (− 10 to 0)], postoperative complications [13.8% vs. 18.3%, OR (95%CI) 0.71 (0.342 to 1.473)], postoperative recovery, total harvested lymph nodes [(34.25 ± 13.43 vs. 35.44 ± 14.12, mean difference (95%CI) − 1.19 (− 4.871 to 2.485)] and textbook outcomes [(81.7% vs. 76.1%, OR (95%CI) 1.39 (0.724 to 2.684)]. Among pathological stage II–III patients receiving chemotherapy, the initiation of adjuvant chemotherapy in the RG group was similar to that in the LG group [median (IQR): 28 (25.5–32.5) vs. 32 (27–38.5) days, median difference (95%CI) − 3 (− 6 to 0)]. The 3-year OS (RG vs. LG: 80.7% vs. 81.7%, HR = 1.048, 95%CI 0.591 to 1.857) and DFS (78% vs. 76.1%, HR = 0.996, 95%CI 0.584 to 1.698) were comparable between the two groups. Conclusion: RG conferred comparable lymph node dissection, postoperative recovery, and oncologic outcomes in a selected cohort of patients with BMI ≥ 25 kg/m2. [ABSTRACT FROM AUTHOR]

With advancements in sedation techniques,painless gastrointestinal endoscopy has expanded from a diagnostic role to surgeries. This study aims to explore strategies for enhancing patient satisfaction, improving safety, and reducing complications. Tailoring preoperative assessments beyond American Society of Anesthesiologists classification is crucial, especially for the elderly and pediatric populations. Integration of scales and point-of-care testing (POCT) provides a precise baseline evaluations. Optimizing anesthetic strategies through improved drug selection and enhanced perioperative monitoring follows accurate patient evaluations. While post-procedural follow-up is essential, existing studies in this area are limited. This article outlines current painless gastrointestinal endoscopy technology, emphasizing POCT establishment, personalized monitoring, and optimized anesthesia strategies for a positive impact on patient outcomes. [ABSTRACT FROM AUTHOR]

Dendrobium officinale (D. officinale) as a well-known herbal and functional food material is often adulterated with lower-price Dendrobium species. In this study, we aimed to develop an integrated method of nuclear magnetic resonance spectroscopy and artificial neural network (NMR-ANN) to identify and quantify the adulteration of D. officinale powder with other cheaper species. Microwave-assisted water extraction was selected as a time-saving and green method for sample preparation. The results indicate that the NMR-ANN method effectively quantified the adulteration rate of D. officinale powder with the root mean squared error (RMSE) of 4.92, mean absolute error (MAE) of 3.56 and coefficient of determination (R2) of 0.98 in the model test phase and with the RMSE of 7.65, MAE of 6.30 and R2 of 0.98 in the double-blinded test phase. The whole evaluation process can be done in 6 min and 5 s. Therefore, the NMR-ANN method can be used as a rapid, green and accurate tool for evaluating the quality of D. officinale or even other food materials. [ABSTRACT FROM AUTHOR]

Purpose: Acute myeloid leukemia (AML) is a refractory hematologic malignancy that poses a serious threat to human health. Exploring alternative therapeutic strategies capable of inducing alternative modes of cell death, such as ferroptosis, holds great promise as a viable and effective intervention. Methods: We analyzed online database data and collected clinical samples to verify the expression and function of BMAL1 in AML. We conducted experiments on AML cell proliferation, cell cycle, ferroptosis, and chemotherapy resistance by overexpressing/knocking down BMAL1 and using assays such as MDA detection and BODIPY 581/591 C11 staining. We validated the transcriptional regulation of HMGB1 by BMAL1 through ChIP assay, luciferase assay, RNA level detection, and western blotting. Finally, we confirmed the results of our cell experiments at the animal level. Results: BMAL1 up-regulation is an observed phenomenon in AML patients. Furthermore, there existed a strong correlation between elevated levels of BMAL1 expression and inferior prognosis in individuals with AML. We found that knocking down BMAL1 inhibited AML cell growth by blocking the cell cycle. Conversely, overexpressing BMAL1 promoted AML cell proliferation. Moreover, our research results revealed that BMAL1 inhibited ferroptosis in AML cells through BMAL1-HMGB1-GPX4 pathway. Finally, knocking down BMAL1 can enhance the efficacy of certain first-line cancer therapeutic drugs, including venetoclax, dasatinib, and sorafenib. Conclusion: Our research results suggest that BMAL1 plays a crucial regulatory role in AML cell proliferation, drug resistance, and ferroptosis. BMAL1 could be a potential important therapeutic target for AML. [ABSTRACT FROM AUTHOR]

We present a numerically stable one-point quadrature rule for the stiffness matrix and mass matrix of the three-dimensional numerical manifold method (3D NMM). The rule simplifies the integration over irregularly shaped manifold elements and overcomes locking issues, and it does not cause spurious modes in modal analysis. The essential idea is to transfer the integral over a manifold element to a few moments to the element center, thereby deriving a one-point integration rule by the moments and making modifications to avoid locking issues. For the stiffness matrix, after the virtual work is decomposed into moments, higher-order moments are modified to overcome locking issues in nearly incompressible and bending-dominated conditions. For the mass matrix, the consistent and lumped types are derived by moments. In particular, the lumped type has the clear advantage of simplicity. The proposed method is naturally suitable for 3D NMM meshes automatically generated from a regular grid. Numerical tests justify the accuracy improvements and the stability of the proposed procedure. [ABSTRACT FROM AUTHOR]

Cat states, as an important resource in the study of macroscopic quantum superposition and quantum information applications, have garnered widespread attention. To date, preparing large-sized optical cat states has remained challenging. We demonstrate that, by utilizing interaction-free measurement and the quantum Zeno effect, even a fragile quantum microscopic system can deterministically control and become entangled with strong light fields, thereby generating large-amplitude optical cat states. During the entire preparation process, our method ensures that the microscopic system functions within a weak field environment, so that its quantum property can be protected. Furthermore, we show that the preparation of cat states is possible even when the quantum microsystem suffers from significant photon loss, provided that optical losses from classical devices are kept low, which implies that the fidelity of the cat state can be enhanced by improvements to and the perfection of the classical optical system. In quantum physics, superposition—illustrated by Schrödinger's cat being both dead and alive—inspires 'cat states', utilized in quantum technologies. The authors propose a theory where the optical state, through multiple indirect atom interactions in an interferometric setup, can generate large-amplitude optical cat states, advancing quantum applications. [ABSTRACT FROM AUTHOR]

The failure of piles often starts from localized damage caused by stress concentration. However, little is known about such progressive process of pile failure involving crack initiation and propagation. Here, we propose a finite difference method (FDM)–discrete element method (DEM) coupling method to simulate the mechanical behavior of a slope reinforced by piles. The FDM is employed to model the macroscale behavior of the slope, while the DEM is employed to reveal the micro-mechanism of the progressive failure of anti-slide pile. The method is validated and then is used for mechanical analysis of a pile–slope system. The response of displacement, strain, and soil pressure is analyzed to investigate the failure mechanism of a slope reinforced with piles. The results show that slope deformation causes the initiation of cracks in the pile located proximal to the sliding surface, and the crack tip gradually expands as the breakage of the contact force chain in the pile until the pile completely fails. The progressive failure process of the pile is reproduced through monitoring the evolution of contact forces and the breakage of the contact force chains. The simulation of the interaction between soil and piles can be realized using the large-strain mode. Compared with conventional methods, the FDM–DEM coupling method considers detailed microscopic information with a lower computational cost, and provide a powerful tool for revealing the mechanical behavior of pile-reinforced slopes. [ABSTRACT FROM AUTHOR]

Background: The impact of hepatic resection type on long-term oncological prognosis of patients with early-stage hepatocellular carcinoma (HCC) has not been systematically investigated. We sought to determine risk factors, recurrence patterns, and survival outcomes after anatomical resection (AR) versus non-anatomical resection (NAR) for early-stage HCC. Methods: From a prospectively collected multicenter database, consecutive patients undergoing curative hepatectomy for early-stage HCC were identified. Recurrence patterns, overall survival (OS), recurrence-free survival (RFS), and risk factors were investigated in patients undergoing AR versus NAR using propensity score matching (PSM), subgroup analysis, and COX regression analysis. Results: A total of 3585 patients with early-stage HCC were enrolled, including 1287 and 2298 in the AR and NAR groups, respectively. After PSM, the OS and RFS of patients in the AR group were 58.8% and 42.7%, which were higher than those in the NAR group (52.2% and 30.6%, both p < 0.01). The benefits of AR were consistent across most subgroup analyses of OS and RFS. Multivariable COX regression analysis showed that AR was independently associated with better OS and RFS. Notably, although recurrence patterns were comparable, the risk factors for recurrence were not identical for AR versus NAR. Microvascular invasion and narrow resection margin were only associated with a higher recurrence rate after NAR. Conclusions: This study demonstrated that AR decreases the risk of tumor recurrence and improves OS and RFS in patients with early-stage HCC. AR should be adopted as long as such a surgical maneuver is feasible for initial treatment of early-stage HCC. [ABSTRACT FROM AUTHOR]

In the Tunnel Boring Machines (TBMs) construction of soft rock tunnels, adverse geological conditions, such as water-rich and wet strata are often encountered. Water in strata can change the stress state and weaken the mechanical performance of rock mass, further affecting the tunneling process and rock breaking efficiency. To study the effect of water content on mudstone fragmentation characteristics and cutter force during TBM cutter indentation, the water softening effect is considered in the moisture diffusion-fracture coupling model based on the finite-discrete element method (FDEM). Then, the micro parameters (fracture energy release rate, swelling coefficient and moisture diffusion coefficient) of mudstone are calibrated by uniaxial, triaxial compression and swelling tests. Subsequently, the water content and swelling deformation evolution of mudstone samples during water migration are revealed. Finally, the coupling model is utilized to investigate the fragmentation characteristics and cutter force of mudstone samples with different water contents under various confining pressures during TBM cutter indentation. The fragmentation zone, cutter force, acoustic emission (AE), and crack number during cutter indentation are quantitatively analyzed. Results indicate that the vertical extent of fragmentation range (Ev) decreases with the increase of water content, while the horizontal extent of fragmentation zone (Eh) does not decrease obviously until the water content reaches 3%. The increase of confining pressure reduces the effect of water content on Ev, and the increase of water content also reduces the effect of confining pressure on Ev, indicating that confining pressure and water content have a mutual inhibition effect on Ev. Besides, both the peak value of normal force and the fluctuation range of tangential force for the TBM cutter decrease with the increase of the water content. The AE counts show that the failure pattern of mudstone is mainly shear failure during TBM cutter indentation. Specifically, many shear cracks are generated in the compression zone under the cutter, while few tensile cracks propagate in mudstone on both sides and deeper below the cutter. For mudstone under different confining pressures, the proportion of shear cracks increases with the increase of water content. Moreover, the effect of cutter penetration velocity on mudstone fragmentation characteristics and cutter force is discussed. The results in this paper have theoretical guidance for TBM construction of soft rock tunnels in water-rich and wet strata. Highlights: A FDEM moisture diffusion-fracture coupling model is first applied to study the effect of water content on rock fragmentation by TBM cutter. Shear failure is the main failure pattern of mudstone during TBM cutter indentation. The fragmentation zone and cutter force are greatly affected by water content during TBM cutter indentation. Water content and confining pressure have a mutual inhibition effect on the vertical extent of fragmentation zone. [ABSTRACT FROM AUTHOR]

The surrounding rock in deep underground engineering is often subjected to true three-dimensional high-stress conditions. Excavation unloading results in changes in the stress state and induces damage in the surrounding rock, subsequently, dynamic disturbance triggers catastrophic in the damaged surrounding rock and increases the risk of engineering. Therefore, it is necessary to elucidate the dynamic mechanical behavior and fracture evolution mechanisms of deep surrounding rock. In this study, a novel three-stage true triaxial static-dynamic coupling loading test method was proposed to model stress paths experienced by the rock during disturbance failure after excavation damage in deep engineering. With acoustic emission (AE) monitoring, a set of true triaxial tests was conducted to investigate the influence of initial damage degree on the disturbance mechanical properties and failure mechanisms of monzogabbro, including bearing capacity, deformation, macro and mesoscopic fracture characteristics, and anisotropic disturbance fracture evolution mechanisms. AE activity can reflect the disturbance failure processes (decay stage, steady stage, and accelerated stage), and tensile-shear mechanisms evolution based on AE parameters AF/RA are well investigated. The disturbance critical stress is defined and calculated based on the disturbance life, and it can be used as the criterion for rock disturbance failure. The transition conditions of disturbance deformation in three stages can be linked with static strains corresponding to damage stress and peak strength under true triaxial stress. When initial damage degree increases from 80 to 93% of peak strength, disturbance life of monzogabbro decreases by 98%, deformation differential index DI values increases by 31%, and the disturbance failure mode changes from localized tensile splitting failure/ tensile-shear mixed failure to macroscopic shear failure. The study also explores the implications of initial damage degree on the disturbance fracture mechanisms of different buried depths and deteriorated surrounding rock. Highlights: A novel three-stage true triaxial static-dynamic coupling loading (TTSDC) test method is proposed for modelling the excavation-induced damage and then far-field disturbance fracture of surrounding rock in deep engineering. With the increase of initial damage degree, the disturbance life of monzogabbro decreases, and the disturbance failure mode changes from localized tensile splitting failure/tensile-shear mixed failure to macroscopic shear failure. A new differential index is proposed to characterize the influence of initial damage degree on disturbance deformation anisotropy. The tensile-shear mechanism during disturbance failure evolution is well investigated with AE parameters. The triggering conditions of rock disturbance failure evolution under true triaxial stress are interpreted. [ABSTRACT FROM AUTHOR]

The numerical manifold method (NMM) introduces the mathematical and physical cover to solve both continuum and discontinuum problems in a unified manner. In this study, the NMM for solving steady-state nonlinear heat conduction problems is presented, and heat conduction problems consider both convection and radiation boundary conditions. First, the nonlinear governing equation of thermal conductivity, which is dependent on temperature, is transformed into the Laplace equation by introducing the Kirchhoff transformation. The transformation reserves linearity of both the Dirichlet and the Neumann boundary conditions, but the Robin and radiation boundary conditions remain nonlinear. Second, the NMM is employed to solve the Laplace equation using a simple iteration procedure because the nonlinearity focuses on parts of the problem domain boundaries. Finally, the temperature field is retrieved through the inverse Kirchhoff transformation. Typical examples are analyzed, demonstrating the advantages of the Kirchhoff transformation over the direct solution of nonlinear equations using the Newton-Raphson method. This study provides a new method for calculating nonlinear heat conduction. [ABSTRACT FROM AUTHOR]

We investigated the application of ensemble learning approaches in geotechnical stability analysis and proposed a compound explainable artificial intelligence (XAI) fitted to ensemble learning. 742 sets of data from real-world geotechnical engineering records are collected and six critical features that contribute to the stability analysis are selected. First, we visualized the data structure and examined the relationships between various features from both a statistical and an engineering standpoint. Seven state-of-the-art ensemble models and several classical machine learning models were compared and evaluated on slope stability prediction using real-world data. Further, we studied model fusion using the stacking strategy and the performance of model fusion that contributes to slope stability prediction. The results manifested that the ensemble learning model outperformed the classical single predictive models, with the CatBoost model yielding the most favourable results. To dive deeper into the credibility and explainability of CatBoost composed of multiple learners, the compound XAI fitted to CatBoost was formulated using feature importance, sensitivity analysis, and Shapley additive explanation (SHAP), which further strengthened the credibility of ensemble learning in geotechnical stability analysis. [ABSTRACT FROM AUTHOR]

Background: Robotic gastrectomy (RG) has been widely used to treat gastric cancer. However, whether the short-term outcomes of robotic gastrectomy are superior to those of laparoscopic gastrectomy (LG) for elderly patients with advanced gastric cancer has not been reported. Methods: The study enrolled of 594 elderly patients with advanced gastric cancer who underwent robotic or laparoscopic radical gastrectomy. The RG cohort was matched 1:3 with the LG cohort using propensity score-matching (PSM). Results: After PSM, 121 patients were included in the robot group and 363 patients in the laparoscopic group. Excluding the docking and undocking times, the operation time of the two groups was similar (P = 0.617). The RG group had less intraoperative blood loss than the LG group (P < 0.001). The time to ambulation and first liquid food intake was significantly shorter in the RG group than in the LG group (P < 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P = 0.14). Significantly more lymph nodes were dissected in the RG group than in the LG group (P = 0.001). Postoperative adjuvant chemotherapy was started earlier in the RG group than in the LG group (P = 0.02). Conclusions: For elderly patients with advanced gastric cancer, RG is safe and feasible. Compared with LG, RG is associated with less intraoperative blood loss; a faster postoperative recovery time, allowing a greater number of lymph nodes to be dissected; and earlier adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Due to the proliferation of high-quality copying devices and the significant profits of counterfeit products, it is critical to establish an effective scheme for detecting and preventing the counterfeiting of goods. At present, most anti-faking schemes leave much to be desired in terms of cost, convenience, and ability to facilitate pre-sale authentication. The paper designs a unique textured pattern and proposes a triple anti-counterfeiting authentication (TACA). First, the textured pattern consists of triple encryptions (the first is that the key area of the QR code is covered, the second includes scale and Arnold transformation, and the third involves replacing the black areas of the pattern with random multi-level grayscales), the abundant details in the texture not only effectively conceal information, but also that their distortion will increase. Second, TACA comprises interpretability analysis (IA), spectral feature analysis (SFA), and spot matching analysis (SMA) in a cascaded way. In further detail, IA mainly exploits the positional transformation of individual pixels and the block features of local regions to restore interpretability. SFA uses the low-frequency subgraph of discrete wavelet transform (DWT) at a specified scale to capture macroscopic structural information. SMA is able to capture the detailed information of the pattern by utilizing SURF to detect the peak region rate positions and employing BRISK to accurately describe them before. Finally, this paper investigates the robustness of the proposed anti-counterfeiting scheme under a variety of copying methods (replicating, scanning-printing), capturing devices (smartphones), and attack scenarios (no attack, cropping, noise, blur). [ABSTRACT FROM AUTHOR]

Autophagy involves the sequestration and delivery of cytoplasmic materials to lysosomes, where proteins, lipids, and organelles are degraded and recycled. According to the way the cytoplasmic components are engulfed, autophagy can be divided into macroautophagy, microautophagy, and chaperone-mediated autophagy. Recently, many studies have found that autophagy plays an important role in neurological diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, neuronal excitotoxicity, and cerebral ischemia. Autophagy maintains cell homeostasis in the nervous system via degradation of misfolded proteins, elimination of damaged organelles, and regulation of apoptosis and inflammation. AMPK-mTOR, Beclin 1, TP53, endoplasmic reticulum stress, and other signal pathways are involved in the regulation of autophagy and can be used as potential therapeutic targets for neurological diseases. Here, we discuss the role, functions, and signal pathways of autophagy in neurological diseases, which will shed light on the pathogenic mechanisms of neurological diseases and suggest novel targets for therapies. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to translate and culturally adapt the standardized outcomes in nephrology–hemodialysis fatigue (SONG–HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG–HD fatigue (C-SONG–HD fatigue) scale. Methods: Forward and back translations were used to translate the SONG–HD fatigue scale into Chinese. We used the C-SONG–HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test–retest reliability, and convergent validity, respectively. Responsiveness was also evaluated. Results: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG–HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test–retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77. Conclusion: The Chinese version of the SONG–HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients. [ABSTRACT FROM AUTHOR]

Although deep learning algorithms have addressed the issue of identifying the source camera to a certain extent, developing a straightforward and effective network remains a challenging task. At present, most of the excellent network schemes in source camera identification are deep networks, which heavily rely on the strong feature extraction ability of deep networks. Although deepening network layers has achieved certain results, training a deep convolutional neural network model requires a large dataset, sophisticated hardware and lengthy training time, and there is a waste of resources. To solve the problem of redundant structure and resource waste of deep convolutional neural networks, this paper proposes the SE-BRB module, which we call a new network module based on the residual module and SE module. Based on this, an adaptive dual-branch fusion network (ADF-Net) with a simplified structure is designed to identify the source of digital images. Specifically, the bottleneck residual module can achieve direct backward transfer of shallow features to avoid images being over-compressed and is suitable for capturing weak source features in images; Additionally, the introduction of a channel attention mechanism can increase the weight of effective feature channels in the network and improve network performance. Finally, multiscale camera feature fusion is realized through a dual-branch network structure to further improve the network performance. The accuracy of the model proposed in this paper is 99.33% and 98.78% on the Dresden dataset and the self-built complex dataset, respectively, and the classification accuracy is far ahead of the existing source camera identification methods. [ABSTRACT FROM AUTHOR]

Influenza virus continuously evolves to escape human adaptive immunity and generates seasonal epidemics. Therefore, influenza vaccine strains need to be updated annually for the upcoming flu season to ensure vaccine effectiveness. We develop a computational approach, beth-1, to forecast virus evolution and select representative virus for influenza vaccine. The method involves modelling site-wise mutation fitness. Informed by virus genome and population sero-positivity, we calibrate transition time of mutations and project the fitness landscape to future time, based on which beth-1 selects the optimal vaccine strain. In season-to-season prediction in historical data for the influenza A pH1N1 and H3N2 viruses, beth-1 demonstrates superior genetic matching compared to existing approaches. In prospective validations, the model shows superior or non-inferior genetic matching and neutralization against circulating virus in mice immunization experiments compared to the current vaccine. The method offers a promising and ready-to-use tool to facilitate vaccine strain selection for the influenza virus through capturing heterogeneous evolutionary dynamics over genome space-time and linking molecular variants to population immune response.Seasonal influenza vaccine effectiveness depends on including virus strains in the vaccine that closely match those circulating in the upcoming season. In this study, the authors develop a computational model of influenza virus evolution to predict future circulating strains and therefore support vaccine strain selection. [ABSTRACT FROM AUTHOR]

Hyaluronidases catalyze the degradation of hyaluronan (HA), which is finding rising applications in medicine, cosmetic, and food industries. Recombinant expression of hyaluronidases in microbial hosts has been given special attention as a sustainable way to substitute animal tissue–derived hyaluronidases. In this study, we focused on optimizing the secretion of hyaluronidase from Homo sapiens in Pichia pastoris by secretion pathway engineering. The recombinant hyaluronidase was first expressed under the control of a constitutive promoter PGCW14. Then, two endoplasmic reticulum–related secretory pathways were engineered to improve the secretion capability of the recombinant strain. Signal peptide optimization suggested redirecting the protein into co-translational translocation using the ost1-proα signal sequence improved the secretion level by 20%. Enhancing the co-translational translocation by overexpressing signal recognition particle components further enhanced the secretory capability by 48%. Then, activating the unfolded protein response by overexpressing a transcriptional factor ScHac1p led to a secreted hyaluronidase activity of 4.06 U/mL, which was 2.1-fold higher than the original strain. Finally, fed-batch fermentation elevated the production to 19.82 U/mL. The combined engineering strategy described here could be applied to enhance the secretion capability of other proteins in yeast hosts. Key points: • Improving protein secretion by enhancing co-translational translocation in P. pastoris was reported for the first time. • Overexpressing Hac1p homologous from different origins improved the rhPH-20 secretion. • A 4.9-fold increase in rhPH-20 secretion was achieved after fermentation optimization and fed-batch fermentation. [ABSTRACT FROM AUTHOR]

QR codes are widely used in the traceability of commodities, but the QR codes are easy to become blurred during the acquisition process of mobile phones, which affects their normal identification, so it is necessary to deblur them. This paper proposes a sub-regional deblurring method based on prior knowledge of the gradient and intensity of positioning patterns. Firstly, the QR code is divided into four regions according to the positions of three finder positioning patterns and one alignment positioning pattern. The content invariance of the four positioning patterns can avoid the interference of the content to the estimation of the blur kernel, and also take into account the non-uniformity of the QR code blur. Then the gradient and intensity priors are used to estimate the blur kernels of the position patterns in the four regions, and the calculated blur kernels are applied to the corresponding respective regions for deblurring. Finally, the four deblurred regions are stitched together to obtain the entire deblurring image. The experimental results show that the proposed method performs well in terms of deblurring effect and computational time, surpassing similar deblurring methods. [ABSTRACT FROM AUTHOR]

Introduction: LUAD (Lung adenocarcinoma), the most common subtype of lung carcinoma and one of the highest incidences and mortality cancers in the world remains still a substantial treatment challenge. Ivermectin, an avermectin derivative, has been traditionally used as an antiparasitic agent in human and veterinary medicine practice during the last few decades. Though ivermectin has been shown to be effective against a variety of cancers, however, there is few available data reporting the antitumor effects of ivermectin in LUAD. Methods: The effect of ivermectin on cell viability and proliferative ability of LUAD cells was evaluated using CCK-8 and colony formation assay. Apoptosis rate and autophagy flux were detected using flow cytometry based on PI/Annexin V staining and confocal laser scanning microscope based on LC3-GFP/RFP puncta, respectively. Western blotting experiment was conducted to verify the results of changes in apoptosis and autophagy. LUAD-TCGA and GEO databases were used to analyse the expression and predictive value of PAK1 in LUAD patients. Xenograft model and immumohistochemical staining were used for verification of the inhibitor effect of ivermectin in vivo. Results: Ivermectin treatment strikingly impeded the colony formation, and the viability of the cell, along with cell proliferation, and caused the apoptosis and enhanced autophagy flux in LUAD cells. In addition, ivermectin-induced nonprotective autophagy was confirmed by treating LUAD cells with 3-MA, an autophagy inhibitor. Mechanistically, we found that ivermectin inhibited PAK1 protein expression in LUAD cells and we confirmed that overexpression of PAK1 substantially inhibited ivermectin-induced autophagy in LUAD cells. Based on TCGA and GEO databases, PAK1 was highly expressed in LUAD tissues as compared with normal tissues. Furthermore, LUAD patients with high PAK1 level have poor overall survival. Finally, in vivo experiments revealed that ivermectin efficiently suppressed the cellular growth of LUAD among nude mice. Conclusion: This study not only revealed the mechanism of ivermectin inhibited the growth of LUAD but also supported an important theoretical basis for the development of ivermectin during the therapy for LUAD. [ABSTRACT FROM AUTHOR]

This article explores the chemical constituents of Salvia cavaleriei var. simplicifolia, a plant used for medicinal purposes by the Miao and Dong nations in Guizhou Province, China. The researchers isolated seven compounds from the plant, including dehydrodiisoeugenol and 14-formyl-2,7-dihydroxycadalene, which were isolated from the Salvia genus for the first time. The article provides detailed information about the extraction and purification processes used to obtain these compounds. The compounds were analyzed using nuclear magnetic resonance spectroscopy, and their structures and characteristics were determined. Some of the compounds showed potential hemostatic activity. The research was supported by various funding sources. [Extracted from the article]

Coastal upwelling regions are among the most productive marine ecosystems but may be threatened by amplified ocean acidification. Increased acidification is hypothesized to reduce iron bioavailability for phytoplankton thereby expanding iron limitation and impacting primary production. Here we show from community to molecular levels that phytoplankton in an upwelling region respond to short-term acidification exposure with iron uptake pathways and strategies that reduce cellular iron demand. A combined physiological and multi-omics approach was applied to trace metal clean incubations that introduced 1200 ppm CO2 for up to four days. Although variable, molecular-level responses indicate a prioritization of iron uptake pathways that are less hindered by acidification and reductions in iron utilization. Growth, nutrient uptake, and community compositions remained largely unaffected suggesting that these mechanisms may confer short-term resistance to acidification; however, we speculate that cellular iron demand is only temporarily satisfied, and longer-term acidification exposure without increased iron inputs may result in increased iron stress. Coastal upwelling regions are among the most productive marine ecosystems but may be threatened by amplified ocean acidification. Here the authors show from community to molecular levels that phytoplankton in an upwelling region respond to short-term acidification exposure with iron uptake pathways and strategies that reduce cellular iron demand. [ABSTRACT FROM AUTHOR]

Epoxidation of the carbon-carbon double bonds on unsaturated rubber macromolecules can produce novel modified rubber species with special properties, and construct eco-friendly crosslinking pathway via the reaction of epoxide groups to solve the problems brought by conventional sulfur vulcanization system. In this contribution, a novel modified product of isobutylene isoprene rubber (IIR), epoxy-functionalized IIR (EIIR) was successfully prepared by in situ epoxidation technique for the first time, and the crosslinking of EIIR was achieved by the reaction of oxirane groups with maleic anhydride (MAH) without additional additives. The reaction conditions for preparing EIIR were optimized through systematic research on the epoxidation process. Under optimal condition, the degree of epoxidation of the rubber reached around 99% without side reactions. The obtained EIIR/carbon black composites cured by MAH had excellent mechanical properties comparable to those of IIR composites. More importantly, compared with IIR composites, the air-tightness of the EIIR composites was improved by about 50%, and the flexural fatigue life of first-level cracks and sixth-level cracks was increased by several times. The significant improvement of these properties is of great significance for the application safety and energy saving of IIR materials. [ABSTRACT FROM AUTHOR]

This study investigates an e-commerce supply chain comprising a supplier and an online retailer, wherein the supplier determines the quality improvement of products and the online retailer decides whether or not to acquire information on consumer preference. Consumer preference is ex-ante unknown to both the supplier and online retailer but can be resolved by the online retailer's information acquisition behavior. We consider two widely adopted information acquisition strategies, namely, the committed acquisition strategy and contingent acquisition strategy, which differ in whether the online retailer's information acquisition decision is made prior to or after the supplier's quality improvement decision. We find that, under either strategy, the online retailer acquires information only when the cost of information acquisition is relatively small. Moreover, compared with the contingent one, the committed acquisition scheme boosts the online retailer's motivation to gain information. Additionally, by comparing firms' equilibrium profits under these two acquisition strategies, we uncover that the supplier always prefers the committed acquisition scheme. However, the online retailer's preference toward these two information acquisition strategies is not unidirectional, that is, the online retailer prefers either the committed or the contingent strategy. Specifically, the online retailer is indifferent between these two acquisition strategies when the acquisition cost is either sufficiently low or high; otherwise, when the cost of information acquisition is moderate, the online retailer will shift her strategy from the contingent strategy to the committed strategy as the acquisition cost increases. [ABSTRACT FROM AUTHOR]

Current understanding of the leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) in intestinal stem cells (ISCs) is well established, however, the implications of ISC heterogeneity and homeostasis are poorly understood. Prior studies have provided important evidence for the association between heterogeneity of ISC pools with pathogenesis and therapeutic response of malignant disease. Leveraging the advantages of organoids and single cell RNA sequencing (scRNA-seq), glandular development has been simulated and cell heterogeneity has been clarified. Based on this research, several potential ISCs were identified, such as LGR5 + p27 + quiescent ISCs, LGR5 + Mex3a + slowly proliferating stem cells, and CLU + reverse stem cells. We also illustrated major factors responsible for ISC homeostasis including metabolism-related (LKB1, TGR5, HMGCS2), inflammation-related (IFB-b, IFN2, TNF), and Wnt signaling-related (CREPT, Mex3a, MTG16) factors. ISCs play complex roles in intestinal tumorigenesis, chemoresistance and occasional relapse of colon cancer, which bear discussion. In this review, we focus on novel technical challenges in ISCs fate drawing upon recent research with the goals of clarifying our understanding of complex ISCs, elucidating the integrated intestinal crypt niche, and creating new opportunities for therapeutic development. [ABSTRACT FROM AUTHOR]

Diabetes has been reported to induce brain metabolic disturbance, but the effect of transient neonatal hyperglycemia (TNH) on brain metabolism remains unclear. Herein the rats were treated with a single intraperitoneal injection of 100 µg/g body weight of streptozotocin within 12 h after birth and displayed a typical clinical characteristic of TNH. Then we used NMR-based metabolomics to examine the metabolic changes in the hippocampus between TNH and normal control (Ctrl) rats at postnatal 7 days (P7) and 21 days (P21). The results show that TNH rats had significantly increased levels of N-acetyl aspartate, glutamine, aspartate and choline in the hippocampus relative to Ctrl rats at P7. Moreover, we found that the levels of alanine, myo-inositol and choline were significantly lower in TNH rats, although their blood glucose levels have been recovered to the normal level at P21. Therefore, our results suggest that TNH may have a long-term effect on hippocampal metabolic changes mainly involving neurotransmitter metabolism and choline metabolism. [ABSTRACT FROM AUTHOR]

Due to the salient feature of cutting operation, the numerical manifold method (NMM) can deal with an any-shaped problem domain by the simplest regular grid. However, this usually creates many irregularly shaped lower-order manifold elements. As a result, the NMM not only needs lots of integration points, but also encounters severe locking issues on nearly incompressible or bending-dominated conditions. This study shows a robust single-point integration rule to handle the above issue in the two-dimensional NMM. The essential idea is to separate the virtual work of an element in terms of moments to the center, so that a zero-order main term and higher-order stabilizing terms are obtained. Further, the volumetric locking and the shearing locking are avoided by modifications to the spherical part and shearing part of the stabilizing terms, and hourglass deformation is overcome since stabilizing terms are always non-zero. Consequently, in addition to fewer integration points, the rule improves accuracy since it is free from locking or hourglass issues. Numerical examples verify the robustness and accuracy improvement of the new rule. [ABSTRACT FROM AUTHOR]

CREB-regulated transcription coactivator2 (CRTC2 or TORC2) is a transcriptional coactivator of CREB(cAMP response element binding protein), which affects human energy metabolism through cyclic adenosine phosphate pathway, Mammalian target of rapamycin (mTOR) pathway, Sterol regulatory element binding protein 1(SREBP1), Sterol regulatory element binding protein 2 (SREBP2) and other substances Current studies on CRTC2 mainly focus on glucose and lipid metabolism, relevant studies show that CRTC2 can participate in the occurrence and development of related diseases by affecting metabolic homeostasis. It has been found that Crtc2 acts as a signaling regulator for cAMP and Ca2 + signaling pathways in many cell types, and phosphorylation at ser171 and ser275 can regulate downstream biological functions by controlling CRTC2 shuttling between cytoplasm and nucleus. [ABSTRACT FROM AUTHOR]

During spinal cord injury (SCI), the homeostasis of the cellular microenvironment in the injured area is seriously disrupted, which makes it extremely difficult for injured neurons with regenerative ability to repair, emphasizing the importance of restoring the cellular microenvironment at the injury site. Neurons interact closely with other nerve cells in the central nervous system (CNS) and regulate these cells. However, the specific mechanisms by which neurons modulate the cellular microenvironment remain unclear. Exosomes were isolated from the primary neurons, and their effects on astrocytes, microglia, oligodendrocyte progenitor cells (OPCs), neurons, and neural stem cells were investigated by quantifying the expression of related proteins and mRNA. A mouse SCI model was established, and neuron-derived exosomes were injected into the mice by the caudal vein to observe the recovery of motor function in mice and the changes in the nerve cells in the lesion area. Neuron-derived exosomes could reverse the activation of microglia and astrocytes and promote the maturation of OPCs in vivo and in vitro. In addition, neuron-derived exosomes promoted neurite outgrowth of neurons and the differentiation of neural stem cells into neurons. Moreover, our experiments showed that neuron-derived exosomes enhanced motor function recovery and nerve regeneration in mice with SCI. Our findings highlight that neuron-derived exosomes could promote the repair of the injured spinal cord by regulating the cellular microenvironment of neurons and could be a promising treatment for spinal cord injury. [ABSTRACT FROM AUTHOR]

The phase field method (PFM) has been proposed and incorporated into the finite element method (FEM) for complex crack evolution problems. However, explicit cracks cannot be obtained in the phase field FEM (PFFEM). In the field of rock engineering, explicit cracks are indispensable for hydraulic fracturing problem in which crack opening displacement should be known, and compression-shear crack problems in which contact region should be determined. In this paper, the recently proposed phase field numerical manifold method (PFNMM) is developed to model rock fracturing processes. In PFNMM, PFM is regarded as a fracturing criterion, which deals with crack initiation, propagation, bifurcation and coalescence in a unified form; then crack paths are reconstructed and reproduced from smearing cracks; finally, the physical patches and manifold elements are cut with the reconstructed paths to obtain explicit cracks. The numerical results for several typical examples indicate that rock fracturing processes, including crack initiation without any preset cracks, crack propagation and crack merging, can be explicitly predicted. Besides, the results are in good agreement with the literature. Compared with PFFEM, explicit cracks and jump displacement fields across rock crack faces can be easily obtained by PFNMM. Highlights: The combination of PFM and NMM can reproduce the explicit fracture process in rock. The proposed method is capable of simulating the free opening and closing of cracks. The PFNMM can predict the evolution mechanism of multi-cracks and merging crack. [ABSTRACT FROM AUTHOR]

Nicotinamide mononucleotide (NMN), a naturally occurring biologically active nucleotide, mainly functions via mediating the biosynthesis of NAD+. In recent years, its excellent pharmacological activities including anti-aging, treating neurodegenerative diseases, and protecting the heart have attracted increasing attention from scholars and entrepreneurs for production of a wide range of formulations, including functional food ingredients, health care products, active pharmaceuticals, and pharmaceutical intermediates. Presently, the synthesis methods of NMN mainly include two categories: chemical synthesis and biosynthesis. With the development of biocatalyst engineering and synthetic biology strategies, bio-preparation has proven to be efficient, economical, and sustainable methods. This review summarizes the chemical synthesis and biosynthetic pathways of NMN and provides an in-depth investigation on the mining and modification of enzyme resources during NMN biosynthesis, as well as the screening of hosts and optimization of chassis cells via metabolic engineering, which provide effective strategies for efficient production of NMN. In addition, an overview of the significant physiological functions and activities of NMN is elaborated. Finally, future research on technical approaches to further enhance NMN synthesis and strengthen clinical studies of NMN are prospected, which would lay the foundation for further promoting the application of NMN in nutrition, healthy food, and medicine in the future. Key points: • NMN supplementation effectively increases the level of NAD+. • The chemical and biological synthesis of NMN are comprehensively reviewed. • The impact of NMN on the treatment of various diseases is summarized. [ABSTRACT FROM AUTHOR]

Cys2His2 zinc finger (ZF) domains engineered to bind specific target sequences in the genome provide an effective strategy for programmable regulation of gene expression, with many potential therapeutic applications. However, the structurally intricate engagement of ZF domains with DNA has made their design challenging. Here we describe the screening of 49 billion protein–DNA interactions and the development of a deep-learning model, ZFDesign, that solves ZF design for any genomic target. ZFDesign is a modern machine learning method that models global and target-specific differences induced by a range of library environments and specifically takes into account compatibility of neighboring fingers using a novel hierarchical transformer architecture. We demonstrate the versatility of designed ZFs as nucleases as well as activators and repressors by seamless reprogramming of human transcription factors. These factors could be used to upregulate an allele of haploinsufficiency, downregulate a gain-of-function mutation or test the consequence of regulation of a single gene as opposed to the many genes that a transcription factor would normally influence. Zinc finger design is facilitated with a deep-learning model. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to examine the clinical characteristics and outcomes of patients with estrogen receptor-negative (ER−)/progesterone receptor-positive (PR+) early breast cancer. We also aimed to investigate the benefits of adjuvant endocrine therapy (ET) in this patient population. Methods: Patients with early breast cancer diagnosed at West China Hospital were divided into the ER−/PR+, ER+, and ER−/PR− groups. The chi-square test was used to analyze differences in clinical and pathological features among the groups. Multivariable Cox and Fine–Gray regression models were used to compare mortality and locoregional recurrence (LRR)/distant recurrence (DR), respectively. We performed a subgroup analysis to determine which ER−/PR+ patients can benefit more from ET. Results: From 2008 to 2020, we enrolled 443, 7104, and 2892 patients into the ER−/PR+, ER+, and ER−/PR− groups, respectively. The ER−/PR+ group showed more unfavorable clinical features and aggressive pathological characteristics than the ER+ group. The mortality, LRR, and DR rates were higher in the ER−/PR+ than in the ER+ group. Most clinical features and pathological characteristics were similar between the ER−/PR+ and ER−/PR− group and their outcomes were comparable. In the ER−/PR+ group, patients who received ET showed significantly lower LRR and mortality rates than those who did not; however, no difference was observed in DR. Subgroup analysis suggested that ER−/PR+ patients age ≥ 55 years, and postmenopausal status can benefit from ET. Conclusion: ER−/PR+ tumors have more aggressive pathological characteristics and more unfavorable clinical features than ER+ tumors. ET can reduce the LRR and mortality rates in ER−/PR+ patients. Postmenopausal and age ≥ 55 years ER−/PR+ patients can benefit from ET. [ABSTRACT FROM AUTHOR]

Extensive tracheal injury or disease can be life-threatening but there is currently no standard of care. Regenerative medicine offers a potential solution to long-segment tracheal defects through the creation of scaffolds that support the generation of healthy neotissue. We developed decellularized tracheal grafts (PDTG) by removing the cells of the epithelium and lamina propria while preserving donor cartilage. We previously demonstrated that PDTG support regeneration of host-derived neotissue. Here, we use a combination of microsurgical, immunofluorescent, and transcriptomic approaches to compare PDTG neotissue with the native airway and surgical controls. We report that PDTG neotissue is composed of native tracheal cell types and that the neoepithelium and microvasculature persisted for at least 6 months. Vascular perfusion of PDTG was established within 2 weeks and the graft recruited multipotential airway stem cells that exhibit normal proliferation and differentiation. Hence, PDTG neotissue recapitulates the structure and function of the host trachea and has the potential to regenerate. [ABSTRACT FROM AUTHOR]

Background and Purpose: Arsenic trioxide (ATO) exerts anticancer effects on lung cancer. However, the clinical use of ATO is limited due to its systemic toxicity and resistance of lung cancer cells. The present study aimed to investigate the effects of ATO, alone and in combination with 125I seed implantation on tumor growth and proliferation in lung cancer xenograft mice, and investigate the possible molecular mechanisms. Methods: The transmission electron microscope observed the tumor ultrastructure of lung cancer xenograft mice. The proliferation index of Ki-67 and the number and morphology of tumor microvessels were detected with immunohistochemical staining. The protein and mRNA expression were examined by western blot and real-time PCR assay. Results: The in vivo results demonstrated that ATO combined with 125I seed significantly inhibited tumor growth and proliferation, as well as promoted apoptosis, and decreased the Ki-67 index and microvessel density in lung cancer xenograft mice. Moreover, ATO combined with 125I seed decreased the protein and mRNA expression levels of HIF-1α, VEGF, and BCL-2, and increased those of BAX and P53. Conclusions: ATO combined with 125I seed significantly inhibited tumor growth and proliferation in lung cancer, which may be accomplished by inhibiting tumor angiogenesis and inducing apoptosis. [ABSTRACT FROM AUTHOR]

Bacteroidetes are abundant members of the human microbiota, utilizing a myriad of diet- and host-derived glycans in the distal gut1. Glycan uptake across the bacterial outer membrane of these bacteria is mediated by SusCD protein complexes, comprising a membrane-embedded barrel and a lipoprotein lid, which is thought to open and close to facilitate substrate binding and transport. However, surface-exposed glycan-binding proteins and glycoside hydrolases also play critical roles in the capture, processing and transport of large glycan chains. The interactions between these components in the outer membrane are poorly understood, despite being crucial for nutrient acquisition by our colonic microbiota. Here we show that for both the levan and dextran utilization systems of Bacteroides thetaiotaomicron, the additional outer membrane components assemble on the core SusCD transporter, forming stable glycan-utilizing machines that we term utilisomes. Single-particle cryogenic electron microscopy structures in the absence and presence of substrate reveal concerted conformational changes that demonstrate the mechanism of substrate capture, and rationalize the role of each component in the utilisome.A structural and functional analysis of the systems involved in oligosaccharide uptake in gut Bacteroidetes describes multicomponent complexes termed utilisomes that include pre-processing and transport subunits. [ABSTRACT FROM AUTHOR]

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